Rheumatic Fever and Rheumatic Heart Disease PDF

Rheumatic Fever
and
Rheumatic Heart Disease
Rheumatic Fever
and
Editors
M Satpathy MD DM
Former Professor (Cardiology)
Cuttack, Odisha, India
BR Mishra MD DM
Cardiologist
Eko Imaging Institute
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Rheumatic Fever and Rheumatic Heart Disease

First Edition: 2013
ISBN 978-93-5090-173-1
Printed at
Dedicated to
Swachhala, Mamul, Mili, Tanuja
Gitanjali, Gaurav
Contributors
Bharati Das MD DNB JP Das MRCP FAMS DTM & H (Edin) Santanu Guha Dip Card MD DM
Consultant Cardiologist FRCP DM FACC Professor and Head
Medical Road, Mangalabag Former Professor and Head Department of Cardiology
Cuttack, Odisha, India of Cardiology Kolkata Medical College
Heart Clinic, Ranihat Kolkata, West Bengal, India
BR Mishra MD DM Cuttack, Odisha, India
Cardiologist TK Mishra MD DM
EKO Imaging Institute M Satpathy MD DM Associate Professor (Cardiology)
Cuttack, Odisha, India Former Professor (Cardiology) SCB Medical College
Cuttack, Odisha, India Cuttack, Odisha, India
C Satpathy MD DM
Assistant Professor (Cardiology) NK Mohanty MD DM
SCB Medical College Assistant Professor (Cardiology)
Cuttack, Odisha, India SCB Medical College
HN Mishra MD DM
Professor and Head SN Routray MD DM
Department of Cardiology Associate Professor (Cardiology)
SCB Medical College SCB Medical College
Cuttack, Odisha, India Cuttack, Odisha, India
Preface
Rheumatic fever and its dreaded sequel rheumatic heart disease continue to ravage millions of young people
in the developing countries, causing considerable disabilities. Although innumerable literatures are published
on this subject from the developing countries, there is no precise clinical book on Rheumatic Fever and
Rheumatic Heart Disease for easy understanding of the subject for the students of medicine and pediatrics.
Coronary artery disease is sweeping across the world with percutaneous interventions seems to be the
order of the day and many physicians and cardiologists in the developing countries have also jumped into this
bandwagon in this new millennium. Amidst this scenario of dwindling interest in rheumatic heart disease, we
strongly feel that there is definite need for such a book exclusively dealing with all the fundamental aspects of
the subject including management and its preventive aspects.
The descriptions in the book are written in simple terms. We have done away with intricate molecular
biology and genetics. We have attempted to maintain a proper balance between bedside medicine and special
investigatory tests for diagnosis in stagewise manner so that students of different grades will understand the
subject clearly.
Because basically, this is a clinical book and intended for students and practicing physicians, deliberately
the long-reference lists are omitted, instead relevant references are given in brackets and in the form of
“Further Reading” at the end of each chapter.
We hope this book will be of interest to undergraduate, postgraduate students of medicine, pediatrics and
practicing physicians and it will be best serve its purpose.
M Satpathy
BR Mishra
Acknowledgments
I am indebted to my late teachers PL Wahi and DR Bidwai of Postgraduate Institute of Medical Education and
Research (PGIMER), Chandigarh, India, who entrusted me to collect all literatures possible on Rheumatic
Fever and Rheumatic Heart Disease, for purpose of an international seminar on the subject in the year 1979.
It gave me the inspiration in my mind to write a book on this subject.
I am grateful to all the contributors for their valuable contribution in spite of their busy schedules.
My special thanks to M Behera, SS Mishra, CK Mishra, B Das and DR Das of Cuttack, Odisha, India, for
their timely help.
I owe a debt to AN Patnaik, Nizam's Institute of Medical Sciences (NIMS), Hyderabad, Andhra Pradesh,
India; PK Dash, Chief Cardiologist, Sri Sathya Sai Institute of Higher Medical Sciences (SSSIHMS),
Bengaluru, Karnataka, India. TK Mishra and SN Routray for their unhesitant help and inspiration from
time to time.
My sincere thanks to Sidharth Das, Head, Department of Medicine, Arakhita Swain, Professor of
Pediatrics and NK Patnaik, Professor of Cardiothoracic, SCB Medical College, Cuttack, Odisha, India, for
their timely help.
I must thank Susama Mohanty, Librarian and Shabana Azmi, SCB Medical College Library, Cuttack,
Odisha, India, for their cooperation.
I thank my grandson Swagat Tripathy, a student of standard Xth of Skyline High School, Ann-Arbor,
Michigan, USA, for helping me in typing during his summer holidays. I must thank my wife Swachhala
Satpathy for her full-hearted cooperation.
My special thanks to BR Mishra, the other editor especially for doing all computer-related work for
completion of the entire manuscript. I also thank his wife Gitanjali Kar for her cooperation and patience all
throughout the period of preparing the manuscript.
I am grateful to Shri Jitendar P Vij (Group Chairman) and Mr Ankit Vij (Managing Director), M/s Jaypee
Brothers Medical Publishers (P) Ltd, New Delhi, India. My special thanks to Tarun Duneja (Director-
Publishing) and particularly to Samina Khan her timely help. Mr KK Raman (Production Manager), Mr Sunil
Kumar Dogra, Mr Rajesh Kumar, Mr Manoj Pahuja, Mr Mohit Ghai, Mr Sunil Rawat, for their unhesistent
help to complete the work in time and finally my sincere thanks to all the associates of the company.
M Satpathy
Contents
Section 1: Acute Rheumatic Fever
1. Historical Aspect of Rheumatic Fever and Rheumatic Heart Disease...............................................3

M Satpathy
• Greek Medicine 3
• Egyptian Medicine 3
• Sumerian Medicine 3000 BC 3
• Oriental Medicine (Ancient Hindus, Chinese and Japanese Medicine) 3
– Ancient Hindus Medicine 3
• History of Recognition of Rheumatic Fever and Rheumatic Heart Disease in India 5
2. Epidemiology of Rheumatic Fever and Rheumatic Heart Disease....................................................7

M Satpathy
• RF and RHD in Developed Countries: Past and Present Status 7
– RF and RHD in Asian Countries: Past and Present 8
– RF and RHD in India: Past and Present 9
– Has Rheumatic Heart Disease Really Declined? 9
3. Etiopathogenesis of Rheumatic Fever...............................................................................................14

HN Mishra
• Factors Responsible for Pathogenesis of Rheumatic Fever 14
– Agent Factor, Group A Beta Hemolytic Streptococcus 14
– The Host Factor (Patient) 17
– The Environmental Factor 17
4. Pathology of Acute Rheumatic Fever................................................................................................19

M Satpathy
• Pathology of Cardiac Lesions 19
– Pericardium 19
– Myocardium 19
– Endocardium 20
– Coronary Arterial Lesion 20
– Extracardiac Manifestations 20
– Central Nervous System 21
– Lungs 21
– Kidneys 21
5. Clinical Manifestations of Rheumatic Fever....................................................................................22

M Satpathy
• Major Manifestations of RF 22
– Carditis 22
– Arthritis 25
xiv Rheumatic Fever and Rheumatic Heart Disease
– Chorea 26
– Subcutaneous Nodules 26
– Erythema Marginatum 27
• Minor Manifestations 27
– Fever 27
– Arthralgia 28
6. Laboratory Diagnosis of Acute Rheumatic Fever.............................................................................29

BR Mishra
• Streptococcal Antibody Titer 29
• Throat Swab Culture 30
– Rapid Antigen Test for Group A Streptococcus 30
• Hematological Investigations 30
– Acute Phase Reactants 30
– Troponin Test 31
• Noninvasive Tests 31
– Electrocardiography 31
– Roentgenography 31
– Echocardiography 31
– Nuclear Imaging 32
• Invasive Procedures 33
– Synovial Fluid Analysis 33
– Endomyocardial Biopsy 33
7. Diagnosis and Differential Diagnosis of Rheumatic Fever..............................................................34

BR Mishra
• Modified Jones Criteria (2003) 34
– Major Criteria 34
– Minor Criteria 34
– Essential Criteria 34
– Characteristic Features of Major Criteria 34
– Characteristic Features of Minor Criteria 35
– Jones Criteria not Applied for 35
– Probable Rheumatic Carditis 35
• Clarification of Certain Doubts 35
– Problems for Diagnosis of Acute Rheumatic Fever 36
– Peculiar Observation of Acute Rheumatic Fever 36
– Differential Diagnosis of Acute Rheumatic Fever 36
– Differential Diagnosis of Carditis 37
– Chorea 38
– Differential Diagnosis of Erythema Marginatum 39
– Differential Diagnosis of Subcutaneous Nodules 39
8. Management of Rheumatic Fever.....................................................................................................40

TK Mishra
• Introduction 40
– General Measures 40
– Management of Streptococcal Pharyngitis (Antimicrobial Therapy) 40
• Management of Inflammatory Process (Anti-inflammatory Drugs) 41
– Management of Heart Failure 43
– Management of Chorea 43
Contents xv
– Prophylaxis of Rheumatic Fever 44

– Primary Prophylaxis 44
– Secondary Prophylaxis 45
– Duration of Secondary Prophylaxis 46
– Prospects of Vaccine Against Acute Rheumatic Fever 47
– Control Programs for Acute Rheumatic Fever and Rheumatic Heart Disease 47
Section 2: Rheumatic Heart Diseases
9. Approach to Diagnosis of Rheumatic Heart Disease.......................................................................51

BR Mishra, M Satpathy
• Introduction 51
– Clinical Approach 52
– Functional Classification of Dyspnea, Fatigue and Palpitation New York Heart Association
Classification (NYHA) 52
– Basic Hemodynamic Parameters 53
– Normal Valve Areas 55
– Level of Evidence of Treatment/Interventions/Procedure 55
– Medical Management of Congestive Heart Failure 55
10. Mitral Stenosis................................................................................................................................... 59

SN Routray, BR Mishra
• Definition 59
– Incidence and Prevalence 59
– Anatomy of Mitral Valve 59
– Etiology 60
– Pathology 60
– Pathophysiology 61
– Clinical Features 62
– Investigations 64
– Cardiac Catheterization and Angiocardiography 68
– Diagnosis 68
– Differential Diagnosis 68
– Complications 69
– Mitral Stenosis with Pregnancy 69
– Management 69
11. Mitral Regurgitation.........................................................................................................................74

• Definition 74
– Etiology 74
– Pathology 75
– Diagnosis 81
– Management 81
xvi Rheumatic Fever and Rheumatic Heart Disease
12. Rheumatic Aortic Stenosis................................................................................................................84

Santanu Guha, M Satpathy
• Definition 84
– Anatomy of the Aortic Valve 84
– Etiology 84
– Pathology 85
– Clinical Manifestations 87
– Management 92
– Nonsurgical Interventional Management 93
– Surgical Procedure 93
13. Aortic Regurgitation.........................................................................................................................95

BR Mishra
• Definition 95
– Incidence 95
– Etiology 95
– Pathology 95
– Clinical Manifestations 96
– Peripheral Signs 97
– Investigation 99
– Radionuclide Imaging 101
– Magnetic Resonance Imaging (MRI) 101
– Cardiac Catheterization and Angiocardiography 101
– Diagnosis 103
– Treatment 104
14. Tricuspid Valve Disease...................................................................................................................106

M Satpathy
• Tricuspid Stenosis 106
– Definition 106
– Incidence 106
– Etiology 106
– Anatomy of Tricuspid Valve 107
– Pathology 107
– Diagnosis 111
– Management 112
• Tricuspid Regurgitation 113
Contents xvii
– Definition 113
– Etiology 113
– Acute TR 113
– Hemodynamics 113
– Diagnosis 117
– Management 118
15. Pulmonary Valve Disease................................................................................................................120

M Satpathy
• Anatomy of Pulmonary Valve 120
• Incidence 120
• Causes of Pulmonary Stenosis 120
• Causes of Pulmonary Regurgitation 121
• Clinical Manifestations 121
– Symptoms 121
• Investigations 121
– ECG 121
– Roentgenography 121
• Management 122
16. Combined Valvular Lesions............................................................................................................123

M Satpathy
• Introduction 123
– Incidence 123
– Parameters to Determine Dominance of Lesion 123
– Management 127
17. Infective Endocarditis.....................................................................................................................134

C Satpathy, NK Mohanty
• Definition 134
• History 134
– Epidemiology 134
– Changing Clinical Pattern of Endocarditis 134
– Classification 135
– Pathogenesis and Pathology of Infective Endocarditis 135
– Extracardiac Manifestations 138
– Investigation 139
– Diagnosis 141
– Prevention 142
– Treatment of Infective Endocarditis 143
– Summary 144
– Surgical Treatment 145
– Prognosis 145
– Future Perspectives 145
xviii Rheumatic Fever and Rheumatic Heart Disease
18. Natural History of Rheumatic Fever and Rheumatic Heart Disease.............................................147

M Satpathy, Bharati Das, JP Das
• Introduction 147
– Historical Aspect 147
– Magnitude of the Problem 147
– Evolution of Rheumatic Fever (Birth of RF) 148
– Natural Course of Rheumatic Fever 148
– Natural History of Rheumatic Manifestations 149
– Natural History of Rheumatic Heart Disease 151
– Stenotic Lesions 152
– Regurgitant Lesions 153
– Natural Problems Emerging 154
Index .......................................................................................................................................... 157

Section 1
Acute Rheumatic Fever
CHAPTER 1
Historical Aspect of Rheumatic Fever
and Rheumatic Heart Disease
M Satpathy
The history of medicine is vital and inspiring. It gives Egyptian Medicine

step-wise information about a disease, so that one Egyptian medicine dates back to 3400 BC. The main
can understand it thoroughly. It may be a surprise advancement occurred in the last phase; known as
to many that rheumatic fever and rheumatic heart New empire (1580–1200 BC). The first medical Pa-
disease got its recognition during early part of nine- pyri were written in 1550 BC which stated the ‘moon
teenth century all over the globe, although it has been god’ like ‘Apollo’ in Greece as special deity of medi-
described from the time of Hippocrates. cine. There is a clear description of arthritis in these
Papyri. There are descriptions about deformity of
joints in Egyptian mummies and temple pyramids in
Greek Medicine
1800 BC (described by Hippocrates).
Greek civilization goes back to almost 3400 BC but
the most notable period for development of medicine
known as ‘the classic period’ dates back from 460 to Sumerian Medicine 3000 BC
136 BC. The earliest known ancient Greek physician Although Sumerian culture dates back to 3000 BC,
was Aesculapius (2500 BC). This fact was mentioned it is in the later part, during 600 BC, Babylonian,
by Homer in pre Hippocratic era of medicine (1200 Persian and Jews medicine were well advanced. As
BC). During the classic period it was Hippocrates mentioned in Jews medicine (Bible and Talmud) that
who gave medicine it’s scientific touch and its ethi- blood is vital, identical to soul and the heart is es-
cal ideals (Hippocratic Oath). He is known as ‘Father sential for life.
of Medicine’. The notable developments pertinent to
Rheumatic Heart Disease are:
• Hippocrates in 400 BC described migratory poly- Oriental Medicine (Ancient Hindus,
arthritis to differentiate from gout even with hints Chinese and Japanese Medicine)
of enlargement of heart and liver. He correlated
arthritis with dropsy (Congestive Heart Failure). Ancient Hindus Medicine
• Erasistratus and Herophilus of Alexandria in 300 The earliest Sanskrit docu-ments that deal with medi-
BC described gross anatomy of heart and polyar- cine are Atharva and Rig Veda written by Vyasadeva
thritis. in 1500 BC. The leading Granth Charaka Samhita
• Celsus in Greek-Roman period of Galenic era of written by Charaka in second century BC described
medicine also described polyarthritis but under about rheumatism (arthritis). Charaka metnioned,
gout in 156 BC. he was a true follower of Rishi Agnivesh who was one
• Galen (131–201 AD) the great Greek physician of the main diciple of Rishi Atreya (6th century BC).
after Hippocrates wrote number of medical books Rishi Atreya was the son of Debarshi Atri, known as
on different subjects including one on ‘pulse’. earthly incarnation of Lord Brahma. He described
4 Acute Rheumatic Fever
about Hrudaya (heart) and its ailments in his Chara- • Thomas Sydenham (1624–1689) clearly described
ka Samhita. Dhanwantari (200 BC) described clearly rheumatism as a separate entity. He is known as
the diseases like malaria, madhumeha (diabetes) and ‘English Hippocrates’. He described chorea as St
heart diseases. The first medical educational center Vitus dance and it ultimately known as Sydenham’s
was started at Banaras by the King Ashoka (226 BC). chorea.
During the period of Alexander’s India expedition • Rene Laennec discovered stethoscope in 1819.
(327 BC) it is mentioned that the Hindu physicians • Edward Jenner in 1710 tried to distinguish RF
and surgeons had good reputation and knowledge in from RHD.
surgery and medicine. • Richard Bright (1789-1858), described.
Chinese medicine advanced with work of Tsang Rheumatism in his Lumleian Lecture at College of
Kung (170 BC) before Buddhism was introduced Physician, London.
in China in 68 AD. In the encyclopedia of Chinese • Richard Putney (1761) first described clinical
medicine description of different viscera and organs manifestation of RF and RHD.
of human body are found dating back to 1644 AD, • Botkin a Russian physician who was a student of
where “Heart being King and director” is mentioned. Virchow first wrote a book ‘Clinical Lectures’ on
The oldest Japanese medical book, ‘Ishinho’ was RF and RHD in 1880.
written by Wasuhore Tambu in 982 AD. There was • Morgagni a Dutch physician first described mitral
paramount Chinese and Dutch influence over an- stenosis in autopsy series in 1714.
cient Japanese medical approach. • George Fordyce (1798) described RHD as a rheu-
The important developments of modern medi- matic metastasis in heart.
cine pertinent to rheumatic fever (RF) and rheumatic • Thomas Addison (1837) described the associa-
heart disease (RHD) are: tion of rheumatism with Chorea. He first treated
• Refus during the period (68–117 AD) described hepatic dropsy (CHF) with digitalis (known as
about pulse, heart beat and systole as synchro- Addison’s pill).
nous. His treatize on gout was translated into • Raymond Vieussens described for the first time
Latin. mitral stenosis, Aortic regurgitation (AR) and
• Aretaeus of Cappadocia first described famil- ‘Water Hammer Pulse’ in 1715.
ial distribution of a fever, later called rheumatic • Jean Baptiste Bouillaud (1796–1881) is known
fever which leads to congestive heart failure (2nd in western world as “Father of Rheumatic Heart
century AD). He was a famous Greek physician Disease”. He first described in a systematic way the
ranked next to Hippocrates. auscultation of the heart and also about acute RF
• Giovanni Maria Lancisi (1654–1720) (Pope’s phy- in 1836 in his book “Nouvells Recherches Sur le
sician) described first the deformity of cardiac Rheumatism Articulaire”. Another Russian phy-
valves vegetations (1707) and classified cardiac sician Gregory Ivanovich Sokolsky in 1836 made
diseases. similar observation. RF is known as Sokolsky—
• Guillaume de Baillou (1538–1616), a French phy- Bouillaud disease in Russia.
sician, first used the term rheumatiomos that is • Dundas (1809) emphasized RHD as a separate
rheumatism as a separate entity to distinguish disease entity.
it from gout. He is known as “Father of Cardiac • William Charles Wells (1810) presented a clinco-
Rheumatism”. His views were published posthu- pathological paper (on 3rd April, 1810) by which
mously in 1642. long controversy ended regarding existence of
• William Harvey described the blood circula- RF and RHD as separate entities in European
tion in 1628. But long before Erasistratos of Keos countries.
310-315 BC, the first experimental physiologist • Rheumatic nodule goes by the name of Meynet
conceived the idea that heart is a pump. (1875) as Nodules deMeynet. Although Charles
Historical Aspect of Rheumatic Fever and Rheumatic Heart Disease 5
Wells described rheumatic nodule way back in • Wilson in 1959 demonstrated broth culture posi-
1812; but it was not given any importance at that tivity for GAS strains.
time. • T Duckett Jones’ criteria to diagnose rheumatic
• Watler Butier cheadle (Harvean lecture in 1889) fever was first accepted universally in 1965. He is
described endocarditis, pericarditis, pleurisy, ery- known as “Father of Modern Rheumatic Fever”.
thema, chorea, nodules and tonsillitis as manifes- These are important historical landmarks of de-
tations of RF known as ‘Cheadles Cycle’. velopment of rheumatic fever and rheumatic heart
• Osler in 1892; described in detail Rheumatism disease described in nutshell.
and its manifestations.
• Sir Arthur Newsholme (1895) presented the
first epidemiological survey conducted in Great History of Recognition of
Britain and Scandinavian countries in his famous Rheumatic Fever and Rheumatic
Milroy Lecture. Heart Disease in India
• Willem Einthoven in 1903 invented string galva- It may be surprising for many physicians to mention
nometer for electrocardiographic tracing. that, although rheumatic fever and rheumatic heart
• Ludwig Aschoff in 1904 described Aschoff ’s disease were prevalent since 1835 till about 1950
nodule in myocardium in RF. Talalaev in Russia (that is more than 100 years) there was a strong no-
described rheumatic granuloma in rheumatic tion that this disease was very rarely seen in India.
myocarditis. This goes by the name Aschoff-Tala The earliest report on RF was published by Capt
laev granuloma. Tull in March, 1895 in Indian medical gazette. He has
• A rumor of infectious etiology of RF spread dur- mentioned that prior to his report Malcolmson from
ing 1920 to1930 like tuberculosis, so patients were Madras Medical Service reported in 1835 that rheu-
treated at sanatoria and treated with Sulfonamide matism was most prevalent among sipoys and also
and Penicillin. mentioned by Moore while working in a dispensary
• Snow bird migration of children from New York in Rajasthan in 1870 observed that there were nu-
to Miami in winter did not solve the problem merous cases of subacute and chronic rheumatism.
of RF. On the other hand, RF was reported in Vaishnava S from Vellore published in Ind J Child
English troops stationed in the hot desert of Libya health (1960:9;290) that first acute rheumatism was
in World War II, since then the notion gradually reported exactly 125 years back.
changed that RF is not only manifested in temper- But unfortunately some reports in early part of
ate climates but also in tropical climates. twentieth century showed rheumatic fever and rheu-
• Rebecea Craighill Lancefield (1928-1940) classi- matic heart disease were rare in India and this notion
fied Streptococcus into different groups. prevailed till 1950. These reports are as follows:
• Griffith (1926) classified Streptococcus as per their • Sir Leonard Rogers (1910) mentioned that he did
sero types. not find a single case of typical endocarditis in
• Collis (England) and Cobam (USA) established 4800 postmortem records in 37 years except one
the relation between GAS and RF in 1931. doubtful case. Sir Leonard Roger reported valvu-
• Todd in 1932 discovered a method to determine lar heart disease was due to syphilis in 1925.
antibody titre (streptolysin O) known as Todd’s • Megaw JWD mentioned RHD was rare in India in
unit. Indian Medical Gazette, 1910, volume XIV, page 81.
• After a long period of silence even after the influ- • Col Keates in 1932 mentioned he never saw
ential Harveian lecture of Cheadle the informa- inflamed mitral valve in 600 postmortem exami-
tion of different manifestations of RF were codi- nation performed in Amritsar.
fied by T Duckett Jones (popularly known as • Clark 1930 reported that streptococcal infection
Jones’ Criteria) in 1944. (cause for RF) in tropics was rare.
• Even as late as 1952 Paul White in his textbook • Kelley (1940) from UP and also from Bombay
(Heart Disease, MacMillan Co, New York, 4th ed, published definite cases of RF and RHD.
1951) and in 1958 William Boyd in his textbook • Vakil from Bombay reported RHD present in
mentioned that RF and RHD were rare in tropics. 27.6 percent of cases with congestive heart failure
• Roger L and Megaw JWD in their book on amongst all cardiac cases (Ind. HJ 1949;1:15) and
“Tropical Medicine” in 1952 edition also men- also reported RHD in Ind. HJ1953;5:198).
tioned that RF and RHD were rarely seen in India. • Col Wig and Malhotra (1953) from Amritsar,
Contrary to these above reports it was from the reported 500 cases of congestive heart failure with
year 1920 many physicians from different parts of In- 36.8 percent of RHD.
dia reported RF and RHD are common diseases seen • Padmavati S. cardiac patients in underdeveloped
in clinical practice and in hospitals. countries. Am. HJ 1959:58;418 and reported heart
The physicians those who reported authenti- diseases in Delhi in Ind. HJ 1958;10:33).
cally that RF and RHD are frequently seen in clini- Tradition die hard, in spite of these hard evi-
cal practice and prevalent all throughout the country dences certain textbooks used to write till 1960 that
between the period 1920 to 1950, are: RHD was rare in tropical countries. But by the year
• Kamath in 1921 from South India reported in 1940; it was definite countrywide impression that
Indian Medical Gazette, 1921. RF and RHD were very common diseases seen in
• UP Basu from Calcutta in March issue of Indian clinical practice, contrary to the notion it was rare
Medical Gazette (1925, 60, 305) reported 10 cases in India.
of infective endocarditis in mitral valve lesions.
• UP Basu again in 1931 reported 25 cases of RHD
(Indian Medical Gazette). Further Reading
• Kutumbiah P from Visakhapatnam reported 20 1. History of medicine by FH Garrison, 4th edition,
cases of RF in Ind J Paediatric, 2: 215, 1935. Again 1929.
he reported cases of RHD in Ind J Paediatric, 8:62, 2. Rheumatic Fever and Streptococcal Infection by Gene
1941. H Stollerman, Grune and Stratton Publisher, New
• TA Hughes and Md Yusuf in May issue of Indian York.
Medical Research, 1930 from Mayo Hospital, 3. Rheumatic Fever by J Narula, Renu Virmani, K
Lahore (undivided India) reported definite evidence Srinath Reddy and R Tondon, 1999 published by
of RHD in 35 cases of mitral stenosis in Punjab. American Registry of Pathology, Washington.
• Col Hughes again published another paper in 4. Rheumatic Fever: 2nd edition, Milton Markowitz and
Indian Medical Gazette from Punjab in 1935 Leon Gordis, WB Saunders Company, Philadelphia,
where he mentioned 30 cases of RF. 1972.
• Col K. Lal Wig from Lahore published 45 cases 5. Hughes TA, Yusuf Md. Further observation in
stressing RF and RHD present in high frequency heart disease in the Punjab, Indian Medical Gazette
in children; in Indian Medical Gazette 1935. 1931;31:423-6.
• Scott from Agra and Lucknow, 1930 published 20 6. Hughes TA, Yusuf Md. Heart Disease in Punjab in
cases of RF and RHD (Ind. Med. Gaz. 1938;78:330). special reference to mitral stenosis, Indian Medical
• Plummer in 1938 reported high frequency of strep- research, 1930;18:483.
tococcal infection in tropical countries including 7. Basu UP. The Prevention of Heart Affection in India,
India. Indian Medical Gazette 1932:566-70.
CHAPTER 2
Epidemiology of Rheumatic Fever
M Satpathy
Introduction “A peculiar disease of the heart” which made clear that

Rheumatic fever (RF) and rheumatic heart disease RHD is a separate disease entity itself. John Haygarth
(RHD) have been reported in literature from differ- in 1805 detected acute rheumatism in Europian coun-
ent countries time after time since early seventeenth tries. William Cullen observed acute rheumatism in
century. Its protean clinical manifestations compelled young persons and chronic rheumatism in old adults
the physicians to conduct surveys to find out the during the year 1776 to 1794 in England. Ultimately
incidence, prevalence and epidemiological features this long controversy ended after a clinico-patholog-
of the disease to assess the magnitude of the problem ical paper presentation on RF and RHD by William
in a scientific way for better care of the patients and Charles Wells on 3rd April 1810. Jean-Baptiste Bouil-
for its prevention. lard, the “Father of Rheumatic Heart Disease” in 1840
After a long controversy RF and RHD as sepa- became famous for his lecture “Laws of Coincidence”
rate disease entities were accepted unanimously in and for his first systematic auscultation of the heart
European countries as late as 1810. The global notion of patients with acute RF. In the same period simi-
was that it was a disease of temperate climate and un- lar independent observations on presence of RF and
common in tropical countries. This notion persisted RHD were made by the Russian clinician Gregory
up to 1940s, till serial reports on presence of RF and Ivanovick Sokolsky in 1838. In Russia, rheumatic fe-
RHD came out from India and other tropical coun- ver is known as Sokolsky-Bouillard disease. Cheadle
tries in different national and international journals. in his celebrated Harveian lecture in 1889 mentioned
RHD was a common disease in Europe. After massive
immigration of people during the period of 1800 to
RF and RHD in Developed countries: 1900 from different countries, RF and RHD became
Past and Present Status rampant in crowded places in the USA. William Potts
Thomas Sydenham, known as “English Hippocrates” Dewes described number of cases of RHD from Phil-
in 1686 mentioned that there were a number of adelphia (USA) in 1824. It was a common disease and
cases of acute and chronic polyarticular joint affec- also a common cause of death between age group 5 to
tions like RF, in European Countries which were 20 years in the USA during the period 1920 to 1930.
not gout. Although he mentioned chorea at that Even in 1943, it was reported from some areas of the
time he did not correlate it as a manifestation of RF. USA that the incidence of RHD was ranging from 25
Edward Jenner 1710, tried to distinguish RF from to 100/1000 population.
RHD, similarly George Fordyce in 1798 described The first epidemiological survey of RF was con-
RHD as rheumatic metastasis on heart. David ducted by Sir Arthur Newsholme in British Islands
Dundas in 1809 presented a paper under the heading and Scandinavian countries. He mentioned in his
famous Milroy lecture in 1895 that RF and RHD were RF and RHD in Asian Countries:
common in the UK and Scandinavian countries. Past and Present
John R Paul conducted epidemiological study is the
USA in 1930. Although decline of RF was noticed in The incidence of RF and RHD has also declined sig-
the USA, the UK and European countries since 1921, nificantly in Japan. In the year 1958, it was 4.6 but in
significant decline in both RF and RHD were noticed 1972 it declined to 2.6/1000, while in 1981 it was only
and reported from different developed countries 0.1/1000. In China RF and RHD are still prevalent
after industrial revolution consequent to better hy- but the incidence has declined as compared to the
giene and housing programme after 1940. Puddu year 1950. In 2001 the incidence of RF was 1.5 per
observed that in most of the European countries par- 1000 in school going children and the prevalence of
ticularly in Italy the incidence of RF among school RHD was 2 per 1000 in Chinese adults.
children was high, varies from 7.7 to 20/1000 even In Pakistan high prevalence of RHD is still pre-
in the year 1953. The decline was very significant af- sent without any significant decline over last 30 years.
ter sulfonamide and penicillin used for streptococcal The incidence of RHD on hospital based study, was
sore throat during the year 1950 to 1960. At present 23 percent amongst all cardiac cases in 1993, and in
acute RF occurs rarely in these countries. However the year 2004 also the prevalence was 5.7 per 1000
there are reported cases of RHD seen below 25 years population. Mohammed Faheen et al from Pakistan
of age. Gordis estimated that the incidence of RF in have reported in 2006 that rheumatic heart disease is
Baltimore (USA) was 24 per 100,000 populations still a common problem in their country. In Bangla-
(between 5 to 19 years of age) during the period 1960 desh, the prevalence of RHD was 34.0 percent and in
to 1964. Stambler observed decline in incidence of Thailand, 34.0 percent in the year 1993. Similarly there
RF amongst school children to less than 2 per 1000 in is no significant decline of incidence of RF and RHD
Chicago (USA) during the year 1962. Table 2.1 indi- in Srilanka, the prevalence was 6.0 per 1000 in school
cates significant decline of prevalence of RF amongst going children in the year 1998. Vongprateep reported
school children in the USA. there was no change in incidence of RF and RHD in
Incidence of RF and RHD was 100 per million in Thailand from 1933 to 1980. Table 2.2 shows preva-
1962 but by the year 2007, it was 0.23 to 1.8 per million lence of RF in different countries of WHO region.
in the USA. Similarly RF and RHD became extremely According to Jonathan R Carapetis “RHD is
rare in Sweden and other Scandinavian countries by indeed an ongoing problem in Asia. Moreover two
the year 1970. Resurgence of rheumatic fever in the most rigorously performed studies from Pakistan
USA was reported during mid-eighties (1987) and and Cambodia confirm that careful research will
from European countries but it was effectively con- uncover many more cases than would otherwise
trolled. have been detected which suggest the true number
Remember: In developed countries like USA, UK, of RHD cases even greater than presented here.”
and European countries, RF and RHD are rarely seen (Circulation. 2008;118:2748-53).
in clinical practice, since 1960. Recent survey report by Marijon E et al from Af-
rica (in Tonga) in 2007 shows that the prevalence of
Table 2.1: Showing declining incidence of Rheumatic RHD based on echocardiographic study is as high as
fever in the USA
21.5 to 30.4/1000 in school children. There is wide
Location Year Age group Rate/1000 variation in prevalence of RF and RHD from country
New York City 1920 6–17 4.3 to country for example in Havana (Cuba) the preva-
New York City 1961 5–18 1.6 lence is 0.2 per 1000 while in Samoa it is 77.8 per 1000
Los Angeles 1966 6–15 0.5
in the year 1999. Again incidence and prevalence of
RF and RHD vary amongst population groups of the
Los Angeles 1984 6–15 0.005
same country like:
Epidemiology of Rheumatic Fever and Rheumatic Heart Disease 9
Table 2.2: Prevalence of RHD in school children Table 2.3: Hospital based study 1920–1970
WHO/SAARC region countries Author Year Place % RF/
Country and Author Year Prevalence/1000 RHD
Nepal, Regmi PR et al 1997 1.2 UP Basu 1925 Calcutta 25 cases
Egypt, Kassen AS et al 1990 5.0 Das Gupta B 1930 Calcutta 20 cases
Ethiopia, K. Oli et al 1992 4.6 Col Hughes TA 1931 Lahore 30 cases
Saudi Arabia, AL-Sekait MA 1990 2.4 and Md Yusuf
et al Raman TK 1935–1946 Vizag 35.6
Sudan, Ibrahim-Khalil S 1992 3.0 Kutumbiah P 1932–1938 Vizag 39.5
Pakistan, Mallick et al 1981 1.5 Banerjee JC 1936–1943 Calcutta 44.6
Srilanka, Mendis et al 1998 6.0 Vakil RJ 1941–1945 Bombay 24.7
India, ICMR 1995 1.0–5.4 Sarojini KS 1946 Madras 46.8
Nepal, ManBahadur et al 2002 1.2 Devichand 1946 Lahore 27.6
Bangladesh, Ahmed et al 2005 1.3 Padmavati S 1951–1955 Delhi 39.1
Abbreviations: WHO—World Health Organization; Vakil RJ 1946–1955 Bombay 29.7
SAARC— South Asian Association for Regional Datey KK 1952–1956 Bombay 22.5
Cooperation.
Devichand 1954–1957 Shimla 50.6
• Maoris and non-Maoris in New Zealand Malhotra RP 1949–1959 Amritsar 26.6
• Samoans and Chinese in Hawaii Rastogi SK 1960 Gwalior 27.8
• Aboriginals and non-aboriginals in Northern Mathur KS and 1947–1961 Agra 30.4
Australia Sapru RP
• Black and White in the USA Sepaha GC 1952–1962 Indore 16.5
Similarly the mortality rate for RHD also varies
Joshi NK 1957–1962 Ahmadabad 35.6
from 0.5 per 100,000 in Denmark to 8.2 per 100,000
in China. After implementation of prevention pro- Bhargav 1945–1964 Bikaner 33.4
gram by WHO, it is observed that the prevalence, Somani OT 1964 Bombay 12.8
morbidity, and mortality rate of RF and RHD has sig- Warrier CWC 1967 Kerala 39.0
nificantly decreased in Havana (Cuba), Costa Rica,
Cairo (Egypt), and Martinique-Guadalupe (Mexico). lence rate by epidemiological (community and school
Note: RF and RHD are still prevalent in Asian coun- survey) and hospital based studies, mainly from the
tries and is one of the main cause of morbidity and year 1920. For further information refer Chapter 1
mortality amongst children and young adults. and Tables 2.3 to 2.9.
RF and RHD in India: Past and Present Has Rheumatic Heart Disease Really
Declined?
Although RF and RHD was reported since 1835,
because of some reports by Sir Leonard Rogger and Opinions of some authors are as follows:
Megaw JWD in 1910 it was believed that the disease • S Padmavati: “The big question is has there been
was rarely seen in India. a significant decline in RF and RHD in India? The
Realizing the magnitude of the problem physi- answer is definitely no”. Ind. HJ 2001;53:35-7.
cians from different parts of India and other tropical • Anil Grover. “The prevalence of RHD has declined
countries started assessing the incidence and preva- in the west but continues to be an important cause
Table 2.4: Hospital based study 1970–2010 Table 2.7: School surveys for prevalence of RF/RHD
(1950–1980)
Author Year Place % RF/
RHD Author Place Year Age Prevalence
Agarwal BL 1966–1973 Allahabad 40.6 range per 1000
RHD
Vijay Kumar M 1966–1985 Delhi 37.9
Athavale VB Bombay 1958 3–19 2.0
Dhar SN 1978 Kashmir 12.5
Rao BRH Vellore 1961 5–16 7.0
Padmavati S 1976 Delhi 33.2
Padmavati Delhi 1962 5–14 1.5
Rao Brahmaji 1969–1974 Hyderabad 34.0 S
Satpathy M 1980 Burla, Orissa 43.5 Devichand Shimla 1963 0–16 39.6
Jose V Jacob 1999–2000 CMC, Vellore 23.0 Zaheer M Aligarh 1973 3–15 3.9
RHD Registry, 1999–2000 MMC, Chennai 26.0% Malhotra RP Calcutta 1973 7–18 4.6
CSI
Sharma M Amritsar 1978 12–19 0.1
Mishra TK 2003 Cuttack 45.0
ICMR Overall 1977 5–16 5.6
The data in above table shows no decrease in inci-
dence of RHD in hospital based study. ICMR Delhi 1979 5–16 11.0
ICMR Hyderabad 1979 5–16 6.1
Table 2.5: Community survey of RF and RHD
ICMR Alleppy 1980 5–16 2.1
Author Place Year Age RHD per
Shah Bombay 1968 5–6 0.15
group thousand
Nair DV Kerala 1978 5–18 0.2
Rastogi SK Gwalior 1964 – 27.8
Souza Goa 1980 6–18 0.13
Jhatakia Bombay 1964 – 3.2
KU The prevalence rate has shown decreasing trend dur-
ing recent years.
Roy SB Delhi 1971 5–30 2.2
Mathur KS Agra 1971 5–30 2.0
Berry JM Chandigarh 1972 All ages 1.44
of cardiovascular morbidity and mortality in
India.” Ind. HJ 2002:54;104-7.
Grover A Chandigarh 1993 5–40 0.9
• GS Sainani: “The main question is whether RF
Verma Kanpur 2004 >15 4.58 and RHD in India have declined significantly that
we can ignore the problem. The answer is no.”
Table 2.6: Autopsy data of RF and RHD
Supplement JAPI. 2006;54:42-7.
Years of Author % RF / RHD • Savitri Srivastav: “So we still have to continue
Study among cardiac with and intensify all our endeavors to control RF
cases and RHD rather than take a recluse in thinking
Up to 1925 Scott H 26 that incidence and prevalence of RF and RHD is
1926–1939 Raghavan P 6 declining in India.” Ind. HJ 2007;59:9-10.
1960–1961 Reddy DB 30 • R Tondon: “A survey conducted by ICMR involv-
ing 133,000 children of 6 to 16 years age, the inci-
1964–1975 Chopra P 36
dence of RHD shows 5.3/1000”. (Ghai Essential
1966–1970 Kinare SG 33 Pediatric, 7th Edition, 2008)
1972 Roy SB and Tondon R 44.97 • R Krishnakumar: “Although the disease burden
1964–1978 Datta BN 20 appears to have declined in parts of India that have
The autopsy data indicate RHD were present in signifi- experienced an improvement in human devel-
cant number of cases. opment, there are many parts where the disease
Table 2.8: School surveys for prevalence of RHD (1981–2010)

Author Place Year Age Prevalence per 1000
ICMR Delhi 1982–1990 5–15 2.9
Sukumar IP Vellore 1982 – 5.0
ICMR Agra 1982 5–16 5.1
ICMR Ballabgarh 1982–1990 5–15 1.0
ICMR Vellore 1982–1990 5–15 2.9
ICMR Varanasi 1982–1990 5–15 5.4
Padmavati S Delhi (urban) 1984–1994 5–10 3.9
Patel DC et al Anand 1986 8–18 2.03
Avasthi G et al Ludhiana 1987 6–16 1.3
Grover A et al Raipurrani 1988–1991 5–15 2.1
Kumar R et al Rajasthan 1992 5–15 3.34
Gupta I et al Jammu 1992 6–16 1.36
Thakur et al Shimla 1992–1993 5–16 1.98
Vaishistha VM et al Agra 1993 5–15 1.42
Kaul RR et al Srinagar 1999–2000 5–15 5.09
Lalchandani A et al Kanpur 2000 7–15 4.54
Jacob Jose V Vellore 2001–2002 5–18 0.68
Mishra M et al Gorakhpur 2003–2006 4–18 0.5
Soman Kochi 2003–2006 5–16 0.12
Periwal KL et al Bikaner 2006 5–14 0.67
The above table shows the prevalence of RHD has decreased in recent years.
Table 2.9: Incidence of Changing Pattern of RHD (1950–2010)

Name of Author and Place Year of 1st observation Percentage of Year of 2nd Percentage of
RHD observation RHD
Bhargava RK Madhya 1945–1954 30.01 1955–1965 34.32
Pradesh
Mathur KS Agra 1947–1951 38 1957–1961 30
Vakil RJ Bombay 1941–1945 24.7 1946–1955 29.7
Somani OT Bombay 1956 22.2 1965 20.8
Nair DV (School Survey) 1968–1969 8/1000 1972–1975 2/1000
Kerala
Dhar SON, Kashmir 1965–1967 12 1973–1975 9.1
Bhatia MC, AIIMS 1959–1969 33 1977–1978 34.5
Wahi PL, Chandigarh 1973 24.2 1978 25.0
Satpathy M, Burla Orissa 1971–1975 44 1976–1980 43
Mishra TK, Cuttack 1981–1990 46.9 1991–2000 45
Table shows there is no significant decrease in incidence of RHD between two periods of observations.
burden may be high. ECAB Clinical Update Although school surveys data mentioned in
Cardiology, CSI, 2008. Table 2.7 show decline of RHD it does not, repre-
• S Ramkrisnan: “RHD is not gone but forgotten” sent the true picture because children (5–18 years)
Cardiology update, CSI, 2008. not attending school and 18 to 40 years of age were
• V Jacob Jose: “It is still a major problem in India. not considered. So it is premature to draw any con-
However recent data suggest that there is a notice- clusion. Similarly the decrease in incidence of RHD
able decline in our country specifically in some has been reported from tertiary hospitals of India
states.” Cardiology update, CSI, 2009. because these hospitals mainly deal with coronary
In recent years the incidence of typical RF (as per artery disease and congenital heart lesions. Their
Jones criteria) has declined in India (Table 2.8). But information does not reflect the true picture of the
the definite decline in prevalence of RHD is debat- whole population. On the contrary, statistical data
able, for example: from general hospitals have shown no significant de-
• Lalchandani A et al from Kanpur (UP), reported crease in RHD (Table 2.9). The fact is that there is
prevalence of RHD from school survey was a paucity of large scale epidemiological (community
4.54/1000 in Indian Heart Journal (abstract). based) study amongst the general population from
2000;52:672. different parts of India to project the actual informa-
• Mishra TK et al hospital study reported the inci- tion. This is also the situation in most of the develop-
dence of RHD was 45% of all cardiac cases. (Indian ing countries.
Heart Journal. 2003;55;2:152-7). Disappearance and reappearance of rheumato-
• Mishra M et al from Gorakhpur (UP) reported the genic strain of GAS responsible for resurgence of RF
prevalence in school survey was 0.5/1000. (Indian is matter of concern in developed countries, (for ex-
Heart Journal. 2007;59:42-3). ample the resurgences that occurred in 1987 in Salt
• Lalchandani A et al Kanpur (UP) recently Lake city of USA). This sporadic outbreak indicates
reported the prevalence rate of RHD amongst that the causative organism and the disease sidelined
women of child bearing age is 5.1/1000. (Indian to a corner are not totally extinct even in developed
Heart Journal, 2009,61:6;553). countries.
• Dash PK observed the incidence of RHD not Although it is more than hundred years past since
declined significantly in a hospital based study at the recognition of the disease, yet the magnitude of
SSSIHMS, Bengaluru till 2011. the problem is difficult to access accurately in India.
One of the possible reasons is, because of indis- Rheumatic heart disease is still a major health prob-
criminate use of antibiotics and analgesics in both lem particularly for younger age group. It is the lead-
rural and urban places by local treating physicians ing cause of morbidity and mortality at the prime age
and health workers, the typical presentation of RF of life in developing countries (which covers three-
might have been modified, so that typical features of fourths of World’s population) causing a huge eco-
acute RF are no longer seen. But the rheumatic pro- nomic burden to the family and the society as well.
cess in some of these susceptible hosts continues in RF and RHD are largely preventable disease yet
a sub-clinical manner for years together till it gives there is a long way to go for taming the streptococ-
rise to full fledged valvular lesion. This may be the cal infection in India and other developing countries.
reason why the incidence and prevalence of RHD has Although eradication of RF is still a distant dream,
not decreased in spite of decrease of RF. Other fac- all possible measures as mentioned below should be
tors responsible for decrease in incidence of RF are taken to prevent and eradicate the disease.
improved living conditions (housing, sanitation and a. Sample population survey (rural, urban and
health care) and gradual disappearance of rheumato- tribal) to know the magnitude of the real prob-
genic (M protein) of group A betahemolytic strepto- lem and also to find out population at high-risk in
coccus (GAS) in certain parts of India. developing countries.
b. WHO program on prevention of RF may be 2. Carapetis JR, Steer AC, Mulholland EK, Weber M.
strictly followed in all developing countries (all The global burden of group A streptococcal disease.
stress on primary and secondary prevention and Lancet Infect Dis. 2005;5:685-94.
improved living condition including health care 3. Diagnosis and management of acute rheumatic fever
system). Similarly Indian Council of Medical and rheumatic heart disease in Australia An evi-
Research (ICMR) guidelines should be followed dence-based review, 2006. National Heart Foundation
for better registry and uniform management of of Australia and the Cardiac Society of Australia and
RF throughout the country. New Zealand.
The important ways to reduce rapidly the inci- 4. Padmavati S. Rheumatic heart disease: prevalence
dence, prevalence and to eradicate RF and RHD can be and preventive measures in the Indian subcontinent.
achieved by two ways. One through primary preven- Heart. 2001;86:127.
tion that is to identify and treat all cases of streptococ- 5. Padmawati S. Rheumatic Fever and Rheumatic Heart
cal sore throat and second, by routine use of vaccine. Disease in India at the turn of the century. Indian
The first one primary prophylaxis is an uphill task and Heart J. 2001;53:35-7.
almost impossible for its implementation in India 6. Rheumatic Fever and Streptococcal Infection by Gene
and also in many developing countries. The second H Stollerman, Grune & Stratton Publisher, New York.
one is the vaccine. It should be safe, cost-effective, 7. Rheumatic Fever by J Narula, Renu Virmani, K
potent and multivalent vaccine should be available in Srinath Reddy and R Tondon, 1999 published by
near future to eradicate the disease in this new mil- American Registry of Pathology, Washington.
lennium, as it has happened in the past against the 8. Rheumatic Fever: 2nd Edition, Milton Markowitz and
deadly disease that is smallpox. Leon Gordis, WB Saunders Company, Philadelphia,
To conclude rheumatic heart disease is still ram- 1972.
pant in India and also in some developing countries. 9. The WHO global programme for the prevention of
The significant decrease in incidence and prevalance RF/RHD. Report of a consultation to review progress
of RF and RHD, of some school surveys from select- and develop future activities. Geneva, World Health
ed areas may not distract the attention of alarming Organization, 2000 (WHO/CVD/00.1).
frequency (High frequency) of the disease reported 10. Vijaya Kumar M, Reddy MS. Rheumatic Heart Disease
all over the country. The realistic form of preven- in India: Epidemiology and strategies for prevention.
tion at present available is the secondary prophylaxis Advance in Clinical Medicine–I, Ed MMS Ahuja.
which should be strictly followed. Hope by middle 11. Who technical report series, 923, Rheumatic
of the century the prevalence of RHD will decrease fever and Rheumatic heart disease: Report of a
significantly. It is always ‘prevention is better than WHO expert consultation Geneva, 29 October–1
cure’. November 2001, World health organization, Geneva
2004.
12. WHO/CVD Unit. WHO programme for the preven-
Further REading tion of rheumatic fever/rheumatic heart disease in
1. Bitar FF, et al. Rheumatic fever in children: a 15-year 16 developing countries (AGFUND). Report from
experience in a developing country. Pediatric Cardio Phase I (1986–1990). Bulletin of the World Health
logy. 2000;21(2):119-22. Organization. 1982;70(2):213-8.
CHAPTER 3
Etiopathogenesis of Rheumatic Fever
HN Mishra
Introduction the research workers. To explain the etiopathogenesis

Acute rheumatic fever (ARF) is a delayed nonsup- of acute ARF, the agent, the host and the environmen-
purative sequel of pharyngeal infection with group A tal factors are held primarily responsible (Fig. 3.1).
beta hemolytic Streptococcus (GABHS). After a latent
period of two to three weeks following initial pharyn-
Agent Factor, Group A Beta Hemolytic
gitis various signs and symptoms of ARF appear. But
Streptococcus
there is no direct proof that GABHS is responsible for
the manifestations of ARF. In other words ARF and Rheumatic fever and its manifestations develop after a
Rheumatic heart disease (RHD) although commonly latent interval of initial streptococcal throat infection.
seen in clinical practice particularly in developing There are no definite clinical signs to diagnose Strepto-
countries, the exact etiopathogenesis remains poorly coccal pharyngitis or to differentiate from other types
understood. of throat infection. GABHS is thought to be the agent
responsible for causing ARF and for its recurrences.
Factors Responsible for
Pathogenesis of Rheumatic Fever Streptococcal Bacterial Morphology
Since the beginning of twentieth century different hy- Lancefield Group A beta hemolytic streptococci has
potheses have been postulated in different years, to ex- an external capsule consisting of mainly hyaluronic
plain the exact mechanism but it is still a challenge to acid, the next inner layer the ‘cell wall’ consist of pro-
Fig. 3.1: Interactions of agent, host and environment in pathogenesis of RF and RHD
Etiopathogenesis of Rheumatic Fever 15
tein (type M, T and R), carbohydrate and rhamnose. fibrillae. Type specific immune determinants are
The innermost layer consist of mucopeptides like N- located within the NH2-terminal, situated in the
acetyl D-glucosamine, D-glutamic acid, L-lysine, L- distal portion of the M-protein fibrillae. Genes of
alanine and then comes the cytoplasmic membrane M-protein have definite arrangements, of chromo-
(having RNA and DNA protein) (Fig. 3.2). Not all somal pattern which is the distinct feature of rheu-
streptococci are culprit to produce ARF. The type of matogenic strain of GABHS. These encapsulated
Streptococcus that causes ARF is known as ‘rheuma- strain form large mucoid colonies over the cell wall.
togenic strain’ consisting of more than 130 M sero- This cell wall has potent immunologic property to
types (Griffith classification) is responsible for ARF. produce host antibody responses and also helpful for
It has the following specific features. production of vaccines.
• The bacteria is very rich in M-protein (M sero- One of the early hypotheses was that group A
types 3,5,6,14,18,19, and 24) streptococci directly affect heart valves and the myo-
• It is highly resistant to phagocytosis. cardium, because initially Group A Streptococcus (L
• It has a large hyaluronidase capsule which forms form) was demonstrated from patients of ARF which
distinct mucoid colonies in blood agar media. led some workers to think its involvement in patho-
• If properly stored, its virulent character is retained genesis of ARF. But subsequently it was not accepted
for a long time. because the hypothesis was based on erroneous ob-
• It lacks the serum opacity factor (SOF), because servation. GABHS or any of its products is yet to be
group A Streptococcus belongs to class I antigenic recovered from the heart muscle or valves. In other
group. words, it has not been isolated from the heart valves
The electronic microscopic picture shows small of the patients dying from ARF. So the concept of di-
projections over streptococcal capsule known as rect invasion by the organism is no more tenable. The
pathogenesis of recurrence of ARF is still an enigma.
In certain places (like aboriginal Australians), it has
been demonstrated that ARF might be due to strep-
tococcal infection of Group C or group G, which
inherited certain group A streptococcal antigen for
initiating ARF.
Then the hypothesis that toxins (toxic effect of
Streptococcus on target organs like myocardium,
valve and synovial joints) produced by Streptococcus
are responsible for pathogenesis of ARF was also not
acceptable due to lack of animal model experiments.
One major point against the role of streptococcal
products in the pathogenesis is that carditis is not
present during the time of streptococcal infection (it
comes after a latent period).
Antibody titer against all streptococcal antigens
is increased in ARF. But antigen and antibody com-
ponents are not seen in the sarcolemma of cardiac
muscle. Streptolysin S or streptolysin O are of interest
because they are cardiotoxic, particularly streptoly-
sin O titer is increased in ARF. The pepsin generated
Fig. 3.2: Morphology of group A beta hemolytic fractions of M-protein and streptococcal pyogenic
Streptococcus (colors used to demarcate different layers) exotoxin behave as superantigens which release
cytokines and adhesion molecules to localize im- repeated streptococcal infection may be a pre-requi-
mune response in different tissues. site for induction of the disease. That is why, ARF oc-
In recent years the hypothesis of autoimmunity curs commonly after four to five years of age, (rarely
has gained ground, it states that ARF occurs due below 4 years of age). Infiltration of T cells (T- lym-
to immunological response to GABHS. It is now phocyte) in valve tissue (mainly mitral valve) in pa-
believed that inflammatory process involved in tients of rheumatic fever again indicates that cellular
ARF is one kind of hyperimmune reaction due to immunity plays an important role. Because of lack of
streptococcal allergy or is an autoimmune process. enough proof, the humoral immunity is not thought
The reasons are to be the primary mediator for the pathogenesis of
• Usually immune response occurs after a latent ARF. Postulations are that initial damage occurs due
period of any infection and the same happens in to expression of VCAM-1 in endothelium as a result
case of ARF. of humoral immune response, followed by activation
• The mean antibody response is higher in patients of cellular immune response resulting in adherence
who develop ARF then those who do not suffer of CD4+, CD8+, T-lymphocytes and mecrophages to
from ARF. the endothelium which migrate to connective tissue
• Immunoglobulin and complements or heart anti- producing an intense inflammatory reaction.
bodies which are gamma globulin and specific The hypothesis of immune mechanism that plays
antibody against myocardial sarcolemmal fiber an important role in pathogenesis of ARF can be
react with streptococcal membrane antigen. These summarized in a chronological manner. In 1945, for
are found in myocardium of patients dying of ful- the first time autoantibodies for ARF was detected.
minating rheumatic myocarditis. Subsequently antibodies were found in heart tissues
• Penicillin therapy for Streptococcus infection pre- (myosin and myocardial fiber). In 1980, M-protein
vents development of ARF. involved as anti heart antibody responses in ARF was
The streptococcal M-protein and N-acetyl glu- demonstrated. During the period 1985 to 1995, the
cosamine (multiple epitopes) mimic cardiac con- most convincing finding that M-protein shows im-
tractile protein (auto antigens of myosin and tropo- munologic and structural homology with myosin
myosin) and also with keratin, laminin and vimentin and alpha-helical proteins (molecular mimicry) was
present in cardiac interstitial tissue. It is known as mo- described. In the same year (1995), the T cells cross
lecular mimicry which is the hallmark of pathogene- reactive property with M-protein and also heart pro-
sis. It was first described by Fujinami and Oldstone in tein were isolated from the valve of the patients suf-
1983. This molecular mimicry between certain types fering from ARF.
of streptococcal components and cardiac proteins
is most probably the cause for cellular and humoral
Note
reactions which are responsible for pathogenesis of
ARF and RHD. The evidence in support of this view 1. The exact mechanism by which GABHS initiates
is that heart antibodies which are gama globulin spe- ARF is still conjectural.
cific for cardiac sarcolemmal membranes are found 2. The theory of autoimmunity, although acceptable,
in abundance in patients who died of rheumatic car- has its own limitation.
ditis. Here whether the cellular mediated or humoral 3. Why some strains of GABHS are rheumatogenic,
immunity or both initiate the inflammatory process not all strains? There is no clear answer to it.
is not known. The cellular immunity has definite role 4. Why only pharyngeal infection with GABHS is
in formation of classic lesion like Aschoff ’s nodules responsible for ARF? Again there is no answer to
due to delayed hypersensitive reaction. Moreover it.
Etiopathogenesis of Rheumatic Fever 17
5. When symptoms appear (2-3 weeks of latent the development of ARF. Similarly some races (like
period), why the culprit (GABHS) is not found at Samoans in Hawaii) show increased susceptibility
the site, is also a mystery. to ARF. Subsequently its relation to other markers
like major histocompatibility molecules (MHC) or
The Host Factor (Patient) human leukocytes antigens (HLA) were described.
HLA is further classified into class I and class II as
All patients suffering from rheumatic fever do not per its gene (chromosomal) location. Class I has
develop rheumatic heart disease. It is only susceptible three major isotypes, HLA-A, B and C and class II has
patients who develop ARF. Epidemiological evidence HLA DR (1, 2, 3, 4 haplotypes), DQ, and DP. Patients
shows that the host factor plays an important role in susceptible to ARF have certain varieties of genes, in
pathogenesis of ARF. the HLA–DR loci and beta cell alloantigen (D8/17).
• Out of all streptococcal throat infection only in To clarify further the monoclonal antibody to β cell
three percent of cases Group A beta hemolytic, alloantigen (D8/17) is present in almost all patients
(rheumatogenic M-protein type) have been iso- having rheumatic fever (In very few normal persons
lated. it is also present). It is observed that patients of dif-
• Among these cases again (0.3–3%) are susceptible ferent geographical region and patients of different
to develop ARF; and subsequently some of them ethnic groups in the same region have some specific
develop RHD. types of HLA class I or class II isotypes. As for ex-
• Children belonging to age 5 to 15 years are mainly ample HLA-DR4 is more associated with Caucasian
affected by ARF and it is rare below four years of and Saudi Arabian patients having RHD, where as
age. HLA-DR3 and DQW2 are associated with increased
• The patients having previous history of ARF with frequency in Indian and Asian patients. Antibody
untreated GABHS pharyngitis develop recurrence leveled D8/17 is present in 100 percent in USA and
of ARF in about 50 percent of cases. Another in 60 percent of Indian patients. HLA-DR3 is more
observation needs mention that although both seen in African Americans with RHD. Some selected
sexes are equally predisposed to develop ARF, population of Australia and New Zealand reported to
chorea occurs mainly in females (rare in adoles- have high incidence of RF and RHD, which leads to
cent or adult males) think of genetic predisposition.
Why all patients do not develop ARF or RHD? To
explain the implicity of this observation, the host im-
The Environmental Factor
mune factor is thought to play a primary role. The im-
munological system of the host including both cellu- Environmental factors like overcrowding and poor
lar mediated and humoral immunity is the important hygienic living conditions and no access to health care
factor for the susceptibility to ARF. It is thought that (not using antibiotics) are responsible for epidemic
patients suffering from ARF have inherent suscepti- spread of streptococcal pharyngitis which leads to
bility for ARF but whether this immune process re- increased number of ARF and RHD. The epidemio-
lated to heredity (genetically determined) is not clear. logical studies reveal that streptococcal (group A beta
hemolytic) throat infection is common in the areas of
overcrowding, dampness (slum areas) and amongst
Genetic Markers of Rheumatic Fever
poor economic status. The outbreak of ARF closely
Evidence that the genetic factor plays some role dates follows the epidemics of streptococcal pharyngitis,
back to 1959, when it was observed that patients hav- so there is a definite correlation between streptococ-
ing ABO blood group were susceptible to RF. There cal infection and ARF. It is population density does
is higher concordance among monozygote twins for not correlate with increased of incidence of ARF. No
significant seasonal variation is observed as regards should be given top priority for its complete preven-
incidence of ARF in developing countries. tion and eradication.
Summary Further Reading

Though the fact that GABHS is responsible for ARF 1. Carapetis JR, McDonald, Wilson NJ. Acute rheu-
is accepted from the clinical, epidemiological, immu- matic fever, Lancet. 2005;366:155-68.
nological and prophylactic evidences, there remain 2. McDonald M, et al. Acute rheumatic fever: a chink
certain reservations in their role in the etiopathogen- in the chain that links the heart to the throat? Lancet
esis. The chain that binds the heart to the throat as Infect Dis. 2004;4:240-5.
discussed by Warnamaker in the Duckett Jones me- 3. Rheumatic Fever by J Narula, Renu Virmani, K
morial lecture in 1972, still remains an enigma. How- Srinath Reddy and R Tondon, 1999 published by
ever, it is nature’s irony that simple pharyngeal infec- American Registry of Pathology, Washington.
tion demands such a high price (amounting to life) 4. Rheumatic Fever: 2nd edn, Milton Markowitz and
from the host. Because young adults are victims and Leon Gordis, WB Saunders Company, Philadelphia,
the national productivity is hampered, this problem 1972.
CHAPTER 4
Pathology of Acute Rheumatic Fever
M Satpathy
introduction fever is one of the common causes of acute pericar-

Acute rheumatic fever (ARF) is primarily a post ditis. This inflammatory process results in effusion
streptococcal connective tissue disorder. In acute inside pericardial cavity. It is usually mild to moder-
stage it affects mainly the heart and/or the big joints. ate; rarely large amount of fluid is accumulated. The
Other organs like brain, lungs, skin and kidney later effusion is a sterile one and exudative in nature. It
on may be affected. leads to thickening of the pericardium with fibrin-
The basic pathology is a diffuse exudative, prolif- ous exudates over it and serosanguinous fluid inside
erative inflammatory reaction in the connective tis- the pericardial cavity. This characteristic shaggy
sues. This acute process can be described under three appearance is known as bread and butter appearance.
phases. Aschoff ’s nodules (consist of cellular reaction of lym-
1. Initially there is diffuse proliferation with exu- phocytes with scattered polymorphs) may be found
dative inflammatory reaction involving synovial in the epicardium. When inflammatory process is
serous and mucous membrane known as exuda- abated it leaves minimum residual lesion like one to
tive-degenerative phase. It is also known as fibri- two opaque patches of thickened epicardium known
noid degenerative phase. as milk’s spots and they may be adherent to pericar-
2. Next phase is mainly proliferative phase. In this dium. There occurs no scarring or constriction of the
phase the characteristic and pathognomonic pericardium.
Aschoff ’s nodule is present in the myocardium. Note: Constrictive pericarditis never occurs in set-
3. The last phase is the healing phase; the acute pro- ting of rheumatic pericarditis.
cess heals either without any residual sign or with
fibrosis and scar formation.
Myocardium
In acute phase of rheumatic fever the organs hav-
ing mesenchymal supporting collagen/connective In ARF interstitial myocarditis is mainly present.
tissue are affected. Mainly it affects the heart with all The pathognomonic lesion of ARF is Aschoff body
its layers and also joints (big joints). which is commonly seen in myocardium. It was first
described by Aschoff in 1904. Aschoff bodies may be
active or senescent type. Active type of Aschoff body
Pathology of Cardiac Lesions consists of inflammatory collagen tissue where as
senescent type consists of hyalinization and scarring
Pericardium
of collagen tissue. On the whole it is a mass of altered
In ARF both the layers of pericardium (parietal and collagen tissue consisting of fibrinoid, fibrins and
visceral) show signs of inflammation. Rheumatic gama globulins containing Aschoff cells, anitschkow
cells, plasma cells, lymphocytes, polymorphonuclear their incomplete closure leads to AR. Ultimately the
leukocytes and also fragmented hypereosinophillic thin and translucent leaflets become thick, opaque
collagens. The Aschoff cells are large ovoid cells with and of leathery appearance.
irregular border and basophilic cytoplasm with one In most of the cases, mitral stenosis becomes sig-
to five nuclei. Anitschkow cells are elongated hav- nificant in younger age group (below 20 years) but
ing eosinophilic cytoplasm with single nuclei. The aortic stenosis develops very slowly (mainly above 20
nuclear chromatins of anitschkow and Aschoff cells years) to become clinically significant.
are so arranged the appearance is termed Owl’s nu- In rheumatic process mainly the mitral valve is
clei or caterpillar (Lattice) nuclei. When healing oc- affected, next in sequential order are aortic, tricus-
curs they leave a fibrous scar (senescent type which is pid and extremely rarely pulmonary valve. The small
seen over left atrial appendage, in majority of cases). warty vegetations or verrucosae (1–3 mm), a mass of
A thickened and opaque endocardial patch, (con- platelet thrombi, are seen on the atrial surface of the
glomeration of Aschoff nodules) seen close to poste- atrioventricular valve and also over semilunar valve.
rior mitral leaflets inside the left atrium, is known as These rheumatic vegetations are firmly adherent to
‘‘MacCallum’s patch”. the endocardial surface so do not detach to cause em-
Note: bolization.
1. Rheumatic myocarditis does not lead to heart fail- Note: Embolic phenomena are not seen in rheumatic
ure, the histological damage is very meager (myo- endocarditis but common in infective endocarditis.
cardial contractility is preserved), the cause is not Aschoff nodules are present over mural endocardial
known. surface and also seen in bundle of His.
2. Aschoff nodule although pathognomonic of ARF (Pathology of individual valve lesions are described in
its formation and nature of function still remains their respective chapters)
a mystery.
Coronary Arterial Lesion
Endocardium
The intima and media are edematous. The fibrinoid
In rheumatic inflammatory process, the valve appa- degeneration and thrombosis cause myocardial in-
ratus mainly the cusps are affected producing mitral farction. Coronary arteritis is a well recognized path-
or aortic valvulitis leading to mitral or aortic regurgi- ological lesion described as Shwartzman like lesion.
tation (AR). The mitral regurgitation (MR) produced Rheumatic arteritis completely recovers without re-
by mitral valvulitis disappears in majority of cases sidual lesion where as arteritis due to any other etiol-
but AR persist in most of the cases of aortic valvuli- ogy may cause permanent damage.
tis. In the acute stage of inflammation there is rough-
ening and in chronic stage there is thickening of the Extracardiac Manifestations
surface linings. When signs of inflammation subside,
eventually the sclerotic process starts, resulting in Joints
fusion of cusps, chordae tendineae and also mitral
ring. Even after inflammation subsides, valve dam- Swelling of articular and periarticular space occurs
age progresses over time because of blood flow across due to effusion. These effusions are exudative and
an abnormal valve cause further fibrosis and calcium sterile in nature (never purulent). Microscopic pic-
deposition. This process leads to more narrowing of ture shows fibrinoid lesions with granulomas. Periar-
mitral valve (mitral stenosis) or to incomplete clo- ticular tissue are edematous. No cartilage erosion is
sure of leaflets (mitral regurgitation). Similarly fu- seen. This inflammatory process heals without scar-
sion of aortic valve cusps leads to aortic stenosis or ring and deformity. Subcutaneous nodes are present
Pathology of Acute Rheumatic Fever 21
over bony prominences. The histological picture is Kidneys

that of Aschoff body.
In most of the ARF histopathologic picture is that
of acute glomerulolitis. It is distinctly different from
Central Nervous System
histopathological changes that occur in acute post
Arteritis of small vessels inside cerebrum are usu- streptococcal glomerulonephritis.
ally noticed. Perivascular round cell infiltration and Note: As mentioned by Lague the famous pathologist
scattered petechial hemorrhages are seen through- in 1867 “RF licks the joints but bites the heart”, is the
out the cortex, cerebellum and basal ganglia. main center of interest for the clinicians.
Note: Aschoff nodules are never present in central For academic information it may be mentioned
nervous system. that “Lupus (SLE) licks the skin but bites the kidney”.
Lungs Further Reading

Pathological changes in the lung fields are usually 1. Paul Wood’s Diseases of the Heart and Circulation,
secondary to cardiac involvement. Due to carditis, 3rd edn, Eyre and Spottiswood Ltd, 1968.
lungs parenchyma shows evidence of congestion 2. Rheumatic Fever and Streptococcal Infection by Gene
with hemorrhagic spots. There may occur alveolitis H Stollerman, Grune and Stratton Publisher, New York.
leading to fibrosis and hemosiderosis deposits. 3. Willium Boyed, Textbook of Pathology, 7th edn, Lea
Note: Aschoff bodies are never found in lungs. and Febiga, 1961.
CHAPTER 5
Clinical Manifestations of
Rheumatic Fever
M Satpathy
The clinical manifestations of rheumatic fever (RF) pericarditis, myocarditis, and endocarditis. Carditis
vary widely. The most important point for a clinician is a major manifestation of acute RF. Its incidence
is at what stage or at what duration of disease the varies from 40 to 60 percent cases; of acute RF. Cardi-
patient is first examined. It is so; because the symp- tis and/or arthritis are seen in majority of cases (90%)
toms and signs are so varied, that they appear, disap- of acute RF. Before 1960, it was observed that cardi-
pear and again may appear during the course of the tis was more often seen in USA than in developing
disease. That is why the diagnosis of acute RF as a countries.
separate entity was in a state of confusion for years
together until T Duckett Jones formulated a set of Mode of Presentation
diagnostic criteria in 1944.
The seminal idea of diagnosis of RF was men- As mentioned earlier the clinical feature of rheumatic
tioned by Bouillard as “Laws of coincidence, not carditis depends at what stage or at what duration of
uncoincidental”, where fever, arthritis and carditis the disease the patient is being examined. Its onset
were commonly observed together. Subsequently, may be acute, subacute or insidious. It may be detect-
it was observed by other physicians that RF can be ed early or may be missed for long time until the pa-
diagnosed by constellation of several symptoms and tient presents with valvular lesions, congestive heart
signs. Cheadle mentioned fever, chorea, arthritis and failure (CHF) or chorea.
carditis in the year 1889 as one entity which became Acute presentation means history of fever either
known as “Cheadle’s Cycle”. Ultimately, the diagnos- with acute arthritis or arthralgia and breathlessness
tic problem was solved when T Duckett Jones laid (dyspnea even at rest) which forced to bring the pa-
down the criteria for diagnosis of acute rheumatic tient to physician. In some cases patients present
fever which has been subsequently modified from with acute arthritis and severe carditis leading to
time to time as mentioned in Table 5.1. acute heart failure known as ‘fulminating carditis’
Australian guidelines, 2005 included echo evi- which led to death in most of the cases in preantibi-
dence of subclinical carditis, polyarthralgia and asep- otic era. It is the extreme form of acute presentation,
tic monoarthritis as major criteria, in the subgroup of at present uncommon even in developing countries.
population who are at high risk of developing RF. Subacute presentation means breathlessness on
exertion, arthralgia, low grade fever and on examina-
tion a short systolic murmur over apical area creating
Major Manifestations of RF a suspicion for diagnosis of rheumatic carditis.
Insidious presentation means the course of the
Carditis
disease is very slow in form of irregular fever, athral-
Rheumatic carditis by definition is due to inflam- gia, vague chest pain. The patient may have a short
mation of all the layers of the heart (pancarditis), i.e. systolic murmur over apex, unless very carefully
Clinical Manifestations of Rheumatic Fever 23
Table 5.1: Year-wise modification of Jones criteria

Jones Criteria Original Modified by Reviewed by Endorsed by Updated by Reviewed Australian
Jones AHA 1956 AHA 1965/ WHO 1988 AHA 1992 by WHO Guideline
Criteria 1984 2003 2005
1944
Carditis Major Major Major Major Major Major Major
Polyarthritis Major Major Major Major Major Major Major
Subcutaneous Major Major Major Major Major Major Major
nodule
Chorea Major Major Major Major Major Major Major
Erythema Minor Major Major Major Major Major Major
marginatum
Arthralgia Major Minor Minor Minor Minor Minor Major (in
high risk
group)
Fever Minor Minor Minor Minor Minor Minor Minor
High ESR Minor Minor Minor Minor Minor Minor Minor
Prolonged PR Minor Minor Minor Minor Minor Minor Minor
interval
Epitasis and Minor Omitted Omitted Omitted Omitted Omitted Omitted
abdominal pain
History of RF/RHD Major Major Minor Minor Minor Specific Major (in
considera- high risk
tion group)
Evidence of previ- Minor Essential Essential Essential Essential Essential
ous streptococcal
infection
Echocardiography – – – – – * Major
Abbreviations: AHA—American Heart Association; WHO—World Health Organization.
*Echocardiography and Doppler studies were discussed to be enrolled as a major criterion for diagnosis of carditis/
subclinical carditis but not included yet even as minor criteria in the last American Heart Association (AHA) and
World Health Organization (WHO) review in 2003.
examined the physician may not suspect rheumatic Clinical Features of Rheumatic Carditis
carditis. Ultimately, because the symptoms are very
vague and signs are very subtle and transient, the dis- General complaints are puffiness of face, breathless-
ease is missed until it presents with signs of CHF and/ ness on exertion (dyspnea of various grades), fatigue,
or with chronic valvular affection. In recent years this cough, loss of appetite (anorexia), irregular fever, ar-
is the common mode of presentation because of in- thritis or arthralgia and palpitation.
discriminate use of antibiotics and analgesics. On examination disproportionate tachycardia,
Rheumatic carditis is also classified as per the sleeping pulse more than 100 beats/min and rarely
clinical presentation like mild, moderate and severe. bradycardia (pulse rate less than 60/min) are the
Subclinical carditis is diagnosed by Doppler echocar- signs of acute carditis. The apex is out and down and
diogram. usually left ventricular type (heaving). The apex may
not be felt if there is associated pericardial effusion. should suspect pericarditis. It is present in 10 to 15
Cardiomegaly indicates either myocardium or endo- percent of cases of carditis and always associated with
cardium is involved. mitral regurgitation. Presence of pericardial rub, a
First heart sound is muffled, second heart sound scratchy, superficial, grating sound heard over left
is normally heard, tachycardia with S3 gallop (tic parasternal border or over base of the heart indicates
tac rhythm) is invariably present. Cardiac murmur pericarditis. The rub may be hard all over precordium
(grade 2-4/6) must be present for clinical diagnosis or localized only over apical area. It masks the pres-
of carditis particularly endocarditis (valvulitis). Inci- ence of short systolic murmur and also sometimes
dence of carditis is 76.1 percent of cases as reported third heart sound. If heart sounds are muffled and/or
by Routray SN (Ind HJ, 2003:55;152-7). Mitral valve there is cardiomegaly, associated pericardial effusion
is commonly affected (90% cases) followed by the is the most probable diagnosis.
aortic valve. At early stage of carditis, very often the Congestive heart failure is evidenced by short-
murmur changes its character, intensity, and duration. ness of breath, raised JVP, edema feet, hepatomegaly,
Mitral vulvulitis presents with S3 and a pansystolic or cardiomegaly, third heart sound and with a systolic
pansystolic blowing murmur (grade 2-4/6) of mitral murmur. This systolic murmur may not be audible
regurgitation (MR) and in some cases accompanied when severe congestive heart failure is present.
by a mid-diastolic murmur known as Carey-Coomb’s Remember: For clinical diagnosis of carditis (valvuli-
murmur (Figs 5.1A to C). The Carey-Coomb’s mur- tis) presence of a cardiac murmur is mandatory. The
mur is a low pitched, mid-diastolic murmur (no pre- dictum is “No murmur, no carditis”.
systolic accentuation) and audible for a short period Note
(transient or evanescent murmur). It is due to swell- 1. When there is myocarditis with endocarditis, the
ing and stiffness (tautness) of mitral valve leaflets in etiology is mostly rheumatic. In pericarditis or
presence of increased blood flow into LV cavity (due myocarditis if endocarditis is not associated the
to MR) in early diastole. It is usually confused with cause is non-rheumatic.
S3 but not with mid diastolic murmur of mitral ste- 2. Pericardial effusion of rheumatic origin very
nosis (MS) because MS murmur has a distinct rum- rarely goes for cardiac tamponade and never
bling character with presystolic accentuation. The develops constrictive pericarditis.
systolic murmur of MR may completely disappear in 3. Subclinical carditis is diagnosed by echocardio-
due course of time or may develop into a full blown, graphy only. (Echocardiographic evidence of MR
high pitched mitral regurgitation murmur. The aortic and/or MR without murmur).
valve involvement is much less common as compared 4. Cases of acute arthritis and congestive failure and
to mitral valve. Aortic vulvulitis gives rise to a short, raised anti streptolysin-O (ASO) titer are taken
soft, early diastolic murmur due to aortic regurgita- as active carditis, even in the absence of clinically
tion (AR) heard just after second heart sound, over audible murmur.
second aortic area and better heard on expiration In brief cardiomegaly, disproportionate tachy-
in leaning forward position with diaphragm of the cardia (with high sleeping pulse rate), muffled heart
stethoscope. Unlike MR murmur, it usually persists sounds, S3 gallop, presence of MR (with or without
and gradually leads to chronic aortic regurgitation. A AR) murmur, and rarely pericardial rub indicate
short systolic murmur over aortic area is sometimes presence of rheumatic carditis. So the cardinal signs
audible in AR due to either increased flow or due to for diagnosis of rheumatic carditis are cardiomegaly,
anterior upward excursion of mitral valve in systol organic murmur (not previously present), pericardial
(not due to aortic stenosis). rub, S3 and presence of congestive heart failure.
Patients having fever and arthritis when com- In setting of RHD when new onset of murmur
plains of chest pain (more on deep inspiration) one or changing character of pre-existing murmur appear
A B c
Figs 5.1A to C: (A) 2-D Echo showing thickened and nodular mitral leaflets in a child with carditis, left panel
in systole shows prolapse of anterior leaflet to LA in systole (open arrow), right panel shows beaded appear-
ance of the valve in diastolic frame (arrow); (B) Color Doppler shows presence of mitral regurgitation (arrow);
(C) Right panel shows pericardial effusion (arrows) in carditis, left panel shows mitral regurgitation (open arrow).
Abbreviations: Ao—Aorta; LA—Left atrium; LV—Left ventricle
along with raised ASO titer it is taken as recurrent or in milder form or severe form, it is present in about
mimetic carditis. Clinical diagnosis of recurrent car- 75 to 85 percent of cases. Incidence of polyarthritis
ditis banks upon following features: in 44.2 percent and arthralgia is 43.1 percent of cases
a. Appearance of new murmur. as reported by Routray SN (Ind HJ, 2003;55:152-7).
b. Change in character of previous murmur. The bigger joints like knee, ankle, elbow and wrist
c. Appearance of pericardial rub indicating pericar- are mostly affected in a chronological order with his-
ditis. tory of febrile onset. The big joints are affected one
d. The patient becomes suddenly more symptomatic after another (rarely two joints are affected at a time),
due to marked congestive cardiac failure. this typical pattern is known as ‘migratory’ or ‘fleet-
Clinical conditions related to appearance and ing arthritis’ which is seen in about 50 to 60 percent
disappearance of carditis is described under certain of cases. Acute joint pain with signs of inflammation
specific terminologies: (with or without effusion) persists nearly 1 to 2 weeks
• When manifestations of RF again appear after dis- and then it subsides even if untreated. In some cases
continuation of drugs within six weeks of initial it may persist in an insidious form for 3 to 4 weeks.
treatment is known as rebound phenomena. One specific feature of this affection is excruciating
• Worsening of RF while under treatment, showing pain on slightest movement or even no movement,
evidence of carditis after an initial period of recov- highly disproportionate to the external appearance of
ery is known as relapse. the signs of inflammation which are often minimal
• In a case of previous RF with carditis after dis- or absent. The affection of fingers and toes are very
continuing the schedule treatment for pharyngeal uncommon. Spine is not involved. Aseptic monoar-
infection (secondary prophylaxis) for more than thritis (single joint affection) is unlikely to be due to
eight-week if again signs of RF appear it is termed acute RF, but in area of high prevalence of RF it may
as recurrence. be considered as one of the major manifestations.
Remember: Carditis leads to chronic valvular heart (In Australian guidelines it is considered as a major
disease in 50 to 60 percent of cases. manifestation in high risk subgroup). Acute arthritis
not responding to non-steroidal anti-inflammatory
drugs (NSAIDs) within 2 to 3 days may not be due
Arthritis
to acute RF. Recurrence of joint affection after ini-
Joint pain is the most common complaint that brings tial attack occurs in mostly untreated cases. Patients
the patient or the parents to physician’s notice. Either presenting with mild joint pain (athralgia) do not
have painful and restricted movement. It is observed rea. Most of these cases resolve within six months of
that these patients having arthralgia develop carditis time, rarely prolong beyond one year. The acute phase
more often within 3 to 4 weeks of time as compared reactants become normal when chorea appears. ASO
to cases of acute arthritis. titer may also be negative. It is a self-limiting disease
but may persist with behavioral changes for a longer
Chorea period.
Note
Rheumatic chorea is also known as Sydenham’s cho- 1. Chorea at appropriate age group (pediatric age
rea or St Vitus’s dance. It appears alone after a long group) may be the only sign to diagnose RF (Jones
gap, may be several months of preceding streptococ- criteria are not applicable for diagnosis of isolated
cal throat infection and not usually accompanied by chorea).
carditis and arthritis. About 50 percent of patients 2. The peculiarity is that, these abnormal move-
having chorea develop carditis and 20 percent of ments are absent during sleep.
them develop chronic rheumatic heart disease. Inci- 3. Chorea is rarely associated with arthritis.
dence of chorea is 9.4 percent of cases are reported by 4. Pyramidal tract not involved although muscular
Sharma M et al (Ind HJ, 1999;51:652). hypotonia present.
It is an involuntary, jerky, irregular nonrepetitive,
purposeless (quasipurposive) movement associated Subcutaneous Nodules
with muscular weakness (muscular hypotonia) and
emotional lability with grimacing gesture. It is a type It is a major manifestation of rheumatic fever; it is
of neuro-psychiatric disorder. Handwriting becomes always associated with carditis of several weeks du-
clumsy, i.e. difficulty in writing in a normal fashion. ration. Incidence varies from country-to-country. In
It is more common in girls less than 20 years of age earlier days, it was noticed more frequently in west-
and rarely seen in adolescent or adult males. The pro- ern countries (incidence was 21% in UK and 10% in
nator sign, spooning sign and milkmaid signs are of- Boston, USA). It is also seen in developing countries
ten positive. and its incidence varies widely from 2 to 20 percent
• Pronator sign is positive when the patient keeps of cases (M Behera, Ind HJ, 1993;45:463, 267 in 12.5
his arm above his head, the arm and the palm turn percent and Sharma M et al, Ind HJ, 1999;51:652
outside (cannot keep steadily). in 20.4 percent of cases). These are hard, painless
• Spooning sign is positive when flexion of wrist and (nontender), pin head to pea sized (0.5–2.0 cm),
extension of fingers occur if the hand is extended nonpruritic, discrete and freely movable swellings
forward or sideward. over extensor surfaces of elbows, wrists, knees, an-
• Milkmaid sign also known as milkmaid grip is kles, Achilles tendon and over knuckles. It is fixed to
positive when rhythmic squeezing type of move- bones or tendons but the skin over it is freely mobile.
ment occurs when the patient grasps the examin- They may be present over spine on posterior spinal
er’s finger. process (Figs 5.2A to C) and particularly over nape
The peculiar tongue movement is known as ‘Jack of the neck area in the occipital region. Sometimes
in the box’ tongue (inability to maintain protrusion it is associated with severe or protracted carditis. It
of tongue). Some described it as ‘bag of worms’ appears late when signs and symptoms of rheumatic
movement. The speech is staccato type (halting fever and carditis are less marked or are not suspect-
speech). ed. They are usually missed unless sought for care-
Chorea is due to involvement of the caudate fully at these specific sites. These are mainly multiple
nucleus in the basal ganglia of the brain. There is no and occurs in crops. They take weeks to disappear
pyramidal tract or sensary involvement. Chorea may and sometimes reappear again in crops. Patients with
affect only one side of the body known as hemicho- subcutaneous nodules have poor prognosis.
A B c
Figs 5.2A to C: Subcutaneous nodules in a patient with Rheumatic Fever; (A) Over sternocostal joint (arrow); (B) Over
knee joints (arrows); (C) Over spines (arrows) (Courtesy: M Behera, Cuttack)
our country it is rare. These are small, pink colored,

raised macules (either oval, ring form or crescenic
with irregular margins but well defined) seen over
inner aspect of upper arm, thigh and buttocks (on
proximal parts), particularly in fair skin patients.
When the rashes fuse together, they take serpiginous
pattern. It never occurs over the face. They are evanes-
cent (appear, disappear and reappear) and attenuated
by heat application, blanch on pressure. These are also
nonpruritic and painless rashes. It is not responsive to
anti-inflammatory drugs. When circular, it is known
as erythema annulare. It is commonly associated with
carditis and sometimes with subcutaneous nodules.
Fig. 5.3: Erythema marginatum (arrows) over the trunk in
one of our patients aged 14 years of acute rheumatic fever
with carditis and athritis
Minor Manifestations
Although the minor manifestations are present in
most of the cases of rheumatic fever, they are includ-
Note: Subcutaneous nodules are almost always asso- ed under minor criteria because none of them are
ciated with carditis. specific for rheumatic fever.
Erythema Marginatum Fever

It is included as a major manifestation presenting Fever although taken as a minor criteria, it is present
usually in early phase of acute rheumatic fever and in almost all cases. Usually it is of high grade (more
it is a distinctive rash (Fig. 5.3). When it is associ- than 39° C) and persists for 7 to 10 days. Some-
ated with athralgia and signs of carditis, the diagnosis times it may be low grade, irregular or intermit-
becomes certain. Erythema marginatum was seen in tent which may persist for 2 to 3 weeks. Presence of
about 10 to 15 percent cases in western countries. In fever (high or low) indicates persistence of rheumatic
activity. Fever subsides without treatment, but if Further Reading

treated with analgesics the patient becomes afebrile
within a week. 1. Albert DA, Harel L, Karrison T. The treatment of
rheumatic carditis: a review and meta-analysis.
Medicine. 1995;74:1-12.
Arthralgia
2. Diagnosis and management of acute rheumatic fever
Joint pain without obvious findings (signs of inflam- and rheumatic heart disease in Australia. An evi-
mation) may occur at any time of the rheumatic ac- dence-based review. National Heart Foundation of
tivity (early, in-between and persists for 2–3 weeks). Australia and the Cardiac Society of Australia and
Large joints are involved without swelling or ten- New Zealand, 2006.
derness on pressure or on movement. Arthralgia of 3. Markowitz M. Evolution of the Jones criteria for the
rheumatic etiology may also be migratory in nature. diagnosis of acute rheumatic fever. In: Narula J, et al.
Epistaxis/Abdominal pain/Splenomegaly/Rheu- (Eds). Rheumatic fever. Washington, DC, American
matic pneumonia are nonspecific minor criteria Registry of Pathology. 1999.pp.299-306.
which are present very infrequently and it is diffi- 4. Markowitz M Gordis L. Rheumatic fever, 2nd edn.
cult to prove their rheumatic origin. Younger chil- Philadelphia, WB Saunders Co, 1972.
dren with high fever and signs of carditis if develop 5. Special Writing Group on the Committee of
features of pneumonia, rheumatic pneumonia was Rheumatic Fever, Endocarditis and Kawasaki Disease
a possibility in preantibiotic era. Many times it was of the Council on Cardiovascular Disease in the
confusing with pulmonary signs of congestive heart Young of the American Heart Association. Guidelines
failure (due to carditis), i.e. it may be confused with for the diagnosis of rheumatic fever: Jones criteria,
congestive heart failure due to carditis. Nowadays, 1992 update. JAMA. 1992;268:2069-73.
no much clinical importance is given on these subtle 6. Stollerman GH. Rheumatic fever. Lancet. 1997;
signs and symptoms. 349:935-42.
CHAPTER 6
Laboratory Diagnosis of
Acute Rheumatic Fever
BR Mishra
Introduction There are two types of streptolysin; one is oxygen

Acute rheumatic fever (ARF) is a postinfectious stable ‘streptolysin-S’, and the other is oxygen labile
connective tissue disorder. Although group A beta ‘streptolysin-O’. Streptolysin-O induces antibody
hemolytic streptococcal (GAS) sore throat gives response; in the host. Streptolysin-S is not immu-
rise to ARF after a latent period, there are no spe- nogenic. Assay of antibody to streptolysin-O in the
cific laboratory tests to confirm the diagnosis. Thus, serum; is expressed as ASO titer which was originally
establishing diagnosis of ARF, combination of clini- described by Todd in 1932. The other antibody tests
cal manifestations and laboratory tests are necessary. to prove antecedent GAS infection are antideoxyri-
The laboratory tests are: bonuclease B test (Anti-DNase B) and antihyaluro-
1. Supporting evidence (antecedent streptococcal nidase test. Nowaday antihyaluronidase test is no
infection) of GAS infection. longer used.
2. Hematological investigations. Combined detection of serum antibodies to mul-
3. Noninvasive investigations. tiple streptococcal antigens by slide agglutination test
4. Invasive procedures. (Streptozyme test) is easy to perform in large scale
Supporting evidences of a preceding streptococcal screening purpose. As it is not well-standardized, the
infection are: test is not acceptable as definitive.
• Elevated or rising antistreptolysin-O (ASO) titer ASO titer begins to rise after about one week and
or other streptococcal antibody tests. peaks around 3 to 6 weeks of throat infection; where
• Isolation of group A beta-hemolytic Streptococcus as Anti-DNase B begins to rise after 1 to 2 weeks of
(GAS) by throat swab culture. infection and peaks at about 6 to 8 weeks. Both ti-
• Rapid antigen test for GAS. ters remain high for 2 to 3 months before declining.
• History of recent scarlet fever. Antibody titers remain high during the period when
clinical manifestations are present. In 20 percent of
cases ASO titer may be negative where anti-DNase B
Streptococcal Antibody Titer titer remains elevated facilitating to make a diagno-
Detection of serum antibody against GAS is a proof sis of ARF. The normal range of each antibody titer
of invasion by the bacteria. Isolation of GAS in throat depends upon the community, the geographical area,
swab culture indicates presence of organism in the seasonal variation and age of the patient. Tradition-
throat but cannot differentiate carrier state from ac- ally antibody titers are determined by neutraliza-
tive infection. Streptolysin also called hemolysin is a tion assays. Newer methods like latex agglutination
toxin produced by GAS that causes hemolysis sur- and nephelometric assays are not standardized yet.
rounding streptococcal colonies in blood agar media. Although a single elevated antibody titer is taken as
an evidence of preceding GAS infection, it is recom- examination test, the diagnostic kits are available, to
mended that an additional test is to be performed detect streptococcal carbohydrate antigen with more
3 to 4 weeks after the onset of acute rheumatic fe- than 95 percent specificity but the negative result
ver for confirmation of rising titre. ASO titer more does not rule out streptococcal infection. The dis-
than 240 Todd units in adult and 330 Todd units in advantage is that the test is not easily available and,
children are taken as high. A low ASO titer does not very costly, so not practically suitable for developing
exclude RF. When anti-DNase B titer is more than countries.
120 Todd units in adult and more than 240 Todd unit
in children, it is suggestive of ARF.
Hematological Investigations
Throat Swab Culture Acute Phase Reactants

A positive throat culture directly demonstrates pres- The blood parameters measured during acute phase
ence of GAS in throat. But the bacteria may disap- of inflammation often show higher value and they are
pear during the latent phase producing a false nega- known as acute phase reactants. The common tests are:
tive result or it may also be false positive in a carrier 1. Erythrocyte sedimentation rate (ESR).
state. When GAS is present in the throat without in- 2. C-reactive protein (CRP).
vasion; means it stays as a carrier state. In these cases 3. Leukocyte count.
pharyngitis is due to another organism (commonly a Besides these commonly used tests, other tests
viral infection). There are no definite clinical symp- like serum mucoprotein, serum hexosamine and se-
toms and signs to diagnose streptococcal pharyngitis rum protein electrophoresis are no longer clinically
or to differentiate from other types of infection. Cor- used.
rect procedure and meticulous care should be taken Acute-phase reactants are characteristically
for taking throat swab and for its culture in blood elevated in ARF as a marker of inflammation. Raised
agar media. If no growth occurs within first 24 hours erythrocyte sedimentation rate (ESR) more than
additional incubation is done for another 24 hours. 30 mm in 1st hour is significant. Raised levels of se-
Note: Quantification of GAS is no proof of true rum protein which helps the RBC for rapid rhoul-
infection; a sparse growth may be present in actual eaex formation increase the rate of sedimentation.
infection. It is measured commonly by Westergreen method.
ESR remains high as long as 3 to 6 months even after
symptomatic relief. In presence of congestive heart
Rapid Antigen Test for Group A Streptococcus
failure (CHF), normal ESR is also significant as ESR
Antigen detection in the throat swab is highly spe- decreases in CHF. Serum C-reactive protein (CRP)
cific test for presence of GAS in the throat. The spec- more than 30 mg/L is invariably present with onset
ificity of a positive test is between 85 to 100 percent. of clinical manifestations. CRP levels rise and peak
But due to their low sensitivity, these tests are not early and fall with resolution of symptoms.
substitute for throat swab culture. Negative results Leukocytosis is also present in ARF as an indica-
do not rule out presence of organism in the throat tion of intense inflammation, and after a week or so it
and, therefore, has to be confirmed by a blood agar comes down to normal range. Acute phase reactants
culture. These tests are immunological methods to are included as minor diagnostic criteria. Anemia
identify unique streptococcal cell wall carbohydrate may be due to suppression of erythropoiesis but is not
antigen. Like throat culture this test is unable to dis- included in diagnostic criteria as it is nonspecific.
tinguish between actual infection and carrier state ESR and CRP tests are nonspecific but raised ESR
with concomitant viral pharyngitis. It is a bedside and CRP have definite supportive role in diagnosis
Laboratory Diagnosis of Acute Rheumatic Fever 31
of ARF. In setting of suspected ARF if ESR and CRP ditis. Wenckebach phenomenon and AV dissociation
values are normal, the diagnosis of ARF is no longer may be seen rarely.
feasible. CRP level rises early and quickly comes to
normal when the inflammation abated. If ESR re-
Roentgenography
mains high but CRP level is normal, it indicates no
more active inflammation is present. Chest X-ray features are neither specific nor diagnos-
Remember: tic of ARF. Cardiomegaly is common due to LA and
• Raised or rising ASO titer is suggestive of recent LV enlargement in carditis. Sometimes pericardial
streptococcal infection. Increased ASO titer does effusion may contribute to cardiomegaly. Pulmonary
not mean that patient is having ARF. venous hypertension is seen due to increased LA
• ASO titer should be measured in a standard labo- pressure. In severe MR, features of pulmonary con-
ratory (to avoid unusual variation). gestion leading to pulmonary edema may be seen.
• Absence of raised CRP is strongly against the
diagnosis of ARF.
Echocardiography
• ASO titer and CRP should be correlated with
clinical picture for diagnosis of ARF (for correct Considering the extreme sensitivity of echocardio-
advice of penicillin prophylaxis). graphy (Echo) in diagnosis of valvular regurgitation
and detection of pericardial effusion, there are sug-
gestions to perform 2-D and Doppler echo in every
Troponin Test
suspected case of rheumatic carditis and to make it
In the recent years troponin T and troponin I tests one of the diagnostic criteria. The term subclinical
used as a biomarker in setting of ARF with severe car- carditis (silent carditis) is applied to cases of ARF
ditis, which show no raised value, because rheumatic having no clinical evidence of carditis but with echo
carditis (associated with myocarditis) has no signifi- evidence of mitral or aortic regurgitation. Echo crite-
cant myocardial muscle necrosis. Heart failure in ARF ria for diagnosis of subclinical rheumatic carditis are:
is always due to valvular regurgitation, not due to my- 1. Annular dilatation.
ocarditis. The clinical implication is if it is raised it goes 2. Posterior-lateral direction of jet of MR.
in favor of viral myocarditis not rheumatic carditis. 3. Chordae of the anterior mitral leaflet are elon-
gated and there is typical prolapse of the anterior
leaflet.
NonInvasive Tests 4. No billowing of the medial septal leaflet.
Echo is more sensitive than auscultation in
Electrocardiography
diagnosing valvular regurgitation. But at the same
PR prolongation is seen in 25 percent of cases of ARF. time, there is possibility that trivial or physiological
It is a nonspecific finding which is present in healthy MR (rarely AR) in otherwise healthy children may
children but the difference is that in ARF the PR in- be taken as pathological lesion, as there are no
terval returns back to normal over next few weeks. distinct criteria to differentiate physiological from
PR prolongation is not related to presence of carditis. pathological regurgitation. Although WHO and
It is a minor diagnostic criterion. This phenomenon AHA in 2002, recognized the concept of subclinical
is due to vagal overtone. It may rarely lead to tran- carditis but for its long-term consequences not yet
sient asymptomatic high grade AV block or sinus recommend for its inclusion in Jones criteria. On
bradycardia. Though tachycardia is commonly pre- the other hand, the joint committee recommended
sent in carditis, bradycardia due to AV conduction where echo facility not available particularly in
abnormality is occasionally present in setting of car- developing countries, it should not be taken as
A B
Figs 6.1A and B: (A) Echocardiography in carditis showing typical appearance of mitral valve in parasternal long axis
view, left frame shows thickened leaflets with beaded appearance (arrow), left frame shows color Doppler evidence of
MR (open arrow); (B) Another case of carditis, right panel shows echo-free space around the heart (black arrows) due to
mild pericardial effusion indicating pericarditis
limitation for diagnosis of ARF. But National Heart cates the onset of mitral stenosis, pulmonary arte-
Foundation of Australia and the Cardiac Society of rial hypertension and deterioration of LV function.
Australia and New Zealand in 2006 have included In chronic RHD, timing of surgery is decided on
echocardiography as a major criteria. the basis of echo finding. There is definite role of
Echocardiography with Doppler plays a sig- transesophageal echocardiography which sometimes
nificant role in diagnosis of carditis. It confirms the shows clearly the nodules if present over mitral or
valvular regurgitation, helps in estimating its seve- aortic valve confirming rheumatic etiology (thereby
rity, assessing chamber size and ventricular function. it plays a definite role for long-term prophylaxis).
When a previous echo finding is known, it helps in Remember: In golden era of auscultation, some
diagnosis of recurrent carditis. Echo can exactly re- cases of minimal valvular lesion were missed (under
veal the amount of pericardial effusion when present. diagnosed) and the term subclinical carditis was not
In suspected cases of ARF and a cardiac murmur, it there in pre-echo era. It was only after Doppler echo,
can establish the diagnosis of rheumatic mitral or minimal lesion (known as subclinical carditis) is
aortic valvulitis. Echo criteria for rheumatic carditis detected. In the recent era of echocardiography (some
are (Figs 6.1A and B): physicians of developed countries think auscultation
• Leaflet thickness ≥ 4 mm. is a dying art) the diagnosis of minimal or subclini-
• Increased echogenicity of subvalvular structure. cal rheumatic carditis is more often diagnosed (over
• Presence of rheumatic nodule (beaded appear- diagnosed).
ance).
• MV/AV/TV prolapse. Nuclear Imaging
• MV or AV or TV regurgitation.
• Decreased valve mobility. The role of nuclear imaging with Gallium-67 imag-
• Chordal tear. ing, radiolabeled leukocyte and radiolabeled an-
Serial echocardiographic examination helps timyosin antibody scintigraphy, are performed to
in identifying progression of disease and also indi- identify rheumatic carditis but results are nonspecific
Laboratory Diagnosis of Acute Rheumatic Fever 33
and inconsistent. The evidence is too less to make it Note: This invasive procedure carries risk and not in-
a routine diagnostic criteria. But these studies have formative for the diagnosis of rheumatic carditis so
confirmed that rheumatic carditis is an infiltrative, not taken as a routine investigation.
not degenerative process.
further reading
Invasive Procedures 1. Carapetis JR, McDonald M, Wilson NJ. Acute rheu-
Synovial Fluid Analysis matic fever. Lancet. 2005;366:155–68.
2. Consensus Guidelines on Pediatric Acute Rheumatic
Synovial fluid analysis shows increased leukocytes, Fever and Rheumatic Heart Disease. Working Group
no crystals or any organisms are detected in the fluid. on Pediatric Acute Rheumatic Fever and Cardiology
This test is not done routinely as it has no definite role Chapter of Indian Academy of Pediatrics, Indian
in diagnosis of ARF, contrary it is helpful in cases of Pediatrics. 2008;45:65–73.
nonrheumatic origin. 3. Narula J, et al. Endomyocardial biopsies in acute
rheumatic fever. Circulation. 1993;88:2198–205.
4. Narula J, Kaplan EL. Echocardiographic diagnosis of
Endomyocardial Biopsy
rheumatic fever. Lancet. 2001;358:2000–10.
Studies have been performed to establish the role of 5. Stollerman GH. Rheumatic Fever and Streptococcal
endomyocardial biopsy in the diagnosis of carditis. Infection. Grune and Stratton Publisher, New York.
Biopsies were performed during the first attack car- 6. Vasan RS, Shrivastava S, Vijayakumar M, et al.
ditis, indolent or quiescent carditis, in pre-existing Echocardiographic evaluation of patients with acute
RHD suspected to have a recurrence of carditis and rheumatic fever and rheumatic carditis. Circulation.
in rheumatic fever without evidence of clinical cardi- 1996;94:73–82.
tis. All these cases have shown that right ventricular 7. WHO technical report series, 923, Rheumatic fever
endomyocardial biopsy has no additional role to sup- and Rheumatic heart disease: report of a WHO expert
plement clinical diagnosis of carditis; only in some consultation, Geneva, 29 October–1 November 2001,
cases (30–40%), Aschoff nodules are present. World Health Organization, Geneva, 2004.
CHAPTER 7
Diagnosis and Differential Diagnosis
of Rheumatic Fever
BR Mishra
Diagnosis of acute rheumatic fever (ARF) depends Lab Tests

upon constellation of several clinical and laboratory Acute phase reactants
features. The criteria laid down by T Duckett Jones in • Raised ESR
1944 for diagnosis of ARF is still followed with some • Positive C-reactive protein
periodic modifications (see Chapter 5, Table 5.1). • Leukocytosis.
The last update of Jones criteria was done by AHA
and WHO in 2003 with the aim to improve the speci- ECG
ficity. In 2005, the Australian guidelines for diagnosis Prolonged PR interval.
of ARF in their country has modified application of
Jones criteria into high-risk and low-risk population Essential Criteria
group. The whole aim is neither to over diagnose nor
to miss the diagnosis of ARF. Documentation of recent streptococcal infection
The peculiarity of clinical diagnosis of acute (within 45 days) is necessary for diagnosis of ARF,
rheumatic fever is that it does not bank upon only that is one of the following tests should be positive.
symptoms and signs but the laboratory support is 1. Positive throat culture
mandatory for diagnosis. 2. Raised or rising streptococcal antibody tire (Anti
streptolysin O or Anti DNAse B)
3. Rapid antigen detection tests for Group A
Modified Jones Criteria (2003) Streptococci.
For diagnosis of ARF, two major or one major plus
Major Criteria
two minor with essential criteria are necessary.
• Carditis
• Polyarthritis Characteristic Features of
• Chorea
Major Criteria
• Subcutaneous nodules
• Erthema marginatum. Arthritis/polyarthritis—big joints, fleeting type,
very painful even on slight movement.
Carditis—hallmark of carditis is presence of systolic
Minor Criteria
murmur over apex due to mitral valvulitis (repre-
Clinical sents mild-to-severe MR) or carditis can affect aortic
valve causing aortic valvulitis clinically detected by
• Fever presence of early diastolic murmur (EDM, mild aor-
• Polyarthralgia tic regurgitation).
Diagnosis and Differential Diagnosis of Rheumatic Fever 35
Chorea—involuntary movement (nonpurposive and thralgia and aseptic monoarthritis under major cri-
nonrepeatative) mainly seen in teenagers, female pa- teria besides modified Jones criteria, 2003.
tients. Echocardiography and Doppler studies dis-
Subcutaneous nodules—small pin head to pea sized, cussed to enroll as a major criteria for diagnosis of
nontender, skin over it freely mobile, and mainly pre- carditis/subclinical carditis but not yet accepted and
sent over elbow, knee, occipital region and spine. not included as a major/minor diagnostic criteria.
Erythema marginatum—small raised macules, non- As per Australian guidelines even subclinical cardi-
pruritic, evanescent, rashes mainly seen over proxi- tis detected by echocardiogram is included as major
mal part of the body (never over face). criteria in high-risk group.
Because arthralgia is much more commonly pre-
sent than acute arthritis in developing countries it
Characteristic Features of Minor Criteria
was proposed to include it as major criteria (by Pad-
Fever—high fever (more than 39°C or 102°F). It fol- mavati S, George Cherian and KS Mathur). But in re-
lows no characteristic pattern and continues on aver- cent recommendation of WHO and AHA it has not
age for 2 to 3 weeks. been accepted.
Polyarthralgia—it involves big joints migratory
in nature but intensity of pain and joint affection is Jones Criteria not Applied for
much less. It may continue for few weeks and mainly
associated with carditis. 1. Late onset carditis or indolent carditis
ESR—raised ESR (more than 30 mm in 1st hour) 2. Cases of pure chorea
C Reactive Protein (raised ≥ 30 mg/L) 3. Recurrent attack of ARF
Leukocyte count (leukocytosis more than 10,000/ 4. Patients presenting with valvular lesion (MS, MR,
mm3). AR) do not require any criteria for diagnosis of
PR interval—prolonged. (Normal upper range of PR RHD.
interval in 3 to 12 years 0.16 sec, in 12 to 14 years Patients having rheumatic heart disease with
0.18 sec and in more than17 years of age 0.20 sec). It congestive heart failure if acute surface reactants are
is mostly due to affection of conduction system. It is raised in presence of evidence of recent streptococ-
not an indicator of carditis. cal sore throat acute carditis is suspected even with-
Recently the Australian guidelines (2005) for out other criteria for rheumatic fever. This carditis is
diagnosis of ARF is approved by National Heart known as ‘indolent carditis’.
Foundation of Australia (NHFA) and Cardiological
Society of Australia and New Zealand (CSANZ) for Probable Rheumatic Carditis
diagnosis of ARF. It includes modified Jones criteria
plus other parameters as mentioned below. For diag- In area of high incidence of ARF, patient of vulner-
nosis of ARF and RHD the Australia population has able age group, three or more minor manifestations
been divided into two groups (1) High-risk group (without major criteria) plus evidence of recent
and (2) Other groups (low-risk). High-risk group streptococcal sore throat are taken as ‘probable ARF’
are those who live in community with high rate of and advised secondary prophylaxis with regular fol-
ARF (incidence more than 30 per lakh per year) low-up.
and chronic RHD (prevalence rate more than two
per thousand). It is very difficult and practically not
possible to put the patients of developing countries Clarification of Certain Doubts
particularly India into these two categories. Doubt arises that subcutaneous nodules, chorea, and
This criteria includes subclinical carditis (evi- erythema marginatum being uncommon worldwide
dence of valvulitis on echocardiography), polyar- and particularly erythema marginatum rarely seen in
India and tropical countries, how they are included Note: It is rightly told by Lague, the famous patholo-
as major criteria? The answer is: it is not the com- gist of early nineteenth century that ‘RF licks the joint
monness but if at all they are present with febrile on- but bites the heart’
set it is very specific for acute RF. The clinical examination remains the basis of
Febrile onset is a very common feature but not diagnosis of RF and carditis. The physicians should
included as major criteria because this occurs in use clinical judgment to diagnose carditis. Diagnosis
many conditions and so not specific for rheumatic of acute RF is not at all difficult in most of the cases
fever. when it presents with its typical features; like in teen-
agers with fever and fleeting arthritis with cardiac
murmur in developing countries.
Problems for Diagnosis of Acute
Rheumatic Fever
Differential Diagnosis of Acute
Clinical signs and symptoms misleading the diagno-
Rheumatic Fever
sis of acute rheumatic fever are:
• When fever is associated with arthritis (involv- In absence of particular diagnostic feature and diag-
ing bigger and smaller joints) one should think of nostic test, diagnosis of acute rheumatic fever (ARF)
ARF (not to diagnose ARF). depends upon constellation of several clinical fea-
• In early stage of rheumatic fever only fever (mild/ tures and laboratory tests, that is why a number of
moderate/high), may be misled the physicians till clinical conditions simulate ARF, come under dif-
joint pain develops. ferential diagnosis. Many times it is easy to exclude
• Mild joint pain and irregular fever do not satisfy them by careful history taking, clinical examination
the Jones Criteria, so many cases may be missed and simple laboratory examinations.
(till present with cardiac lesions) in developing
countries. The common clinical conditions are:
• Fever with carditis, generalized body ache or 1. Poststreptococcal reactive arthritis
arthralgia, may not be rheumatic carditis, may be 2. Juvenile rheumatoid arthritis
viral or of some other etiology. 3. Infectious arthritis
• High ESR/ASO titer not necessarily mean the 4. Connective tissue disorders: (a) Rheumatoid
patient is having acute rheumatic fever. arthritis, (b) Systemic lupus erythematosus (SLE)
Less common clinical lesions are:

Peculiar Observation of Acute
1. Infective endocarditis
Rheumatic Fever
2. Henoch-Schonlien’s Purpura
• Acute arthritis never associated with chorea 3. Drug reactions
• When there is fleeting acute arthritis, carditis 4. Serum sickness
is uncommon in these cases but with arthralgia 5. Lyme disease
(persistent or recurrent), it is carditis very fre- 6. Sickle cell disease
quently associated. 7. Septicemia
• Acute rheumatic arthritis with all signs of inflamma- 8. Leukemia
tion and being extremely painful, leaves no residual 9. Tuberculosis.
signs of joint involvement when it is subsided.
• Acute rheumatic arthritis is extremely painful and Poststreptococcal Reactive Arthritis
harsh to patient but patient gets cured completely
whereas carditis may be completely asympto- Poststreptococcal reactive arthritis (PSRA) comes
matic, but leads to serious complications and may under most common differential diagnosis. It deve
ultimately to death (carditis is a silent killer) lops following a short latent period of about a week
after throat infection and is not associated with synovial fluid culture can differentiate and confirm
other major manifestations of ARF and also does not these conditions.
respond well to anti-inflammatory drugs (in contrast
to dramatic response in ARF). In other words patients
Systemic Lupus Erythematosus
with acute arthritis following a streptococcal upper res-
piratory infection not necessarily considered to have It mainly occurs in adolescents with irregular fever
ARF if they do not fulfill the Jones criteria. In these cas- and arthralgia which often confuse with manifesta-
es small joints and spine are involved, arthritis may be tions of ARF. The typical rash on the face (butterfly
migratory in nature and may persist longer unlike cases rash) if present differentiates it from ARF. Moreover
of ARF. Because reactive arthritis may subsequently positive LE sell test is confirmatory of systemic lupus
develop valvular heart disease, they should be carefully erythematosus (SLE).
observed for development of carditis. Although not
well established, there are suggestions that they may be
Henoch-Schonlein’s Purpura
considered for secondary prophylaxis for one year and
if after one year there is no valvular involvement, sec- Some patients present with irregular fever or high fever,
ondary prophylaxis may be discontinued. athralgia/arthritis, skin lesions, abdominal pain, and
positive ASO titer which sometimes difficult to differ-
entiate from acute rheumatic fever. But petechiae over
Juvenile Rheumatoid Arthritis (Still’s Disease)
lower limbs are specific of purpura, not seen in ARF.
When rheumatoid arthritis (RA) presents with high Subacute bacterial endocarditis in children with
fever and polyarthritis involving big joints at younger manifestations of arthritis and irregular fever also
age group it may confuse with the diagnosis of ARF. confuse with rheumatic fever. Other rare conditions
Polymayalgia rheumatica causes morning stiffness simulate with rheumatic fever and arthritis are sickle
(never occurs in ARF). But in case of Juvenile rheu- cell hemoglobinopathy, post-infective arthritis and
matoid arthritis in subacute form, the process of septic arthritis. But all these conditions can easily be
arthritis continues for months to years and poorly ruled out by their specific clinical signs and symp-
respond to anti-inflammatory drugs. These cases toms and also by specific investigations (like sickling
in long-term develop lymph node enlargement and test and spinal fluid examination).
splenomegaly, besides macular patches. Laboratory
diagnostic findings like ESR, CRP are often raised in Lyme Disease
both conditions at initial phase, so not of much help.
Similarly rheumatoid factor may be negative in juve- Lyme disease may present with fever, arthritis, skin
nile RA poses a diagnostic problem. When deformity rash and cardiac involvement that mimic ARF. Geo-
of small joints and some time big joints are present, it graphical location, history of tick bite and positive
goes in favor of RA. In Still’s disease and also in rheu- serological test (titers against Borrelia burgdorferi)
matoid arthritis, subcutaneous nodules appear which confirms Lyme disease.
are bigger than that of ARF. Note: Besides ARF migratory arthritis is also a fea-
ture of (a) viral arthritis, (b) SLE, (c) Acute leukemia.
Similarly fever preceding arthritis other than ARF are
Infectious Arthritis
SLE, reactive arthritis, viral arthritis and Still’s disease.
Bacterial, viral arthropathy (Epstein-Barr virus and
parvovirus), fungal, mycobacterial and other infec- Differential Diagnosis of Carditis
tious arthritis are easily separated out due to mainly
monoarticular involvement with severe systemic The following conditions come under differential
manifestations. Blood culture, serological tests and diagnosis:
1. Innocent murmur (anemia and physiological Pericarditis

murmur).
2. Mitral valve prolapsed (MVP). Pericarditis due to rheumatic origin is always associ-
3. Congenital heart disease (mainly bicuspid aortic ated with myocarditis. Isolated rheumatic pericardi-
valve). tis is extremely rare. The heart sounds and murmur
4. Myocarditis (Viral/idiopathic) may be muffled due to extensive pericardial rub or
5. Infective endocarditis pericardial effusion. It vanishes within one to two
6. Pericarditis (viral/ idiopathic) weeks of its appearance. Pericarditis due to rheuma-
Innocent murmur in setting of irregular fever toid arthritis is associated with history of joint pain
with arthritis or arthralgia many times misdiagnosed (arthritis or arthralgia) simulating ARF but other
as acute rheumatic carditis. During school survey in- features of rheumatoid arthritis differentiate it from
nocent murmurs should be properly excluded oth- ARF. Isolated viral pericarditis is mostly transitory
erwise number of rheumatic carditis case will be and associated with fever. Sometimes it is associated
wrongly diagnosed and the incidence will be more. with myocarditis which leads to myocardial damage
In about 25 percent of children this innocent mur- leading to congestive heart failure. Absence of signifi-
mur is present over left parasternal or pulmonary cant valvular regurgitation differentiate viral pericar-
area. The parasternal murmur is known as Still’s ditis from rheumatic carditis.
Murmur or vibratory murmur or physiological bruit.
These murmurs are audible over left parasternal bor-
Chorea
der, grade 1-2/6 at best 3/6 in intensity, vary with
respiration and change of posture, usually musical or The following conditions come under differential
twanging-string quality. The intensity of the murmur diagnosis of chorea:
is increased in setting of hyperdynamic circulatory 1. Ticks disorder
state like tachycardia, anemia, and after exercise. This 2. Choreoathetoid movements
murmur when heard over pulmonary area is con- 3. Huntington’s chorea
fused with congenital pulmonary stenosis murmur 4. Intracerebral tumors
but it is a short, soft murmur heard in early part of 5. Drug induced involuntary movement (anticon-
the systole. Stills murmur is produced due to changes vulsants and antidepressants)
with respiration (vibratory or strangulatory sound of 6. Hyperthyroidism, Hypoparathyroidism
pulmonary valve) and due to flow of blood from right 7. Pediatric autoimmune neuropsychiatric disorders
ventricle to pulmonary artery. associated with streptococcal infections (PANDAS).
PANDAS was described in children in associa-
tion with streptococcal infection. These are a type of
Myocarditis
obsessive compulsive disorder with or without ticks
Children with irregular fever, malaise, arthralgia with are thought to be due to autoimmune reactions to
a systolic murmur over apex, not necessarily always group A streptococcal infection. They respond to IV
suffer from acute rheumatic carditis but may be also immunoglobulins and plasma exchange.
due to viral or other myocarditis. In both the cases in Chorea may occur due to a variety of disorders
due course of time the murmur may disappear (heal- like genetic (Huntington’s disease and other famil-
ing occurs without residual signs). If murmur per- ial chorea), endocrine, collagen vascular disease like
sists, it is most likely of rheumatic etiology. In viral SLE, neoplastic and metabolic conditions (Wilson’s
myocarditis, congestive heart failure is present with- disease). History, clinical examination give sufficient
out appreciable murmur, and the patient become sick clue with appropriate laboratory tests to rule out or
but in rheumatic carditis heart failure is associated confirm the cause of chorea. Atypical seizure may be
with cardiac murmur. confused with chorea but has distinct EEG abnor-
mality. Drugs such as phenytoin, amitriptyline, me- or over the spines). Similar nodes also appear in Still’s
toclopramide and fluphenazine may produce chore- disease and in Juvenile Rheumatoid arthritis (Felty’s
form movements. syndrome). They are differentiated from rheumatic
In the pediatric age group tic and athetosis and in nodule because they are bigger in size, not mobile
adult age group convertion reaction also come under and do not reappear rather persist for years together
differential diagnosis. and cardiac lesions are not associated. Other nodes
like Osler’s node seen in infective endocarditis are
Differential Diagnosis of Erythema very small and tender that appear on pads of the fin-
gers which is easily differentiated.
Marginatum
The minor criteria for diagnosis of ARF are fever,
Erythema marginatum type of rashes is produced arthralgia, high ESR and leukocytosis. They are asso-
by a variety of disorders like septicemia, acute glo- ciated with innumerable diseases. Because these are
merulonephritis, and adverse drug reaction (unci- all nonspecific findings need not be discussed under
nate erythematous rash, raised papular with pruritic differential diagnosis.
rash). Juvenile rheumatoid arthritis may have erythe-
matous rash along with arthritis which may confuse
with ARF. Exanthematous fever have erythematous further reading
skin rashes resembling erythema marginatum. Lyme 1. Carapetis JR, McDonald M, Wilson NJ. Acute rheu-
disease produces a typical rash known as erythema matic fever. Lancet. 2005;366:155-68.
chronicum migrans. Erythema nodosum and multi- 2. Dajani AS, Ayoub E, Bierman FZ, et al. Guidelines
forme rash due to tubercular or meningococcal in- for the diagnosis of rheumatic fever: Jones criteria,
fection some time confuse with erythema margina- updated 1992. Circulation. 1993;87:302-7.
tum. Although these rashes at the first sight look like 3. Narula J, Kaplan, EL. Echocardiographic diagnosis of
erythema marginatum, they are easily differentiated rheumatic fever. Lancet. 2001;358:2000-10.
because they lack in typical distribution, the typi- 4. Rheumatic Fever and Streptococcal Infection by Gene
cal appearance without itchiness and no response to H Stollerman, Grune and Stratton Publisher, New York.
anti-inflammatory drugs. 5. Rheumatic Fever: 2nd edn, Milton Markowitz and
Leon Gordis, WB Saunders Company, Philadelphia,
1972.
Differential Diagnosis of Subcutaneous
6. Vasan RS, Shrivastava S, Vijayakumar M, et al.
Nodules
Echocardiographic evaluation of patients with acute
The subcutaneous nodules are present in certain spe- rheumatic fever and rheumatic carditis. Circulation.
cific sites like bony prominences (knees, ankle, elbow 1996;94:73-82.
CHAPTER 8
Management of Rheumatic Fever
TK Mishra
Introduction when there is congestive heart failure or severe ar-

Acute rheumatic fever (ARF) is a consequence of thritis. The patient can be ambulated when fever sub-
throat infection with Group-A beta hemolytic Strep- sides, joint pain is relieved and when there is no more
tococcus (GABHS). It leads to long-term damage to dyspnea and palpitation. Caution should be observed
the cardiac valves resulting in rheumatic heart dis- for patients with carditis, for whom a rest period of
ease (RHD) which is responsible for considerable 4 weeks is generally recommended but for patients
morbidity and mortality in developing countries. with congestive heart failure, bed rest for six weeks is
With socioeconomic development, less overcrowd- advised. Then restricted physical activity is advised for
ing, better access to medical care, the disease has another month even after anti-inflammatory drugs are
disappeared from developed countries. However, in discontinued. Patients with chorea need a protective
developing countries, the disease continues to ravage environment and should remain under close observa-
millions of people where poverty is rampant, thus tion so that they do not injure themselves. For arthri-
setting the milieu for widespread occurrence of the tis, rest for 2 weeks is adequate. Fluid and salt restric-
disease. tion may be needed in heart failure, but the diet should
Though the disease is known to be prevalent contain adequate protein and calorie commensurate
since medieval days, its etiopathogenesis continues to with metabolic need of a growing child. Patient and
remain enigmatic. As one flounders for the etiology family education must be done at every opportunity so
of the disease, management also remains mainly as to address their concern and ensure complete coop-
empirical. It does not alter the course or outcome eration in patient management.
of the disease. Management of rheumatic fever is
described under the following headings:
Management of Streptococcal Pharyngitis
• General measures
(Antimicrobial Therapy)
• Antimicrobial therapy
• Anti-inflammatory drugs Once the patient is diagnosed to have ARF, antimi-
• Treatment of heart failure and chorea crobial therapy is given to eradicate Streptococcus
• Primary and secondary prophylaxis of the rheu- from pharynx (Table 8.3). Although eradication of
matic fever. Streptococcus from pharynx does not have any im-
pact on the course of rheumatic fever (ARF); once it
appears, it should always be eradicated to remove the
General Measures
potential source of another attack. Injection benza-
Bed rest is generally advised until resolution of symp- thine penicillin G is given intramuscularly at a dose
toms and normalization of acute phase reactants of 1.2 million units in a child weighing more than
(ESR and CRP). Hospitalization may be required 27 kg or 0.6 million unit weighing less than 27 kg
Management of Rheumatic Fever 41
after sensitivity test. Procaine penicillin 600,000 units nosis is confirmed. In the meantime, paracetamol or
per day for ten days is also advised. In some cases codeine can be used to treat joint pain.
oral penicillin V 250 mg 4 times daily is also recom-
mended. Those who are allergic to penicillin, either
Aspirin
erythromycin 250 mg 4 times daily or azithromycin
(12.5 mg/kg/day once daily) or oral cephalosporins Acetyl salicylic acid (aspirin) has been the most wide-
(Cefadroxil, Cefalexin) for 10 days are advised. Tet- ly used and validated anti-inflammatory, antipyretic
racycline and Co-trimoxazole are not recommended. and analgesic agent for use in ARF (Table 8.1). Aspi-
In treatment failure with penicillin, Amoxicillin plus rin, 100 mg/kg/day divided in 4 to 5 doses, is usually
Clavulanate, Clindamycin, Cephalosporins and Pen- adequate. In children, the dose may be increased to
icillin plus Rifampicin are effective. When the patient 125 mg/kg/day, and in adults, up to 6 to 8 g/day can
is unable to take by oral route, cefazoline or ceftriax- be given. If symptoms like anorexia, nausea, vomit-
one (50 mg/kg IM or IV) may be advised. ing and tinnitus appear, they usually subside after a
Note: The purpose of the treatment with antimicro- few days; despite continuation of the medication. Se-
bial therapy is to eradicate or remove GABHS from rum salicylate levels of around 20 mg/dL are required
pharynx. for optimal anti-inflammatory effects. Hence, salicy-
late level in blood should be monitored if facilities
are available.
Management of Inflammatory Process
Aspirin leads to rapid resolution of fever,
(Anti-Inflammatory Drugs)
arthritis and arthralgia. However, the available
There is no specific disease-modifying therapy for evidence suggests that salicylates should not be
ARF. The anti-inflammatory therapy is targeted at used for the treatment of severe carditis, and results
reducing the constitutional symptoms, controlling of comparison of salicylates with no treatment or
toxic manifestations, and improving cardiac func- bed rest alone; suggest that they do not decrease
tion. Anti-inflammatory therapy is given with ei- the incidence of residual RHD. Hence, salicylates
ther aspirin or steroid (prednisolone). Superiority of should be used only for the symptomatic treatment
either drug has not been demonstrated over other in of fever, arthritis, and arthralgia. In patients allergic
treating ARF except in severe carditis with heart fail- to aspirin, naproxen has been used (10–20 mg/kg/
ure where steroids relieve symptoms more promptly day) successfully.
and may have mortality benefit. Similarly, in arthritis Side effects of salicylates: Anorexia, nausea, vom-
aspirin relieves symptom more quickly than steroid. iting, tinnitus are common side effects. If patient
Several recent literatures have remarked against the cannot tolerate in spite of antacids then other non-
use of steroids in ARF as there are no significant ben- steroidal anti-inflammatory drugs (NSAIDs) are rec-
efit in the face of potential adverse effects. ommended as second line drug.
The arthritis of ARF is exquisitely responsive to Note: Salicylates remains the mainstay in treatment
treatment with aspirin and other nonsteroidal anti- of rheumatic arthritis since 1876 till recent years.
inflammatory drugs (NSAIDs). Indeed, this can be a
useful diagnostic feature, as arthritis continuing una- Steroids
bated more than 3 days after starting NSAIDs thera-
py is unlikely to be due to ARF. Equally, withholding Routine use of glucocorticoids started since 1949.
NSAIDs in patients with monoarthralgia or mono- Corticosteroids are potent anti-inflammatory agents
arthritis to observe the development of polyarthritis used in patients with ARF. Prednisolone in a dose of
can help to confirm the diagnosis of ARF. Therefore, 1 to 2 mg/kg/day in single or divided doses up to a
aspirin or NSAIDs should be withheld until the diag- maximum of 80 mg/day is the drug of choice. In life
Table 8.1: Drugs for control of inflammation in acute rheumatic fever

Inflammation Doses
Arthritis ± mild carditis Regime I
aspirin* Starting doses:
Children 100 mg/kg/day for 2–3 weeks
Adult 6–8 g/day—divide in 4–5 doses
Tapering doses: Once symptoms resolved, taper to 60–70 mg/kg/day. For
older children 50 mg/kg/day (Level of evidence: Class I)
Regime II
50 to 60 mg/kg/day for total 12 weeks
(Level of evidence: Class Ib)
Naproxen*(If aspirin intolerance 10–20 mg/kg/day
detected) Switch over to steroid. Rule out other conditions like chronic inflammatory/
No response to aspirin in four days myelo-proliferative disorders before switching over to steroids
Moderate to severe carditis Regime I
Steroids* Prednisolone: 2 mg/kg/day, maximum 80 mg/day till ESR normalizes—usually
2 weeks. Taper over 2–4 weeks, reduce dose by 2.5–5 mg every 3rd day. Start
aspirin 50–75 mg/kg/day simultaneously, to complete total 12 weeks. (Level of
evidence: Class I)
Regime II
Prednisolone same doses × 3–4 weeks. Taper slowly to cover total period of
10–12 weeks (Level of evidence: Class IIb)
Nonresponders If no response to oral steroid therapy then start IV methyl prednisolone 30
Methyl Prednisolone (Intravenous) mg/kg/day for 3 days
* Consider antacids. Avoid gastric irritants. Allow frequent feeding. Medicines must not be taken on empty stomach.
Source: Consensus Guidelines on Pediatric Acute Rheumatic Fever and Rheumatic Heart Disease. Working Group on
Pediatric Acute Rheumatic Fever and Cardiology Chapter of Indian Academy of Pediatrics, Indian Pediatrics. 2008;45:565.
threatening situations, intravenous methyl predniso- benefits of steroids and other newer anti-inflamma-
lone is often used to initiate therapy. tory agents on acute rheumatic carditis and long-
Steroids greatly reduce the inflammatory re- term cardiac outcome. Moreover, most interven-
sponse to ARF, especially fever and raised concen- tions to alter the outcome of ARF will be hampered
trations of acute phase reactants. Many physicians by the inherent delays at different stages of diagnosis
believe this lead to more rapid resolution of cardiac that is:
compromise than other drugs and can be life saving 1. From initial streptococcal infection (latent period,
in severe cases of acute carditis, though there is lit- 1–5 weeks) to onset of symptoms.
tle objective evidence. Results of randomized trials 2. Onset of signs and symptoms to seek physician’s
done before echocardiography became widely avail- advice.
able and those of subsequent meta-analyses have not 3. From physical examination by physicians till the
shown benefit of steroids over placebo or salicylates diagnosis is confirmed.
in the prevalence of residual RHD in 10 years after This inherent delay will further complicate the
ARF. However, all of the studies included in meta- assessment of new treatment because of natural im-
analysis were done more than 40 years ago and most provement of rheumatic carditis that occurs in the
studies did not test the steroids that are in common absence of recurrences, in some cases.
use today. At present, in spite of the controversies, steroids
Hence, large, probably multicenter, randomized are recommended in patients with significant cardiac
controlled trials are needed to assess the potential involvement (with pericarditis and heart failure). The
use of steroids result in faster resolution of inflamma- Note:

tion, toxic state and pericardial effusion as compared 1. Patients with arthritis: Salicylates (aspirin) is the
to aspirin in these conditions. drug of choice.
Prednisolone is the steroid of choice. ACTH 2. Patients with carditis: Steroid (prednisolone) is the
nowadays is seldom used. It is observed that with drug of choice.
high doses of steroid chance of rebound is more. 3. Patients with carditis and CHF: Steroid is the drug
Reappearance of symptoms after discontinuation of of choice, aspirin is added during tapering of
treatment is known as rebound. The mechanism of steroid to prevent rebound.
rebound phenomenon is not well understood.
Side effects of prolonged use of steroid therapy in
Management of Heart Failure
high doses are:
1. Water and salt retention Salt and fluid restriction are usual measures. Diuretics
2. Hypokalemia are added when heart failure (HF) is present. Bed
3. Hypertension rest and steroids are supposed to help in resolution
4. Gastric ulceration of HF symptoms. However, gradual mobilization is
5. Cushingoid syndrome advised once the initial symptoms begin to resolve
6. Steroid psychosis which usually takes about 4 weeks in patients with
Side effects should be carefully managed. carditis. Patients with severe symptoms will need
Note: The distinct advantage of steroid therapy digitalis and ACE inhibitors, though data supporting
(prednisolne) is to ameliorate the signs of carditis the use of these agents in ARF is lacking. The clinical
and heart failure very early. No definite evidence that conditions do improve with these drugs. However,
use of steroid in ARF, prevents carditis. digitalis is used with caution in acute rheumatic
carditis with heart failure (likely to cause arrhythmias
and conduction defect). In severe uncontrolled heart
Duration of Therapy
failure (refractory HF) particularly in case of chordal
The duration of therapy is arbitrarily based on the rupture, mitral valve surgery (repair or replacement)
severity of illness and response to therapy and should is life saving. Table 8.2 enlists the drugs and their
be individualized. Mild attacks of ARF with no or dosages to control HF.
little cardiac involvement can be treated with aspirin
only for about 4 weeks or until there is sufficient evi- Management of Chorea
dence of anti-inflammatory activity. If serum levels
can be monitored, it is suggested that after maintain- A quiet environment is required for mild chorea, hos-
ing therapeutic levels for 2 to 3 weeks, the dose of pital care is needed in severe cases. Attention should
aspirin can be reduced to 60 to 70 mg/kg daily and be paid for adequate maintenance of nutrition and
treatment continued for further 3 to 6 weeks. fluid. Sedatives are used in more severe cases as per
In more severe cases of ARF (moderate to severe following regime:
carditis) when prednisolone is chosen as the inflam- 1. Oral phenobarbitone (15–30 mg three times daily)
matory agent, the therapeutic dose should be contin- or diazepam (2–5 mg three times daily).
ued for 8 to 12 weeks, followed by gradual tapering 2. If there is no response, other drugs that can be
(20–25%) every week. Overlap with aspirin (75 mg/ used are:
kg/day) is recommended during the tapering phase • Haloperidol (0.25–0.5 mg/kg/day),
to reduce the chance of rebound (Table 8.1). Approx- • Sodium valproate (15 mg/kg/day), or
imately 5 percent of patients continue to demonstrate • Carbamazepine (7–20 mg/kg/day) and
rheumatic activity in spite of prolonged therapy. • Chlorpromazine (25 mg three times daily).
Table 8.2: Drugs and dosages for heart failure

Drug Dose
Digoxin 30 mcg/kg total digitalization dose, 7.5 mcg/kg/day maintenance dose (Evidence level : Class I)
Diuretics Frusemide 0.5–2 mg/kg/day, Metolazone: 0.2–0.4 mg/kg/day in children and 2.5–10 mg/day in
adults (Evidence level: Class I)
ACE inhibitors Captopril: 0.25 mg/kg: Test dose, build-up doses from 1.5 mg/day to 3 mg/kg/day in three
divided doses (Evidence level: Class I)
Sodium (Uncontrolled CHF) 0.5–10 mcg/kg/min infusion, monitor cyanide level. (Evidence level: Class I)
nitroprusside
Inotropes Dobutamine: 2–20 mcg/kg/min infusion; Dopamine: 2–20 mcg/kg/min infusion; Milrinone: 0.5–1
mcg/kg/min infusion (Evidence level: Class I)
Surgery Severe mitral regurgitation due to chordal rupture leading to refractory CHF (Evidence level:
Class I)
Resistance cases are treated with plasmapheresis Primary Prophylaxis

or pimozide for 2 to 4 weeks. Intravenous immuno- The mainstay of primary prophylaxis is timely and
globulin therapy is also effective in decreasing the se- complete treatment of Group A beta hemolytic Strep-
verity of chorea. tococcus (GABHS) sore throat with antibiotics so that
Treatment should be continued for 2 to 4 weeks it will not lead to develop ARF. As it prevents the first
after clinical improvement. Steroids have no role in attack, it is known as primary prophylaxis. Effective
chorea with ARF but sometimes recommended when antibiotic therapy eradicates GABHS from the up-
it is associated with carditis or congestive failure. It is per respiratory tract and can prevent ARF, if therapy
prudent for the physician to give particular attention is started within 9 days after onset of symptoms. To
to their emotional status and psychiatric disturban- arrive at a diagnosis, one should take into account
ces if present. One small study has suggested that use factors such as age (younger than 15 years), history
of intravenous immunoglobulin might hasten recov- of fever, tonsillar swelling or exudates, tender anteri-
ery from Sydenham’s chorea, but it is not conclusive or cervical lymphadenopathy and absence of cough.
and has potential toxic effects. If 4 or 5 of factors are present, the likelihood ratio
(LR) for GABHS infection is 4.9 (approximately 50%
of cases); if 3 factors are present the ratio decrease to
Prophylaxis of Rheumatic Fever
2.5 (approximately 25% of cases); and if only 2 factors
The overall lack of effective treatment for ARF means are present the ratio becomes 0.9 (approximately 10%
that any reduction of burden of ARF and RHD will of cases). Throat swab culture and antistreptolysin-O
most likely come from meticulous measures for pre- titers (ASO) aid in diagnosis.
vention. The prophylaxis of ARF can be primordial A single intramuscular injection of 1.2 million
primary or secondary. units of benzathine penicillin is often enough to
Ideally, primordial prevention entails elimina- eradicate GABHS from throat. Oral penicillin V (500
tion of major risk factors for streptococcal infection, mg twice daily) has to be given for full 10 days (Table
particularly poverty, overcrowding and inadequate 8.3). First generation cephalosporins are also useful.
hygiene infrastructure. This is difficult to achieve in Present day’s macrolide antibiotics (Erythromycin,
a poor, overpopulated country like India. It is very Azithromycin) are used in patients with penicillin
difficult to carry out primordial prophylaxis. allergy. Although sulfa drugs (sulfadiazine) were
used for streptococcal infection in the initial period to be practical, affordable or cost-effective in a poor
(1925–1960); at present it is of historical interest. But country like ours. At present, no practical and afford-
the prevalence of macrolide resistant strains is high able strategy exists for primary prophylaxis of ARF in
and may pose problems. Antibiotics should not be developing countries.
prescribed to GABHS carriers, as they are unlikely to Note: Primary prophylaxis is more of a theoretical
spread to contacts and are at low risk of developing application strategy for developing countries because
ARF. selective approach to identify and treat GABHS is
However, primary prophylaxis is effective on a practically not possible in absence of easily available
wide scale, in populations at high-risk for ARF, is dif- diagnostic criteria to distinguish streptococcal sore
ficult to prove unless accompanied by a comprehen- throat from other sore throat.
sive health-care program and general improvement
in health services delivery. Highly sensitive and spe-
Secondary Prophylaxis
cific clinical diagnostic algorithms for GABHS phar-
yngitis are not available, microbiological diagnosis is Prevention of streptococcal sore throat after an at-
expansive and not feasible in primary care settings in tack of ARF or in diagnosed case of RHD is highly
most developing countries, and little is known about essential as ARF tends to recur and with each recur-
health-seeking behavior for sore throat in these rence further damage is caused to heart valves. The
population. Even in optimum circumstances, the ef- only proven cost-effective intervention is secondary
fectiveness of primary prophylaxis is limited by the prophylaxis. It helps to prevent recurrences and de-
fact that up to two-thirds of patients with ARF do not terioration of RHD. The best drug for this purpose
get a symptomatic sore throat and do not therefore is intramuscular injection of benzathine penicillin-G
seek medical attention. Hence, even the most inten- administered once every 3 weeks (Table 8.3). Ben-
sive program of sore throat diagnosis and treatment zathine penicillin is a repository form of penicil-
might not lead to substantial reduction in ARF in- lin-G designed to provide a sustained bactericidal
cidence. Although awareness of primary prophylaxis serum concentration. Serum levels of penicillin re-
should be promoted to health staff and the patients main above the minimum inhibitory concentra-
with sore throats, coordinated programs are unlikely tion for Group-A streptococci for 3 to 4 weeks. The
Table 8.3: Drugs for the treatment of streptococcal pharyngitis (primary prophylaxis) and secondary prophylaxis
Drugs Dose Sore-throat treat- Secondary prophylaxis
ment (duration) (interval)
Benzathine Penicillin G 1.2 million unit (> 27 kg) after sensitivity test Single dose 21d
(deep IM inj) (AST)
0.6 million unit (<27 kg) Single dose 15d
(after sensitivity test) contraindication: penicil-
lin allergy
Penicillin-V (oral) Children: 250 mg qid 10d Twice a day
Adult: 500 mg bid contraindication: penicillin 10d Twice a day
allergy
Azithromycin (oral) 12.5 mg/kg/day once daily 5 Not recommended
Cephalexin (oral) 15–20 mg/kg/dose bid 10d Not recommended
Erythromycin (oral) 20 mg/kg/dose max 500 mg contraindication: Not Twice a day
liver disorder recommended
reconstituted or lyophylized penicillin should be per clinical situation. Steroid and antihistamines are
stored at temperatures not exceeding 30°C and be not helpful. Airway should be kept free. Intubation
protected from moisture. may be required in some cases. Volume replacement
Sensitivity testing should be done prior to the by normal saline or colloids is essential to manage
injection every time. Hypersensitivity to penicillin is hypotension. Aminophylline or deriphyllin is used
reported to occur in 2 to 5 percent of patients while parenterally in persistent bronchospasm. Steroids
anaphylactic reactions occur in about 0 to 2 percent may be given parenterally in some cases to prevent
of patients. The most common allergic manifesta- delayed recurrence of anaphylaxis.
tions is skin rash. Allergic reactions are less com-
mon in children under 12 years of age and duration
Duration of Secondary Prophylaxis
of prophylaxis does not increase the risk of allergic
reactions. Skin testing with intradermal penicil- The duration of secondary prophylaxis is determined
lin is appropriate method for identifying patients at by many factors, in particular the time since the last
high-risk of allergic reactions as chances of serious episode of ARF (recurrence becomes less likely with
reactions are extremely low in patients with a nega- increasing time), age (recurrences are less likely with
tive skin test. Detailed history of allergy to beta lac- increasing age, and the severity of RHD (if severe, it
tam antibiotics (including all types of penicillin and is prudent to avoid even a small risk of recurrence
cephalosporins) should however be obtained from because of the potentially serious consequences).
all patients prior to skin testing on each visit. Per- Table 8.4 lists the category of patient and duration of
sons performing skin testing should be trained in the prophylaxis.
technique and in managing anaphylaxis, which may The Indian Council of Medical Research (ICMR)
occur rarely with skin testing itself. Techniques used has started ARF registry for secondary prophylaxis.
to reduce the pain of benzathine penicillin injections Control programs have added benefits beyond im-
include use of small gauze needles, increased injec- proving adherence to secondary prophylaxis, such
tion volumes, and addition of 1 percent lignocaine. as ensuring good clinical follow-up of patients with
Simple measures of applying direct pressure to the ARF and RHD, providing a means to undertake edu-
injection site, warming the medication to room tem- cational and health problems activities, and provid-
perature, ensuring that skin swabbed with alcohol is ing accurate epidemiological data for monitoring
dry before injecting, distracting the patient with con- and research purposes.
versation, and delivering the injection slowly (prefer-
ably over 3 minutes) ensure that the injection is well
Table 8.4: Suggested duration of secondary prophylaxis
tolerated.
Category of patient Duration of prophylaxis
Management of Anaphylaxis Reaction Patient without proven For 5 years after the last
carditis attack, or until 18 years of
Anaphylaxis is a sudden generalized reaction fol- age (whichever is longer)
lowing parenteral injection of benzathine penicillin. Patient with carditis For 10 years after the last
The symptoms start with sudden itchiness, urticar- (mild MR or healed attack, or at least until 25
ial rashes, sneezing and voice change. There occurs carditis) years of age (whichever is
laryngeal spasm, hypovolemic shock (severe hypo- longer)
tension) and intense bronchospasm and sometimes More severe valvular Lifelong
tracheal spasm. disease
Treatment is immediately started. IV, adrenaline After valve surgery Lifelong
is life saving; given in a dose of 0.5 ml of 1 in 1000 Source: WHO technical report series, 923. Rheumatic
injected IM or subcutaneously. It may be repeated as Fever and Rheumatic Heart Disease, 2001
Note a mucosal stimulant for the production of protective

• Secondary prophylaxis has no role on existing IgA type specific antibodies.
RHD. Several practical issues have so far impeded de-
• Secondary prophylaxis protects patients from velopment of a viable GABHS vaccine. These include
fresh attacks of ARF. orphan status of the vaccine (vaccine has not been
• Secondary prophylaxis definitely prevents damage wholeheartedly accepted by the pharmacological in-
caused by rheumatic recurrences. dustry), potential of GABHS to mutate rapidly thus
making a polyvalent vaccine made from locally prev-
alent strains ineffective, paucity of clinical trials, and
Prospects of Vaccine Against Acute
likely exorbitant cost of the vaccine.
Rheumatic Fever
Remember: In developing countries including India
In view of lack of any clear and viable strategy for because of multiple factors primary prevention and
primary prophylaxis for treating Group-A beta even secondary prevention may not alter the prevail-
hemolytic Streptococcus (GABHS) infections, there is ing scenario of ARF and RHD. It is only an effective
definitely a place for safe, efficacious and affordable antistreptococcal multivalent vaccine (because of dif-
GABHS vaccine. An effective vaccine against Group- ferent rheumatogenic M serotypes) that can be used
A streptococcal infections would serve not just in for mass prophylaxis which can significantly alter the
preventing acute rheumatic fever (ARF) and RHD, epidemiology and able to prevent ARF and RHD.
but also poststreptococcal glomerulonephritis, sore
throat, impetigo, and invasive forms of streptococ- Control Programs for Acute Rheumatic
cal infections including poststreptococcal reactive
Fever and Rheumatic Heart Disease
arthritis.
Several GABHS protein components and the A coordinated control program is the most effec-
streptococcal polysaccharide have been considered tive approach for improving adherence to penicillin
for utilization in developing a vaccine. Most work has prophylaxis and clinical follow-up of people with
been done with the M-protein, considered to be the rheumatic heart disease (RHD). Desirable elements
virulent factor for the GABHS. Gentle acid extrac- of acute rheumatic fever (ARF) and RHD control
tion from the surface of GABHS by dilute pepsin has program include a central register of patients, a
yielded the peptide, Pep-M, which is the terminal of dedicated coordinator, an advisory committee, guar-
a very long molecule and is a feature of rheumato- anteed funding, guaranteed supply of benzathine
genic, but not other strains of Group-A streptococci. penicillin-G, mechanisms for finding new patients,
The Pep-M, a coiled-coil polypeptide, frequently un- facilitating communication between health proce-
dergoes genetic recombination leading to loss in op- dures in hospital and communities and providing
sonizing ability of type-specific antibodies. Vaccines education for health staff and the wider community.
directed at the Pep-M are therefore strain-specific. A study conducted at Puducheri, on the free eco-
Since more than hundred different strains have been nomics of ARF, concludes that primary prophylaxis
identified, it is essential that the vaccines must be is the most viable economic option in the long run.
polyvalent, that is, it should incorporate all strains Maintaining register of people with RHD or a his-
prevalent in the community. tory of ARF is a key element of ARF/RHD control
The Pep-M protein is separated from the more at individual, community, and national level. Register
proximal, toxic part of the M molecules. The recom- based programs help in detecting new cases and en-
binant hybrid protein is then linked to the B subunit sures continuation of secondary prophylaxis. Regis-
of Escherichia coli labile toxin LTB, which serves as ters also provide epidemiologic data for monitoring,
reaserch and development of newer modalities of rheumatic fever is the antimicrobial therapy (mainly
treatment. Active screening in high-risk populations benzathine penicillin) to eradicate the streptococcal
and legislated notification of ARF and RHD should infection in the pharynx.
also be actively considered. However, the major challenge for prevention for
acute rheumatic fever is to make available an active,
effective, safe and cost-effective polyvalent vaccine
Conclusion to eradicate the streptococcal infection in India and
Rheumatic fever and rheumatic heart disease contin- other developing countries.
ue to be major public health problem in India. Con-
siderable number of children and adolescents still suf-
fer from ARF and its long-term sequel such as RHD, Further Reading
causing enormous morbidity and morality. Reports 1. Bessen D, Fischetti VA. Synthetic peptide vaccine
of declining incidence of ARF/RHD in some selected against mucosal colonization by group-A strepto-
parts of India having good human development in- cocci. I. Protection against a heterologous M sero-
dices (HDI) should not distract our attention from type with shared C repeat region epitopes. Journal of
the alarming frequency of the disease in less devel- Immunology. 1990;145(4):1251-6.
oped areas. Actually, there is paucity of epidemiologi- 2. Diagnosis and management of acute rheumatic fever
cal data from poorly served rural population, urban and rheumatic heart disease in Australia an evi-
slums and tribal pockets where the disease prevalence dence-based review. National Heart Foundation of
is expected to be high. Australia and the Cardiac Society of Australia and
Although conventionally ARF is treated with New Zealand, 2006.
anti-inflammatory agents, till date, there is no evi- 3. Kumar RK. Epidemiology of rheumatic fever and
dence that anti-inflammatory therapy during ARF al- rheumatic heart disease in India. In: Kumar RK (Ed).
ters the course of carditis or incidence of subsequent ECAB Clinical Up-date: Cardiology, 2008.pp.1-20.
heart disease. 4. Pichichero ME. A review of evidence supporting the
Efficacy of primary prophylaxis on wide scale in American Academy of Pediatrics recommendation
population is difficult to prove unless accompanied for prescribing cephalosporin antibiotics for penicil-
by a comprehensive health care program and lin-allergic patients. Pediatrics. 2005;115:1048-57.
general improvement in health services delivery. 5. Rheumatic fever and streptococcal infection by Gene H
Even in optimum circumstances, the effectiveness Stollerman, Grune and Stratton Publisher, New York.
of primary prophylaxis is limited by the fact that 6. Rheumatic Fever: 2nd edn, Milton Markowitz and Leon
up to two-thirds of patients with ARF do not have Gordis, WB Saunders Company, Philadelphia, 1972.
a symptomatic sore throat and therefore do not seek 7. WHO technical report series, 923, Rheumatic fever
medical attention. The only proven cost-effective and Rheumatic heart disease: Report of a WHO
intervention at present is secondary prophylaxis: expert consultation Geneva, 29 October–1 November
the long-term administration of antibiotics to 2001, World health organization, Geneva, 2004.
patients with history or ARF and those having RHD, 8. Working group on pediatric acute rheumatic fever
to prevent recurrences and deterioration of valve and cardiology chapter of Indian academy of pediat-
damage. Secondary prophylaxis is best delivered in rics. Consensus guidelines on pediatric acute rheu-
the context of a formal, register based ARF and RHD matic fever and rheumatic heart disease. Indian
control program. The sine qua non of prophylaxis in Paediatr. 2008;45:565-72.
Section 2
Rheumatic Heart Diseases
CHAPTER 9
Approach to Diagnosis of
Introduction 1. History taking.

The traditional teaching is that for every disease there 2. General examination.
should be a clinical diagnosis. The final diagnosis is 3. Systemic examination. In this chapter our vision is
derived after two major steps such as, one clinical di- mainly focused on rheumatic fever (RF) and rheu-
agnosis (which includes differential diagnosis) and matic heart disease (RAD).
the other one diagnosis after investigations. Rheumatic heart disease mainly presents with
The clinical diagnosis has its own merit in sense history of:
diagnosis can be made at any place, any time and does 1. Dyspnea
not depend upon sophisticated laboratory help. It is an 2. Palpitation
art that the young physicians should learn and develop 3. Edema feet
their clinical skill before jumping for available sophis- 4. Chest pain
ticated investigations to get a readymade diagnosis. 5. Arthralgia/Arthritis
It is difficult to interpret the findings of the so- 6. Fever
phisticated investigations like ultrasounds, echo- 7. Syncope.
cardiography, MRI and CT scans unless clinical di- 1. From the very history taking one can infer and
agnosis is made and the results of investigations are form a probable diagnosis. For example:
correlated. Before interpreting investigations one a. A child with history of fever and recent com-
should know the basic anatomy and pathophysiol- plaints of breathlessness, palpitation think of
ogy to differentiate between physiological findings, rheumatic carditis (or myocarditis of any etiol-
age related changes and normal variants. One bright ogy). History of arthralgia or fleeting arthritis if
example is Doppler mitral regurgitation (MR) or tri- present, firmly suggest rheumatic origin.
cuspid regurgitation (TR) (physiological) which has b. A young person if complains of palpitation and
practically no clinical significance. So unless the phy- breathlessness (dyspnea) on accustomed exer-
sician is aware of this fact most of the cases will go tion with past history of fever and arthritis,
with diagnosis of pathologic regurgitation and may think of valvular lesions (AR or MR). Similar
be treated wrongly. No doubt laboratory help is man- symptoms may occur with left to right shunts
datory before confirming the diagnosis and going for and primary myocardial disease besides ane-
medical or surgical management but due to lack of mia and thyrotoxicosis. It is auscultation that
standardization of laboratory findings many times can suggest or rule out the possibilities.
the results are variable and confusing. c. Young adults with dyspnea and swelling of legs
To arrive at a clinical diagnosis the fundamental with past history of arthritis/arthralgia, think
principles are: of congestive heart failure the cause may be
52 Rheumatic Heart Diseases
valvular lesions. Myocardial disease besides Class II: Symptoms like fatigue, palpitation and dysp-
common conditions like severe anemia may nea occur on ordinary exertion (accustomed exer-
also present with swelling of the legs. Clinical tion) but comfortable at rest.
examination and auscultation can easily differ- Class III: Symptoms occur on less than ordinary ex-
entiate these conditions. ertion, there is marked limitation of physical activity
d. Young persons with history of dizziness or syn- but comfortable at rest.
copal attacks particularly with exertion, think Class IV: Symptoms occur at rest that is inability to
of severe stenotic lesions (like AS or PS) or carry out any physical activity without discomfort.
arrhythmias. These conditions can easily be
diagnosed by auscultation.
Variant Forms of Dyspnea
e. Young adults with sudden onset of weakness
of one side of the body or one limb think of • Paroxismal nocturnal dyspnea (PND): Patient
embolic stroke. Mitral stenosis is a common wakes up from sleep (day time or night time, that
cause of stroke in young. Simple auscultation is why nocturnal word is a misnomer) with a sense
can make a diagnosis. of suffocation and becomes comfortable after sit-
f. Young children or adolescents present with ting upright for a while. It indicates presence of
abnormal movement think of rheumatic chorea significant mitral or aortic valve disease.
as a possibility besides functional or neurologi- • Orthopnea: Dyspnea occurs on supine position.
cal causes. Nowadays many young physicians It indicates left sided heart failure of any etiology
have forgotten to think of a condition like rheu- (severe AR, MR or MS).
matic chorea, although in our country it is still • Tachypnea: Rapid breathing. It occurs on exertion
seen in clinical practice, (not uncommon). in healthy persons, if occurs at rest it is pathologi-
cal. It indicates both cardiac or respiratory cause.
• Trepopnea: Dyspnea occurs on lateral position. It
Clinical Approach
mainly occurs due to LA mass (either myxoma or
Common cardiac symptoms related to RF and RHD. thrombus) or due to pulmonary causes.
• Platypnea: Dyspnea on upright position but relieved
by supine position. It may occur due to LA myxoma.
Dyspnea
Thorough general examination reveals clue to
Shortness of breath (SOB) or undue breathlessness, diagnose many systemic diseases, yet it is nowadays
(in other words difficulty in breathing or sense of rarely followed. For example facial appearance is typ-
suffocation) is taken as dyspnea . No doubt it is very ical of many diseases. In mitral stenosis the puffy face
subjective and there is wide individual variations . with malar flush (mitral facies) may be seen. Typical
Different grades of dyspnea are: exanthematous lesions, petecheal hemorrhages and
1. Simple sense of suffocation. presence of small or big nodular lesions pertain to
2. Definite dyspnea (breathlessness). certain specific systemic disease (petecheal hemor-
3. Severe form of dyspnea like paroxysmal nocturnal rhages in setting of prolonged fever with valve lesions
dyspnea/orthopnea/cardiac asthma. think of infective endocarditis). Similarly typical site
and distribution of nodular (fine non-tender pea
sized) lesion indicate subcutaneous rheumatic nod-
Functional Classification of Dyspnea,
ules (unless searched for they are missed). The eva-
Fatigue and Palpitation New York Heart
nescent rash of erythema marginatum may be missed
Association Classification (NYHA) unless looked for.
Class I: Symptoms occur on heavy exertion. In other Irregular pulse in a young person with or without
words patients having cardiac lesions but no restriction congestive heart failure (CHF) may be due to mitral
of ordinary physical activities (no fatigue or dyspnea). stenosis with AF. A low volume slow rising pulse is
Approach to Diagnosis of Rheumatic Heart Disease 53
suggestive of aortic stenosis and a high volume pulse largement and ventricular function. Color Doppler
may be due to aortic regurgitation (besides anemia helps in assessing valve regurgitation. 2D, Doppler
and thyrotoxicosis). When unusually low diastolic and color flow gives accurate informations for as-
blood pressure is recorded, one should think of aortic sessing severity of lesion, ventricular function and
regurgitation. pulmonary arterial pressure. Echo helps in decision
Similarly examination of neck veins reveal clue making regarding further management. Transtho-
for many diseases. Normal wave forms are shown in racic echo (TTE) is usually adequate in assessment of
Figure 9.4. Apart from raised JVP in CHF of any eti- valvular disease, but sometimes when TTE informa-
ology, absent ‘a’ wave is found in atrial fibrillation. ‘a’ tion is not adequate particularly when infective en-
wave is prominent in pulmonary artery hypertension docarditis is suspected or in case of prosthetic valve
and very prominent in tricuspid stenosis. A large ‘v’ evaluation transesophageal echo (TEE) is performed.
wave with a rapid ‘y’ descent is seen in tricuspid re- 3D echo is more accurate in assessing valve anatomy,
gurgitation. ‘y’ descent is slow in tricuspid stenosis. but yet it has not been used routinely.
The art of cardiac auscultation can be mastered It should be noted that echocardiography with
with long practice and knowledge of events through color Doppler detects small amount of regurgita-
the cardiac cycles. Abnormal intensity and split- tions in healthy individuals called physiologic regur-
ting of normal sounds; extra sounds like third heart gitation. They do not require follow-up neither they
sound (S3), fourth heart sound (S4), opening snap require infective endocarditis or rheumatic fever
(OS), ejection click (EC) and presence of murmur prophylaxis. It has no clinical importance.
should be noted. Timing (systolic/diastolic), loca- Echocardiograms showing normal patterns of
tion, duration, intensity (grade) and nature (crescen- cardiac valves are shown in Figures 9.1A to G.
do/decrescendo) of murmur are important param- In some cases where echo is inconclusive, they
eters to note. Intensity of systolic murmur is graded require cardiac catheterization and angiocardiography
in a scale of 1 to 6 with increasing intensity. Systolic for final diagnosis. Coronary angiography is routinely
murmurs may be pansystolic, mid systolic (ejection performed before valve surgery after age 40 years to
systolic murmur) or late systolic. Similarly diastolic exclude coronary artery disease.
murmurs may be early diastolic, mid diastolic or pre
systolic. Sometimes maneuvers like change of pos-
Basic Hemodynamic Parameters
ture (standing, sitting), exercise or Valsalva are used
to note change in character of murmur for clinical Dyspnea is produced by increased pulmonary
diagnosis. venous pressure.
Abdominal examination for hepatomegaly, sple- Left ventricle (LV) end-diastolic pressure = LA
nomegaly and respiratory system examination for mean pressure = Pulmonary venous pressure (PVP) =
pulmonary findings (mainly rales and rhonchi) are Pulmonary capillary wedge pressure (PCWP) = Pulmo-
part of routine cardiac examination. nary arterial diastolic pressure = 12 mm Hg. According
Accordingly a clinical diagnosis is made and then to PVP dyspnea is classified into 4 grades (Table 9.1).
the patient is subjected to basic investigations like an Oxygen saturation of different chambers of heart
ECG and chest X-ray (PA view). The information ob- and great vessels are shown in Figure 9.2. Oxygen
tained from clinical examination is correlated with saturation in pulmonary veins is 100 percent. In left
ECG and chest X-ray findings for possible diagnosis. atrium (LA) and in left ventricle (LV) oxygen satura-
After which an echocardiography is done to reach at tion is around 97 to 99 percent. The explanation is
a definite diagnosis. Echo very accurately determines bronchial veins drain to pulmonary veins and thebe-
the site of origin and type of murmur. M-Mode, 2D sian veins drain directly to LV, so the saturation is less
echo precisely diagnose valve anatomy, chamber en- than 100 percent (but normally never below 96%).
A B C
D E F
G
Figs 9.1A to G: Normal Echocardiograms: (A) M-Mode of Aortic valve, long arrow indicates diastolic closure line, small
arrows indicate open position in systole, anteriorly right coronary cusp and posteriorly non-coronary cusps are visual-
ized; (B) M-Mode of LV, Dimensions are measured in systole and end-diastole for calculation of ejection fraction; (C)
M-Mode of mitral valve, close arrow indicates anterior leaflet having early diastolic and presystolic anterior motion,
open arrow indicates posterior leaflet moving posteriorly; (D) 2D echo in parasternal long axis shows normal diastolic
position of mitral leaflets; (E) 2D echo in apical 4 chamber view showing both mitral and tricuspid valve in systole;
(F) Normal mitral diastolic Doppler flow, E-early diastolic flow, A-flow during atrial systole; (G) Normal aortic flow in systole
(arrow). Abbreviations: LA—Left atrium; LV—Left ventricle; RA—Right atrium; RV—Right ventricle, Ao—Aorta
For academic interest: Any step-up or step-down in Remember

oxygen saturation in any chamber or great vessels in- • Peak right ventricular (RV) pressure = Pulmonary
dicate shunt lesions. artery systolic pressure = 25 mm Hg.
Normal pressure tracings in different cardiac • RV diastolic pressure = Mean right atrial (RA)
chambers is shown in Figures 9.3A and B. pressure = 7 mm Hg
Normal pulse tracings correlated with heart • Cardiac output = Heart Rate X Stroke volume
sounds and ECG is shown in Figure 9.4. (normal 4–8 L/min).
Table 9.1: Grading of dyspnea • Left ventricular (LV) Ejection fraction (EF) = (End
Grade Degree of exertion to PVP (mm Hg) diastolic Volume–End systolic volume)x100/End
produce dyspnea diastolic volume. (normal EF is 55–80%). Commonly
Grade 1 Severe unaccustomed <12 (Normal) EF is measured by Echo, it may be measured by angi-
exercise ocardiography and radioneuclide imaging.
Grade 2 Moderate exertion 12—18 When EF = 40–50 percent indicates mild LV dys-
function.
Grade 3 Mild exertion 19—24
When EF = 30 to 40 percent indicates moderate
Grade 4 Dyspnea at rest >25 LV dysfunction.
PVP—Pulmonary venous pressure When EF = < 30 percent indicates severe LV dys-
function.
Normal Valve Areas

Mitral Valve Area: 4 to 6 cm2
Aortic Valve Area: 2.6 to 3.5 cm2
Tricuspid Valve Area: 5.0 to 10.0 cm2
Pulmonary Valve Area: 2.0 to 3.0 cm2
Level of Evidence of Treatment/

Interventions/Procedure
(The American College of Cardiology/American
Heart Association (ACC/AHA) classification).
Class I: Definite evidence of benefit, general agree-
ment exists.
Class II: Reasonable agreement, but conflicting evi-
dence and divergence of opinion.
Fig. 9.2: Schematic diagram showing normal oxygen satu- Class IIa: Weight of evidence/opinion in favor.
ration at different levels, oxygen saturation in right side Class IIb: Credibility less well-established, but most
(RA, RV and PA) is approximately 75% and in left side (LA, agree.
LV and aorta) is 97%. Abbreviations: PV—Pulmonary vein; Class III: Intervention not indicated, may be harmful.
RPA—Right pulmonary artery; LPA—Left pulmonary artery; A: Data derived from multiple randomized clinical
SVC—Superior vena cava; IVC—Inferior vena cava trials.
B: Data derived from a single randomized trial or
• Cardiac index = Cardiac output/body surface area nonrandomized studies.
(normal 2.6–4.2 L/min/m2) C: Consensus opinion of experts not based on trials.
• Systemic vascular resistance (SVR) = mean aortic
pressure–mean RA pressure/cardiac output X80. Medical Management of Congestive
(Normal 700–1600 dynes/sec/cm–5 or 20 Woods
Heart Failure
units).
• Pulmonary vascular resistance (PVR) = Mean Heart failure by definition is inability of heart to
pulmonary artery (PA) pressure – Mean LA pres- pump blood commensurate with metabolic need or
sure)/Pulmonary blood flow (Qp) X80. (Normal do so with increased filling pressure. Left sided fail-
20–120 dynes/sec/cm–5 or 2 Woods units). ure is manifested by features of pulmonary conges-
A B
Figs 9.3A and B: Normal pressure tracing at different sites as determined during cardiac catheterization. Abbreviations:
RA—Right atrium; LV—Left ventricle; RV—Right ventricle; PA—Pulmonary artery. Figures show pressure in mm Hg
Fig. 9.4: Simultaneous recording of jugular venous pulse (JVP), carotid pulse, and ECG. A wave of JVP coincides with
1st heart sound (M1), V wave coincides with 2nd heart sound (A2), X descent is in systole, Y in diastole corresponds to
S3, in carotid pulse tracing. Abbreviations: A—Anacrotic notch; P—Percussion wave; T—Tidal wave; DN—Dicrotic notch;
D—Dicrotic wave
tion like various grades of dyspnea, orthopnea, PND toxicity were often reported if not managed in a cor-
and hemoptysis. In right sided failure, there occur rect direction.
systemic venous congestion as evidence by edema, Note:
ascitis, hepatomegaly and raised JVP. When features • Digitalis retains its supremacy as number one drug
of both right and left sided heart failure are present, for CHF with AF.
it is known as congestive cardiac/heart failure (CCF/ • Digitalis occupies second place in treatment of
CHF). Acute heart failure due to acute MR or acute CHF with sinus rhythm (ACE, antiarrhymics drug
AR present with features of acute pulmonary edema and diuretics preferred).
which needs immediate management. • Digitalis is contraindicated in HOCM and pre-
The nonpharmacologic approach for manage- excitation syndrome.
ment include dietary advice (sodium and fluid re- • Digitalis is used with caution in CHF due to high
striction) and restriction in physical activity. output state and renal failure.
Diuretics particularly potent loop diuretics (fru-
semide and torsemide) are main drugs to relieve fluid
Drugs Used in Management of CHF
congestion. As per the clinical situation frusemide
• Cardiac glycosides (digoxin). (20–80 mg/day) or torsemide (10–40 mg/day) is used
• Diuretics. orally (20–80 mg/day) or in severe cases it is used in-
• Angiotensin converting enzyme (ACE) inhibi- travenously (dose varies as per the case). But exces-
tors/angiotensin receptor blockers (ARBs). sive diuresis may produce hypovolemia, hypotension
• Cardioselective beta blockers. and the loss of critical preload to maintain forward
• Vasodilators. cardiac output. Diuretics should be used with cau-
• Positive inotropic agents. tion. Electrolyte imbalance particularly hypokalemia
• Miscellaneous (ancillary therapy). is common which may precipitate arrhythmia and
Cardiac glycosides (digitalis/digoxin) are the digitalis toxicity, therefore, it is prudent to combine a
age old inotropic drug to treat heart failure. It was potassium sparing diuretic like spironolactone, ami-
discovered by William Withering in 1785. The usual loride and triameterine with loop diuretics or give
starting dose is 0.0625 to 0.25 mg daily depending on oral potassium supplement.
age and renal function. Rapid digitalization (10–15 ACE inhibitors and ARBs in general are very use-
mcg/kg 6 hourly for 3 days followed by one-third of ful in CHF, but in severe stenotic lesions with CHF,
loading dose as maintenance to achieve therapeutic these may be harmful. In regurgitant lesions ACEIs
serum level of 0.6–1.2 mcg/ml) advised previously; has are helpful. Captopril is not used now days, instead
become obsolete. However, the conventional main- enalapril (2.5 mg bid), lisinopril (2.5–5 mg od) and
tenance dose is half to one tablet (one tablet is 0.25 ramipril (1.25–5.0 mg od) are used. ACE inhibitors
mg) daily 5 to 6 days in a week (to prevent cumulative are not used in stenotic lesions (particularly AS and
accumulation of serum level due to its long half life any vascular stenotic lesions); in severe anemia in
which may be toxic). The therapeutic serum level of pregnancy and lactating period. The common side
digoxin is 1 to 2.6 nmol/L and digitalis toxicity occurs effects like hypotension, persistent cough, mouth
when it is beyond 3.0 nmol/L. The common toxicities ulcer and angioneurotic edema are to be watched and
are anorexia, nausea, vomiting, hallucination, blurred if necessary drug may be discontinued.
vision (colored vision), arrhythmias like multiple Cardioselective beta blockers are often used in
premature ventricular and atrial complexes and chronic CHF particularly when there is tachycardia.
sometimes ventricular tachycardia, AV block from The common drugs used are metoprolol extended re-
first degree to complete AV block. Once the digitalis lease (12.5–25 mg od), carvedilol (3.125 mg bid) and
toxicity appears, it is to be managed immediately bisoprolol (1.25 mg od). Sometimes beta blocker may
by stopping the drug and also diuretics along with worsen the situation by its negative inotropic effect in
potassium supplementation. Death due to digitalis situation of valvular heart disease.
Vasodilators like sodium nitroprusside are used mg 6 hourly with a loading dose of 300 mg. simi-
in setting, such as acute AR and acute MR. It is given larly the dose of amiodarone is 200–400 mg/day and
as intravenous infusion with hemodynamic monitor- propafenone is used orally 100–300 mg three times
ing in ICU setup. Inotropes like dobutamine (dose 2.5 daily. The side effects of these antiarrhythmic drugs
to 10 µgm/kg/min, can be infused for 72 hours) do- are to be watched carefully when used for a prolonged
pamine, milrinone are used in persistant hypotension period. (As for example when amiodarone is used,
cases, but unless corrective intervention/surgery is TSH test should be done at regular intervals). Ven-
done, their role is limited. Intra-aortic balloon coun- tricular rate control is achieved by atrio-ventricular
ter pulsation is used in cases of persistent hypotension blocking drugs like digoxin, verapamil (40–80 mg
to stabilize the patient and to buy time before surgery. thrice daily), diltiazem (30–90 mg thrice daily) or
Atrial fibrillation (AF) occurs commonly in set- beta blockers either alone or in combination. Vera-
ting of RHD. The main aim is to control the rhythm pamil and amiodarone increase serum digoxin level,
(converting and maintaining sinus rhythm), ventricu- therefore digoxin dose should be reduced (half the
lar rate (to keep a stable heart rate) and to start an- dose) when used with these drugs. Oral anticoagula-
ticoagulation therapy to prevent thromboembolism. tion with wafarin or nicoumalone are used to prevent
Antiarrhythmic drugs, class Ia (quinidine, procaina- thromboembolism with suitable dose to maintain in-
mide, disopyramide), class Ic (propafenone) and class ternational normalized ratio (INR) of 1.5 to 2.5.
III (amiodarone) are used for rhythm control but are To conclude congestive heart failure and atrial fi-
not very effective in cases of RHD having atrial dila- brillation are common complications of chronic rheu-
tation. Dronedarone (400–800 mg/day) is recently matic heart disease. Judicious medical management is
used in case of AF with or without CHF. Disopyra- essential for symptomatic relief before the patient is
mide is commonly used by oral route with 100–200 subjected to interventional procedures and surgery.
CHAPTER 10
Mitral Stenosis
SN Routray, BR Mishra
Definition Anatomy of Mitral Valve

When there is obstruction to blood flow from left Mitral valve develops from mainly two sources: (1)
atrium (LA) to left ventricle (LV) during diastole due Endocardial cushions (anterior mitral leaflet from
to incomplete opening of morphologically abnormal superior and inferior and posterior mitral leaflet
mitral valve (MV), the clinical condition is known as from left lateral endocardial cushion), (2) LV muscle
mitral stenosis (MS). There occurs a diastolic pres- wall by process of delamination.
sure gradient across the mitral valve depending upon The mitral apparatus consist of the following
the severity of obstruction. components (Fig. 10.1):
1. Mitral annulus: It is a fibrous ring anchored to
Incidence and Prevalence the fibrous skeleton of the heart (a fibrous tissue
frame work which firmly holds the atrial and ven-
Incidence and prevalence of rheumatic fever (RF) tricular musculature together with the valve tis-
and rheumatic heart disease (RHD) has slowly sue). The size of the annulus is 4 to 6 cm2 (equiva-
decreased from 5.5 to 0.5/1000 over last two decades lent to mitral valve area) and its circumference is
as per school surveys conducted in different places in 8 to 10.5 cm.
India (refer Chapter 2, section I). But our observa- 2. Leaflets: MV has two leaflets (cusps) (all other
tion is that there is no significant decrease in RF and heart valves have three leaflets). The larger one is
RHD according to the hospital data. The incidence anterior or septal leaflet (AML), it is semicircular
reported was 44.4 percent amongst all cardiac cases and has three scalops. The smaller one is poste-
admitted during the period 1999-2000 (Routray SN, rior or mural leaflet (PML). Posterior leaflet is
Ind HJ, 2003;53:252-57) and out of these lone mitral rectangular and also has three scallops. Although
stenosis was seen in 34.7 percent of cases. Similarly the surface area of both leaflets are same, AML
others have also reported lone mitral stenosis in 18.4 appears larger as its annular attachment is smaller
percent (AN Patnaik, NIMS, 2002) and in 29.3 per- than the PML.The histological picture of the
cent of cases of RHD (Adarsh Kumar, Ind HJ 2009; valves shows a central collagen core surrounded
61:14-23). by fibrosa which is covered by loose fibroelastic
Juvenile mitral stenosis is seen very often in clini- tissue. The whole valve is covered by endothelial
cal practice. Pediatric MS constitutes 10 percent of all layer.
MS (R Tandon). Predominance of male sex is report- 3. Commissure: The free margin of leaflets that sepa-
ed in juvenile MS where as female sex dominance is rate it from each other or the coaptation line is the
observed amongst all cases of MS. commissure.
or recurrent carditis which may or may not mani-

fest clinically is responsible for producing mitral
stenosis later. Amongst all patients with RHD iso-
lated MS is present in 25 percent and associated
with mitral regurgitation (MR) in 40 percent of
cases. Two–thirds of all patients of MS are females.
2. Mitral annular calcification: In elderly patients
severe mitral annular calcification may restrict
valve motion producing MS.
3. Other rare causes of MS are:
Malignant carcinoid, systemic lupus erythema-
tosus (SLE), rheumatoid arthritis, mucopolysac-
charidosis, amyloidosis, methysergide therapy,
Fabry’s disease, Whipple disease.
Fig. 10.1: Mitral valve anatomy. Abbreviations: MA—Mitral 4. Functional MS (with a normal valve) may occur
annulus; AML—Anterior mitral leaflet; PML—Posterior with obstruction of LA outflow due to LA myxoma,
mitral leaflet; AL PM—Anterolateral papillary muscle; PM LA thrombus and large vegetation in mitral valve.
PM—Posteromedial papillary muscle; LA—Left atrium;
LV—Left ventricle
Congenital
4. The chordae tendinae: There are primarily two Rarely in infant and young children MS is congeni-
types: (1) Commissural and (2) Cuspal. There are tal. Cor-triatriatum, supravalvular ring are also rare
several chords that are attached to the commis- forms of obstruction from LA to LV apart from val-
sures which fan out from the head of the papillary vular MS.
muscles. Chordae to anterolateral halves of both
leaflets arise from anterolateral papillary muscle
Pathology
and chordae to posteromedial halves of both leaf-
lets arise from the posteromedial papillary mus- Acute rheumatic fever (ARF) typically produces mi-
cle. The total numbers of chordae are 120 attached tral valvulitis where the valve becomes edematous
to both sides of leaflets. with rheumatic vegetations along the line of closure
5. Papillary muscles: There are two papillary muscles of the leaflets and on the chordae tendinae. Subse-
(anterolateral and posteromedial) arising from the quently gradual healing occurs by deposition of fi-
LV free wall. Each papillary muscle has six heads brous tissue. In recurrent carditis, this process of
from which chordae tendinae arise to be attached valvulitis and healing occurs alternatively, resulting
to the leaflets. Anterolateral papillary muscle is in more fibrosis, thickening and fusion of valve com-
supplied by both left and right coronary arteries missures and chordae. This deformed valve is sub-
where as posteromedial papillary muscle is sup- jected to further fibrosis and calcification even with-
plied by posterior descending branch of the right out episodes of carditis due to constant trauma caused
coronary artery. by turbulent blood flow. Fusion of cusps occurs spe-
cially at the edges, resulting in reduction of orifice
area. Thickening, fibrosis and fusion of commissures,
Etiology
cusps and chordae tendinae produce a funnel shaped
mitral valve with a ‘fish mouth’ or ‘button hole’ like
Acquired Causes
mitral orifice. Gradually calcium is deposited on the
1. Rheumatic: Ninty-nine percent of cases of MS are valve leaflets, which may extend to the valve ring
of rheumatic origin. A previous rheumatic carditis (annulus) and subvalvular apparatus, thereby the
Mitral Stenosis 61
valve mobility decreases. When fusion of commis- collagen tissue in the left atrial myocardium give rise
sures is predominant, it results in dominant MS, but to atrial fibrillation (AF). Initially it may be episodic
when fusion of chordae occurs without fusion of or transient but sooner or later AF becomes persis-
commissures, it results in dominant MR. tent. AF increases the risk of LA thrombus formation
In temperate climate (developed countries) this and systemic embolism. It also abolishes the atrial
process usually takes one to two decades from the stage contribution to LV filling, therefore decreases car-
of carditis to develop a significant MS. But in tropi- diac output and contributes to symptoms. Recently
cal climate (developing countries) this latent period role of atrial natriuretic factor (ANF) which is pro-
is short and sometimes less than two years. Therefore duced due to atrial stretch in controlling pulmonary
significant MS may be seen in children and adolescents arterial (PA) pressure and cardiac output has been
(less than 20 years of age) called ‘juvenile MS’. Smoul- identified. Increased heart rate reduces diastolic time
dering rheumatic process or repeated episodes of car- and reduces time to fill the LV, therefore LA pressure
ditis (due to fresh streptococcal infection) is thought increases further. In course of time symptoms appear
to be the factors producing such rapid deterioration. during tachycardia due to exercise or during episodes
Left atrial enlargement, hypertrophy and fibrosis with of atrial fibrillation (AF) with fast ventricular rate.
mural thrombi are seen consequent to severe MS. De- Pulmonary venous hypertension (PVH) cause
pending upon severity and duration of MS; obliterative passive increase in PA pressure which gradually
changes are seen in pulmonary vascular bed. It subse- causes structural changes in the pulmonary vascular
quently gives rise to pulmonary arterial hypertension bed. Fibrosis and thickening of pulmonary arterioles
(PAH) and right ventricular hypertrophy. increase pulmonary vascular resistance (pulmonary
Remember: Main pathological changes are com- vascular disease). Onset of pulmonary vascular dis-
missural fusion, cuspal thickening and fibrosis with
thickened and shortened chordo-papillary system. Table 10.1: Severity of MS according to mitral valve area
Severity of MS by mitral valve area Valve area in cm2
Pathophysiology Normal 4–6
Narrowing of mitral valve orifice in diastole impedes Mild 1.6–2.0

filling of blood from LA to LV. Normal mitral valve Moderate 1.1–1.5
area in adult is 4 to 6 cm2. Even narrowing of valve Severe ≤ 1.0
area up to 50 percent of normal does not produce
hemodynamically significant obstruction of blood
flow. Valve area less than 2 cm2 causes elevation of LA
pressure to fill the LV and to maintain cardiac out-
put. An area of less than 1.0 cm2 is considered to be
severe MS. Severity of MS according to mitral valve
area is shown in Table 10.1. In MS although the LA
pressure is increased, normal LV diastolic pressure is
maintained, therefore, a pressure gradient is present
across the mitral valve in diastole (Fig. 10.2).
Mitral stenosis (MS) progresses slowly over years.
The LA pressure remains persistently high and gradu-
Fig. 10.2: Hemodynamics in mitral stenosis, pressure trac-
ally increases further and further. Increased LA pres-
ing from LA and LV shows diastolic gradient. Heart sounds,
sure causes pulmonary venous hypertension which is mid-diastolic murmur with pre-systolic accentuation are
responsible for dyspnea. Left atrial enlargement and also represented corresponding to the pressure tracing in
structural changes such as fibrosis and deposition of the lower panel
ease that is increased pressure at precapillary pul-

monary arteriolar level cause increase in pulmonary
vascular resistance known as the ‘second stenosis’
(pulmonary arteriolar narrowing). In MS, increased
pulmonary vascular resistance is protective against
occurrence of pulmonary edema by preventing surge
of blood to pulmonary bed, but at the same time
increases RV pressure, reduces cardiac output pro-
ducing symptom of low cardiac output. Persistent
increase in RV pressure gradually produces RV dila-
tation, functional tricuspid regurgitation (TR), and
increase in mean right atrial (RA) pressure which
is clinically expressed as right heart failure (that is
raised JVP, hepatomegaly and peripheral edema).
In the initial stages of severe MS increased car-
diac output (pregnancy, anemia, thyrotoxicosis) and
increased heart rate, as occurs in AF with rapid ven-
tricular rate may produce acute pulmonary edema
as pulmonary venous pressure exceeds plasma on-
cotic pressure. Sometimes pulmonary edema devel-
ops suddenly during labor, noncardiac surgery and
acute tachyarrhythmias known as ‘Flash Pulmonary Fig. 10.3: Pathophysiology of mitral stenosis
Edema’. later fibrotic changes are produced in the
Table 10.2: Hemodynamic parameters showing severity
pulmonary vascular bed and in pulmonary alveoli of MS
decreasing its permeability and therefore decrease oc-
curance of pulmonary edema. Pathophysiology of MS Mean Severity Mitral valve Pulmo artery
Gradient of MS area syst pressure
are summarized in Figure 10.3. Hemodynamic param-
(mm Hg)
eters of different grades of MS are shown in Table 10.2.
< 7 mm Hg Mild 1.6–2.5 cm2 Less than 30
7–12 mm Hg Moderate 1.1–1.5 cm 2
30–50
Clinical Features
More than 12 Severe Less than or More than
mm Hg equal to 1.0 50
Symptoms
cm2
Patients of mild-to-moderate MS remain asymptomatic
with normal activities. Dyspnea on effort, fatigability Hemoptysis is not an uncommon presentation
and palpitation are early common clinical presentations. due to rupture of bronchial veins secondary to pul-
Dyspnea is sometimes precipitated due to tachycardia monary venous hypertension. It is sometimes mas-
induced by various causes such as fever, exercise, emo- sive which may be life-threatening, known as ‘pul-
tion, pregnancy and during labor. As mentioned earlier, monary apoplexy’. Other causes of hemoptysis are
these episodes at early stage of the disease that is before acute pulmonary edema (blood tinged frothy spu-
obliterative changes occur in pulmonary vascular bed tum), pulmonary infarction and winter bronchitis
may induce acute pulmonary edema (orthopnea with (streaks of hemoptysis).
cough and frothy sputum). So in the early phase symp- Other common symptoms in relatively late phase
toms typical of left sided heart failure like dyspnea, PND are fatigability due to low cardiac output secondary
and orthopnea are common features. to severe pulmonary arterial hypertension (PAH)
Mitral Stenosis 63
and palpitation due to atrial fibrillation. Systemic will be the OS. Therefore, in severe MS opening snap
embolism from a LA thrombus is another mode of occurs early (close to A2). The A2-OS gap is a clinical
presentation in mitral stenosis (MS) which may oc- indicator of severity of MS. S2-OS interval < 80 msec
cur in a known patient of MS or may be the first is severe and > 120 msec is mild MS. As disease pro-
presentation. Cerebral embolism producing sudden gresses fibrosis and calcification reduce valve mobil-
onset of hemiplegia is commonest manifestation of ity and the OS is absent in calcific and fibrotic valves.
systemic embolization. Embolism may occur in pe- LV third heart sound (S3) is very unusual, its presence
ripheral artery (in limbs), mesenteric artery or may rules out significant MS and indicate severe MR or
lodge in iliac bifurcation causing ‘saddle embolism’. AR is associated.
Rare symptoms may be hoarseness of voice (Ort- A low pitched rough rumbling mid-diastolic
ner syndrome) or dysphagia due to compression of murmur (MDM) with presystolic accentuation is the
recurrent laryngeal nerve or esophagus respectively characteristic murmur of MS. It is best heard at the
by a large left atrium (LA). apex, in left lateral position and often localized to a
small area over the apex. In sinus rhythm atrial con-
traction increases flow across the stenotic MV, there-
Signs
fore, increases the intensity of murmur (presystolic
A typical mitral facies (pink colored swollen cheeks accentuation). Presystolic accentuation disappears
with malar flush) is better observed in fare colored un- with AF. Rarely presystolic accentuation may even
treated patients. Nowadays rarely seen in clinical prac- be present with AF because of onset of systole nar-
tice although it was often seen only four decades back. rows the mitral orifice before the actual closure of the
It is due to low cardiac output, peripheral vasocon- leaflets, thereby increasing pressure gradient before
striction (causing cyanosis) and venous congestion. S1. In mild MS sometimes murmur is better appre-
Peripheral pulse is usually normal, may be of low ciated only after exercise when flow increases across
volume (low cardiac output) and irregular in pres- the MV. The murmur starts with opening of the MV
ence of AF. In JVP the ‘a’ wave is prominent due to (with OS) that is after a short interval from S2, there-
forceful atrial contraction in presence of right ven- fore called mid-diastolic murmur. Duration of the
tricular hypertrophy. When significant TR is present, murmur is correlated with severity of MS. Longer
‘v’ wave is also prominent. In atrial fibrillation the ‘a’ the murmur more severe the stenosis. In tachycardia,
wave is absent. Raised JVP indicates presence of con- heart failure, and other low cardiac output states the
gestive heart failure (right heart failure). murmur may not be heard. In severe PAH when RV
The apex is tapping (palpable S1) in nature. A occupy the apical area and there is decreased flow
diastolic thrill is often palpable over the apex. A through MV, MDM is not audible, this clinical situa-
sustained left parasternal heave is felt due to RV hy- tion is known as ‘silent MS’.
pertrophy. In some cases P2 is also palpable (due to Longstanding PAH leads to right ventricular over-
severe PAH). load and dilatation produce tricuspid regurgitation
First heart sound (S1) is loud. It is due to closure (TR). It gives rise to a pansystolic murmur best heard
of mitral leaflets from a wide apart distance at end- over left lower sternal border, the intensity of TR mur-
diastole against pressure gradient between LA and mur increases with inspiration (Carvallo’s sign). How-
LV. Second heart sound (P2) is also loud due to PAH. ever, it should be differentiated from MR murmur
In MS, opening snap (OS) is characteristic, it is sine which is often associated with MS. Pansystolic murmur
qua none of MS. This sound is produced by sudden of MR is best heard over the apex with no respiratory
cessation of the motion of domed part of the ante- variation and radiates to axilla and back. A high pitched
rior mitral leaflet in early diastole. Loud S1 and sharp decrescendo diastolic murmur of pulmonary regurgita-
OS indicate pliable mitral valve. OS is best heard tion (PR) may also be heard over upper left sternal bor-
medial to the apex. Higher the LA pressure earlier der (Graham Steell murmur) due to severe PAH. Al-
though early diastolic murmur in setting of MS is often • Sinus rhythm with left atrial enlargement is pre-
due to associated AR, it is the inspiratory accentuation sent in most of the cases of moderate to severe MS.
that differentiates PR murmur from AR murmur. • Atrial fibrillation occurs in chronic severe MS.
With huge left atrial enlargement (LAE), fibrilla-
Juvenile Mitral Stenosis tory waves may be coarse indicating LAE.
• Right axis deviation, right atrial enlargement
Incidence of MS in pediatric age group among (besides left atrial enlargement) and right ven-
all rheumatic MS was reported in 10 percent tricular hypertrophy (RVH) are often present in
(R Tondon, 7th edn, Ghai Pediatrics, 2008) and chronic severe MS due to severe PAH.
juvenile MS (below 20 years) amongst all rheu-
matic heart disease was reported in 34.9 percent of
Roentgenography
cases in a series of hospital based study. (TK Mishra
et al, Ind H J, 1999;51:653). The salient roentgenographic features are (Fig. 10.5):
Juvenile MS is characterized by: 1. Straightening of left cardiac border due to promi-
1. Below 20 years of age with New York Heart nent main pulmonary artery (full pulmonary
Association (NYHA) functional class II to class bay), prominent left atrial appendage combined
IV symptoms. with inconspicuous aorta and a lifted apex (RV
2. Usually severe MS (MVA < 1 cm2). type). This characteristic finding of MS is also
3. Low incidence of atrial fibrillation. known as ‘mitralization of left cardiac border’.
4. Presence of severe PAH. 2. Double density shadow on right side in postero-
5. Usually no mitral valve calcification. anterior view due to left atrial enlargement (LAE).
The term juvenile mitral stenosis was first coined by The degree of LAE is related to severity of MS.
Sujoy B Ray et al in 1963 in India (lancet,11;1193-1195). Other radiologic features are elevation of left main
Prior to it there were some reports under the heading stem bronchus and prominent LA appendage in
of 'mitral stenosis in young' have been published (V left cardiac border between pulmonary artery and
Vaishnava et al, Vellore, Juvenile Rheumatism in South left ventricle.
India, Ind J Child Health, 1960;9:290 and Kutumbiah 3. Features of PVH like Kerley B lines which are short
P, Ind J Pediatric, 1935;2:215) and another article was horizontal lines (perpendicular to pleural surface) at
published under the heading of ‘mitral stenosis in costo-phrenic angles due to distension of lymphat-
young’ in editorial, Lancet in 1935. ics with edema fluid in the thickened interlobar sep-
tae are present. It indicates LA pressure more than
20 mm Hg. Sometimes dense lines may be seen due
Investigations
to interstitial edema near the hilum called Kerley A
Electrocardiography (ECG) lines.
4. Redistribution of blood flow to the upper lobe with
The salient ECG (Fig. 10.4) features are: prominent upper lobe veins indicating PVH which
Fig. 10.4: ECG in mitral stenosis showing right axis, left atrial enlargement and right ventricular hypertrophy
Mitral Stenosis 65
2D echo is the basis for diagnosing MS. The fol-

lowing features are looked for in 2D echo:
1. Valve leaflet thickening (more than 5 mm).
2. Doming of anterior leaflet in diastole also known
as hockey stick appearance (Fig. 10.6A).
3. Immobility or fixity of posterior mitral leaflet.
4. Calcification of leaflets and chordae (Fig. 10.6H).
5. Fish mouth like valve orifice in short axis of MV
(Fig. 10.6B) from which view valve area is directly
measured by tracing the orifice called ‘planimetric
method’ for mitral valve area estimation.
6. Other parameters to be seen in 2D echo are:
a. LA size and volume estimation.
b. To look for LA spontaneous echocontrast which
are smoke like opacities seen in LA cavity indi-
cating stagnation of blood (therefore chance of
increased thrombogenicity).
Fig. 10.5: Chest X-ray in MS showing double right cardiac c. Scanning of LA, particularly the appendage for
border (black arrow), straightening of left cardiac border presence of thrombus (Fig. 10.6F). Different
(white arrow) with RV contour apex and evidence of pul-
views are used to see the whole of LA for pres-
monary venous hypertension
ence of thrombus (Fig. 10.6G). Transesophageal
echocardiography (TEE) is superior to transtho-
is well correlated with severity of MS. Later on fea- racic echo for detection of LA clot.
tures of PAH like dilated proximal pulmonary arter- d. Measurement of LV and RV size and their func-
ies with peripheral pruning appear (Tapering of vas- tions.
cular shadows in the lateral one third of lung fields). Spectral Doppler is very useful in estimating valve
5. Calcification of valves better seen under fluoro- area and determining other hemodynamic parameter.
scopic examination. If annular calcification is seen The parameters seen in spectral Doppler are:
it indicates nonrheumatic origin. 1. Mean diastolic gradient across the mitral valve
6. Pulmonary hemosiderosis (bilateral granular obtained by tracing the diastolic mitral spectrum
appearance due to iron deposition in the alveolar (Fig. 10.6D). Normally, the mean gradient is less
space) is not uncommon in setting of long standing than 5 mm Hg. A mean gradient of more than 12
severe MS (it is often missed unless searched for). mm Hg is considered to be severe MS.
2. Valve area measurement by pressure half-time
Echocardiography method. Rate of decline of pressure gradient
across the mitral valve estimates the valve area.
Echocardiography is the diagnostic modality of Pressure half-time (Pt1/2) is the time required for
choice to identify MS. From M-mode, 2D, spectral pressure gradient to fall to 50 percent of its initial
Doppler, color Doppler to 3D echo all are helpful in value. Valve area is 220/Pt1/2.
diagnosis of MS. Combined they give useful anatom- 3. Pulmonary arterial pressure is estimated from TR
ic and hemodynamic data. jet. From TR velocity, pressure gradient is estimated
M-mode is not used for diagnosis of MS in recent between RA and RV in systole. RA pressure is esti-
years. But valve thickening, reduced EF slope and mated clinically from JVP or by echo from diameter
anterior motion of posterior leaflet are very typical of inferior vena cava. RA pressure added to the TR
findings in M-mode echo (Fig. 10.6E). gradient is equivalent to RV systolic pressure and
A B
C D
E F
Figs 10.6A to F
Mitral Stenosis 67
G H
I
Figs 10.6G to I
Figs 10.6A to I: (A) Echo in MS, A 2D Echo in parasternal long axis showing thick leaflets, chordal thickening (narrow
arrow) and doming of AML (bold arrow); (B) Mitral valve in short axis in MS showing a fish mouth appearance (arrow);
(C) Color Doppler in MS showing a flame shaped jet across the stenotic MV; (D) CW Doppler tracing in severe MS, the
diastolic spectrum shows a mean gradient of 18.93 mm Hg and valve area by pressure half-time method of 0.87 cm2; (E)
M-mode shows typical decreased EF slope of AML (Bold arrow) with anterior motion of PML (Narrow arrow); (F) Arrow
shows a big clot in LA appendage in short axis; (G) Clot in LA cavity (arrow) seen in apical 4 chamber view; (H) Arrow
shows calcification of AML in parasternal long axis view; (I) RV systolic pressure (pulmonary arterial pressure) estimation
from TR jet. Abbreviations: LA—Left atrium; LV—Left ventricle; RA—Right atrium; RV—Right ventricle; AML—Anterior
mitral leaflet; PML—Posterior mitral leaflet
is also equal to pulmonary artery systolic pressure method which is infrequently used. Color Doppler is
(Fig. 10.6I). Similarly from a pulmonary regurgitant essential to know associated MR and other valvular
jet RV end-diastolic pressure (equivalent to pulmo- lesions.
nary arterial diastolic pressure) is estimated. Note: Mitral valve area is judged by: (1) Planimetric
Color Doppler shows turbulent flow across method, (2) Pressure half-time method, (3) Continu-
the stenotic valve described as a flame shaped jet ity equation method, (4) PISA method
(Fig. 10.6C). From color Doppler valve area can be Echo is useful in deciding type of treatment
estimated by proximal isovelocity surface area (PISA) whether balloon valvotomy, open valvotomy/valve
repair or valve replacement is indicated. To decide area measurement and pulmonary arterial pressure
suitability for valvotomy a scoring system is used assessment is accurately done and management is
(Wilkins-Weyman’s score). Considering four pa- planned accordingly.
rameters and assigning scores from 0 to 4 for each
of valve thickening, mobility, calcification and
Differential Diagnosis
subvalvular thickening, a total score of 0 to 16 is
obtained. A score of 8 or below gives good long-term There is rarely any diagnostic problem in recogniz-
results after balloon valvotomy. ing a case of mitral stenosis. However, other common
Transesophageal echocardiography (TEE) is conditions having diastolic murmur over apex comes
mandatory to detect the presence of thrombus (clot) under differential diagnosis. They are large ostium
in left atrium or atrial appendage before valvotomy secundum ASD, Lutembacher’s syndrome, left atrial
and if thrombus is present TEE is repeated after six myxoma.
weeks of anticoagulation therapy. ASD secundum: In setting of large ASD secundum,
the tricuspid mid diastolic flow murmur (not rum-
bling or presystolic) audible over left lower paraster-
Cardiac Catheterization and
nal border up to apex confuse with MDM of MS.
Angiocardiography
But prominent precordial pulsation, wide and fixed
Routine catheterization is not required. However, car- splitting of second heart sound, and ejection systolic
diac catheterization of both left and right side of heart murmur over left upper parasternal border easily dif-
give exact estimation of pressure gradient across MV, ferentiate large ASD from MS.
degree of associated MR, associated other valvular le- Lutembacher’s syndrome: By definition this syn-
sions, ventricular function and valve area. Calculation drome consists of rheumatic MS with large ostium
of valve area from catheterization data (Gorlin meth- secundum ASD. So most of the signs and symptoms
od) is the gold standard for valve area measurement. are similar for both the conditions but a systolic
Coronary angio is performed in presence of symptom thrill over left parasternal border and no presystolic
of coronary artery disease and routinely above 40 murmur over apex distinctly favors Lutembacher’s,
years of age to rule out coronary artery disease. syndrome besides absent left atrial enlargement and
presence of incomplete RBBB in ECG. It is echocar-
diography which confirms the diagnosis.
Diagnosis
Left atrial myxoma: It is an uncommon condi-
Patients with dyspnea on effort with or without histo- tion but when a patient presents with constitutional
ry of rheumatic fever (RF) on examination if reveal, symptoms (fever, arthralgia, loss of appetite with
loud first heart sound (S1), accentuated second heart high ESR), symptoms of heart failure and a systolic
sound (P2), opening snap (OS) and apical mid dias- and diastolic murmur over apex with normally heard
tolic rough rumbling murmur, the diagnosis is mi- first heart sound and no evidence of pulmonary hy-
tral stenosis. ECG changes of right axis, left atrial or pertension, left atrial myxoma is highly suspected.
biatrial enlargement, right ventricular hypertrophy, However, echocardiography gives the diagnosis.
atrial fibrillation (in 25 percent of cases) and chest Note: For academic interest other causes of diastolic
X-ray pictures of left atrial, pulmonary arterial and murmur over apex are:
right ventricular enlargement with features of pul- 1. Congenital mitral stenosis
monary venous and arterial hypertension strongly 2. Cor Triatriatum
suggest moderate to severe MS. Echo is diagnostic 3. Flow mitral diastolic murmur over apex due to
with 2-D features of mitral valve and subvalvular post tricuspid large left to right shunts like VSD,
thickening, calcification, diastolic doming of anterior PDA, Aortopulmonary window, Rupture of sinus
mitral leaflet, combined with Doppler study, valve of Valsalva aneurysm into RV
Mitral Stenosis 69
4. Hyperkinetic state—Anemia and thyrotoxicosis heart failure. Atrial fibrillation with fast ventricu-
5. Severe AR (Austin Flint murmur) and MR (flow lar rate may precipitate CHF. Moreover, tachycar-
MDM) dia due to fever (upper respiratory tract infection),
6. Rheumatic mitral valvulitis (Carey Coombs mur- pregnancy, and concurrent other infections may
mur). produce CHF.
Pulmonary Regurgitation and Tricuspid Regurgita-
Complications tion: Functional pulmonary regurgitation (PR) and
tricuspid regurgitation (TR) occur due to severe pul-
Atrial fibrillation, hemoptysis, winter bronchitis, sys- monary artery hypertension. PR occurs due to pul-
temic embolism and pulmonary edema are although monary valve ring dilatation and TR due to tricuspid
described under clinical manifestations are in true annular dilatation secondary to right ventricular en-
sense complications of MS. The other complications largement.
like right heart failure, pulmonary hypertension,
pulmonary embolism, tricuspid regurgitation are Mitral Stenosis with Pregnancy
also very often present besides infective endocarditis
(rarely occurs). Patients with MS are many a times first diagnosed
Atrial fibrillation: It is detected quite often in pa- during pregnancy. Second trimester of pregnancy
tients having long standing severe MS. Sudden dete- produces increase in cardiac output as much as
rioration of clinical signs and symptoms due to fast 30 percent. This increases flow rate across a stenotic
ventricular rate draws the attention of the physician. mitral valve increases LA pressure that leads to in-
LA thrombus formation leading to systemic embo- creased pulmonary venous pressure thereby patients
lism is the sequale of this complication. It is to be become symptomatic. These patients carry a high
treated early and effectively. risk of flash pulmonary edema during labor due to
Thromboembolism: It is often associated with atrial tachycardia and increased cardiac output secondary
fibrillation. Cerebral or peripheral thromboembo- to redistribution of blood flow to maternal circulation
lism may occur with sinus rhythm in presence of LA with each uterine contraction which further increases
thrombus due to intermittent AF. The atrial throm- following labor. In this stage meticulous medical man-
bus are often large ball like, freely mobile that may agement is necessary mainly with loop diuretics (intra-
obstruct mitral orifice (ball valve thrombus) which venous frusemide) and to keep intake output chart for
are easily recognized by 2D echocardiography. It monitoring fluid balance and blood pressure. Routine
gives rise to sudden onset of hemiplegia (due to cer- prophylaxis for rheumatic fever is continued during
ebral embolism) or vascular obstruction (peripheral pregnancy. Since two decades balloon mitral valvoto-
thromboembolism) in the limbs. It may cause inter- my (BMV) has been the routine procedure of choice
mittent claudication leading to gangrene or cause se- in case of pregnancy with MS (prior to it CMV was
vere abdominal pain (mesenteric artery embolism). done). When the MVA is less than 1 cm2 and the valve
Hemoptysis and Winter Bronchitis: Pulmonary ve- is suitable, balloon valvotomy is ideally performed in
nous hypertension may cause rupture of bronchial second to third trimester with shielding of abdomen
veins causing hemoptysis, which may be massive in and pelvis (to prevent radiation to the fetus).
nature known as pulmonary apoplexy. Winter bron-
chitis occurs due to pulmonary congestion which Management
makes the lungs vulnerable for acquiring infection,
particularly in cold weather (winter season). Medical Management
Congestive Heart Failure: Congestive Heart Failure
(CHF) is a common complication occurs in long Asymptomatic patients with mild to moderate MS
standing severe MS secondary to pulmonary ar- are followed-up yearly with clinical, ECG and Echo
tery hypertension which subsequently leads to right parameters. Patients with severe MS need early
evaluation with echocardiography to know whether In some cases of sinus rhythm (with no CHF)
their valve morphology is suitable for balloon/surgi- beta blockers like atenolol or metoprolol give symp-
cal valvotomy or requires replacement/repair. tomatic relief by decreasing heart rate. Lower heart
In symptomatic severe MS medical management rate increases diastolic time and improves LV filling,
has limited role. It is aimed at prophylaxis against thereby reduce pressure gradient between LA and LV.
rheumatic fever, palliative management of pulmonary Digoxin has no definite role when patient is in
venous hypertension and congestive heart failure and sinus rhythm and there is no CHF. In setting of mitral
prevention of thromboembolism. In moderate-to- stenosis if patient complains of repeated hemoptysis,
severe MS, orally given loop diuretics reduce pulmo- diuretics (such as frusemide or torsemide) are used
nary congestion and improve symptomatic status. to reduce pulmonary venous pressure.
When congestive heart failure is present, it is
treated with conventional antifailure regime like diu-
Balloon Mitral Valvotomy
retic, digoxin and general managements like salt and
fluid restriction with restricted physical activity. Loop Synonym: Percutaneous transvenous mitral commis-
diuretics like frusemide 40 to 80 mg/day of torsemide surotomy (PTMC).
10 to 20 mg/day are used in combination with po-
tassium sparing diuretics (spironolactone, amiloride,
Indications
triameterine) or with oral potassium supplement to
prevent hypokalemia. In severe cases diuretics may Bolloon mitral valvotomy (BMV) is performed when
be given intravenously. valve morphology is favorable (Wilkin’s score ≤ 8).
When patient becomes symptomatic with onset The indications are:
of AF needs treatment for 1. Rhythm control, 2. Rate • Symptomatic patients with moderate-to-severe MS.
control and with 3. Anticoagulation. Antiarrhythmic • Asymptomatic patients with moderate to severe
drugs for converting to sinus rhythm and maintain- MS who have PAH. Pulmonary artery systolic
ing it are class Ic (propafenone/flecainide), class Ia pressure (PASP) > 50 mm Hg at rest or > 60 mm
(quinidine/disopyramide/procainamide) and class Hg with exercise.
III drugs (amiodarone and sotalol). However, it is • When pulmonary artery wedge pressure rise more
difficult to maintain sinus rhythm due to dilated LA than 25 mm Hg with exercise.
in face of potential adverse effect of antiarrhythmics. • Recent AF (in the absence of LA thrombus or
Therefore the mainstay of management of AF is to moderate to severe MR)
lower the ventricular rate. AV node blocking agents • Patients for major noncardiac surgery are also
like digoxin, calcium channel blocker (verapamil) candidates for BMV.
and beta blockers are used for this purpose either • BMV is also indicated during pregnancy (second
as single agents or in combination. Anticoagulation to third trimester).
therapy (with wafarin/nicoumalone) is indicated in • Restenosis following initial BMV if valve mor-
patients of mitral stenosis having. phology is favorable and there is no significant
1. Atrial fibrillation MR.
2. LA thrombus • Patients who are at high risk for mitral valve sur-
3. Spontaneous echocontrast in LA gery like elderly, frail, associated ischemic heart
4. Giant LA (> 55 mm) disease or malignancy.
5. History of previous thromboembolism, unless
there is specific contraindication like active bleed-
Contraindications
ing (peptic ulcer, hemorrhoids). With anticoagu-
lation therapy prothrombin time is monitored 1. Mitral valve area (MVA) more than 1.5 cm2
to keep international normalized ratio (INR) 2. LA thrombus
between two and three. 3. Moderate-to-severe MR
Mitral Stenosis 71
4. Multivalvular lesions In our series of 900 cases (M 310, F 509, AF 20.6

5. Significant calcification percent, mild MR 10 percent, mean echo score was
6. Technical difficulties in introducing catheter 7.21, pregnancy 12 percent, and restenosis 8 per-
(Giant LA, atrial septal aneurysm and venous cent). BMV was performed using Inoue (n=78),
anomalies). Accura (n=279) or Jomiva balloon catheter (n = 543).
Transesophageal echocardiography is preferred Mean MVA increased from 0.84 cm2 to 1.96 cm2 with
to exclude LA thrombus, to assess the severity of MR improvement of NYHA functional class in most of
as well as severity of MS and morphology of mitral the patients. Complications included pericardial
valve when information with transthoracic echo is tamponade (2.3 percent), cerebral embolism (1 per-
inadequate. cent), cardiac perforation (1 percent), severe MR
BMV was first performed in 1984 by K. Inoue requiring urgent MVR in 2 percent and death 1 per-
and became a clinically approved technique in 1994. cent of cases. Residual small left to right shunt across
It is performed by introducing a balloon catheter (In- atrial septum was seen in about 5 percent of cases.
oue, Accura) through transvenous approach (Femo- Results of BMV are comparable to surgical val-
ral vein → IVC → RA → interatrial septal puncture/ votomy. With favorable morphology of mitral valve,
dilatation → LA → Mitral valve → LV) and inflating long-term results are excellent with 65 percent symp-
the balloon across the mitral valve and splitting the tom free survival at 7 years.
fused commissures (Figs 10.7A and B). Antegrade
over the wire (Jomiva Balloon Catheter) method
Surgical Valvotomy
can also be used. Rarely retrograde approach is used
(Femoral artery → Aorta → LV → Mitral valve → The first successful closed mitral valvotomy/Com-
LA). BMV is safe and effective with low complication missurotomy (CMV/CMC) without use of cardio-
rate. pulmonary bypass through LA approach was done
A b
Figs 10.7A and B: Balloon mitral valvotomy: (A) Balloon across stenotic MV (arrow) before dilatation; (B) After
dilatation
by Harken in 1948 in USA and also by PK Sen of with restenosis following initial BMV but success rate
Bombay in the same year. First valve replacement by is low.
Ball-valve prosthesis was done by Starr and Edward
in 1961 and in India by PK Sen of Bombay in 1964
Mitral Valve Replacement
(Albert Starr gifted the prosthetic valve to PK Sen).
CMV/CMC is performed in a valve with similar cri- When the valve is severely calcific, associated with
teria as for BMV in a beating heart by introducing moderate to severe MR or when BMV is contraindi-
a finger guided metal dilator through LA puncture. cated as mentioned above, mitral valve replacement
This procedure is not preferred in developed coun- is indicated. Mechanical prosthetic valve replace-
tries now and replaced by open mitral commissurot- ment have excellent long-term outcome with 80
omy. But still CMV/CMC is performed in developing percent survival at 10 years. Long-term oral antico-
countries due to its lower cost. agulation to maintain INR between 2.5 and 3.5 is a
Open Mitral Valvotomy/Commissurotomy must with mechanical prosthetic valve. Complica-
(OMV/OMC) is performed under cardiopulmonary tions like prosthetic valve thrombosis, mechanical
bypass. It has several advantages over closed valvot- dysfunction, prosthetic valve endocarditis and he-
omy and BMV in the sense that debridement of cal- molysis (due to shear-stress) are to be managed cau-
cium, splitting of chordae, repair of papillary muscle tiously.
and removal of LA clot can be performed in addition
to valvotomy under direct visualization. This also
gives opportunity for assessment of MR after com- further reading
missurotomy and tricuspid annuloplasty in case of 1. Alan S, Ulgen MS, Ozdemir K, et al. Reliability and
severe TR. It has an operative mortality of 1 to 2 per- efficacy of metoprolol and diltiazem in patients hav-
cent. ing mild to moderate mitral stenosis with sinus
rhythm. Angiology. 2002;53:575-81.
2. Alpert, JS, et al. Mitral valve disease. In: Textbook
Intervention for Atrial Fibrillation
of Cardiovascular Medicine. 2003. Topo, et al (Eds).
Catheter based radiofrequency ablation during BMV Lippincott, Williams and Wilkins.
or Maze procedure may be done during surgery si- 3. Bonow RO, Carabello BA, Chatterjee K, et al. ACC/
multaneously when facility and expertise are avail- AHA 2006 guidelines for the management of patients
able. with valvular heart disease. J Am Coll Cardiol
2006;48:1-148.
4. Braunwald’s Heart Disease, 8th edn. Saunders, an
Restenosis
Imprint of Elsevier, 2008.
Valvotomy does not reverse the disease process; 5. Carabello BA. Modern management of mitral steno-
it sets the valve backward for over a few years. The sis. Circulation, 2005;112:432-7.
valves come to a stage what it was a few years before. 6. Cox JL. Intraoperative options for treating atrial
The progression of disease goes on due to constant fibrillation associated with mitral valve disease. J
trauma of blood flow over deformed domed valve. Thorac Cardiovasc Surg 2001;122:212-5.
After adequate commissurotomy (below 20 years of 7. Doukas G, et al. Left atrial frequency ablation during
age) restenosis (repeat valvotomy or valve replace- mitral valve surgery for continuous atrial fibrillation, a
ment) was 11 percent at 10 years (Stanley John et randomized controlled trial. JAMA. 2005;294: 2323-9.
al, J Thoracic cardiovascular surgery, 1975;69:631). 8. James E dalen, Paul E Fenster. Mitral Stenosis,
Restenosis occurs early if there is suboptimal result Valvular Heart Disease 3rd edn, Joseph S Alpert (Ed),
or repeated valvulitis. Repeat BMV is also performed Lippincott Williams and Wilkins.
Mitral Stenosis 73
9. Lee JW, et al. Surgical outcome of the Maze procedure 13. Rahimtoola SH, Durairaj A, Mehra A, et al. Current
for atrial fibrillation in mitral valve disease: Rheumatic evaluation and management of patients with mitral
versus degenerative. Ann Thorac Surg. 2003;75:57-61. stenosis. Circulation. 2002;106:1183-8.
10. Paul Wood’s Diseases of the Heart and circulation, 14. Routray SN, et al. Balloon mitral valvuloplasty during
3rd edn. Eyre and Spottiswoode Ltd. 1968. pregnancy. Int J Gynaecol Obstet, 2004;85:18-23.
11. Pendergast BD, et al. Contemporary criteria for the 15. Topol EJ. Anticoagulation with prosthetic cardiac
selection of patients for percutaneous balloon mitral valves. Arch Intern Med 2003;163:2251-2.
valvuloplasty. Heart J. 2002;87:401-4. 16. Yau T, et al. Mitral valve repair and replacement for
12. Radhakrishnan S, Shrivastava S. Balloon mitral valvot- rheumatic heart disease. J Thorac Cardiovasc Surg.
omy: our perspective. J Postgrad Med. 1993;39:49-50. 2000;119:53-61.
CHAPTER 11
Mitral Regurgitation
Definition 3. Ischemic MR (Coronary artery disease causing

When blood from left ventricle (LV) leaks back to left ischemia of mitral valve apparatus).
atrium (LA) during systole, the clinical condition is 4. Primary myocardial disease (Cardiomyopathies).
known as mitral regurgitation (MR) or mitral incom- 5. Infective endocarditis.
petence (MI). MR occurs because of improper clo- b. Less common conditions
sure (inadequate apposition or coaptation) of mitral 1. Connective tissue disorders: Rheumatoid arthri-
valve due to abnormality of one or more components tis, systemic lupus erythematosus (SLE),
of mitral valve apparatus. Marfan’s syndrome, Hurler’s syndrome, Ehlers-
Danlos syndrome.
Incidence and Prevalence 2. Trauma
3. Idiopathic
The incidence of rheumatic heart disease (RHD) has c. Uncommon conditions
not declined significantly as already mentioned in 1. Endomyocardial fibrosis
chapter 2, section I. The incidence of isolated rheu- 2. Amyloidosis
matic MR varies widely and when associated with 3. Carcinoid syndrome (rare in left side of heart)
mitral stenosis it becomes more. It is observed under 4. Hypereosinophilic syndrome
echocardiographic screening that lone MR is present in
7.9 percent by SN Routray (Ind H J, 2003; 53:252), in Etiological Classification
12.1 percent by AN Patnaik (NIMS, Hyderabad, 2002)
and in 21.2 percent of cases by Adarsh Kumar (Ind H 1. Post-inflammatory: Rheumatic, SLE.
J, 2009; 61:14-28). There is no sex predilection for MR. 2. Infection: Infective endocarditis.
3. Connective tissue disorders: MVP, idiopathic rup-
ture of chordae, Marfan syndrome, ankylosing
Etiology
spondylitis, rheumatoid arthritis.
Mitral Regurgitation is associated by a number of 4. Myocardial disease: Ischemic and cardiomyopa-
diseases unlike mitral stenosis which has mainly thies.
rheumatic etiology. MR is classified as follows. 5. Infiltrative disease: Amyloidosis.
6. Miscellaneous: Carcinoid syndrome, hypereosino-
philic syndrome, endomyocardial fibrosis.
Clinical Classification
a. Common conditions Structural Changes of Mitral Valve Apparatus
1. Mitral valve prolapse (MVP).
2. Rheumatic MR (common in developing coun- The mitral apparatus consists of mitral annulus, the
tries). anterior and posterior leaflets, the chordae tendinae,
Mitral Regurgitation 75
the anterolateral papillary muscle, posteromedial pap- perforation of leaflet and extension of infection to
illary muscle and adjacent myocardium. Disorders of the mitral annulus causing loss of valve support.
any one or in combination of the above components of • Acute rheumatic fever: Because of severe valvulitis,
the mitral apparatus results in MR. They are as follows: leaflet prolapse and rupture of chordae tendinae
• Disorder of mitral annulus: In adults mitral annu- leads to acute MR.
lus is 10 cm in circumference. It is soft and flex- Acute MR due to rheumatic cause itself is un-
ible. When LV contracts it is constricted leading common unless associated with infective endocardi-
to proper closure of mitral valve. But when mitral tis. It is mainly due to ischemic or other non-ischem-
annulus is dilated, mitral valve closure is not ade- ic ( primary) causes.
quate so that blood from LV leaks back to LA
resulting in MR. Main cause of annular dilatation
Pathology
is dilatation of LV cavity which may be of any eti-
ology. Mitral annular calcification causes MR by Normally mitral valve leaflets close properly in sys-
immobilizing mitral leaflets. It may be degenera- tole so that there is no leakage (or regurgitation)
tive or atherosclerotic. to LA and forward flow occurs to aorta. Because
• Disorder of leaflets and valves: Causes are RHD of abnormal closure or coaptation of mitral leaflets
(scarring and contracture causing distortion of blood from LV leaks back to LA in systole. This leak-
leaflet tissue is the main cause of MR in rheu- age passage is known as regurgitant orifice. In RHD
matic setting), Mitral valve prolapse (MVP), the important pathological changes causing MR are
Infective endocarditis, Carcinoid heart disease, thickening and retraction of valve cusps (fibrous an-
Hypertrophic cardiomyopathy, Ergotamine and kylosis of valve), so that they cannot close properly in
other appetite suppressing drugs. systole. Shortening of chordae tendinae also causes
• Disorder of chordae tendineae: Causes are RHD less adherenceness of the valve and improper closing.
(because of chordal fibrosis and calcification cause In chronic MR mitral ring (annular) dilatation also
MR), MVP and Ruptured chordae caused by myx- contribute to MR.
omatous degeneration leads to MR. Abnormal Note: A very small amount of blood leaks back to
lengthening and rupture of chordae tendinae are the LA in systole as seen in color Doppler echo known as
cardinal features of MVP syndrome. It is the chordae physiological MR.
to posterior leaflet which rupture more frequently.
Severity of MR and type of MR depends upon the
Pathophysiology
number of chordae tendineae that has ruptured.
• Disorder of papillary muscles: Mainly it is involved In MR there occurs LA and LV volume overload. LA
in non-rheumatic MR. Ischemic heart disease volume overload means LA receives its normal quota
most commonly produce MR due to papillary from pulmonary circuit plus the regurgitant volume.
muscle dysfunction, other rare causes are cardio- Similarly in diastole LV volume overload occurs as LV
myopathy, and congenital (single papillary mus- gets its normal quota plus the regurgitant blood (Vol-
cle, parachute mitral valve, AV canal anomaly). ume of blood regurgitated to LA in systole returns
Papillary muscles are not involved in RHD but back to LV in diastole). The pressure gradient between
secondary involvement may contribute to MR. LA and LV starts with mitral valve closure (with S1)
and persists throughout the systole, so regurgitation
occurs during whole of systole from onset of isomet-
Causes of Acute MR
ric contraction (before the aortic valve is open) to S2.
• Infective endocarditis: It is due to rupture of In rheumatic condition the leaflet and valve lesions
chordae tendinae and valvular destruction like are relatively stable (fixed one) without much change
in regurgitant orifice size, so flow occurs almost lar to acute MR. Another group on the other extreme
equally throughout the systole, but late in the disease have marked dilatation of LA (Giant LA) but with
process the regurgitant volume may decline during normal or near normal mean LA pressure (increased
late systole due to decrease pressure gradient. LA compliance) without or with minimal increase
In all chronic valvular lesions there occurs LV of pulmonary artery pressure. This group of patients
remodeling as an adaptation to handle the extra develop atrial fibrillation because of giant LA (due to
load. The normal shape of LV cavity is changed. LV structural abnormality of LA myocardium) that leads
is dilated along with hypertrophy of LV myocardium to hemodynamic deterioration and precipitate heart
(eccentric hypertrophy) so that the wall stress or the failure and low cardiac output state (hypotension).
after load is maintained within normal limits (com- But many patients of chronic MR remain in-between
pensatory state) for a long time. In other words LV is these two groups whose hemodynamic status and LA
able to handle the large volume without increase in compliance remain stable (that is compensated state)
mean LA or LV end-diastolic pressure. for a long period.
Note: MR patients remain in a compensatory state for a In acute MR the hemodynamics differs, as the LV
long period. In chronic MR, LV dilatation increases the and LA does not have time to adapt and compensate
mitral annulus orifice area (annular diameter) thereby to volume load. LA pressure sharply rises in systole,
more blood regurgitate back to LA in each systole. giving rise to acute increase in pulmonary venous
Ultimately decompensation occurs, as compensa- and pulmonary capillary pressure leading to pulmo-
tory mechanisms fail to match with increasingly severe nary edema and cardiogenic shock.
MR. With decompensation, the LV wall thickness does
not go with cavity dilatation (afterload mismatch), LV
Clinical Features
systolic function deteriorates, forward cardiac output
decreases and LV end-diastolic pressure along with Symptoms
LA mean pressure increase. The exact mechanism of
LV dysfunction is not known, however, it is postulated Patients remain asymptomatic with mild-to-moder-
that causes like myofibrillae loss and increase of calci- ate MR and even with severe chronic MR for a long
um triggered calcium release play some role resulting period. In other words these patients remain in a
in loss of contractile elements (not due to less coronary compensated state, because forward cardiac output is
flow). LV dysfunction may be irreversible, even may maintained without significant rise in mean LA pres-
not improve after valve replacement. sure. Palpitation (precordial pulsation) more marked
Note: The gradual LV decompensation gives rise to during exertion is the early complaining symptom.
more dilatation of LV which leads to more dilatation Fatigability and dyspnea on accustomed exertion im-
of mitral annulus, so severity of MR further increases. proved by rest are early features of decompensation
Therefore, it is said ‘MR begets more MR’. (indicating low cardiac output and increased pulmo-
High LA pressure leads to pulmonary venous nary venous pressure). Patients gradually progress
hypertension, increased pulmonary capillary pres- from class I to class IV New York Heart Association
sure and subsequently to pulmonary arterial hyper- (NYHA) symptoms. Tachycardia due to atrial fibril-
tension (PAH). This PAH increases right ventricular lation or triggered by exertion, anemia and fever may
pressure (afterload) and is responsible for subsequent precipitate symptoms which ultimately lead to ortho-
RV failure that gives rise to congestive heart failure. pnea, PND and congestive heart failure.
There is wide variation in LA compliance. One
group of patients may have minimal dilatation of
Signs
LA with markedly increased in mean LA pressure
(reduced compliance) with evidence of pulmonary Pulse is normal or may be high volume but not col-
arterial hypertension. This pathophysiology is simi- lapsing. Apex beat is forceful, hyperdynamic (ill
sustained) and in chronic MR displaced outwards to increased flow across the mitral valve in diastole
and downwards. A precordial lift may be felt due to (flow rumble). Presence of a MDM, S3 and a soft S1
systolic expansion of LA anteriorly. Systolic thrill favor flow murmur due to significant MR where as a
and sometimes third heart sound (S3) are palpa- loud S1 and opening snap indicates associated MS.
ble in moderate to severe MR over apical area. On In severe persistent MR, features of right heart
auscultation first heart sound (S1) is diminished (due failure like peripheral edema, raised JVP and hepato-
to improper closure of mitral leaflets). Second heart megaly may appear due to pulmonary arterial hyper-
sound (S2) is wide split in moderate to severe MR tension. Another pansystolic murmur may also be
(because A2 occurs earlier as the LV ejection period heard over lower left sternal border, increased with
shortens). P2 is loud in chronic MR due to pulmo- inspiration due to tricuspid regurgitation (TR) sec-
nary arterial hypertension. Third heart sound (LV ondary to pulmonary arterial hypertension (PAH).
S3) is characteristic of significant MR, the intensity
increases with expiration. It is due to a large volume Clinical Features of Acute MR
of blood rapidly coming to LV in early diastole, does
not indicate LV dysfunction. In combined lesions of These patients are very symptomatic due to reduced
MR with MS, S3 indicates MR is dominant. cardiac output and pulmonary congestion. On exam-
The murmur of MR is a pansystolic or holosys- ination there is tachycardia, pulse is low volume with
tolic blowing high pitched quality that usually begins narrow pulse pressure, apex is normally felt, there
with S1 and continues throughout the systole with occurs no cardiomegaly, systolic thrill is not palpa-
equal intensity and ends with S2. It is pansystolic ble, first heart sound (S1) is normal or diminished,
because it begins with isometric left ventricular con- second heart sound (S2) is narrowly split with loud P2
traction and continues throughout the systole. The (PAH) and fourth heart sound (right ventricular S4)
murmur continues after A2 as the pressure gradient is audible. The systolic murmur of MR is short (may
persists between the LV and LA even after closure of be only early systolic or may be absent) as there in
aortic valve (A2). (Fig. 11.1 summarises the ausculta- rapid equalization of LV diastolic and LA pressure.
tory findings). The murmur is best heard at the apex No flow MDM is audible which is commonly present
and selectively radiates to the axillary area and to the in severe chronic MR. Short TR murmur is frequent-
left interscapular area. Radiation depends upon the ly audible in acute MR.
direction of regurgitant jet, in rheumatic MR the jet
is usually directed posteriorly (as anterior leaflet is Investigations
more severly affected). The intensity of murmur is
not proportional to the severity of MR. A mid dias- Electrocardiogram (ECG)
tolic rumbling murmur may be heard at the apex due
Salient ECG features are:
• ECG remains within normal limits in most of
the cases of mild-to-moderate MR of rheumatic
origin.
• With sinus rhythm, LA enlargement is a common
finding in moderate to severe MR.
• AF is a late feature particularly in those having
Fig. 11.1: Auscultatory findings in severe MR. Abbreviations:
S1—First heart sound; A2—Aortic component of second
marked LA dilatation in chronic severe MR.
heart sound; P2—Pulmonary component of second heart • LV hypertrophy (LVH) is present with deep nar-
sound; PSM—Pansystolic murmur; MDM—Mid diastolic row q waves in lateral leads with upright T waves
murmur indicating volume overload of LV (Fig. 11.2).
Fig. 11.2: ECG showing LVH by voltage criteria with deep and narrow q waves in lateral leads with upright T waves
indicating moderate to severe MR
• In acute MR sinus tachycardia and nonspecific • Right cardiac border shows double density shadow
ST/T changes are common findings without LA indicating LA enlargement.
enlargement and LV hypertrophy. • Pulmonary venous hypertension with prominent
upper lobe pulmonary veins appears with LV
decompensation.
Roentgenography • Acute MR is characterized by features of acute
pulmonary edema (Bat wing appearance) with
The salient features are (Fig. 11.3): cardiac size remaining normal.
• In chronic severe MR cardiomegaly with LV con- • Calcification of mitral valve is uncommon in MR
tour is the feature in PA view of chest X-ray. of rheumatic origin.
Echocardiography
2D Echocardiography (Echo) with Doppler study is
the key investigation for diagnosis of MR. 2D echo
helps in determining the etiology of MR, assess-
ing the valve and subvalvular anatomy, LA and LV
dimensions and its function. In rheumatic MR, there
are valvular and chordal thickening, fibrosis, fusion
and calcifications which make the appearance very
typical (Fig. 11.4A). Involvement of other valves are
very characteristic feature of rheumatic MR.
A high velocity jet in LA during systole is the
characteristic feature of MR in color Doppler. The
jet area is commonly measured to estimate se-
verity (Fig. 11.4C). Area of > 8.0 cm2 or > 40 per-
cent of LA area is taken as severe and < 4 cm2 or
Fig. 11.3: Chest X-ray in MR showing cardiomegaly with
LV contour, huge LA enlargement < 20 percent of LA area is mild with in-between val-
A B C
D E F
Figs 11.4A to F: (A) Echocardiography in MR A 2D echo showing a typical rheumatic mitral valve in apical 4 chamber view,
valve is thick with calcification in the tip of leaflets with inadequate systolic coaptation (arrow), note the dilated LV and
hugely dilated LA; (B) Color jet seen in LA in MR, note the vena contracta (open arrow) 10.3 mm indicating severe MR;
(C) Jet in a severe MR, note the size of MR jet and its relation to LA area; (D) Eccentric MR jet impinging on posterolateral
LA wall (arrows), jet area appears small but MR is at least moderate as seen by LA and LV enlargement; (E) CW Doppler
spectrum in severe MR, note a triangular dense spectrum (open arrow); (F) PISA method of measurement of severity of
MR (see text). Abbreviations: LA—Left atrium; LV—Left ventricle; RA—Right atrium; RV—Right ventricle
ues taken as moderate MR. Jet area estimation has Table 11.1: Quantification of severity of MR by echocar-
diographic assessment
many fallacies. It overestimates MR in central jets
where as MR is under e stimated in eccentric wall Mild MR Moderate MR Severe MR
impinging jets (Fig. 11.4D). Another criterion is to Small central jet < Central jet Large central MR
measure the vena contracta which is the narrowest 4 cm2 or < 20% of 4–8 cm2 or jet > 8 cm2 or
part of the jet near its origin. In an adequately ob- LA area 20–40% of LA > 40% of LA area
area
tained image vena contracta > 7 mm is severe and <
3 mm is mild MR (Fig. 11.4B). Quantification of MR Vena contracta Vena contracta Vena contracta
can be done by the principle of flow convergence, width < 3 mm width 3–6.9 mm width ≥7 mm
measuring radius of proximal isovelocity surface Systolic reversal of Systolic reversal Systolic reversal
area (PISA) which are rounded color signals proxi- pulmonary venous of pulmonary of pulmonary
flow not present venous flow not venous flow
mal to the regurgitant orifice (Fig. 11.4F). From the
present present
aliasing velocity, and radius (distance from mitral
orifice to the point of color change) volume of regur- Regurgitant vol- Regurgitant Regurgitant
ume < 30 ml/beat volume 30–59 volume > 60 ml/
gitant flow can be calculated.
ml/beat beat
Systolic reversal of flow in pulmonary veins as
measured by PW Doppler indicates severe MR. Simi- Regurgitant Regurgitant Regurgitant
Fraction < 30 Fraction 30–49 Fraction > 50
larly the CW Doppler signal of MR jet taken from an
apical 4 chamber view is more dense and triangular Effective regurgi- Effective regurgi- Effective regurgi-
tant orifice area tant orifice tant orifice area
in severe MR (Fig. 11.4E) but soft and parabolic in
(EROA) < 0.20 cm2 area (EROA) (EROA) > 0.40 cm2
mild MR. Supporting evidence of a significant MR are 0.20–0.39 cm2
LA and LV dilatation, predominant E wave (E>A) in
PW mitral diastolic flow. Transesophageal echo (TEE)
should be used when imaging from transthoracic Cardiac Magnetic Resonance (CMR)
window is inadequate or inconclusive. More so TEE
gives better information regarding feasibility of valve It provides an accurate assessment of regurgitant
repair before surgery than TTE. lesion. This noninvasive procedure is helpful only
Combining the data from 2D and spectral Dop- when echo report shows discrepancy. Because of its
pler, volume of flow can be calculated by the princi- own limitation it is not a routine procedure.
ple of continuity equation. Deducting the aortic flow
in systole from mitral flow in diastole, the amount
of regurgitation (Regurgitant Volume) is calculated.
Angiocardiography
Regurgitant volume divided by mitral inflow volume
is expressed as regurgitant fraction. Regurgitant frac- In recent years routine cardiac catheterization is not
tion <40 percent indicates mild, between 40 and 60 required for either diagnosis or for decision making
percent moderate and >60 percent is severe MR. before surgery, but it was mandatory in pre-echo era.
Recently real time three dimensional echocardi- Now a day cardiac catheterization is mainly done to
ography (3D Echo) is ascertaining its place over 2D know coronary anatomy before surgery and in a few
echocardiography as the anatomy of the lesions is cases where echo is not conclusive. Left ventricular
better delineated which may be helpful to the oper- angiocardiography determines the severity of MR by
ating surgeon. Table 11.1 Summarises different echo degree of opacification of LA from the dye injected to
parameters of determining severity of MR. LV. The severity of regurgitant lesion and anatomical
delineation of mitral apparatus is better visualized by dynamic auscultation (increased on standing and
angiography. decreased on squatting), and associated S4 strongly
The severity of MR is classified into 4 angiographic go in favor of HOCM.
grades,
Grade I: A puff of dye enters into LA during systole
Tricuspid Regurgitation
without opacification of the whole LA.
Grade II: LA becomes faintly opacified after several The tricuspid regurgitation murmur is a pansystolic
heart beats. murmur heard over lower left sternal border, may be
Grade III: Equal opacification of LA and LV. heard over a wider area, sometimes confuses with
Grade IV: Greater opacification of LA than LV. MR murmur. A large ‘v’ wave with rapid ‘y’ descent
Besides severity of MR, LV function (mainly in JVP and the definite inspiratory increase of mur-
end-systolic volume and ejection fraction) are accu- mur indicate TR.
rately estimated from LV angiography.
Ventricular Septal Defect
Diagnosis
The pansystolic murmur of ventricular septal defect
Patients of mild-to-moderate MR are usually asymp- (VSD) when audible up to apex confuses with MR
tomatic. Palpitation and dyspnea on exertion with murmur. Moreover large VSD producing mitral flow
hyperdynamic precordium are common clinical rumble and LV S3 is difficult to differentiate from
presentation. Diminished S1, presence of S3 with an MR. But careful auscultation reveals VSD murmur
apical pansystolic blowing murmur conducted to is mainly prominent over third left sternal border
axilla and also to back are the hallmark of MR. How- (Roger’s area) with a systolic thrill and transmitted
ever, echocardiography confirms the diagnosis and (not conducted) towards apex. The typical ECG pic-
also determines severity of the lesion. ture of VSD (Katz-Wachtel phenomenon) helps to
differentiate from MR. However, echocardiography
well-differentiates these conditions.
Aortic Stenosis Complications

When aortic stenosis murmur is audible over the The common complications are: Atrial fibrillation,
apex, it confuses with MR murmur. But the low vol- Infective endocarditis, Systemic embolism, Pulmo-
ume pulse, forceful and sustained apex, normally nary edema, Hemoptysis and rarely angina pecto-
heard S1, diminished A2, aortic ejection click with ris. All these complications cause serious problems
low pitched rough ejection systolic murmur 3 to 5/6 unless treated judiciously and aggressively.
heard over aortic area conducting to carotids is easily
differentiated from MR. Management
Hypertrophic Obstructive Cardiomyopathy Medical Management

The systolic murmur of hypertropic obstructive Patients of mild-to-moderate MR need no specific
cardiomyopathy (HOCM) may confuse with MR drugs. Routine check-up every year to watch the
murmur of other etiology. But it is a mid-systol- progression of severity (hemodynamic parameters)
ic murmur heard over lower left sternal border of the lesion and penicillin prophylaxis is advised
(not conducted to axilla). It changes its character by in all cases of MR, (even during pregnancy). Infec-
tive endocarditis prophylaxis is also advised as in- Nonsurgical Interventional Management

dicated.
Regular follow-up for onset of symptoms and Recently mitral valve repair and replacement has
echocardiographic assessment of LV function is an been done successfully by percutaneous catheter
important part of medical management to time the based intervention mainly in developed countries.
surgery appropriately, as irreversible LV damage may
occur if surgery is delayed.
Surgical Management
In asymptomatic moderate to severe MR, there
is no definite role of vasodilators. In compensated Indication of Surgery
state the load is normal, when vasodilators are used it Surgery is indicated in all symptomatic patients with
further lowers the after load which may create prob- severe MR. The indications are:
lem for the patient. That is why the role of vasodila- • Those with severe MR and mild-to-moderate LV
tors in compensated state is debatable. But in decom- dysfunction, as measured by echocardiography
pensated stage vasodilators are routinely used and (EF 30–55 percent).
proved to have beneficial effect (reduce cardiac size • In asymptomatic patients with severe MR when
and mass). ejection fraction (EF) < 60 percent (as it indicates
Vasodilators previously used were prazosin, onset of LV dysfunction) and end-systolic dimen-
hydralazine and captopril. Now the newer vasodi- sion (ESD) > 45 mm.
lators used in chronic MR are nifedipine, new gen- • Onset of atrial fibrillation.
eration ACE Inhibitors like enalapril, lisinopril and • Pulmonary arterial pressure > 50 mm Hg at rest
ramipril. However, surgery is preferred over medical and > 60 mm Hg with exercise.
vasodilator therapy once decompensation is noticed. • Effective regurgitant orifice area (EROA) meas-
Beta blockers are preferably used in treatment of ured by echo or MRI > 0.40 cm2 is also taken
non-rheumatic MR secondary to cardiomyopathy or recently as an indication of surgery.
of ischemic origin or in MVP with palpitation and Note: Surgical outcome is poor when EF < 30 percent
chest pain. and ESD > 55 mm.
In setting of severe chronic MR with congestive Surgical treatment by either mitral valve repair
heart failure when surgery is denied (due to irrevers- or replacement (MVR), is the definite management
ible LV damage) or not reachable, medical therapy is of MR. Valve repair is always preferred when feasible.
mandatory to stabilize the patient in an ICU set-up. Rheumatic MR with pliable valve, repair is preferred.
Digoxin, diuretics, vasodilators have definite role for When it is associated with moderate to severe calcifi-
symptomatic relief besides salt and fluid restriction. cation replacement is the only choice. Intraoperative
The main aim of therapy is to reduce LV and LA fill- TEE is routinely used for decision making and sur-
ing pressure and to increase cardiac output. In acute gical evaluation. Even during valve replacement the
MR, IV nitroprusside is used to increase forward sub valvular apparatus is preserved to prevent long-
output and to decrease pulmonary congestion, so the term LV dysfunction (to maintain LV geometry). In
amount of MR is reduced. In spite of inotropic agents rheumatic MR result of valve repair is usually poor
(dopamine, dobutamine) if these patients remain because of fibrosis, calcification and fusion of compo-
in hypotensive stage in some cases intra-aortic bal- nents of mitral apparatus. Metallic prosthetic valves
loon counter pulsation is used to stabilize the patient are usually used because the patients are young and
before surgery. If it is due to infective endocarditis, many have atrial fibrillation where conversion to si-
early identification of organism with suitable antibi- nus rhythm is unlikely due to structural changes in
otics are used as per the recommendations. left atrium. Tissue valves are now increasingly ac-
cepted due to increased durability of such valves and guidelines for the management of patients with val-
concomitant Maze procedure to restore sinus rhythm. vular heart disease. J Am Coll Cardiol. 2006;48:1-148.
Female patients in child bearing age should receive a 2. Borer JS, Bonow RO. Contemporary approach to aor-
tissue valve because of problems with anticoagulation tic and mitral regurgitation. Circulation. 2003;108:
during pregnancy. In general bio-prosthesis valves are 2432-8.
not suitable for young persons because of its limited 3. Enriquez-Sarano M, Tribouilloy C. Quantitation of
durability. With a metallic prosthetic valve oral an- mitral regurgitation: rationale, approach, and interpre-
ticoagulation must continue lifelong to maintain In- tation in clinical practice. Heart. 2002;88 Suppl 4:iv1-3.
ternational Normalised Ratio (INR) of 2.5 to 3.5 by 4. Maurice Enriquez-Sarano, Chronic Mitral Regur-
regularly estimating the prothrombin time. Minimal- gitation, Valvular Heart Disease, 3rd edn, Ed Joshep
ly invasive surgical techniques are less traumatic and S Alpert, Lippincott Williams and Wilkins.
can be used for mitral valve repair or replacement. 5. Navin C Nanda. Echocardiographic Assessment of
Note: Valvular Lesions-A Practical Approach, Cardiology
• MVR should not be advised early neither should Update, CSI, 2002, Editor OS Gambhir.
be delayed. Prosthetic valve implantation should 6. Otsuji Y, Handschumacher MD, Schwammenthal E,
be delayed as much as possible but not at the cost et al. Insights from three-dimensional echocardiogra-
of irreversible LV damage. phy into the mechanism of functional mitral regurgi-
• Mitral valve repair when feasible should always be tation: direct in vivo demonstration of altered leaflet
preferred over mitral valve replacement. tethering geometry. Circulation. 1997;96:1999-2008.
• In acute MR early surgery is life saving. 7. Otto CM. Evaluation and management of chronic
To conclude medical management particularly to mitral regurgitation. N Engl J Med. 2001;345:740-6.
decide the right time for surgery for MR, no doubt 8. Otto CM, Salerno CT. Timing of surgery in asympto-
possess a problem for treating physicians. Similarly matic mitral regurgitation. N Engl J Med. 2005;352:928-9.
the surgical options between valve repair and valve 9. Rosenhek R, Rader F, Klaar U, et al. Outcome of
replacement, possess a dilemma for the surgeon. watchful waiting in asymptomatic severe mitral
regurgitation. Circulation. 2006;113:2238-44.
10. Soumitra Kumar, et al. Management of Valvular
further reading Heart Disease, Current Trends in Cardiology, 2nd
1. Bonow RO, Carabello BA, Chatterjee K, de Leon edn, 2006. Editors Soumitra Kumar, Ramkrishna
AC Jr, Faxon DP, Freed MD, et al. ACC/AHA 2006 Mission Seva Pratisthan, Kolkata.
CHAPTER 12
Rheumatic Aortic Stenosis
Santanu Guha, M Satpathy
Definition Note: Juvenile Rheumatic AS is not reported (ex-

When the obstruction to the blood flow occurs at the tremely rare); where as juvenile MS is very common.
level of left ventricular outflow tract in systole the
clinical condition is known as aortic stenosis (AS).
Anatomy of the Aortic Valve
Such obstruction may occur at different levels like
just below the aortic valve (subvalvular/subaortic), at The semilunar valves (aortic and pulmonary valves)
the aortic valve (valvular) and above the aortic valve are derived from truncus arteriosus and also from
(supravalvular). Rheumatic AS produces obstruction truncal and intercalated valve cushions.
at valvular level only following rheumatic aortic val- The aortic valve consists of the following compo-
vulitis. nents (Figs 12.1A to C).
1. The annulus: It is a fibrous ring strongly anchored to
Incidence and Prevalence the fibro-skeleton of the heart. The circumference is
7 to 9 cm and the area of the annulus is 2.4 to 4 cm2.
Incidence of AS has greatly changed in the last five 2. Aortic valve has three cusps (leaflets) of nearly
decades due to dramatic decline of rheumatic fe- equal size, two anterior (right and left coronary)
ver in developed countries. The rheumatic isolated and one posterior (noncoronary). The cusps are
aortic stenosis has become uncommon, at the same half-moon shaped, therefore known as semilunar
time in consequent to increased longevity; the inci- and they are avascular. Normal cusp separation is
dence of degenerative aortic valve (aortic sclerosis) 15 to 26 mm.
disease has increased. Advent of echocardiography Unlike mitral valve, aortic valve have no chordae
also contributed to increased identification of aortic nor have papillary muscle attached to it. They have
valve (degenerative and bicuspid) disease. However, three equal spaced commissures and three sinuses of
in the developing countries the incidence of isolat- Valsalva (two anterior and one posterior).
ed rheumatic aortic stenosis varies widely. Sepaha
GC et al reported lone AS in 21.7 percent of cases Etiology
(Ind HJ, 1965;17:276-81), Somani OT et al reported
dominant AS with mild MR in 15.3 percent (Ind Causes of valvular aortic stenosis:
HJ, 1965;17:282-5). But under echocardiographic
evaluation the incidence of dominant AS with mild Common Causes
AR is 5.9 percent of cases (Adarsh Kumar, Ind HJ,
2009;61:14-23). Males outnumber females with ratio • Rheumatic, in young adults particularly in India
of 4:1. and other developing countries.
Rheumatic Aortic Stenosis 85
A B C
Figs 12.1A to C: Schematic presentation of anatomy of aortic valve in diastole. (A) Longitudinal cross sectional view;
(B) Unfolded view showing each cusp; (C) Transverse cross sectional view. Abbreviations: Ao—Aorta; RCC—Right coronary
cusp; NCC—Noncoronary cusp; LCC—Left coronary cusp; LV—Left ventricle; AML—Anterior mitral leaflet
• Congenital bicuspid valve in all age groups present vascularization of the leaflets and the valve ring.
worldwide. Subsequently, there is retraction and stiffening of the
• Degenerative (calcific) valves: Seen in both bicus- free border of the cusps. Calcific nodules may form on
pid and tricuspid valve in elderly age (by process both aspects of the valve. The aortic orifice is reduced
of wear and tear phenomenon). to a small rounded or triangular opening. Because
of this unique pathology the rheumatic aortic valve
very often behave as both stenotic and regurgitant
Less Common Causes lesions (there is loss of integrity and proper closure).
Congenital AS with unicuspid/unicommissural valve. In contrast calcific aortic stenosis affecting the elderly
there is absolutely no commissural fusion and no
puckering of the leaflet, hence the integrity of valve
Uncommon Causes closure unusually remain intact (so there is less
Infective endocarditis (obstructing vegetation), radia- regurgitation).
tion (due to secondary trauma), rheumatoid arthritis, The thick, rigid and distorted leaflets give rise to
Paget’s disease, systemic lupus erythematosus (after secondary calcification. Rheumatic aortic stenosis
steroid therapy) and atherosclerotic aortic stenosis is results from both commissural fusion yielding the
seen due to familial hypercholesterolemia. fibrous type of stenosis and also from calcification of
Remember: Subvalvular and supravalvular aortic ste- the valve leaflet.
nosis are never of rheumatic origin. Note: Commissural fusion is the main cause of rheu-
matic AS.
The aorta and the coronary arteries are not af-
Pathology fected by rheumatic process. Left ventricular (LV)
The normal aortic valve orifice is triangular in systole hypertrophy occurs due to obstruction of LV outflow.
with full excursion of leaflets that remain parallel to
the aortic wall. Fibrous scar tissue develop following
Pathophysiology
healing of rheumatic aortic valvulitis which cause
fusion of cusps at their commissures and subsequently The fundamental hemodynamic features is the pres-
give rise to obstruction at the aortic valve level sure overload on LV cavity due to resistance to the
(clinically known as valvular AS). There occurs blood flow at the aortic orifice (due to narrowing of
Fig. 12.2: Pressure tracing of aorta and LV in a normal individual and in aortic stenosis along with
schematic presentation of clinical findings. Abbreviations: S1—First heart sound; S2—Second heart
sound; EC—Ejection click; ESM—Ejection systolic murmur
aortic valve). The aortic orifice area is normally 2 to tribution to the stroke volume in case of AS. Hemo-
3 cm2 and reduction of this orifice area leads to in- dynamic instability occurs in setting of severe AS
crease left ventricular systolic pressure to maintain when atrial fibrillation sets in (atrial support is lost).
forward cardiac output. In other words as the orifice A sustained pressure overload on the myocardium in
size decreases gradually the LV cavity systolic pres- chronic AS eventually results in depression of the con-
sure increases progressively, which leads to increased tractile properties of the myocardium. With declining
pressure gradient across aortic valve (Fig. 12.2). Left contractility the adaptive mechanism of hypertrophy
ventricular hypertrophy is a key adaptive mechanism are ultimately lost to maintain the normal stroke vol-
to the pressure overload in severe AS. The presence of ume. The amount of hypertrophy no more match to
chronic pressure overload typically causes concentric the severity of stenosis (afterload mismatch), as LV
LV hypertrophy that is increased wall thickness with systolic function begin to detoriate, it begins to dilate.
normal chamber size. The benefit of this concentric It is observed that there is a definite gender in-
hypertrophy is that it allows normalization of the LV fluence over LV cavity hypertrophy and LV mass.
wall stress (which is a form of afterload) and helps in With same hemodynamic parameters females fre-
maintaining a normal LV output. The LV hypertrophy quently develop more concentric hypertrophy with
maintains a constant relationship with the increased minimal dilatation and normal wall stress but in con-
pressure. However, this occurs at the cost of increased trast males respond with eccentric hypertrophy with
diastolic stiffness. Because of hypertrophy there occurs chamber dilatation and increased wall stress.
reduced compliance which prevents adequate filling of The hypertrophied LV muscle needs more of cor-
LV under normal pressure. Diastolic dysfunction oc- onary supply (increased demand) but in AS there is
cur as a result of the increased LV muscle mass and reduced coronary perfusion pressure (reduced pres-
interstitial fibrosis that act in concert to impaired stiff- sure gradient between aortic diastolic and LV dias-
ness. This diastolic dysfunction may remain even after tolic pressure (LVEDP increased). Therefore, there
correction of stenotic lesion. In this situation LV needs is reduced coronary flow (decreased supply). This is
atrial support (atrial kick) for adequate filling in late why angina pain is more common in severe AS with
diastole. In fact atrial systole makes a significant con- normal coronaries; because of imbalance in blood
flow between myocardial supply and demand (de-

mand to supply mismatch).
Clinical Manifestations A B
Figs 12.3A and B: Carotid pulse tracing. (A) Normal; (B)
Symptoms Slow rising upstroke of severe aortic stenosis. (Arrow) indi-
Patients of aortic stenosis (AS) may remain asymp- cates anacrotic notch
tomatic for a long period. Breathlessness on ac-
customed exertion is the earliest symptom. With known as pulsus parvus et tardus (Figs 12.3A and B).
physical exertion patients may complain of reeling It is due to prolonged ventricular systole. Sometimes
of head or dizziness (graying out) or syncopal at- bisferiens (double peak pulse) is palpable. Bisferiens
tack. Cardiac syncope occurs due to transient ar- pulse is mainly seen in setting of combined AS and
rhythmia or fixed cardiac output (cardiac output AR of equal dominance. In advanced cases the pulse
cannot increase sufficiently during exercise). Angina volume decreases due to low systolic pressure and
pain frequently occurs with exertion in severe AS. It decreased pulse pressure. The anacrotic notch in the
is due to increased myocardial oxygen demand be- carotid artery becomes prominent with systolic vibra-
cause of hypertrophied muscle mass and decreased tion known as carotid shudder. In JVP ‘a’ wave may be
subendocardial blood supply even with normal prominent due to forceful right atrial contraction. It
coronary arteries. Some asymptomatic patients with happens when a hypertrophied interventricular sep-
severe AS may present with sudden onset of fati- tum encroaches upon RV cavity impending its filling
gability, cough with expectoration, dyspnea at rest (Bernheim effect). Uncorrected severe AS in late stage
leading to orthopnea and pulmonary edema (main present with raised JVP indicating right heart failure.
symptoms of LVF). Dyspnea, chest pain (angina) and Apex beat is forceful and sustained but not
syncope or presyncope are cardinal symptoms of se- displaced till late stage. With onset of LV decom-
vere AS. In very late stage patients of severe AS pre- pensation, LV dilates and the apex beat is displaced
sent with congestive heart failure because of severe downward and outward. Rarely left ventricular S4
pulmonary hypertension leading to RV failure and may be palpable due to hypertrophied and stiff LV
systemic venous congestion. (precordial ‘a’ wave that is forceful left atrial con-
Uncommon presenting symptoms are: traction). In hemodynamically significant stenosis a
• Infective endocarditis: (pyrexia of unknown ori- systolic thrill is usually present over aortic and over
gin), sometimes asymptomatic patients may pre- second aortic area. It is conducted to the carotids.
sent with continued fever and sudden onset of S1 is normal. A2 (aortic valve closure sound) is
LVF. On routine examination AS is detected. delayed and its intensity is decreased (indicate signi
• Embolization: (not due to infective endocarditis). ficant gradient). P2 on rare occasion may be loud due
Patients may present with neurological symptoms to pulmonary arterial hypertension. Prolongation
due to thrombotic micro-embolization in the brain. of left ventricular ejection delays A2, therefore there
Embolization may be the first presentation in AS. is a close splitting of S2. There may be paradoxical
• GI bleeding: Patients present with melena or spliting of S2, when LV systolic function is decreased
hematemesis due to associated arteriovenous mal- which leads to further prolongation of LV ejection.
formation particularly in nonrheumatic AS. LV S4 is audible in severe AS due to strong left atrial
contraction. LV S3 is a late finding that indicates left
ventricular failure. Aortic ejection click (EC) is rarely
Signs
audible because valve mobility is decreased but it is
The characteristic pulse of moderate to severe aortic commonly heard in case of congenital valvular AS.
stenosis is a low volume, slow rising (plateau) pulse, If EC present it is audible over left sternal border. But
unlike pulmonary EC, does not vary with respiration. of the murmur indicate onset of low cardiac output
The characteristic murmur of AS is a low pitched, state and/or heart failure.
rough crescendo decrescendo mid systolic rasping
murmur heard over the aortic area and conducted Investigations
to the carotids. Duration of the murmur is directly
proportional to severity. The high frequency compo- Electrocardiogram
nents of this murmur are sometimes selectively con- The salient features are:
ducted to the apical area with a relatively silent area • Sinus rhythm is usually present.
in-between called Gallavardin phenomenon (more • Atrial fibrillation indicates associated mitral valve
common in calcific AS). Note: Decreased intensity lesion.
Fig. 12.4: ECG showing left ventricular hypertrophy with strain pattern in severe AS
• Left atrial enlargement and left ventricular hyper- Table 12.1: Showing parameters to judge the
severity of AS
trophy with strain pattern (down sloping ST depres-
sion and asymmetrical T inversion) are characteris- Mild Moderate Severe
tic features of severe AS (Fig. 12.4). Jet velocity (m/s) <3 3.0–4.0 >4.0
• Various types of AV block sometimes present due Mean gradient (mm Hg) <25 25–40 >40
to extension of the calcific process into the con- Valve area (cm2) >1.5 1.0–1.5 <1.0
ducting tissue. In infective endocarditis AV blocks
may be seen due to extension of infection into the
conducting tissue. ity is determined. From velocity, peak instantaneous
gradient is obtained by using modified Bernoulli’s
formula. By planimetry of the spectrum, mean gra-
Roentgenography
dient is calculated (Fig. 12.6C). The peak and mean
The salient features in chest X-ray are: gradient are very accurate parameters in assigning
• In most of the cases cardiac size is within normal severity of AS (Table 12.1). In some cases good aor-
limit. tic flow spectrum is obtained from right parasternal
• Rounding of left cardiac border and apex with- window. In low cardiac output state gradient across
out cardiomegaly (concentric LVH) and ascend- aortic valve may be falsely low. In such cases aortic
ing aortic dilatation strongly favors valvular aor- valve area determination using principle of conti-
tic stenosis (Fig. 12.5), cardiomegaly indicates LV nuity equation may be more accurate. At times in
decompensation. these cases of low output state, infusion of inotrope
• Valvular calcification is better visualized on like dobutamine may reveal severe AS by increasing
fluoroscopy or echocardiography rather than in aortic gradient. Pulsed wave (PW) Doppler of mitral
plain chest X-ray. inflow and tissue Doppler of mitral annulus helps
• Pulmonary venous hypertension with prominent in determining diastolic function of the hypertro-
upper lobe veins are seen in both diastolic and phied LV. Transesophageal echocardiography (TEE)
systolic dysfunction. is helpful to visualize the aortic valve anatomy in a
better way and also for measuring the valve area. TEE
Echocardiography is mainly helpful during surgery and in perioperative
management.
2D echo combined with Doppler interrogation is Note: One should be very careful while pressure gra-
highly accurate in identifying and assessing the sever- dient and derived valve area are calculated from LV
ity of AS. Number of valve cusps, thickening, calcifica- outflow tract area and velocity; otherwise the severity
tion and mobility of the valve are apparent on 2D echo. may be either over or under estimated.
A stenotic valve characteristically domes in systole
(Fig. 12.6A). Aortic stenosis developing over trileaflet
valve or associated with other valvular lesions indicate
Angiocardiography
rheumatic origin (mitral valve lesion is very often as-
sociated). Concentric hypertrophy of left ventricle is a Cardiac catheterization is mainly done to know
feature of significant AS. 2D echo also determines left coronary anatomy prior to surgery. By cardiac cath-
ventricular systolic function accurately. eterization, simultaneous pressure recordings are
Color Doppler guided CW Doppler interroga- obtained from LV and aorta by putting catheters
tion of LV outflow in apical 5 chamber view obtains on either side of aortic valve. From pressure trac-
the aortic flow spectrum from which peak veloc- ings peak to peak and mean gradients are obtained
Table 12.2: Differentiating features of rheumatic

AS from congenital AS
Parameters Rheumatic AS Congenital AS
(tricuspid) (bicuspid)
History of Present Absent
rheumatic fever
Age group Adolescent to Infant to
young adults young adults
Syncope Present (even Elderly age
younger age) group
Angina pain Present (even Elderly age
younger age) group
Heart sounds—A2 Normally heard Diminished
Ejection click Rare Common
(Aortic)
Ejection systolic Rough ESM ESM rough
Fig. 12.5: Chest X-ray in a case of AS showing post-sten-
murmur (ESM) with or without
otic dilatation of aorta (open arrow) and LV contour (close
musical tinge
arrow)
Associated lesions Multivalvular With AR and
(AR and/or MR) coarctation of
(Fig. 12.2). Cardiac output is determined using Fick’s aorta
principle or thermodilution method. From flow data
Chest X-ray Poststenotic Ascending aorta
and gradient values, aortic valve area is determined dilated aorta dilated
by Gorlin’s formula. calcification less calcification
common common
Diagnosis Echo Trileaflet, Bicuspid, other
thickened valves normal,
Patients of young adult age group with past history and domed, aortic valve
of rheumatic fever when present with symptoms of concentric LVH, calcification
angina, syncope or dyspnea on effort aortic stenosis calcification of present
is suspected. On examination main clinical features leaflets
of rheumatic AS are low volume and slow rising pulse Cardiac Usually central Mainly eccentric
with slow carotid upstroke, systolic thrill over aortic catheterization jet jet
area, normal or decreased S2 with closed or paradoxi-
cal splitting, presence of LV S4 and rough ejection
systolic murmur grade 3 to 5/6 over aortic area con-
ducted to carotids.
However echo evidence of thickened trileaflet The clinical conditions having basal systolic mur-
aortic valve with doming (often associated with mi- mur prima facie create confusion with diagnosis of
tral valve lesion) and Doppler indicating a gradient AS. The common conditions are: (1) Functional ba-
across AV valve give a definite diagnosis of AS of sal murmur, (2) Ventricular septal defect (VSD, Su-
rheumatic origin (Figs 12.6A to C). pracristal type), (3) Valvular pulmonary stenosis. (4)
Differentiating features of rheumatic As from con- Coarctation of aorta, (5) Hypertrophic obstructive
genital AS as given in Table 12.2. cardiomyopathy (HOCM/HCM).
A B
Figs 12.6A to C: Echocardiography in severe aortic stenosis. (A) Parasternal long axis view showing thickened, domed
aortic valve in systole (arrows), note associated mitral valve involvement and concentric left ventricular hypertrophy; (B)
Short axis view showing trileaflet valve (rheumatic) in AS; (C) CW Doppler spectrum in severe AS showing high velocity,
high gradient flow. Abbreviations: LA—Left atrium; LV—Left ventricle
Functional Murmur to look for onset of symptom like dizziness, near syn-
cope, dyspnea and angina pain on accustomed exer-
Innocent basal ejection murmurs of aortic origin are tion. Patients with severe AS should avoid physical
mid systolic in nature. When associated with high exertion.
cardiac output conditions particularly in young per- In asymptomatic patients echocardiographic re-
sons and in elderly associated with atherosclerosis, it evaluation should be done annually for severe AS,
is difficult to differentiate from valvular aortic steno- every 1 to 2 years for moderate AS, and every 3 to
sis. However, conditions giving rise to high volume 5 years for mild AS. Any change in signs and symp-
pulse (low volume pulse in AS), high pulse pressure toms need immediate re-evaluation. Exercise testing
(low pulse pressure in AS) and normal heart sounds may be necessary in some asymptomatic individuals
(but diminished A2 in AS) besides presence of ejec- to detect covert symptoms, limited exercise capacity
tion systolic murmur (not rough) over aortic area are or abnormal BP response. Exercise testing is abso-
differentiating features from organic AS. lutely contraindicated in symptomatic individuals.
Prophylaxis against infective endocarditis is in-
Ventricular Septal Defect dicated for all patients. Rheumatic fever prophylaxis
is also advised to all patients having lone or com-
When the supracristal ventricular septal defect bined lesions. Once patients are symptomatic needs
(VSD) murmur is heard over left and right upper surgery. Patients of moderate to severe AS having
parasternal border, confuse with AS. But the hyper- angina pain or signs of congestive heart failure should
dynamic precordium, pansystolic murmur (not ESM be treated with conventional antianginal and anti
of AS) associated with thrill over left upper paraster- failure drugs for symptomatic relief before subject-
nal border with typical ECG changes (Katz Watchtel ing for surgery. Cases who cannot afford for surgery
phenomena) in case of VSD make no mistake to dif- or in some cases when surgery is denied they remain
ferentiate from AS. 2D echo with Doppler confirms under conservative management. However, vasodila-
the diagnosis. tors like ACE inhibitors, calcium channel blockers,
nitrates and negative inotropes like beta blockers are
Hypertrophic Obstructive Cardiomyopathy used with caution. Though diuretics may be helpful
in relieving fluid retention, caution needs to be taken
Ejection systolic murmur heard over apex, left ster- to avoid hypovolemia which may reduce end dias-
nal border and over aortic area mainly in adult pa- tolic pressure (pre-load), cardiac output, and cause
tients confuse with aortic stenosis. But positive family postural hypotension. In case of persistent low BP
history (sudden death), double apical impulse, brisk pressure amines (dopamine, dobutamine) are used
carotid upstroke, presence of loud S4 and the systolic for a short period and if there is no response they
murmur which changes its character on dynamic aus- are advised for intra-aortic balloon counter pulsation
cultation (on standing murmur increases and with as a bridge to surgery. When arrhythmias develop
squatting it decreases) go in strong favor of hyper- treatment with antiarrhythmic drugs (Class Ic and
trophic obstructive cardiomyopathy (HOCM). How- III) are advised and if indicated (onset of VF/VT)
ever it is echocardiography gives the final diagnosis. cardioversion/defibrillation with all precautionary
measures are also applied. Medical management is of
Management not much help, however symptomatic patients with
LV dysfunction who are not candidates for surgery
are to follow the above regime. Till now no medi-
Medical Management
cal therapy available to prevent progression of aor-
Asymptomatic patients should be followed-up at reg- tic valve disease. Recently role of statins (HMG CoA
ular intervals and should seek close medical advice inhibitors) in slowing progression of calcific AS has
been demonstrated, but its role in rheumatic AS is tive heart failure or pulmonary edema, where imme-
not yet proved. diate surgery is denied.
Symptomatic patients with severe AS have to be Percutaneous aortic valve replacement (AVR) is
treated surgically with valve replacement as medical a new treatment being adopted for selected patients
therapy has very little to offer. Palliative therapy with with severe aortic stenosis and the procedure is per-
balloon valvotomy is reserved for inoperable patients formed in the cardiac catheterization laboratory.
with comorbidities that preclude surgery, in severe The first nonsurgical implantation of a bioprosthetic
congestive heart failure as a bridge to surgery. heart valve was performed by Cribier in April, 2002
on a patient in inoperable aortic stenosis with life
threatening comorbidities. It is a very recent pro-
Nonsurgical Interventional Management
cedure nowadays gaining popularity. In European
A new era in the field of percutaneous valvular inter- countries registry of endo-vascular implantation of
vention is heading to be the treatment of choice in set- valves in Europe (I-REVIVE) has started.
ting of severe AS, (like in cases of mitral stenosis) and
it is gaining gradually popularity. The procedures are: Surgical Procedure
1. Balloon aortic valvuloplasty (BAV)
2. Percutaneous aortic valve replacement. Indications for aortic valve replacement (AVR) are:
First successful balloon aortic valvuloplasty was 1. All symptomatic patients with moderate to severe
done in 1984 by Lababidi and co-workers and in AS.
India it started as early as in 1996. Patients having 2. Patients with LV dysfunction (low gradient AS).
severe bicuspid aortic valve stenosis belonging to the 3. Asymptomatic patients in whom surgery is indi-
age group infancy to childhood and some cases of cated are:
degenerative severe aortic stenosis (with mild calci- (a) Severe AS with LV dysfunction at rest or an
fication) of elderly age group were subjected to BAV. abnormal response to exercise is noted
The indications for BAV are: (b) Marked LV hypertrophy (LV free wall more
1. Symptoms of angina, syncope and dyspnea with than 15 mm in diastole)
catheter peak to peak gradient more than 50 mm (c) Valve area less than 0.6 cm2
Hg. (d) Severe AS with undergoing coronary artery
2. Peak instantaneous gradient more than 60 mm Hg surgery or other valve surgery.
(by Doppler). When the left ventricular ejection fraction
3. New ECG changes like signs of ischemia over pre- (LVEF) is less than 35 percent the surgical risk is very
vious ECG. high. However, prognosis is extremely poor without
Recently some reports of BAV in severe aortic operation. But in these cases overall survival is im-
stenosis of rheumatic origin are reported from In- proved with AVR.
dia and other developing countries. BAV also been
tried successfully in cases of pregnancy with severe
Open Commissurotomy or Valvuloplasty
aortic stenosis like cases of balloon mitral valvotomy
(BMV). Because of problems of restenosis BAV grad- From 1952 modern aortic dilator was used, to cor-
ually losing its importance in western countries, this rect aortic stenosis by commissurotomy procedure.
procedure is going to be replaced by percutaneous Subsequently a reasonably satisfactory transven-
heart valve (PHV) implantation. tricular approach to the aortic valve was available.
Remember: BAV is used just as a bridge to sur- This open commissurotomy is a choice for limited
gery in patients of severe aortic stenosis with conges- cases of severe AS having noncalcific stenosis. How-
ever, aortic valve replacement (AVR) is the main poor socioeconomic status. Most of these patients
modality of surgery. cannot afford for surgery and completely live on
medical advice.
Aortic Valve Replacement
Aortic valve replacement (AVR) nowadays done further reading
with different artificial valves like metallic pros- 1. Bonow RO, Carabello BA, Chatterjee K, de Leon AC
thetic valves, human (homograft) or porcine (xen- Jr, Faxon DP, Freed MD, et al. ACC/AHA 2006 guide-
ograft) tissue valves. There are more than 40 types lines for the management of patients with valvular
of prosthetic valves but the main prosthetic valves heart disease. J Am Coll Cardiol. 2006;48:1-148.
are caged-ball, central disk, tilting-disk and twin 2. Carabello BA. Clinical practice: aortic stenosis. N
disk valves. The tissue valves are mainly indicated Engl J Med. 2002;346:677-82.
in elderly patients but they have their own limita- 3. David M, Shavelle and Catherine M. Otto, Aortic
tions because of early dysfunction of tissue failure Stenosis, Cardiology 3rd edn, Micael H Crawford,
occurs. However to delay this dysfunction nowa- Churchill Livingstone, Elsevier.
days glutaraldehyde preserved porcine valves are 4. Gilbert E Levinson, Joseph S Alpert, Aortic Stenosis,
used. The advantage of tissue valve is anticoagu- Valvular Heart Disease, 3rd edn, (Eds) Joseph S
lation is not needed. Permanent anticoagulation Alpert, Lippincott Williams and Wilkins.
therapy is mandatory for patients having metallic 5. Hurst’s The Heart, 8th edition, McGraw-Hill, Inc.
prosthetic valves. Routine prothrombin time test 6. Paul Wood’s Diseases of the Heart and Circulation,
for rest of the life is advised and international nor- 3rd edn, Eyre and Spottiswoode Ltd. 1968.
malized ratio (INR) has to be maintained within 7. Soumitra Kumar, et al. Management of Valvular
2.5 to 3.5. Heart Disease, Current Trends in Cardiology, 2nd
To conclude about 90 percent of patients of edn, (Eds) Soumitra Kumar, Ramkrishna Mission
rheumatic aortic stenosis are adults and belong to Seva Pratisthan, Kolkata, 2006.
CHAPTER 13
Aortic Regurgitation
BR Mishra
Definition common cause of AR (isolated or in combination

When blood from aorta leaks back (regurgitate) to with other valvular lesions) in developing countries.
the left ventricle (LV) in diastole the clinical condi- But in elderly degenerative cause predominates all
tion is known as aortic regurgitation (AR) or aortic over the globe.
incompetence. In this situation either the valve leaf- Less common causes: Infective endocarditis may
lets or the wall of the aortic root or both are incom- cause AR both in native valve and in prosthetic valve.
petent to hold back the blood in the aorta. Prosthetic valves may have valvular or paravalvular
leak.
Incidence Uncommon causes (nonrheumatic origin): Rheu-
matoid arthritis, Aortic root diseases—Ankylosing
The incidence of rheumatic aortic valve lesions comes spondylitis, Marfan’s syndrome, Whipple’s disease,
next to mitral valve lesions. Isolated AR of rheumatic Syphilitic aortitis, Idiopathic dilatation of aorta, Dis-
origin is not uncommon in developing countries, but secting aortic aneurysm, Behcet’s syndrome, Psoriatic
AR associated with mitral valve lesions are often seen arthritis, giant cell arteritis, Osteogenesis imperfecta,
in clinical practice. Incidence of lone AR under echo- Reactive arthritis, Systemic Lupus Erythematosus,
cardiographic evaluation was reported in 6.7 percent Jaccoud’s arthritis, Takayasu’s disease.
(AN Patnaik, NIMS, 2002) and in 9.7 percent of cases Acute AR: When AR develops suddenly it is known
(Adarsh Kumar et al. Ind H J, 2009;61:14–23) in two as acute AR. The common causes are acute rheu-
different series. The incidence of combined lesions matic fever and infective endocarditis, the uncom-
like AR with MR or AR with MS are more than lone mon causes are dissecting aortic aneurysm, rupture
AR. of sinus of Valsalva aneurysm to LV outflow tract,
Postoperative aortic prosthetic valve surgery, balloon
valvoplasty and trauma.
Etiology
1. Acquired Pathology
2. Congenital.
In rheumatic fever, AR is produced due to aortic val-
vulitis which heals by fibrosis and subsequently con-
Acquired Causes
tracture of the margins of the cusps makes it shorter.
Common causes: Rheumatic heart disease (RHD) This process affects all the three cusps with different
and degenerative aortic valve disease (with or with- degrees of severity, and is the cause of malalignment
out calcification) are responsible for AR in about 80 of cusps that produce AR. The contracture of leaflets
percent of cases. In younger patients RHD is the most is associated with fusion of two or three commissures
which results in both aortic regurgitation and aortic response becomes inadequate. The LV hypertrophy
stenosis where either of the lesions may be dominant. does not match with increasing volume, the mass to
volume ratio decreases and the left ventricle fails to
Pathophysiology generate sufficient force in systole to meet the meta-
bolic needs (afterload mismatch). This results in in-
Aortic regurgitation (AR) is a type of volume over- crease of end-diastolic pressure of LV which leads to
load lesion of the LV, which receives extra amount increase in mean LA pressure and pulmonary ve-
of blood through the regurgitant aortic valve in ad- nous congestion producing symptoms like dyspnea.
dition to its normal diastolic flow from left atrium. As the disease progresses gradually LV systolic func-
The increased diastolic volume has to pass tion worsens. The LV end-diastolic volume further
through the aortic valve that requires more wall increases, the ejection fraction and forward stroke
stress in systole (increased afterload). Thus in AR volume both are decreased. Initially this may be re-
the volume overload is also combined with pressure versible if aortic valve is replaced earlier, but if AR
overload. This volume and pressure overload act as remains uncorrected irreversible damage to the con-
a mechanical stimulation for gene expression that tractile elements occur and LV function does not
result in remodeling by changing the size, volume recover even if aortic valve replacement (AVR) is
and shape of contractile elements and extracellular done. The compensatory mechanism also involves
matrix of LV cavity. The components of myocardium the arterial system by increased elastance, so that it
such as the myocytes with its sarcomeres containing can handle large amount of cardiac output and keep
contractile protein, the fibroblasts, and the collagen the patient asymptomatic for a long period.
in the extracellular matrix all change their property
of cellular synthesis, degradation and geometry in
Hemodynamics of Acute Aortic Regurgitation
order to maintain sufficient cardiac output in face
of a normal or near normal end diastolic pressure. In acute AR, the volume overload occurs with nor-
Recent research has shed light in the understanding mal LV size, because it gives no time for LV dilata-
of expression, transcription and translation of gene tion, moreover pericardium provides some resist-
coding for specific components of myocardium and ance against LV dilatation. This leads to increased
the molecular basis of pathophysiology of AR. There left ventricular end-diastolic pressure (LVEDP) with
occurs dilatation of LV with increased wall thickness minimal or no LV dilatation and decrease in aor-
by addition of new sarcomeres (eccentric hypertro- tic pressure and forward stroke volume. Increased
phy) so that the extra volume is accommodated with- LVEDP leads to increased mean left atrial (LA) pres-
out increase in end-diastolic pressure and at the same sure which is reflected in increased pulmonary ve-
time sufficient force is generated in systole to pump nous and pulmonary capillary pressure producing
the extra volume. In other words the mass volume acute pulmonary edema. In this setting diastolic mi-
ratio is maintained. tral regurgitation is produced due to significant rise
As the disease progresses the volume and wall of LV end-diastolic pressure which forces the mitral
thickness accordingly increase to maintain a suffi- valve to close in diastole. Figure 13.1 summarizes the
cient forward output without increase in end-dias- hemodynamics of AR.
tolic pressure. This compensation allows long sur-
vival without symptom even for decades in severe
Clinical Manifestations
AR. During exercise peripheral vasodilatation and
tachycardia occurs which decrease amount of AR.
Symptoms
At the same time increased forward cardiac output
during exercise results in good exercise tolerance. Most of the patients of mild-or-moderate AR
But with increasing AR, gradually the compensatory remain asymptomatic for pretty long-time because
Aortic Regurgitation 97
iastolic period thereby increases aortic run off and

d
decreases coronary circulation causing anginal pain.
In some cases in late stages dizziness or syncopal
attacks occur due to low cardiac output because of
systolic dysfunction or due to transient arrhythmias.
Some cases present with unexplained continued fe-
ver which may be the first presentation of AR (due to
infective endocarditis).
Fig. 13.1: LV pressure volume curve. The x-axis represents Signs

LV end-diastolic volume and y-axis represents LV end-
diastolic pressure. On left shows normal curve, after a limit Clinical examination can almost accurately estimate
small increase in volume produces a sharp increase in pres- the severity of AR by a careful assessment of periph-
sure (the ascending part of the curve). Acute AR represents eral and cardiac findings. The precordial movement
the ascending part of the curve. Right curve is in chronic
AR, flat portion represents compensated state, large vol-
is normally felt in mild AR, but in moderate to severe
ume with no or minimal increase in pressure. Here the AR it is hyperdynamic (even visible). In chronic se-
ascending portion represents decompensated state, sharp vere AR, apex is out and down, and forceful in nature.
increase in pressure with minimal increase of volume Measurement of blood pressure in both upper
and lower limbs gives valuable information about se-
verity of AR. In AR the difference between brachial
of effective compensatory mechanism. Symptoms and popliteal systolic blood pressure is more than
like palpitation and prominent precordial pulsation 20 mm Hg (normal difference is maximum up to 20
(more on exertion) are early symptoms. Awareness mm Hg). When the difference is 20 to 40 mm Hg it
of the heart beat and head nodding in chronic severe matches with angiographic 2+ AR (mild AR), dif-
AR are also presenting features. Physical exertion or ference of 40 to 60 mm Hg with 3+ AR (moderate
emotional stress leads to undue tachycardia which AR) and above 60 mm Hg with 4+ AR (severe AR).
cause pounding of head and troublesome palpitation Difference of >60 mm Hg is known as Hill's sign.
(due to large stroke volume). Flushing, sweating, and Remember:- Korotkoff sounds may be audible down
non-specific chest pain do occur in some cases. Some to 10 or up to 0 in severe AR, but does not indicate
patients complain of neck pain (due to stretching of true diastolic pressure, it is the muffling point of the
carotid arteries) and abdominal pain (due to stretch- Korotkoff sound that indicate diastolic pressure. In
ing of abdominal aorta or splanchnic ischemia). Ex- younger persons diastolic pressure more than 70 mm
ertional dyspnea is the earliest symptom of LV de- Hg excludes severe AR.
compensation and gradually PND and orthopnea Note: In patients of severe AR pulse pressure is wide.
appear in due course of time. Angina pectoris is an Systolic pressure may go up to 150 mm Hg. If systolic
uncommon symptom, develops in late stage of se- BP is more than 180 mm Hg, it indicates associated
vere AR. Low aortic diastolic pressure reduce coro- systemic hypertension. Similarly in elderly persons if
nary blood flow compromising oxygen supply to the diastolic pressure is 70 mm Hg or above, severe AR
hypertrophied myocardium (because of mismatch cannot be ruled out (because there may be severe LV
of supply and demand of coronary circulation with- dysfunction or associated systemic hypertension).
out coronary artery disease). History of repeated
nocturnal angina (associated with precordial pain,
Peripheral Signs
orthopnea, tachycardia, abnormal sweating and epi-
gastric pain) is an ominous sign which occurs due to • Water hammer pulse (Collapsing pulse or Corrigan’s
slow heart rate during sleep. Bradycardia increases pulse or pulsus cellar)—The peripheral pulse
(brachial or radial) has a rapid rise or sharp • Landolfi’s sign—Contraction and dilatation of
upstroke followed by a quick fall (abrupt rise pupil with each heart beat (systolic and diastolic
and fall). Water hammer pulse was named after pulsation).
a Victorian age toy of 18th century by Thomas • Gerhardt's sign—When splenic pulsation is
Watson. It is due to reflex vasodilatation of carotid palpable.
baroreceptors (causing abrupt fall of peripheral • Becker's sign—Retinal vessel pulsation.
pulse), consequent to large stroke volume (abrupt • Rosenbach's sign—When liver pulsation is visible
rise). It is well felt by raising the patient’s arm while or palpable.
the patient is in supine position. On auscultation first heart sound (S1) is normally
• Bisferiens pulse—A double systolic impulse felt in heard in chronic severe AR. When decompensation
the arterial pulse (better felt by palpating carotid starts S1 is decreased because of early closure of mi-
artery) tral valve consequent to increased end-diastolic pres-
• Corrigan’s sign—Visible pulsation of carotid artery sure. In acute AR, S1 is decreased or may be absent
(dancing carotid). due to similar mechanism. Second heart sound (S2)
• Pistol short (Traube’s sound)—A loud systolic is normally split. In some cases of severe AR, S2 is
sound heard even the stethoscope is lightly placed variable. A2 moves towards P2 causing close split or
over the femoral artery. A2 is not audible due diminished valve excursion.
Remember: Presence of even mild AS abolish the Loud A2 indicates nonrheumatic AR. Ejection sound
pistol short sound of severe AR. is audible in most of the cases of chronic severe AR
• Palfrey’s sign—It is also a pistol short sound heard due to sudden dilatation of aorta in face of a large
over radial artery. stroke volume. In some cases a loud ejection sound is
• Palmar click—A palpable abrupt flushing of the confused with S1. Left ventricular third heart sound
palms in systole. (S3) is commonly audible in decompensated AR due
• Quincke’s pulse—Exaggerated reddening and to increased left ventricular end-diastolic pressure.
blanching of the finger nail beds. Note: S3 gallop is taken as a marker of LV dysfunction.
• Duroziez’s sign—A systolic and diastolic murmur S4 may be present in severe chronic AR when left ven-
heard over femoral artery when light pressure is tricular end diastolic pressure (LVEDP) is high.
applied by the edge of the stethoscope. When the An early diastolic murmur (EDM) is character-
edge of the diaphragm is pressed distally the dias- istic of AR. In rheumatic AR the early diastolic mur-
tolic murmur is audible (for better remembering, mur is better heard over left sternal border in third
D for D) and when proximal end is pressed sys- and fourth intercostal space (2nd aortic area/Neo
tolic component is audible. aortic area/Erb’s space). It is usually a decrescendo,
• de Musset’s sign—Visible oscillation of head (head blowing high pitched, early diastolic murmur better
bobbing or nodding) with each heart beat. heard on sitting and leaning forward posture while
• Hill’s sign—Abnormal accentuation of popliteal breath is held in expiration. If this diastolic murmur
artery systolic blood pressure (popliteal cuff pres- is better heard over right sternal border it may be
sure) 60 mm Hg or higher than brachial artery due to aortic root dilatation or dilatation of ascend-
pressure. ing aorta. This diastolic murmur may have a musi-
• Minervini’s sign—Strong lingual pulsation (the cal character (Cooing Dove or Seagull cry murmur)
tongue depressor moves up and down on light indicating eversion or perforation of aortic cusps.
pressure. Duration of rheumatic AR murmur well correlates
• Müller sign—Visible and rhythmic pulsation of with severity. A severe chronic AR murmur may be
uvula. audible throughout the diastole called holodiastolic
• Oliver-Cardarelli’s sign—It is the visible and rhyth- or pandiastolic murmur. In severe AR a high pitched
mic laryngeal movement. harsh mid systolic flow ejection murmur grade 3 to
5/6 is audible over aortic area and may be conduct-

ed towards carotids confusing with aortic stenosis.
(Presence of peripheral signs exclude significant AS).
Patients with severe AR often have a long systolic
murmur (3 to 4/6) due to LV dilatation heard over
apex due to mitral regurgitation (functional MR). Fig. 13.2: Auscultatory findings of severe AR. Abbreviations:
Another diastolic murmur is often heard over S1—First heart sound; EC—Ejection click; ESM—Ejection
apex in chronic severe AR, known as Austin Flint systolic murmur; S2—Second heart sound; EDM—Early
murmur. It is a soft low pitched mid diastolic or pre- diastolic murmur; AFM—Austin Flint murmur
systolic murmur produced due to impingent of AR
jet and displacement of anterior leaflet of mitral valve Acute Aortic Regurgitation
producing relative narrowing of mitral orifice in di-
astole. Patients of acute aortic regurgitation (AR) present
Note: Austin Flint murmur indicates severe AR. with sudden onset of undue tachycardia, dyspnea
Other explanations for Austin Flint murmur are vi- and subsequently with orthopnea without peripheral
bration of anterior mitral leaflet between AR jet and signs of chronic AR. Pulse pressure is narrow (not
mitral inflow or it may be due to diastolic mitral wide) and diastolic pressure is more than 30 mm Hg.
regurgitation. Reversal of pressure gradient across First heart sound is decreased or absent because of
MV in diastole is the cause of diastolic MR. If this early closure of mitral valve. Second heart sound is
diastolic murmur becomes shorter in duration in due normally heard. The early diastolic murmur is short
course of time, it indicates LV dysfunction or decom- and soft, as aortic diastolic pressure rapidly equalizes
pensation has started. Table 13.1 gives the important with sharply rising nondilated LV diastolic pressure.
differentiating features between diastolic murmur of In some cases it may be musical or vibratory in qual-
AR (Austin Flint murmur) and diastolic murmur of ity indicating evertion or perforation of aortic valve.
mitral stenosis. Figure 13.2 summarizes the ausculta- There is neither flow MDM nor functional systolic
tory findings of severe AR. murmur. The short diastolic AR murmur is often
overlooked and in initial period the severity of the
Table 13.1: Differentiating features between Austin Flint lesion is underestimated by the clinician.
murmur and mid-diastolic murmur of mitral stenosis
Note: Patients of known AR (mild/moderate/severe)
Austin Flint Mitral stenosis if develops sudden onset of dyspnea, tachycardia,
murmur murmur hypotension and signs of pulmonary edema think of
Rhythm Sinus Atrial fibrillation acute AR has set in (search for the cause, most prob-
Left ventricular heave Common Absent able being infective endocarditis).
Diastolic thrill No or rare Common
Right ventricular lift Absent Present Investigation
First heart sound Normal Loud (tapping)
Electrocardiography
Opening snap Absent Present
Third heart sound Present Absent In severe chronic AR left ventricular hypertrophy is
Diastolic murmur Mid-diastolic Mid-diastolic
usually present (V1 S + V5/V6 R ≥ 35 mm, Sokolow
or presystolic rumbling with voltage criteria ≥ 3.5 mV). The characteristic volume
presystolic overload pattern, that is narrow deep ‘q’ waves may
accentuation be seen in V5, V6, I, aVL (Fig. 13.3) with ‘T’ waves
Signs of pulmonary Uncommon Common remaining upright. Later in the disease process there
hypertension may occur T-inversion and ST depression. In acute
Fig. 13.3: ECG in a chronic severe AR. Note the voltage criteria of LVH with q-waves in I, aVL, V5, V6 with upright,
T-waves indicating volume overload
AR there are no specific ECG features except sinus of AR. Ascending aorta and aortic knob are promi-
tachycardia and non-specific ST/T changes. nent in chronic AR. Left atrial enlargement indicates
associated mitral valve disease or LV dysfunction.
Similarly pulmonary venous hypertension is marked
Roentgenography
when LV dysfunction is present. Calcification of aor-
Cardiomegaly with left ventricular contour is often tic valve may be seen in some cases. Linear calcifi-
seen in moderate to severe chronic AR (Fig. 13.4). cation of ascending aorta (Egg cell calcification) is
Cardiac size is proportionate to severity and duration diagnostic of AR due to luetic (syphilitic) origin is
view is used to estimate severity of AR. A jet width

less than 25 percent is taken as mild where as more
than 65 percent is taken as severe AR (Figs 13.5B to
D). Jet area seen at valve level in short axis also gives
an idea of regurgitant orifice area. CW Doppler taken
in an apical 5 chamber view shows the AR spectrum.
The density of AR spectrum and its slope are used to
determine AR severity. With increasing severity the
slope becomes stiffer (Figs 13.5F and G). From the
slope the pressure half-time (PHT) can be measured.
Slope of AR spectrum is a measure of rate of decline of
pressure from aorta to LV. PHT is the time by which
the initial pressure difference falls to 50 percent. More
severe the AR stiffer the slope and shorter the PHT.
A PHT of less than 200 msec indicate severe AR and
more then 500 msec is mild AR. Diastolic flow re-
Fig. 13.4: Chest X-ray in AR showing cardiomegaly with versal in abdominal aorta taken by PW Doppler also
LV contour indicate severe AR. Other echo parameters like proxi-
mal isovelocity surface area (PISA) to determine the
not seen nowadays. When X-ray chest PA view shows regurgitant orifice area and estimation of regurgitant
signs of pulmonary edema with normal cardiac shad- fraction by using the principle of continuity equation
ow it alerts the physician to think of acute AR. are less commonly used. Premature closure of mitral
valve may be seen in acute AR.
Echocardiography
Radionuclide Imaging
Echocardiography is the investigation of choice for
diagnosis and assessment of severity of AR. It also Radionuclide angiography is necessary when echo
helps in determining the etiology of AR, estimating findings are not conclusive. Severity of AR and LV
LV size, function and associated valvular lesions. A functions are accurately studied by this method. In
rapid high frequency diastolic fluttering of anterior addition measurement of LV/RV stroke volume ratio
mitral leaflet seen in M mode echo (due to impact of ≥ 2 denotes severe AR.
aortic regurgitation) with thickening of the leaflets
indicate presence of moderate-to-severe AR of rheu- Magnetic Resonance Imaging (MRI)
matic origin as it indicates AR in association of mitral
valve involvement (Figs 13.5E and F). LV dilatation It is not a routine investigation although severity of
with hypertrophy (eccentric hypertrophy) indicates AR, LV end-diastolic volume, systolic volume and
significant AR. 2D echo measurement of LV end sys- LV mass are accurately measured by these advanced
tolic volume, LV mass and ejection fraction (EF) helps powerful techniques.
in decision making regarding management. 2D echo
is also helpful in determining the etiology by showing Cardiac Catheterization and
the number of cups (Fig. 13.5A) and helps in exclud-
Angiocardiography
ing aortic root diseases. Color Doppler is essential to
see the regurgitant jet. Commonly the width of the In recent years cardiac catheterization is not routinely
AR jet in proportion to the left ventricular outflow required for diagnosis or for decision making regard-
tract (LVOT) dimension in parasternal long axis ing the management. In pre-echo era this procedure
A B C
D E
F G
Figs 13.5A to G: Echocardiography in AR. (A) Tricuspid aortic valve (arrow) in rheumatic AR seen in short axis, the regur-
gitant orifice in diastole is seen in center; (B) Jet of AR seen in color Doppler (arrow) in a case of a mild AR; (C) AR jet
in moderate AR (arrow); (D) Severe AR, left panel shows a dilated LV with rheumatic involvement of mitral valve, right
panel shows the AR jet (arrow) filling the whole LV outflow tract; (E) M-Mode echo in AR showing flutter of anterior mitral
leaflet (arrow); (F) CW Doppler spectrum in a mild AR with a relatively flat slope (arrow); (G) Severe AR with a stiffer slope
(arrow). Abbreviations: LA—Left atrium; LV—Left ventricle; RA—Right atrium; RV—Right ventricle; Ao—Aorta.
was mandatory to assess the severity of the lesion and Patent Ductus Arteriosus
to know the valve status before surgery. Now cardiac Patent ductus arteriosus (PDA) is also a volume
catheterization is mainly done to exclude coronary overload condition of LV with presence of periph-
artery disease before surgery. eral signs. When ductus murmur is not loud due to
By aortic root cine-angiography, severity of pulmonary hypertension it comes under differential
AR is determined by degree of opacification of the diagnosis of AR. But presence of peripheral signs,
LV which is expressed as 1+ to 4+. From catheter evidence of pulmonary hypertension (loud P2) and
data, regurgitant volume, regurgitant fraction, aortic character of early diastolic murmur (EDM) easily dif-
and LV end-diastolic pressure are calculated. Right ferentiate from PDA. The points that favor PDA is the
heart catheterization is done to know the pulmonary systolic thrill and continuous murmur present over
wedge pressure, pulmonary artery pressure and RV first and second intercostal space on the left sternal
end-diastolic pressure. In acute AR marked increase border. It is 2D echo with Doppler gives the diagnosis.
in left ventricular end-diastolic pressure (LVEDP) is
recorded although left ventricular end-diastolic vol-
Mitral Regurgitation
ume (LVEDV) remains normal or slightly increased.
Severe MR may produce peripheral signs like AR al-
though not as prominent. A flow diastolic murmur
Diagnosis
in MR is confused with Austin Flint murmur when
Mild-to-moderate AR may not produce any symp- present over apex. But the other associated clinical
tom or signs, only on routine examination a short findings like diminished S1, presence of S3 and pan-
early diastolic murmur over left second and third systolic murmur over the apex conducted to axilla
intercostal space over parasternal border is audible. favors the diagnosis of MR (not AR).
This murmur many a times missed by physicians un- Note: For academic interest unusual causes of di-
less one is aware of the clinical situation. It is the early astolic murmur over precordium are, coronary AV
diastolic murmur with peripheral signs that are the fistula, rupture of aneurysm of sinus of Valsalva,
hallmark of diagnosis of chronic severe AR. Simply Anomalous left coronary artery from pulmonary ar-
by bedside examination if Hill’s sign and Austin Flint tery. All these conditions produce continuous mur-
murmur are detected, they indicate presence of se- mur but sometime the diastolic part over left sternal
vere AR. However, echocardiogram is the most im- border gives impression of AR. Severe anemia and
portant noninvasive diagnostic method to judge the hyperthyroidism produce flow murmurs which are
severity and the time of surgery. systolic, but sometimes this increased flow, across a
mitral or tricuspid valve may produce functional di-
astolic murmur.
Pulmonary Regurgitation Complications

In severe pulmonary arterial hypertension, a high Long standing severe AR leads to LV dysfunction and
pitched blowing early diastolic murmur (Graham subsequently congestive heart failure. Arrhythmias
Steell murmur) is heard over the second and third are late features. When present, atrial fibrillation or
intercostal space on left sternal border due to pul- ventricular arrhythmias are commonly seen. Infective
monary regurgitation. Absence of peripheral signs endocarditis is one of the deadly complication which
of AR, evidence of severe pulmonary hypertension is unrelated to the severity of AR. Sometimes patients
(right ventricular heave, narrow split S2 with loud P2 of pyrexia of unknown origin cause being infective
and respitratory variation) well differentiate this con- endocarditis are diagnosed late due to presence of
dition from AR. asymptomatic and previously undiagnosed AR.
Treatment Surgical Management

Medical Management Surgery is indicated in all symptomatic AR.
In case of mild-to-moderate AR without symptom In asymptomatic cases the indications are:
with normal LV function no specific drugs are ad- 1. Onset of symptoms.
vised. All asymptomatic moderate to severe AR pa- 2. Onset of LV dysfunction (as determined by echo-
tients should be evaluated by 2D with color Dop- cardiography) either at rest or exercise induced.
pler echocardiography at regular intervals to detect 3. LV diastolic dimension more than 75 mm.
early signs of decompensation. Once patient starts 4. End-systolic dimension more than 55 mm or LV
going for decompensation, surgery is advised. Infec- ejection fraction is less than 55 percent or ascend-
tive endocarditis prophylaxis is advised as and when ing aortic dimension more than 55 mm (the rule
required, besides routine secondary prophylaxis for of 55).
rheumatic fever. Asymptomatic patients with end systolic dimen-
It is a practice to use vasodilators in asymp- sion less than 40 mm should be followed-up every 2
tomatic moderate to severe chronic AR although years by echo and when the end-systolic dimension
there is debate regarding its beneficial effect on is 40 to 50 mm they should be followed-up yearly, for
long-term use. Vasodilators used are calcium chan- better assessment of LV function to know the time of
nel blockers (nifedipine, felodipine), hydralazine early surgery.
and ACE inhibitors (captopril, enalapril, lisino- Patients of acute AR no doubt need emergency
pril, ramipril). When ACE inhibitors are not tol- surgery, but often there is need to stabilize the clinical
erated, angiotensin receptor blockers (ARB) are condition with correction of abnormal hemodyna
used. These drugs have shown to delay progression mic parameters. These patients are managed in ICU
of valve damage and LV dysfunction. Vasodilators with help of Swan Ganz and intra-arterial catheter
preserve LV function for better surgical result. The to monitor hemodynamic parameters. Pulmonary
mechanisms behind are vasodilators decrease re- edema and hypotension are corrected aggressively by
gurgitant flow, decrease LV volume overload, pre- medical management. In this clinical situation vaso-
vent LV dilatation and increase forward flow (car- dilators (sodium nitroprusside, nitroglycerin) and
diac output). pressure amines (dobutamine, dopamine, milrinone)
In setting of arrhythmias if cardiac output is low are the mainstay of medical therapy. If hypotension
(low BP) vasodilators are used with great caution. persists intra-aortic balloon counter pulsation is
There is no controversy regarding use of vasodila- helpful. Since infective endocarditis is the main cause
tors in decompensated state or in cases of conges- of acute AR, ideally surgery may be deferred till in-
tive heart failure along with other conventional fection is controlled by suitable antibiotics other-
anti-failure drugs like digoxin and diuretics, par- wise chance of prosthetic valve endocarditis is much
ticularly in cases when surgery is denied. In anginal more. Operative risk is far greater in acute AR than in
pain nitroglycerin or other nitrates are of not much case of chronic AR.
help although routinely used. Atrial fibrillation and In young patients metallic prosthetic valves are
bradyarrhythmias are promptly treated with ap- generally advised because of its long durability, they
propriate drugs, to prevent early decompensation. require oral anticoagulation (warfarin, nicoum-
Similarly, beta blockers should be used with caution alone) with prothrombin time estimation at regu-
because of its bradycardic effect. Bradycardia pro- lar intervals to maintain international normalized
longs diastole and therefore the amount of regurgi- ratio (INR) between 2.5 and 3.5. Selection of pros-
tant volume increases. thetic valve depends upon patient related factors
like age of the patient and aortic root size. Similarly 5. Gaasch WH, Schick EC. Symptoms and left ventricu-
in case of women, in child bearing age and in elderly lar size and function in patients with chronic aortic
persons tissue valves like, aortic allograft or pulmo- regurgitation. J Am Coll Cardiol. 2003;41:1325-8.
nary autograft are desirable to avoid anticoagulation 6. Maurice Enriquez-Sarano, Chronic Aortic Regurgita
therapy. tion, Valvular Heart Disease, 3rd edn, Ed Joshep S
Alpert, Lippincott Williams and Wilkins.
7. Soumitra Kumar, et al. Management of Valvular
further reading Heart Disease, Current Trends in Cardiology, 2nd
1. Bonow RO, Carabello BA, Chatterjee K, et al. ACC/ edn, (Eds) Soumitra Kumar, Ramkrishna Mission
AHA 2006 guidelines for the management of patients Seva Pratisthan, Kolkata, 2006.
with valvular heart disease. J Am Coll Cardiol. 8. Stewart WJ and Carabello BA. Chronic aortic valve
2006;48:1-148. disease. In: Textbook of Cardiovascular Medicine.
2. Borer JS, Bonow RO. Contemporary approach Topol EJ, et al (Eds). Lippincott, Williams & Wilkins:
to aortic and mitral regurgitation. Circulation. Philadelphia, 2003.
2003;108:2432-8. 9. Tarasoutchi F, Grinberg M, Spina GS, et al. Ten-
3. Enriquez-Sarano M, Tajik. Aortic regurgitation. years clinical laboratory follow-up after application
N Engl J Med. 2004;351:1539-46. of a symptom-based therapeutic strategy to patients
4. Evangelista A, et al. Long-term vasodilator therapy in with severe chronic aortic regurgitation of pre-
patients with severe aortic regurgitation. New Engl J dominant rheumatic etiology. J Am Coll Cardiol.
Med. 2005;353:1342-9. 2003;41:1316-24.
CHAPTER 14
Tricuspid Valve Disease
M Satpathy
Tricuspid Stenosis Etiology

1. Acquired
Definition
2. Functional
When there is obstruction to blood flow from right 3. Congenital.
atrium (RA) to right ventricle (RV) at tricuspid valve
level in diastole, the clinical condition is known as
Acquired Causes
tricuspid stenosis (TS). It is due to structural abnor-
mality of tricuspid valve causing narrowing of tricus- • Most common: Rheumatic origin. It is always asso-
pid valve orifice. ciated with MS.
• Extremely rare causes are disseminated lupus,
Incidence argentaffinoma and endomyocardial fibrosis.
The incidence of tricuspid valve disease varies from

Functional Causes
10 to 20 percent of all cardiac cases but only in
4 percent of cases, it is clinically diagnosed. Fifteen to Tricuspid stenosis (TS) is produced due to mechani-
thirty percent of all patients with rheumatic valvular cal obstruction in presence of anatomical normal
heart disease have evidence of rheumatic involve- valve. Common causes are:
ment of tricuspid valve at necropsy. Incidence of • Infective endocarditis of fungal origin: Vegetation
tricuspid stenosis on echocardiographic evaluation obstruct the tricuspid orifice (mainly fungal infec-
among all rheumatic heart diseases varies from 6 to tion in IV drugs users).
10 percent in two different studies (Das JP, Ind HJ, • Right atrial thrombus.
1986;38:249 and Mishra HN, Ind HJ, 1990;42:216). • Tumors: Cardiac-Right atrial myxoma/sarcoma.
Although, it is reported that TS occur more fre- Extracardiac-Sarcoma, metastasis from hyper-
quently in females, but our observation shows equal nephroma and carcinoma of thyroid.
sex distribution. Isolated rheumatic TS is not re- • Rare causes are Loeffler’s endocarditis, pericardial
ported yet in Indian literature. It is always associated constriction, carcinoid heart disease and trauma.
with mitral stenosis (MS) and less frequently with
aortic stenosis. Trivalvular stenosis (TS + MS + AS) Congenital Causes
is rare, however, a few reports were published in In-
dian literature. Tricuspid atresia, AV canal anomaly and Ebstein’s
anomaly.
Tricuspid Valve Disease 107
Anatomy of Tricuspid Valve • Chordae tendinae arise from the papillary mus-
cles. Total number of chordae are 25 and they fan
The tricuspid valve develops in the sixth week of out from papillary muscle to the leaflets.
intrauterine life primarily from endocardial cush- Like mitral valve, the tricuspid valve leaflets con-
ion. The tricuspid apparatus consists of six major sist of three layers, fibrosa on ventricular side, atrialis
components (Like mitral valve): on atrial side and spongiosis layer in-between these
1. Annulus two layers.
2. Leaflets Remember: The tricuspid leaflets when close in sys-
3. Chordae tendineae tole look scalloped. All the tricuspid valve compo-
4. Papillary muscles nents must be morphologically healthy to execute in
5. Adjacent right atrial wall a coordinated manner to deliver the normal physi-
6. Right ventricular wall (Fig. 14.1). ological function.
Tricuspid valve is most apically placed compared
to other valves. Distensibility of annulus is unique
Pathology
to tricuspid valve.
• Tricuspid valve area—average 7 cm2. Pathological changes in TS resemble those of mi-
• Tricuspid annular circumference—11 to 12 cm. tral stenosis. During chronic rheumatic process,
• It has three leaflets, anterior, posterior and sep- their occurs scarring and fibrosis of tricuspid valve
tal (medial), anterior leaflet is the largest one, with fusion of leaflets at their edges (commissural
septal leaflet is smallest and posterior leaflet is in fusion) and shortening of chordae tendinae, which
between anterior and septal. subsequently give rise to tricuspid stenosis. In TS,
• Commissures are three in number: right atrium (RA) is dilated and hypertrophied. RV
1. Anteroposterior although initially remains normal but as MS is always
2. Posteroseptal associated, it gradually becomes hypertrophied sec-
3. Anteroseptal. ondary to pulmonary arterial hypertension (PAH).
• Papillary muscles are also three in number: Left atrium (LA) is also dilated in TS because of com-
1. Anterior mon association with MS. When aortic valve lesions
2. Septal (medial) are associated, the LV often gets hypertrophied and
3. Posterior: The anterior one is the largest one. dilated. Superior vena cava (SVC) and inferior vena
cava (IVC) are also dilated in TS because of passive
venous congestion.
Note: Limitation of leaflets mobility, fusion of com-
missures and reduction in tricuspid orifice size leads
to obstruction to RV filling which gives rise to TS.
Whereas fibrosis and shortening of leaflets and chor-
dae usually produce tricuspid regurgitation (TR).
Pathophysiology
Normally there is no diastolic pressure gradient across
tricuspid valve because of low velocity flow in pres-
ence of a large orifice. Any pressure gradient across
TV in diastole, as low as even 2 mm Hg is considered
Fig. 14.1: Schematic presentation of tricuspid valve as significant (Fig. 14.2). The gradient is significantly
anatomy increased with inspiration because there is increase in
10 to 15 cm2, unless it is 2 cm2, clinically TS is not

suspected.
Clinical Features
Symptoms
Symptoms in significant TS are due to systemic
venous congestion and low cardiac output. Anorexia,
Fig. 14.2: Schematic presentation of pathophysiology and nausea, vomiting, abdominal discomfort (with or
clinical signs of tricuspid stenosis. Abbreviations: S1—First without ascitis) are also common complaints because
heart sound; S2—Second heart sound; OS—Opening snap of congestion of liver. Edema feet is due to system-
ic congestion. Patient may present with anasarca.
Table 14.1: Tricuspid valve are according to severity of Syncope is a rare symptom. Although TS is always
tricuspid stenosis (TS) associated with MS, dyspnea, hemoptysis, winter
Severity in TS Tricuspid valve area in cm2 bronchitis, orthopnea and PND are remarkably less
Mild 1.5–2
common. In fact in a patient of significant MS if these
symptoms are absent, one should suspect associated
Moderate 1–1.4
TS. The reason being pulmonary congestion is de-
Severe less than 1 creased due to decreased RV output in severe TS.
The prominent neck pulsation (Giant ‘a’ wave)
blood flow across tricuspid valve that decreases dur- in the jugular vein is very clearly visible which even
ing expiration. Mean pressure gradient of 5 mm Hg or draws the attention of the patient and also of the phy-
more across tricuspid valve in distole indicates severe sician at the first sight. These patients move comfort-
TS (first postulated by Goodwin). Severe TS always ably with prominent neck pulsation (raised JVP) and
gives rise to systemic venous congestion. In sinus abdominal swelling (ascitis), because of absence of
rhythm the right atrial ‘a’ wave is quite tall (because of significant pulmonary congestion.
forceful contraction of hypertrophid RA) and some- Remember: Absence of symptoms of pulmonary
times equal to right ventricular systolic pressure. The congestion (PND and orthopnea) in a patient with
cardiac output decreases which gives rise to relatively moderate-to-severe MS suggests the possibility of
decreased left atrial, pulmonary artery and right ven- TS.
tricular pressure in spite of presence of MS.
In RHD mitral and aortic valve are commonly Signs
affected than tricuspid valve. The probable hemody-
namic explanation is that the mitral valve withstands In setting of rheumatic heart disease with sinus
a systolic pressure of 120 mm Hg in systole and aortic rhythm if there is giant ‘a’ wave in the jugular vein,
valve about 80 mm Hg in diastole, but tricuspid valve arouse strong suspicion of TS, when atrial fibrillation
withstands only 15 to 25 mm Hg of systolic pres- is present, it is absent. Slow ‘y’ descent is characteris-
sure. This high pressure and high flow hemodynamic tic of significant TS (Fig. 14.6). Hepatojugular reflux
burden over mitral and aortic valve as compared to is present. (JVP is raised when pressure is applied
tricuspid valve, make them vulnerable for rheumatic over liver area). When a patient of TS lies flat the
process. face becomes suffused (cyanosed) and the scalp veins
Hemodynamic criteria for severity of TS is given become prominent (dilated), because of systemic
in Table 14.1. Normal tricuspid valve area is about venous congestion (Suffusion Sign).
Note: Note: All these auscultatory signs of TS are many times

• Prominent venous pulsation in cervical region is a over shadowed in presence of MS or MS with AS.
distinct feature of tricuspid valve disease.
• A giant ‘a’ wave in JVP without evidence of pul-
Investigations
monary hypertension or right ventricular enlarge-
ment, strongly suggest possibility of TS. Electrocardiogram
Left parasternal heave when felt, it is due to sig-
nificant MS. Apical impulse is inconspicuous. Presys- In sinus rhythm tall P wave in lead II and V1 is seen
tolic hepatic pulsation may be present. P2 may not be due to RA enlargement (Fig. 14.3). But often P wave
palpable in spite of a sever MS. A diastolic thrill may is widened in lead II, because MS is associated indi-
be palpable at lower sternal border, better felt in in- cating biatrial enlargement (with prominent negative
spiration. deflection of a tall P wave in V1) and absence of RVH
Tricuspid component of first heart sound is (No RV dominance) is very characteristic of TS. R
audible normally (not accentuated as M1 in MS) but wave in V1 is of small amplitude (less than 7 mm). PR
increases with inspiration otherwise first heart sound interval is prolonged (as RA is dilated), Atrial fibrilla-
and second heart sound (P2) are normally heard. Tri- tion occurs in late stages due to large RA . Absence of
cuspid opening snap (OS) is rarely audible (60-70 ms RVH in presence of right heart failure in MS suggest
after P2), as it is of low intensity although increases with TS is associated.
inspiration. Opening snap has no clinical importance
in TS unlike in MS where it indicates valve pliability.
Presystolic or mid-diastolic murmur over lower
left sternal border that increases with inspiration
is very diagnostic (Carvallo’s sign). TS murmur is
increased with inspiration because negative intra-
thoracic pressure lowers RA and RV pressure that
leads to increased venous return and increase blood
flow across the tricuspid valve. This murmur is lo-
calized to left lower parasternal border, rough, rum-
bling in character. Sometimes a scratchy presystolic
murmur may be audible. When TS is dominant, the
diastolic murmur increases and systolic murmur
decreases in inspiration because there is increased
diastolic pressure gradient between RA and RV. The
diastolic murmur of TS is increased by Mueller ma-
neuver, leg rising, prompt squatting and isometric Fig. 14.4: Chest X-Ray in a case of tricuspid stenosis show-
exercise. It is reduced in intensity during expiration ing cardiomegaly with right atrial enlargement (arrow)
and Valsalva maneuver. without pulmonary arterial dilatation
Fig. 14.3: ECG in a case of tricuspid stenosis showing right atrial

enlargement (tall P waves in V1) without significant RV forces
Figs 14.5A to C: Echocardiography in tricuspid stenosis.

(A) M-Mode echo showing thickened anterior and septal
leaflets moving anteriorly above the ventricular septum
(white arrow), on the right side associated mitral stenosis
is evident below the septum by taking a swipe of the cur-
sor (black arrow); (B) 2D echo in tricuspid stenosis seen
in apical 4 chamber view, note doming of both anterior
and septal leaflets (arrows) with a dilated right atrium and
associated mitral valve disease; (C) CW Doppler interroga-
tion showing significant diastolic gradient across tricuspid
valve. Abbreviations: LA—left atrium; LV—Left ventricle;
C RA—Right atrium; RV—Right ventricle
Roentgenography
leaflets with reduced EF slope. By 2D echo, all the
Right atrium is hugely enlarged and forms the right three leaflets of TV are visualized, in multiple planes.
cardiac border, without significant dilatation of pul- The diagnosis of TS is based on diastolic doming
monary artery segment (Fig. 14.4). Double right car- of anterior and septal leaflet of tricuspid valve (Fig.
diac border is often seen due to associated MS. Lung 14.5B). The severity of TS is assessed after visualizing
fields are clear (no interstitial edema). Clear lungs the stenotic jet by color Doppler and then obtaining
fields in presence of MS suggest possibility of TS. Tri- a CW Doppler spectrum. Calculating the gradient by
cuspid valve calcification is not yet reported. modified Bernoulli’ equation (Fig. 14.5C) gives esti-
mation of severity of TS. A mean diastolic gradient ≥
5 mm Hg is taken as significant TS.
Echocardiography
Color Doppler is also used to assess TR, estimate
Echocardiography is very sensitive and specific for the pulmonary arterial pressure and assess the status
predicting the tricuspid valve lesion and its severity. of other valves. Planimetric TV area measurement
In M-mode anterior tricuspid leaflet motion is often and pressure half time method of valve area deter-
recorded (Fig. 14.5A) (rarely septal leaflet motion can mination are less accurate compared to MS and are
be visualized) unlike mitral valve where both leaflets not often used clinically. Transesophageal echocardi-
are seen in M-mode. M-mode echo shows thickened ography (TEE) is not much superior to transthoracic
echo (TTE) in examining TV lesions. Real time 3D Angiocardiography

echo has some advantage over TTE. .
Thickened and restricted mobility of leaflets with a
jet through constricted orifice with dilated and thick-
Salient Echo Features of TS
ened right atrial wall are characteristic finding.
• Reduced EF slope, thickened leaflets seen in a
M–Mode echo. Diagnosis
• Thickened anterior and septal leaflet of TV with
diastolic doming on 2D echo. The clinical diagnosis of tricuspid stenosis is no
• Hugely dilated right atrium, dilated vena cavas doubt, difficult, as the characteristic signs are masked
and coronary sinus on 2D echo. or overshadowed by presence of mitral stenosis.
• Color Doppler guided continuous wave (CW) However, in patient of mitral stenosis when symptom
Doppler spectrum helps in assessing transvalvu- of pulmonary venous congestion is minimal, tricus-
lar gradient and severity of stenosis. pid stenosis is suspected. Large ‘a’ wave in JVP with
slow ‘y’ descent is characteristic. The TS murmur is a
low frequency, crescendo–decrescendo murmur, falls
Cardiac Catheterization
short of S1 (where as MS murmur is crescendo char-
Cardiac catheterization and hemodynamic deriva- acter and merges with S1). Presystolic or mid-dias-
tives for TV disease are now days of historical interest. tolic murmur increased with inspiration is diagnostic
However, in pre-echo era that is before 1978 in India it of TS. The intensity of murmur is not proportional
was the gold standard of assessing accurately the valve to the severity of TS. Echocardiography gives the
area and the gradient across tricuspid valve and taking final diagnosis with its severity and other associated
decision for further management. Still in some selec- lesions.
tive cases catheterization and angiographic informa- Salient diagnostic points
tion do play important role prior to surgery. 1. Prominent neck pulsation with Giant ‘a’ wave in JVP.
During right heart catheterization a diastolic 2. Presystolic or mid-diastolic murmur over left lower
gradient across TV indicates presence of tricuspid parasternal border, increasing with inspiration.
valve stenosis. Careful measurement of diastolic gra- 3. Paroxysmal nocturnal dyspnea (PND) and ortho-
dient must be made with well balanced equisensitive pnea are absent, although MS is associated.
catheter in both the chambers when tricuspid valve 4. ECG shows right atrial enlargement, with less
obstruction is suspected. During RA recording a slow marked RV force (no RVH).
‘y’ decent is very typical of TS. Tricuspid valve area is 5. It is 2D echocardiography with color Doppler give
calculated by Gorlin’s formula is as follows: the final diagnosis.
TVA = Co (ml/min)
DFP × 0.7 × 44.5 √ (RAM – RVMD) Differential Diagnosis
CO = Cardiac output Mitral valve disease with raised JVP (mainly severe
DFP = Diastolic filling period (Sec/ml) PAH), RA thrombus and chronic constrictive peri-
RVMD = Right ventricular mean diastolic pressure carditis come under differential diagnosis. Although
(mm Hg) mitral stenosis is always associated, it has to be differ-
RAM = Right atrial mean pressure (mm Hg) entiated from TS. In moderate-to-severe MS, history
0.7 and 44.5 are two constant numbers. of PND and orthopnea (not a feature of TS), loud first
Remember: Because normally there is no diastolic heart sound (M1), with opening snap and rumbling
pressure gradient across the tricuspid valve, any pres- mid-diastolic murmur with presystolic accentuation
sure gradient as low as even 2 mm Hg is significant at apex not increased with inspiration are the charac-
to diagnose TS. teristic features of dominant mitral stenosis.
Note: Rheumatic TS without MS is not reported but are used to reduce hepatic congestion and relief ede-
MS with TS is often seen. ma feet and ascites before subjecting the patients for
Other differential diagnosis are: surgery. Here, response to diuretics is slow; thereby it
• Right Atrial Myxoma: Constitutional symptoms, gives the false impression to push more diuretics to
tumor plop, variable diastolic murmurs are main reduced venous load. But excessive diuretics lead to
clinical features but 2D echo confirms the diagno- decreased RV filling pressure there by cardiac output
sis. may be further decreased causing clinical deteriora-
• ASD (Secundum): A flow diastolic murmur may tion. So the physician should be aware to use diuret-
be audible at lower left parasternal border in case ics judiciously in this clinical setting of combined
of large atrial septal defect (ASD) resembling TS lesion.
murmur. Hyperdynamic precordium, wide and
fixed splitting of second heart sound (S2) and ejec- Nonsurgical Intervention
tion systolic murmur (3-4/6) over left seond par-
asternal border are diagnostic features of ASD. Tricuspid balloon valvotomy has been done success-
However, 2D Echo confirm the diagnosis. fully. Balloon tricuspid valvuloplasty in case of TS
• Lutembacher’s syndrome (MS with atrial septal was first done in 1987 by Al Zaibag et al and in India
defect): Here JVP is raised without congestive by Khalilullah et al and the results were satisfactory.
heart failure (high LA pressure reflected into RA Balloon valvuloplasty is treatment of choice for both
due to ASD) as seen in TS. Tricuspid flow murmur MS and TS if valves are found suitable. Valvuloplasty
resembling TS murmur is audible at lower par- is also done in trivalvular stenosis with satisfactory
asternal border due to increased left to right shunt result (R Anil Kumar et al, Ind HJ, 1999;51:667).
at atrial level. But the presence of wide and fixed
splitting of S2 with loud P2 and a grade 3-4/6 ejec- Surgical Management
tion systolic murmur over pulmonary area differ-
entiate it from TS. The etiological factor, the clinical impact and severity
• Chronic constrictive pericarditis: At the outset it of stenosis and management of associated lesions are
has some resemblance to TS because of prominent taken into account before final decision for tricuspid
neck vein and pericardial knock (early diastolic valve surgery. Surgery for TS is indicated if the mean
sound) that may confuse with opening snap, but diastolic gradient is more than 5 mm Hg or tricuspid
clinically easily ruled out. Absence of hepatojugu- valve orifice size is less than 1.5 cm2. As moderate-
lar reflux and absence of murmur over lower par- to-severe TS is well tolerated, the surgery is deferred
asternal border or over apex, favor the diagnosis till mitral valve surgery is necessary. Tricuspid val-
of constrictive pericarditis. votomy has been done in many cases but recurrence
Remember: Causes of tricuspid diastolic flow mur- (restenosis) were often reported after three to four
mur are: Severe TR, Large ASD and Anomalous pul- years of surgery. Finger fracture valvotomy as done
monary venous connection (draining to RA). in MS is not helpful, so open commissurotomy is
preferred because tricuspid valve converted into
bicuspid valve, resulting in substantial clinical im-
Management
provement. Care is taken not to touch the commis-
sure between anterior and posterior leaflets because
Medical Management
it may produce TR. However, management is mainly
Patients having tricuspid stenosis with congestive by either tricuspid annuloplasty or replacement with
heart failure (CHF) are treated with decongestive prosthetic valves. Replacement by tissue valve (por-
therapy taking into account the severity of associated cine heterograft) is preferred to metallic prosthetic
lesion (MS or MS with TR). In these cases diuretics valve, reason being tissue valves are more acceptable
and durable for tricuspid valve orifice and antico- normal valve consequence to RV dilatation. The most
agulants are not necessary. Moreover metallic pros- common causes of functional TR are pulmonary ar-
thetic valves are not preferred because of high-risk of terial hypertension of any etiology, dilated cardio-
thrombosis and infection. But the patient having TS myopathy, large ASD secundum, RV infarction and
and MS if only mitral commissurotomy is done does papillary muscle dysfunction secondary to coronary
not show satisfactory improvement and they remain artery disease.
with class III–IV symptoms with restricted physical Almost all cases of chronic rheumatic tricuspid
activities. In these cases prognosis is poor unless tri- valve diseases have mild-to-severe TR and may have
cuspid valve surgery is simultaneously done. some degree of tricuspid stenosis. Majority of these
Many times the decision for type of surgery for cases are also associated with MS and with or without
tricuspid valve is taken during mitral or aortic valve aortic valve disease.
surgery. In this setting intraoperative echo informa- Note: A common denominator of TR is pulmonary
tion is essential for the surgeon to take final decision. hypertension.
Tricuspid Regurgitation Acute TR

Sudden onset of TR is known as acute TR. There is no
Definition
time for compensatory mechanism to handle extra
When blood from right ventricle (RV) leaks back to volume load, therefore, RV may fail acutely without
right atrium (RA) through tricuspid valve in systole, dilatation. In these cases the clinical picture is dif-
the clinical condition is known as tricuspid regurgi- ferent from classical clinical findings of chronic TR.
tation (TR). The regurgitation results from structural
or morphological deformity of tricuspid valve appa- Common causes are:
ratus. Infective endocarditis mainly among IV drug
users, trauma to chest wall or after open heart surgery
(Damage to TV), acute inferior myocardial infarction
Etiology
with RV infarction, acute cor-pulmonale.
These patients are very dyspnic even at rest. JVP
Primary TR (Organic)
however, shows large ‘a’ wave, absent ‘x’ decent and
Acquired: prominent ‘v’ wave. RV S4 is well audible. The TR
Common Cause: Rheumatic origin (in developing murmur is soft and short systolic because low pres-
countries). sure gradient between RV and RA.
Uncommon Causes: Infective endocarditis, Carcinoid
syndrome, Trauma, Metastasis in TV. RA myxoma, Hemodynamics
TV prolapse, Scleroderma, Systemic lupus erythema-
tosus, Marfan syndrome, Endomyocardial fibrosis, Tricuspid regurgitation (TR) is a type of right sided
Transvenous pace maker leads. volume overload condition. The amount of blood
Drugs: Methysergide, Phentermine, Fenfluramine that regurgitate to RA in systole comes back to RV in
(Appetite supressant) and Pregoline (Anti-Parkinso- diastole along with normal systemic venous return,
nian drug). this leads to gradual RA and RV dilatation. Initially,
Congenital: Ebstein’s anomaly and AV septal defect. the right atrial and right ventricular end diastolic
pressure remains normal in both functional and
Secondary TR (Functional) organic TR. RA tracing shows absence of ‘x’ decent
and prominent ‘v’ wave followed by rapid ‘y’ descent.
It is the most common cause of TR occurs due to tri- (RA pressure tracing in TR is similar to LA pressure
cuspid annular dilatation in presence of anatomically tracing of MR). In severe TR, RA tracing is similar
to RV pressure tracing. With decompensation RV • Protein loosing enteropathy causing cardiac

end-diastolic pressure gradually rises and mean RA cachexia.
pressure is increased. Increased mean RA pressure is • Ascites: It is a common finding due to hepatic
reflected in systemic veins causing systemic venous venous congestion and lymphatic congestion,
hypertension which is clinically expressed as right besides salt and water retention.
heart failure (raised JVP, hepatomegaly, edema and • Peripheral edema is common finding.
ascites). Severe TR decreases cardiac output thereby • Engorged neck veins (Characteristic throbbing
symptoms of pulmonary congestion are masked and neck pulsation) due to jugular venous distention
features of right sided heart failure appear. • Head Bob (Right to left head movement).
Note: In pulmonary arterial hypertension (PAH) RV • Anterior motion of eyes (Proptosis).
systolic pressure must be at least 50 mm Hg to pro- • Lateral chest wall movement (Characteristic see-
duce TR. But in case of organic tricuspid valve dis- saw movement of chest wall).
eases TR occurs in presence of normal pulmonary • Low cardiac output: It often produces mild cyano-
arterial pressure. sis of lips and fingers. In severe TR, dyspnea and
TR with normal pulmonary artery pressure: TR orthopnea are much less marked in spite of left
without pulmonary artery hypertension, RV and RA sided heart disease (at the cost of decrease cardiac
are very compliant in nature. Systemic venous conges- output).
tion is less marked (due to low RA and RV pressure).
For this reason, the 'v' wave in JVP is not so promi-
Signs
nent and the regurgitation murmur is of low intensity.
However, the inspiratory increase of murmur and ‘v’ • Pulse—Low volume. It may be regular but often
wave in JVP are important clinical findings. irregular when atrial fibrillation (AF) is present.
TR with increased pulmonary artery pressure: • Hypotension with low pulse pressure.
Common association of mitral valve disease gives • Large ‘v’ wave in JVP followed by rapid ‘y’ decent
rise to PAH and increased RV pressure, leading to se- and prominent ‘y’ trough (Fig. 14.6).
vere TR. RV and pulmonary artery systolic pressure • Systolic pulsation of liver is well felt in both
are high (more than 50 mm Hg). There is a higher organic and functional TR.
pressure gradient between RV and RA in systole. RV • Ascitis/edema feet/tender hepatomegaly are com-
is hypertophied. Therefore, both 'a' and 'v' waves are mon findings.
prominant in JVP. • Systolic pulsation of spleen is occasionally felt.
Note: As TR progresses RV is dilated further caus- In severe TR, the large ‘v’ wave in JVP is also
ing more TR, thus setting a vicious cycle of in- known as ‘cv’ wave or ‘s’ (systolic) wave as it begins
creasing TR. So TR begets TR like MR begets MR.
Clinical Features
Symptoms
Mild TR produces no symptoms but severe TR

increases systemic venous pressure and produce
symptoms of decreases cardiac output.
Noncardiac general manifestations of chronic
severe TR are: Fig. 14.6: JVP wave forms in normal individual, in tricuspid
• Liver: Enlarged, pulsatile, better seen then felt. stenosis showing large ‘a’ wave and slow ‘y’ descent, and in
Chronic passive congestion of liver may produce tricuspid regurgitation shows absent ‘x’ descent, large ‘cv’
jaundice, cirrhosis of liver (cardiac cirrhosis). wave and rapid ‘y’ descent
with systolic ‘c’ wave and continue as a large ‘v’ wave maneuver (Strain phase) and hypovolemic state (de-
(Fig. 14.6). The height of the ‘cv’ wave indicates the se- hydration and RV failure). Sometime in severe TR
verity of TR. A venous systolic thrill is sometimes felt when RV volume is maximum in diastole, no change
in the neck in severe functional TR. When ‘v’ wave in RV stroke volume occurs in inspiration, in this
is prominent with a slow ‘y’ descent associated TS is situation the murmur is not increased in inspiration.
suspected. In severe TR dyspnea and orthopnea much TR murmur is reduced in intensity or acoustically
less marked at the cost of decreased cardiac output. silent in presence of reduced RV stroke volume
Remember: ‘cv’ wave (systolic wave) in JVP should or in RV failure, and this murmur is audible only
not be confused with Cannon ‘a’ wave of atrial con- during inspiration (absent in expiration) known as
traction against closed TV that occurs intermittently “Silent TR”.
in case of complete heart block. Remember:
Apex is RV type (diffuse), first heart sound (S1) • TR murmur of organic origin is often associated
is normally heard (both T1 and M1). The intensity of with organic TS and MS
second heart sound (S2) depends upon associated • The more severe the functional TR, more severe
PAH where P2 is loud. Prolongation of RV systole de- the MS
lays P2. Therefore, S2 is wide split. Loud RV third heart • The pan systolic murmur of TR is increased with
sound (S3) and sometimes S4 (right sided atrial gallop inspiration where as pansystolic murmurs of other
sound) are audible. Both the sounds increase with in- causes (VSD, MR) are not increased. .
spiration. S3 may be even palpable in severe TR. RV S3
is best heard over lower left sternal border, it is a high Investigations
pitched sound simulating tricuspid or mitral open-
ing snap or pericardical knock. Tricuspid opening Electrocardiography
snap may be present due to high velocity tricuspid
valve flow in diastole (also audible in large ASD/Eb- There are no specific ECG findings. Functional TR
stein’s anomaly). It is slightly later than mitral open- due to PAH usually shows right axis, right atrial
ing snap and easily distinguished because it increases enlargement and right ventricular hypertrophy.
with inspiration. Pulmonary ejection click may be Associated left atrial enlargement suggest presence
audible in presence of pulmonary artery hyperten- of mitral stenosis. In organic TR without PAH, in-
sion and it is decreased with inspiration (unlike other complete RBBB with RV dominance is seen indi-
right sided sounds and murmur). cating RV volume overload (Fig. 14.7). Atrial fibril-
Pansystolic murmur (with or without thrill), lation is often seen in severe organic and functional
increasing with inspiration, is a classical physical TR. Tall and peaked P wave in II, III and avF and
finding of TR (inspiratory increase of TR murmur is V1 indicate RA enlargement in both organic and
known as Carvallo’s sign). This murmur is of grade functional TR.
2 to 3/6 intensity high pitched and audible over lower
left fourth intercostal space in the parasternal bor- Roentgenography
der. The intensity of the murmur is not proportional
to the severity of TR. In some cases if there is no Marked cardiomegaly is usually present in severe TR
increase with inspiration TS may be suspected. because of RA and RV are dilated (Fig. 14.8). Dispro-
Occasionally a short tricuspid diastolic murmur due portionate enlargement of right cardiac border indicates
to increased flow is audible, (flow diastolic murmur) huge RA enlargement. Apex is right ventricular type.
in severe TR. When TR is mild the systolic murmur
is short, soft and of low intensity. Echocardiography
TR murmur increases with inspiration, Mueller’s
maneuver, exercise, squatting and leg raising but it is It is the main noninvasive method of assessment to
decreased on expiration, standing posture, Valsalva delineate accurately the morphology of the tricuspid
Fig. 14.7: ECG in tricuspid regurgitation showing RA enlargement with RV dominance
ment of TV in RHD shows a thickened tricuspid

valve, associated mitral valve lesion as such points to
rheumatic etiology. Pulmonary artery and its proxi-
mal branches are well-visualized and appear dilated
which indicate PAH.
TR is visualized by color Doppler in apical four
chamber view which shows mosaic signals originat-
ing from tricuspid valve and entering into RA during
systole (Fig. 14.9A). TR is also seen in left parasternal
imaging plane with a suitable transducer angulation
where right atrial cavity and RV inflow is better seen.
Assessing the severity of TR is not well-standardized
like MR. The severity is estimated by color Doppler
taking the maximum tricuspid regurgitant jet area
using multiple imaging planes. The absolute jet area
or its ratio to right atrial cavity indicates severity.
• In mild TR jet area is less than 20 percent of RA or
Fig. 14.8: Chest X-ray PA view showing marked cardio- below 4 cm2.
megaly with huge RA enlargement (arrow) with prominent • In moderate TR jet area is 20 to 35 percent of RA
upper lobe veins indicating in tricuspid regurgitation with or between 4 to 8 cm2.
associated MS
• In sever TR jet area is more than 35 percent of RA
or more than 8 cm2.
valve, pathological valve lesions and determine se- Vena contracta and PISA method (proximal flow
verity of TR. acceleration) are less commonly used. Systolic flow
2D Echo helps to measure RA and RV cavity reversal in inferior vena cava and hepatic veins seen
size. In TR, RA and RV are dilated with paradoxi- by pulsed Doppler indicates severe TR.
cal ventricular septal motion indicating RV volume Echocardiographic findings of severe TR are as
overload. It also helps to exclude other causes of TR follows:
like Ebstein’s anomaly, vegetation or TV prolapse and • Abnormal tricuspid valve/flail leaflet/poor coap-
to rule out presence of tricuspid stenosis. Involve- tation.
• RV/RA/IVC are dilated. right atrium, produced by regurgitant stream of TR.

• Central jet of TR more than 10 cm2 in area. During RV angiography RA is sharply and quickly
• Vena contracta width more than 7 mm (jet width opacified in contrast to RV in severe TR. Pulmonary
at the valve level). artery angio rules out pulmonary embolism as a
• PISA radius more than 0.9. cause of PAH.
• Systolic reversal of hepatic venous flow.
Transesophageal echocardiography is necessary Diagnosis
in some cases to assess the severity of TR before sur-
gery and also during intraoperative period. In a patient with ascites, edema feet and hepatomeg-
Putting the CW Doppler cursor along the TR aly TR is diagnosed by presence of large ‘v’ wave fol-
jet and obtaining an adequate spectrum (Fig. 14.9B) lowed by rapid ‘y’ descent in JVP and a pansystolic
allows measurement of velocity of TR jet (V), and (Grade – 3 to 4/6) murmur over lower left paraster-
gradient from RV to RA in systole is calculated by nal border increasing with inspiration. It is 2D echo
modified Bernoulli’s equation (gradient = 4 × V2). with color Doppler confirms the diagnosis and deter-
RV systolic pressure is estimated from TR gradient mines the severity and cause of TR.
which reflects the pulmonary artery systolic pressure
in absence of pulmonary stenosis. (TR gradient + RA Differential Diagnosis
pressure = RV systolic pressure = pulmonary artery
systolic pressure). RA pressure is estimated from the The following conditions come under differential
caliber of inferior vena cava and its respiratory varia- diagnosis of TR. They are:
tion. Dilated inferior vena cava with blunted respira- 1. MR: The Murmur is better audible over apex con-
tory variation indicates high RA pressure. A high ve- ducted towards axilla. This murmur does not
locity and high gradient jet indicates hypertensive TR increase with inspiration. JVP is normal in MR.
(high RV systolic pressure) (Fig. 14.9C). TR murmur increases following an ectopic beat
Remember: In about 60 percent of healthy individuals (ventricular extrasystole) but does not change if it
trivial or mild TR is usually detected by Doppler echo is MR.
(physiological TR). It has no clinical significance. 2. Tricuspid valve prolapse: It is a short systolic but
loud musical or honking murmur due to TR pro-
duced by prolapse of tricuspid valve and localized
to left lower parasternal border. In inspiration a
Right heart catheterization and angiocardiography click is audible and the intensity of this systolic
provides information on TV morphology along with murmur is increased.
hemodynamic measurements of RA, RV and pulmo- 3. VSD: The pansystolic murmur of TR audible over
nary artery pressure. One disadvantage is iatrogenic left lower parasternal border sometime confuses
mild TR may be produced as the catheter passes with VSD murmur. The pansystolic murmur
through RA to RV. Increased pulmonary artery (grade 3–4/6) of VSD is audible over left paraster-
wedge pressure indicates left sided lesion is present. nal border (third/fourth intercostal space), but
RA pressure waves show absent of ‘x’ descent and does not increase in inspiration. Moreover, LV
prominent ‘v’ wave that look like RV pressure trac- apex, normal JVP and no sign of systemic venous
ing (ventricularization of atrial pressure). Pulmonary congestion favors diagnosis of VSD.
artery (PA) or RV peak systolic pressure less than
40 mm Hg usually indicate TR is of organic etiology Complications
and if more than 55 mm Hg it is usually of secondary
cause (PAH or pulmonary stenosis). The main complications are infective endocarditis,
During angiography when dye is injected to RA ascites, embolism and pulmonary infarction. The
‘jet sign’ or a filling defect is seen in the opacified prognosis of TR depends upon the underlying cause.
A B
Figs 14.9A to C: Echo in severe tricuspid regurgitation:

(A) Apical 4 chamber view, right panel showing thick tri-
cuspid leaflets with a huge RA enlargement, and left panel
showing color Doppler evidence of severe TR (arrow);
(B) CW Doppler tracing showing TR spectrum with rela-
tively low velocity (Primary TR) and presence of respiratory
variation; (C) TR showing high velocity (4.07 m/s) TR jet
with gradient of 66.13 mm Hg, with assumed RA pressure
10 mm Hg, RV systolic pressure is 76.13 mm Hg (Functional
TR due to PAH). Abbreviations: LA—Left atrium; LV—Left
C ventricle; RA—Right atrium; RV—Right ventricle.
In general prognosis is relatively good. Although the is advised along with the management of underly-
patient remain symptomatic, they survive for a long ing cause. Digitalis, ACE inhibitors and diuretics are
time. When TR is due to idiopathic PAH and cor- main drugs used to control congestive heart failure,
pulmonale the outlook is poor with limited life ex- however, in many cases diuretics are to be used with
pectancy. Death eventually occurs due to progressive caution. Infective endocarditis when associated to be
right heart failure, arrhythmias, pulmonary embo- treated with full medical care (see Chapter 17). Atrial
lism and pulmonary infarction. fibrillation is to be managed with anticoagulants and
antiarrhythmic drugs.
Surgical Management: Surgery is indicated when
Management
structural deformity of the valve or annular dilation
General Management is the cause of symptomatic TR.
Indication for tricuspid valve surgery:
Isolated TR is rare so management is planned as per • Annular dilatation of more than 30 mm in set-
the associated lesions. When patient is symptomatic ting of rheumatic heart diseases, even if TR is not
and evidence of CHF is present decongestive therapy severe.
• Symptomatic right heart failure. (pulmonary 2. Arthur Kitchin, Richard Turner. Diagnosis and
artery pressure even less than 60 mm Hg). Treatment of Tricuspid Stenosis, Br HJ. 1964;26: 354-79.
• Severe TR with other valve surgery. 3. Duran CM. Tricuspid valve surgery revisited. J Card
• Progressive right ventricular dilatation. Surg. 1994;9:242-7.
In case of mitral commissurotomy or valve re- 4. Shimada R, et al. Diagnosis of Tricuspid Stenosis by
placement if TR is mild, it is left as such but with M-Mode and Two-Dimensional Echocardiography,
moderate TR, tricuspid annuloplasty is indicated and Am J Cardiol. 1984;53:164-8.
with severe TR often annuloplasty or valve replace- 5. David E Guyer, et al. Comparision of the
ment is advised. Annuloplasty is considered because Echocardiographic and Hemodynamic. Diagnosis of
it is safe, a simple and effective procedure. Tricuspid Rheumatic Tricuspid Stenosis, JACC, 1984, Vol 3, No
valve replacement is usually done with tissue valves. 5, 1135-44.
Glutaraldehyde processed porcine heterografts are 6. Lalchandani A, et al. Management Strategies of Severe
preferred because metallic prosthetic valves have Tricuspid Regurgitation, Cardiology Update, CSI,
high-risk of thrombosis and infection. Newer tissue 2008, Ed VK Bahl.
valves are also quite durable. In drug (heroin) addicts 7. McCarthy PM, Bhudia SK, Rajeswaran J, et al.
with infective endocarditis the total tricuspid valve is Tricuspid valve repair: durability and risk factors for
excised when infection is not controlled and it is left failure. J Thorac Cardiovasc Surg. 2004;127:674-85.
as such till infection is fully controlled. Later valve 8. Soumitra Kumar, et al. Management of Valvular
replacement is done with prosthetic valves. Heart Disease, Current Trends in Cardiology, 2nd
edn, (Eds) Soumitra Kumar, Ramkrishna Mission
Seva Pratisthan, Kolkata 2006.
further reading 9. Guyer Dairel E, et al. Comparison of Echocardio-
1. Paul Wood’s Diseases of Heart and Circulation, 3rd graphic and Hemodynamics Diagnosis of Rheumatic
Edition, 968, Eyre and Spottiswoode Publisher Ltd. Tricuspid Stenosis. JACC 1984;3(5):1135-44.
CHAPTER 15
Pulmonary Valve Disease
M Satpathy
When there is an obstruction to blood flow from Turner R, in Br J.1984:26;354-79. In this chapter, we
right ventricle (RV) to pulmonary artery (PA) in are presenting a case of rheumatic heart disease hav-
systole the clinical condition is known as pulmonary ing mitral regurgitation with echocardiographic evi-
stenosis (PS). It may be valvular, sub-valvular or su- dence of pulmonary stenosis.
pravalvular. Similarly when blood leaks back to RV
from PA in diastole, it is known as pulmonary regur-
gitation (PR). Causes of Pulmonary Stenosis
1. Congenital: For all practical purposes PS is con-
genital. It is associated with other congenital heart
Anatomy of Pulmonary Valve disease (Tetralogy of Fallot, Transposition of great
Pulmonary valve develops from truncus arteriosus, arteries, Double outlet right ventricle and tricus-
truncal and intercalated valve cushion similar to pid atresia), or with many syndromes like asplenia
development of aortic valve. Because of pulmonary syndrome, Noonan syndrome, William syndrome
cusps are half moon shaped, they are known as semi- and Rubella syndrome.
lunar valve. It is situated at the outflow tract of the 2. Acquired: causes are extremely rare.
right ventricle. It consists of an annulus, three equal • Rheumatic. Isolated pulmonary valve affection
sized cusps two posterior and one anterior, three has not been reported.
commissures and three sinuses of Valsalva corre-
sponding to each cusp (Fig. 15.1). The pulmonary
valve annulus is 7 to 9 cm in circumference.
Incidence
Isolated rheumatic affection of pulmonary valve giv-
ing rise to pulmonary stenosis or regurgitation or
both has not been reported. Pulmonary valve may
be very rarely affected in association with other valve
involvement in rheumatic heart disease (RHD).
Rheumatic pulmonary regurgitation associated with
Fig. 15.1: Anatomy of pulmonary valve, left panel shows
other valve lesions has been reported in the litera- unfolded view showing three cusps, right panel shows
ture by Mc Guire and Mc Namara from Mexico City. transverse cross sectional view in closed position (diastole)
(Am HJ, 1937;14:562) and also incidence of rheu- one anterior (A) and two posterior cusps (P). Abbreviations:
matic pulmonary stenosis reported by Kitchen A and PA—Pulmonary artery; RV—Right ventricle
Pulmonary Valve Disease 121
• Carcinoid heart disease involving pulmonary scendo type murmur better audible over third and
valve, often associated with carcinoid affection fourth intercostal space close to left parasternal bor-
of small gut and RV outflow tract obstruction der. This murmur is known as Graham Still murmur
by aneurysm of Sinus of Valsalva (due to exter- and is similar to aortic regurgitation murmur. It may
nal compression). produce a functional mid diastolic murmur known as
right sided Austin Flint murmur (as audible in AR).
PR murmur due to organic causes (without pulmo-
Causes of Pulmonary Regurgitation nary hypertension) is short and low pitched, heard
1. Acquired (Primary/Organic): Infective endocar- in left parasternal border that increases with inspira-
ditis involving pulmonary valve and after pulmo- tion. Tricuspid regurgitation murmur is also audible
nary valvotomy, rheumatic, syphilis and congeni- over lower left parasternal border when RV is dilated
tal. significantly.
2. Functional/Secondary (Functional pulmonary
regurgitation (PR) is commonly seen)
• Dilatation of pulmonary valve ring due to pul- Investigations
monary hypertension of any cause
ECG
• Idiopathic pulmonary artery dilatation.
• Pulmonary stenosis/regurgitation and tricuspid ECG features depends upon the severity of pulmo-
stenosis/regurgitation are reported in malig- nary artery hypertension. When associated with
nant carcinoid of small intestine with hepatic severe pulmonary artery hypertension RVH or RV
metastasis. dominance is present (RSR’ pattern in V1,V2). RSR’
pattern in V1, V2 may be seen when PR or TR pro-
duces RV volume overload.
Clinical Manifestations
The clinical manifestations of isolated rheumatic PS Roentgenography
or PR have not been described in literature. PR may
be clinically manifest in RHD due to acquired causes Pulmonary trunk is dilated and apex is of RV con-
or due to pulmonary arterial hypertension (PAH). tour. Pruning of peripheral vessel with oligemia sug-
gest severe pulmonary artery hypertension.
Symptoms
Echocardiography
Symptoms of PR due to pulmonary hypertension
are chest pain and features of low cardiac output. On Dilatation of RV cavity, paradoxical septal motion,
examination pulmonary artery is pulsatile, the Doppler studies showing diastolic flow signals in RV
systolic pulsation is felt over left second parasternal outflow tract are the echocardiographic features of
border. Systolic and diastolic thrill is not uncommon pulmonary regurgitation. A mosaic diastolic color jet
in organic PR. S2 is widely split with loud P2, RV S3 and from pulmonary valve to RV outflow tract is diag-
pulmonary ejection click is audible in many cases (as nostic of PR, width of jet and its ratio to RVOT de-
large amount of RV stroke volume enters into dilated termines its severity. A high velocity jet indicates PR
pulmonary artery). In severe pulmonary hyperten- due to PAH. In most normal individual some degree
sion, the pulmonary diastolic murmur is increased of PR is seen by color Doppler which is physiological
with inspiration, high pitched, blowing and decre- with no clinical significance.
A B
C D
Figs 15.2A to D: Rheumatic Pulmonary Valve Stenosis (A) Showing typical rheumatic mitral valve in long axis view;
(B) Short axis in the same patient showing thickened pulmonary valve (arrow); (C) CW Doppler shows a significant gradi-
ent across pulmonary valve; (D) Color Doppler interrogation shows MR (arrow)
Figures 15.2A to D shows evidence of pulmonary Further Reading

stenosis with rheumatic mitral regurgitation (thick- 1. Charles K Friedberg. Diseases of the Heart, 3rd edn,
ened mitral valves with Doppler MR in one of our WB Saunders Co.
patients). 2. Eugine Braunwald, Chronic Valvular Heart Disease,
(Ed) Paul B Beeson in Cecil-LoebTextbook of medi-
cine, 12th edn, 1967, WB Saunders co.
Management 3. Gilbert E. Levinson, Joseph S Alpert, Aortic Stenosis,
For isolated PR, treatment is not required for a long Valvular Heart Disease-3rd edn, (Ed) Joseph S Alpert,
period as patients remain apparently asymptomatic. Lippincott Williams & Wilkins.
Management is scheduled as per the underlying 4. Theo E Meyer, Dennis A Tighe. Tricuspid and
cause. When right heart failure is present, it is treated Pulmonary Valve Disease, Michael H Crawford,
with decongestive therapy. Cardiology 3rd edn, Mosby, Elsevier.
CHAPTER 16
Combined Valvular Lesions
M Satpathy
Introduction Other multivalvular lesions such as AS + MS, MS

It is a well known fact that rheumatic valvular lesions + TS + TR, MS + MR + AR + AS are also not uncom-
mainly present as combined lesions involving more mon.
than one valve. Even a single valve may have both
stenosis and regurgitation. The lesion that is more
Incidence
severe is known as dominant lesion. In pre-echo era
determination of the dominance of lesion by clinical Combined lesions have often been reported by many
evaluation was essential from point of view of medi- authors. One of the series reported recently shows
cal and surgical management. After the non-invasive MS with MR in 15.3 percent, MS with AR 26.7 per-
echocardiography facility is available it has become cent of cases (Routray SN et al, Ind HJ, 2003;55:152-
very easy to determine the dominance of valvular 7). Another series based on hospital study under
lesions without going for invasive procedures like echocardiographic screening shows MS MR in 12.9
cardiac catheterization and angiography. However percent, MS AR in 13.9 percent, AS AR in 4.4 per-
due to some limitations of echocardiography, cardiac cent, MS MR AR in 2.0 percent, MS MR TR in 8.1
catheterization and angiocardiography remains as percent and MS AR TR in 8.02 percent (Patnaik
the gold standard, particularly in combined lesions AN, NIMS, Hyderabad, 2002) and our observation
before going for surgery. of combined lesions below 20 years of age group is
Isolated valvular lesions commonly seen in a MS MR 11.9 percent, MS AR 21.1 percent, MS MR
setting of rheumatic heart disease (RHD) are mitral TS TR 6.4 percent (abstract, Ind HJ, 1999;51:653). In
stenosis (MS) and mitral regurgitation (MR). Lone another series trivalvular stenosis (MS, TS, AS) also
aortic regurgitation (AR) is not common and lone reported in 2.5 percent of cases (Anil Kumar et al,
rheumatic aortic stenosis (AS) is still uncommon. Ind HJ, 1999;51:667).
With long standing (about half century) obser-
vation and from different hospital statistics it is ob-
Parameters to Determine
served that RHD is still rampant in India and about
Dominance of Lesion
60 percent of cases have multivalvular lesions.
The common combined valvular lesions of all age Dominance of lesions is judged by the following
groups are: parameters. 1. History, 2. Physical examination,
1. MS with AR. 3. Auscultation and investigations like ECG, chest
2. MS with MR. X-ray, echocardiography and sometimes cardiac
3. MS, MR with AR. catheterization with angiography. The whole purpose
4. MR with AR. of determining the dominance of lesion is to plan for
5. AR with AS. early medical, interventional or surgical management
6. MS with TS. before irreversible damage occurs.
The fundamental hemodynamic principle to Tricuspid Regurgitation with Associated Lesions

judge the dominance of combined lesions, is based Tricuspid regurgitation is often associated with other
on the fact that the proximal lesion always masks the rheumatic lesions like MS or MS with MR. Function-
severity of distal lesion. al TR is associated with secondary pulmonary hyper-
Table 16.1: Combined mitral stenosis and mitral regurgitation

MS dominant MR dominant
Symptoms Reeling of head, feeling asthenic Breathless, fatigability, palpitation with prominent
(decreased cardiac output), Breathless precordial pulsation
Dizziness, near syncope (in severe MS)
Inspection Normal precordium Precordium may be pulsatile, Apex beat may be
visible
Palpation
parasternal heave Present (due to RV pressure overload) Hyperdynamic precordium (due to LV volume
Apex beat Tapping in nature overload)
Thrill Diastolic thrill palpable Apex forceful, visible
OS sometimes palpable (not as common Systolic thrill palpable
as in lone MS) S3 palpable (not as common as in lone MR)
Auscultation
S1 Loud, may not be snapping S1 diminished, soft
OS/S3 OS often present S3 often present
Murmur MDM present with presystolic accentua- PSM present over apex conducted to axilla (with
tion localized to apical area (with PSM short MDM due to MS)
2-3/6 over apex due to MR)
ECG Right axis with RVH (not as common as Normal axis, full LV force or LVH volume overload
with isolated MS) pattern less common than lone MR
AF common AF not common
X-ray Double contour (left atrium) shadow on Prominent left atrial enlargement, apex LV type
right cardiac border
Straightening of the left border due to
enlarged LA appendage. RV type of apex.
Calcification common Calcification not common
Echo Mitral valve doming with thickening, MV normally opens but thickened, LA and LV dilata-
MVO usually less than 1.0 cm2 with high tion present, left atrial systolic flow present
diastolic gradient
Catheterization Diastolic gradient present, 1+ to 2+ mitral No or minimal gradient but evidence of severe MR
regurgitation present (3+ to 4+)
Note: This combined lesion (Table 16.1) is very commonly seen in clinical practice (Figs 16.1A and B). Cough, dyspnea,
frequent hemoptysis and pulmonary edema indicate MS is dominant where as palpitation and easy fatigability are fea-
tures of severe MR. Pulmonary symptoms (due to pulmonary venous hypertension) is always present when both lesions
are of equal dominance. When S1 normal, OS not snappy or absent, S3 present, MDM with no pre-systolic accentuation
and PSM conducted to axilla are present, it favor MR is dominant where as loud S1, snappy OS, mid diastolic murmur
with pre systolic accentuation favors MS is dominant. In hemodynamic language LV overload due to MR is masked by
presence of MS and at the same time the mitral diastolic gradient is increased due to increased flow.
Combined Valvular Lesions 125
A B
Figs 16.1A and B: (A) CW Doppler recording showing combined mitral stenosis (arrow) and mitral regurgitation (open
arrow); (B) Combined MS (arrow), Color Doppler evidence of MR (open arrow) with Doppler AR (small arrow)
Table 16.2: Combined aortic stenosis and aortic regurgitation
AS dominant AR dominant
Symptoms Reeling of head, near syncope, chest pain (angina Dizziness or near syncope less common palpita-
pain) more marked with exertion tion is more marked, easy fatigability and dysp-
nea on mild exertion
Pulse Slow carotid pulsation (delayed carotid upstroke) Prominent carotid pulsation with head nodding
Precordium Precordium silent, apex localized, normally felt or Precordium pulsatile with forceful apex usually
heaving displaced (out and down)
Peripheral Normally felt or low volume, low pulse pressure Peripheral signs of AR present, wide pulse pres-
Pulses sure (Hill sign absent as AS is associated)
Auscultation
S2 S2 normally heard (not diminished as in lone AS) S2 normally heard
Ejection Click EC rare in Rheumatic AS No EC
Murmur ESM over aortic area conducted to neck vessel, EDM present (not long), no Austin Flint murmur
short EDM over 2nd aortic area or no systolic flow murmur (as AS associated)
ECG LVH with strain pattern commonly present LVH with volume overload pattern
X-ray No marked cardiomegaly but LV contour (no Marked cardiomegaly, LV contour
dilatation)
Echo Aortic valve thickened, aortic valve orifice less than Aortic valve also thickened, AV orifice size
0.7 cm2, concentric LV hypertrophy with normal decreased but more than 0.7 cm2, LV cavity
sized LV cavity, high velocity systolic jet present dilated, diastolic subvalvular turbulence present
Catheterization Pressure gradient present (> 25 mm Hg) Minimal pressure gradient with AR 3+ to 4+
AR 1+ to 2+
Note: This combined lesion is often seen in clinical practice (Table 16.2). In developed as well as in developing countries
because bicuspid aortic valve is common, AS and AR of congenital origin is frequently seen. History of angina or syncope
and slow pulse with slow carotid upstroke indicate AS is dominant. Similarly wide pulse pressure, brisk carotid upstroke, and
displaced apex indicate AR is dominant. It is 2D echocardiography and Doppler clearly determines the severity of the lesions
as mentioned in respective chapters. Catheterization is not routinely done in developing countries because AS, AR mainly of
rheumatic origin and these patients belong to younger age group. But in developed countries angiography is routinely done
because most of the patients belong to elderly age group (> 40 years) having bicuspid or calcific valve. In hemodynamic lan-
guage the severity of AR is underestimated in presence of AS and severity of AS is overestimated in presence of AR (Fig. 16.2).
Fig. 16.2: CW Doppler interrogation from LV outflow in combined AS (open arrow) and AR (arrow)
indicate balanced lesion
Table 16.3: Combined mitral stenosis and aortic stenosis
MS dominant AS dominant
Symptoms Dizziness, syncope, angina pain common but Dizziness, syncope, angina pain common,
hemoptysis, winter bronchitis uncommon, sys- hemoptysis, winter bronchitis uncommon, emboli-
temic embolization may be present zation extremely rare
Pulse Low volume, Carotid pulsation normally felt but Low volume, Carotid pulsation delayed upstroke
slow
Apex Apical impulse not visible Apex beat localized heaving
Thrill Diastolic thrill over apex, uncommon (due to systolic thrill over aortic area, uncommon (due to
presence AS) MS)
S1 Normal or decreased Diminished
S2 P2 may be loud Normal, A2 diminished
S4 Not present Present (but absent in severe MS)
OS Present (Infrequent due to AS) Not present
Murmur Diastolic murmur present, no pre-systolic accen- Prolonged ESM (but intensity decreased) over aor-
tuation (when AS severe) with ESM (due to AS) tic area conducted to carotids but not audible over
apex when MS present (short MDM due to MS)
ECG Left atrial enlargement present, RVH uncommon, Left atrial enlargement present, LVH present but
AF may be present less marked, AF present ( when both AS MS severe)
X-ray Mitral valve calcification rare, ascending aorta AV calcification present, post-stenotic dilatation of
normal aorta present
Echo Doming of MV seen but mitral diastolic gradient Systolic gradient across LVOT underestimated
underestimated
Catheterization Mitral diastolic gradient present but no signifi- Systolic aortic gradient present but no significant
cant systolic aortic gradient mitral diastolic gradient
Note: In presence of MS, the clinical signs of AS are masked, the cardiac output is decreased and LV hypertrophy is less
marked (Table 16.3). To evaluate the exact severity of aortic stenosis in a condition of low flow low gradient situation
is highly essential, particularly going before surgery. The hemodynamics of this combined lesion ‘masking AS by MS’
in 150 cases (largest series) was reported by R Zitnik et al (in Am HJ, 1965;69:22). Similarly another series from India
(Vellore) was reported by Vijayaraghaban G et al (Br HJ, 1977;39:294). BMV is advised if aortic valve lesion is mild and
MS is severe. When both lesions are equally dominant, AVR and OMV is the procedure of choice, otherwise sudden
hemodynamic load on LV will be hazardous when proximal stenotic lesion (MS) is corrected (Fig. 16.3).
Fig. 16.3: 2D echo showing combined mitral stenosis and Fig. 16.4: Combined aortic regurgitation (open arrow)
aortic stenosis (arrows) of equal dominance and mitral stenosis (arrow)
tension due to aortic and mitral valve lesion. Organic and to know the severity of the lesion or dominance
TR is very uncommon if present it is associated with of the lesion, history taking, general and systemic
MS or TS or rarely AS. examination, ECG, X-ray chest and echocardiogra-
The classic murmur of TR is pansystolic blow- phy are necessary. For all practical purposes, echo-
ing murmur audible over left lower sternal border cardiography with Doppler study provides detail ac-
increased with inspiration (Carvallo sign). But when curate informations. In some cases to delineate the
MR is associated the typical character of TR murmur anatomy of regurgitant lesions with their severity
is masqueraded (Fig. 16.8A). The diastolic murmur accurately and to know LV function, cardiac cathe-
audible along with TR, indicate associated TS or MS terization and angiocardiography is of immense help
(Fig. 16.8B). When TR and TS are present inspiratory before surgery.
increase of systolic murmur indicate TR is dominant.
In RHD, TR with no signs of pulmonary artery hy- Management
pertension (PAH) indicates organic involvement of
tricuspid valve. When present with PAH it may be due Patients of multivalvular lesions become symptomatic
to primary pulmonary hypertension (PPH) or due to early. Secondary prophylaxis with penicillin has to be
secondary cause (MS with PAH). Roentgenography is continued till 40 years of age and in some cases where
helpful to differentiate these two conditions. Marked there is evidence of recurrence it may be lifelong. In-
proximal pulmonary artery dilatation with sudden fective endocarditis prophylaxis before surgical pro-
narrowing at distal part (pruning) indicate PPH, where cedures is also advised. Antibiotics for prophylaxis
as redistribution of vascularity mainly over upper lobe vary as per the type and site of surgery concerned.
is a feature of secondary PAH (MS with PAH). It is Congestive heart failure is to be treated with
echo with Doppler decide the etiological factors, tri- conventional antifailure drugs like digoxin, diuret-
cuspid valve morphology and dominance of associated ics and ACE inhibitors. However vasodilators like
lesions. ACE inhibitors are to be avoided or used with cau-
To summarize in setting of multivalvular lesion tion in stenotic lesions. Arrhythmias if present is to
it is mandatory to know the valves affected and the be treated with suitable anti-arrhythmic drugs. In
dominance of lesion. To reach at a definite diagnosis case of atrial fibrillation besides controlling ventricu-
Table 16.4: Combined aortic regurgitation and mitral stenosis

AR dominant MS dominant
Symptoms
Palpitation Present Not a feature
Dyspnea on exertion Present More marked
PND/orthopnea Late feature common
History of embolism Rare Often present
Signs
Precordium Pulsatile Silent precordium
Pulse pressure Not wide (even in severe AR diastolic > Normal pulse pressure
70 mm Hg)
Apical impulse Palpable (forceful and localised) Feeble apex (tapping in nature), but when apical
impulse is prominent it indicates AR is severe
Left parasternal Not felt Felt (over ulnar border of hand on moderate
heave pressure)
Auscultation
S1 Normally heard Loud (May be snappy)
S2 Normally audible S2 loud (P2 louder than A2)
S3 Present Absent
OS Not audible May be audible
Diastolic murmur Long EDM even audible upto apex with MDM rumbling and with presystolic accentuation,
Austin Flint murmur (if MS is mild) short EDM over LPSB with
Systolic murmur Aortic flow systolic murmur uncommon ESM present (due to severe PAH) when AR mild
ECG
AF Rare Often present
RVH Not present May be present
LVH Present Not present
X-ray Cardiomegaly, LV contour No cardiomegaly with RV contour
Echo MV and AV thickened with LV dilatation, MV thickened with diastolic doming and gradient
Color Doppler shows wide diastolic AR across MV and a narrow AR jet
jet
Note: It is a very common combined lesion (Table 16.4). Patients of MS show frequently Doppler evidence of AR but
not clinically significant (Fig. 16.4). As proximal lesion always masks the distal lesion, significant AR may be missed or
under estimated in patients with severe MS. In setting of severe MS and AR, angina is a common symptom. The blunt
impact of AR is restricted due to MS as LV is under filled during diastole The wide pulse pressure, and hyperdynamic
outward (out or downward) apex are absent. If in some cases AR is dominant and MS is mild in this situation the Austin
Flint murmur should be distinguished from diastolic murmur of MS, by clinical maneuvers such as isometric hand grip
and squatting (AR murmur and Austin Flint murmur increased with these maneuvers).
In this combined lesion, proper evaluation of severity of AR is difficult from echo only, so cardiac catheterization is
indicated before surgery.
Table 16.5: Combined aortic regurgitation and mitral regurgitation

AR dominant MR dominant
Symptoms
Dyspnea on exertion Present Fatigability, more marked
PND/orthopnea Present Often present
History of embolism Rare Rare
Pulse High volume High volume but less marked
Blood Pressure Wide pulse pressure (Hill sign) Wide pulse pressure (no Hill sign)
Precordial pulsation Pulsatile Pulsatile
Apical impulse Palpable (heaving and localized) Forceful and localized
Left parasternal Felt Well felt
heave
Auscultation
S1 Normally heard Diminished
S2 Normally audible Normal, rarely S2 loud
S3 Present Present
Murmur Long EDM with short MDM (Austin PSM over apex conducted to axilla, short EDM over
Flint murmur) over apex upper left sterna border (due to AR), mitral dias-
Flow aortic systolic murmur present tolic flow murmur present (when AR is mild)
(when MR is mild)
ECG
AF Rare Rare
LVH Commonly present Present
X-ray Cardiomegaly, LV contour, LAE less Cardiomegaly, LV contour, LAE more marked
Echo marked MV thickened, Large MR jet and narrow AR jet
MV and AV thickened with wide dias-
tolic AR jet and small MR jet in LA
Catheterization
AR 3+ to 4+ 1+ to 2+
MR 1+ to 2+ 3+ to 4+
Note: This combination of AR and MR (Table 16.5) is not uncommon in clinical practice (Fig. 16.5). The peculiarity of
this combined lesion is that presence of one lesion cause adverse hemodynamic effect over the other lesion.
In chronic severe AR increased end-diastolic pressure causes premature closure of mitral valve but presence of MR
leads to direct communication from aorta to LV to LA to pulmonary veins. That is why patients become more symp-
tomatic in this combined lesion. This situation worsens the prognosis and also surgical result.
With this combination management is really problematic because they have different pathophysiology and different
guideline for surgical correction. The principle is to treat the dominant lesion first. If both are equally dominant before
going for double valve replacement, it is AVR with mitral valve repair may be considered.
Remember: The flow systolic murmur over aortic area due to AR and the flow diastolic murmur over the apex due
to MR are not to be confused with additional lesions like MS or AS.
Fig. 16.5: Color Doppler interrogation showing Combined

Aortic Regurgitation (open arrow) Mitral Regurgitation
(arrow) in parasternal long axis view
lar rate, anticoagulation with warfarin are prescribed mitral valve and to replace aortic valve or in case of
for a prolonged period or till development of its side double mitral lesion simultaneous open mitral com-
effect, to avoid embolic phenomena. Prothrombin missurotomy (OMV) with repair of mitral valve may
time is advised to know the international normalized be considered to avoid MVR.
ratio (INR) to regulate dose of anticoagulant. However in about 70 to 80 percent of cases re-
Interventional procedures are not of much help in quiring valve surgery are unable to afford for it due
setting of multivalvular lesions except pure combined to poor economic status. Other 10 to 20 percent pa-
stenotic lesions. In recent years balloon valvoplasty is tients present very late for which surgery is denied.
the procedure of choice in combined stenotic lesions Rheumatic Heart Disease affects mainly young
like MS+TS or MS+TS+AS or MS+AS. It is surgery, people at the prime of their life imposing a huge eco-
the answer and also the remedy. Surgery should be nomic burden to the family and also to the society. As
advised in right time in each particular case to avert there is no permanent cure for RHD, the treatment
progressive left ventricular dysfunction, so preopera- in true sense is palliative. Even after balloon dilata-
tive cardiac status is to be evaluated. Surgery in form tion or surgical valvotomy the disease relentlessly
of repair and valve replacement is considered as per progresses, so many of them require second dilata-
the severity and dominance of valvular lesions con- tion or valve replacement in course of time. These pa-
cerned. Operative risk for double valve replacement tients require constant follow-up for anticoagulation
is much higher than single valve replacement. Long- (to maintain INR), for valve malfunction and for
term survival is also much less with double valve developing infective endocarditis (as they are at
replacement. When both aortic and mitral valves high-risk for IE). Most of these patients of combined
lesions are there all efforts should be made to repair lesions become class III-IV symptomatic within
Table 16.6: Combined aortic stenosis and mitral regurgitation

AS dominant MR dominant
Symptoms
Palpitation Not common Present (more marked)
Dyspnea on exertion Present Present (more in form of fatigability)
Dizziness/near Often present Present
syncope Late feature Often present
PND/orthopnea Rare Rare
History of embolism
Signs
BP Low volume pulse with low pulse pressure Wide pulse pressure
Precordial pulsation Present (not as silent as in lone AS)
Apical impulse Palpable (heaving and localized), may be out Pulsatile
and down Forceful and localized
Left parasternal Not felt Felt
heave
Auscultation
S1 Diminished Diminished
S2 Diminished Normal, rarely S2 loud
S3 Not present Present
S4 Present Not present
Murmur Rough ESM over aortic area conducted to neck PSM (intensity increased) over apex con-
with PSM over apex conducted to axilla ducted to axilla with ESM over aortic area
ECG
AF Rare Rare
LVH Present with systolic strain pattern Present with volume overload pattern
X-ray Cardiomegaly, LV contour, aortic dilatation Cardiomegaly, LV contour, LA enlargement
Echo MV and AV thickened with high velocity aortic MV thickened, Large MR jet and low velocity
systolic jet with small MR jet in LA aortic jet
Cardiac catheterization Aortic gradient present (>50 mm Hg) Mild aortic gradient with MR 3+ to 4+
Note: It is an uncommon lesion, when present is a hazardous combination (Table 16.6). Obstruction to LV outflow
augments MR flow, so palpitation and syncope are common symptoms occur even with mild exertion. Presence of MR
diminishes the ventricular preload necessary for maintenance of LV stroke volume in presence of AS. In this combina-
tion patient become very ill because of low cardiac output with pulmonary signs (due to severe pulmonary venous
hypertension) (Fig. 16.6).
In this situation presence of MR cause difficulty to assess the severity of AS because of decreased forward stroke
volume. These patients are usually more symptomatic with LV dysfunction and pulmonary artery hypertension. They
need early surgical management with AVR when mean aortic gradient is more than 30 mm Hg with mitral valve repair
if feasible.
Table 16.7: Combined tricuspid stenosis and mitral stenosis

TS with MS MS
Symptoms
Dyspnea on exertion Present Present
Orthopnea Uncommon (late features) Common
PND Late feature Often present
Hemoptysis Rare Common
Early fatigability Marked Less marked
Signs
Pulse Very low volume pulse Low volume pulse
BP Low pulse pressure Low pulse pressure
Neck Veins Prominent Not prominent
JVP Raised Not raised
Thrill Diastolic thrill less common Diastolic thrill common
Left parasternal heave absent Commonly felt
Auscultation
S1 Diminished Normal or may be loud
S2 Normal S2 loud (P2 > A2)
OS Tricuspid OS (uncommon) Mitral OS (Common)
Murmur MDM over lower parasternal increasing with Only apical MDM, no respiration
inspiration and MDM over apex variation
ECG
PR May be prolonged Normal
AF Present Present
RAE/LAE Marked RAE Marked LAE
RVH Not present Present
X-ray
PVH Less marked More marked
RAE Prominent Less prominent
Echo MV and TV thickened, domed with significant MV thickened, diastolic gradient only
diastolic gradient across MV and TV across MV
Cardiac catheterization Significant transmitral diastolic gradient, Significant transmitral diastolic gradi-
Increased RA pressure with prominent a wave ent but no pressure gradient between
and pressure gradient between RA and RV RA and RV
(across TV)
Note: Hemoptysis, PND and orthopnea are remarkably absent in MS when TS is associated (Table 16.7). On the other
hand signs of TS are over shadowed by presence of MS (or patients with TS with AS) (Fig. 16.7). Patients with MS if
moves relatively comfortably even with edema feet and ascites, there is strong clinical suspicion of associated significant
TS. For all practical purposes TS is always associated with MS, very rarely TS with AS reported.
Fig. 16.7: 2D echo in apical 4 chamber view showing com-

Fig. 16.6: Combined Aortic Stenosis (arrow) and Mitral bined tricuspid stenosis (white arrow) and mitral stenosis
Regurgitation (open arrow) (black arrow)
A b
Figs 16.8A and B: Echo in apical 4 chamber view showing; (A) Combined tricuspid regurgitation (open arrow) and mitral regur-
gitation (arrow); (B) Combined mitral stenosis (arrow showing typical stenotic flow) and tricuspid regurgitation (open arrow)
fourth to fifth decade of life. They fully depend on 2. Maurice Enriquez-Sarano, Chronic Mitral
medical management and complications at this stage Regurgitation, Valvular Heart Disease-3rd edn, (Ed)
are eminent, so prognosis is very guarded. Joshep S Alpert, Lippincott Williams & Wilkins.
3. Rheumatic Fever: 2nd edn, Milton Markowitz &
Leon Gordis, WB Saunders Company, Philadelphia,
Further reading 1972.
1. Catherine M Otto, Robert O Bonow, Valvular Heart 4. Soumitra Kumar, et al. Management of Valvular
Disease, Braunwald’s Heart Disease a Text Book of Heart Disease, Current Trends in Cardiology, 2nd
Cardiovascular Medicine, 8th edn, Saunders An edn, (Ed) Soumitra Kumar, Ramkrishna Mission Seva
Imprint of Elsevier 2008. Pratisthan, Kolkata 2006.
CHAPTER 17
Infective Endocarditis
C Satpathy, NK Mohanty
Definition death of all cardiac diseases and was more prevalent

Infection of the endothelial surface of the heart with in younger age group as a complication of rheumat-
microorganisms is known as infective endocarditis ic heart disease in both developed and developing
(IE). Because of similar clinicopathological charac- countries. But the scenario of epidemiology of IE
teristic feature, infection of arteriovenous shunts, ar- changed completely in the second half of the twen-
terioarterial shunt (PDA) and coarctation are also in- tieth century after significant decline of rheumatic
cluded within this definition, but the term ‘infective heart disease in developed countries, more so after
end-arteritis’ is used for these extracardiac lesions. the use of penicillin and other antibiotics. Neverthe-
The characteristic lesion of IE is, the vegetation less IE is responsible for 0.16 to 5.4 cases per 1000
which develops commonly on heart valves, and less hospital admissions globally. In India 40 percent of
commonly over other intracardiac structures and IE are related to valvular heart disease and occurs at
mural endocardium. a younger age. Incidence of prosthetic valve endo-
carditis is 10 percent in India where as it is 15 to 20
percent in western countries. (A George Koshy, Car-
History diology Update, CSI, 2008)
One of the earliest reports is by Riviere (1646) and
Lancisi (1706) who described vegetation (nodules) Changing Clinical Pattern of Endocarditis
in intracardiac tissue in autopsy series. Subsequently,
Bouillaud coined the term endocardium in 1824 and Infective endocarditis has changed its presentation
endocarditis in 1825. Virchow in 1869 for the first and course from what was seen in preantibiotic era.
time described the vegetation which is infective in The new trends of today’s endocarditis have the fol-
nature (as bacteria were isolated from the vegetation). lowing characteristics:
Osler described infective endocarditis extensively in • Increased median age of presentation—That is the
his prestigious Goulstonian lecture in 1885. Libman, disease is more often seen in older patients all over
Freiberg and Beeson from USA for the first time the world with increased ratio of males to females.
introduced blood culture as an important investiga- In USA the median age has increased to 58 years
tion for the diagnosis of IE. Penicillin for the first time as reported by Mayo Clinics. That is because of
was used in IV route in a patient of endocarditis in increased longevity with increased incidence of
October, 1940 in New York. degenerative disease and declining incidence of
RHD.
• Incidence of nosocomial IE has increased because
Epidemiology
of the increase in the number of prosthetic valve
In the first half of the twentieth century that is in the surgery and explosive use of health care interven-
pre-penicillin era, IE was responsible for 9 percent tion, both in developed and developing countries.
Infective Endocarditis 135
• There is increased incidence of IE in patients hav- usually caused by less virulent organisms such as
ing human immunodeficiency virus (HIV) infec- Streptococcus viridans.
tion and in IV drug abusers besides prosthetic This broad classification has no clear demarca-
valve infection. In these cases staphylococcal tion (no water tight compartment) between them
and gram negative bacterial infection are more. because the clinical picture depends on the virulence
Recently there occurred a dramatic increase in of the organisms neither endocarditis is always bacte-
Staphylococcus aureus related IE with decreasing rial. Therefore the Newer classification is:
prevalence of Streptococcus viridans. This chang- 1. Native valve endocarditis (NVE): Infection of
ing epidemiology is a challenge to the physicians patient’s own heart valve which was either previ-
due to the virulence of S. aureus, its drug resist- ously normal or structurally damaged by congeni-
ance and ability to infect structurally normal tal or acquired diseases like RHD.
valves. 2. Prosthetic valve endocarditis (PVE): Infection of
• Because of frequent use of antibiotics, the inci- a prosthetic heart valve. ‘Early PVE’ is defined as
dence of IE has decreased. At the same time the IE occurring within 2 months of surgery and ‘late
classical features like clubbing, Roth spot, Osler’s PVE’, if develops thereafter. This includes both
nodes and splenomegaly, etc. are rarely seen in metallic prosthesis and bio-prosthesis.
clinical practice now. With use of antibiotics the According to circumstances by which IE is
rate of resistance has also increased. acquired, it is also classified as:
• Increased application of echocardiography partic- 1. Nosocomial IE: These are endothelial infection
ularly transesophageal echocardiography (TEE) related to intravenous catheters, IV lines, dialysis
now helps in identifying vegetations more accu- shunts, etc. acquired in a hospital environment.
rately and early. 2. Community acquired IE: In contrast to nosocomial
• In developing countries commonly RHD (mainly IE, other IEs that are acquired outside hospital
mitral valve, then aortic valve) is still responsible environment is known as community acquired IE.
for the majority of cases of IE besides congenital The term ‘acute IE’ is also used to describe ful-
heart disease and degenerative heart disease. Poor minant presentation in infections related to highly
oral hygiene in this area remains as prime contri virulent organisms in any of the above type of IE.
butor to IE.
Pathogenesis and Pathology of
Classification Infective Endocarditis
The term bacterial endocarditis and subacute bac- Infective endocarditis (IE) is a localized endothelial in-
terial endocarditis (SABE) were used convention- fection consequent to intermittent or continuous bac-
ally for a long-time. Subsequently, the term infective teremia. Complex interplay of a series of key factors
endocarditis (IE) was preferred instead of bacterial plays a role in the genesis of IE lesion. These include:
endocarditis because other organisms like fungus, • Integrity of the vascular endothelium and under-
Rickettsia and spirilla also cause endocarditis. lying cardiac abnormality (hemodynamic abnor-
The old (traditional) classification: malities). Disruption of vascular endothelium
1. Acute (malignant) bacterial endocarditis (ABE): It predisposes for IE.
progresses over a period of days to 1 or 2 weeks • The host immune system (host defense).
with rapid clinical deterioration and early onset of • Hemostatic mechanism.
complications if not treated adequately. The usual • Microbial properties including its virulence and
causative organism is Staphylococcus aureus. the inciting cause of bacteremia.
2. Subacute bacterial endocarditis (SABE): It pro- Host endothelial damage provides the platform
gresses over a period of weeks to months and is for deposition of platelets and fibrin over it, result-
ing in nonbacterial thrombotic endocarditis (NBTE). occurs in 86 percent, aortic valve 55 percent, tricus-
NBTE creates the receptive milieu for bacterial colo- pid valve 19 percent and pulmonary valve is rarely
nization during episodes of bacteremia forming the affected (1% of cases). Because of flow across a low
nidus for formation of vegetation. Circulating bacteria pressure gradient, large isolated atrial septal defects
gets access to it and grow inside it. As bacteria colo- are immune to IE.
nize, more platelets and fibrin adhere to the surface to Bacterial flora is commonly present in human
form full grown vegetation. These vegetations are pli- being in different sites like gums, oropharynx, ure-
able, white and the size is quite variable, usually seen thra, vagina, anal canal and normally transient low
on the line of the valve closure, they are polypoid with grade bacteremia occur in the circulation in other-
abundant bacteria inside it, with no or scant inflam- wise healthy persons. Manipulation of these sites also
matory cells. Within the vegetation bacteria can reach produces bacteremia in addition to infection of any
extremely high concentration (109 to 1011 organisms organ.
per gram of tissue). Some of these bacteria may be in a
low metabolic state and protected from host defense. Causative Organisms
Vegetations are avascular. They spread along the
mural surface of the endocardium so that they travel Although any microorganism can cause IE, Strepto-
from mitral valve to left atrium and towards chordae coccus viridans, Staphylococcus aureus and Entero-
tendinae. These vegetations or part of it may be de- coccus faecalis are responsible for majority of cases.
tached and move in the circulation causing embolism S. viridans is an alpha hemolytic Streptococcus which
leading to infarction in different target organs (myo- is a commensal of the throat. Coagulase negative
cardium, spleen, brain, mesentery and extremities). staphylococci like S. epidermidis is a skin commensal
Besides there are certain conditions like ad- and Enterococcus faecalis is found in perianal region
vanced malignancy, complications of tuberculosis or of healthy people. These are low virulent organisms
AIDS, where very big vegetations are seen, known as and are responsible for subacute cases of IE.
marantic endocarditis. Big vegetations are also seen Highly virulent staphylococcal infection is usually
in Libman—Sack endocarditis of systemic lupus ery- responsible for nosocomial IE and acute IE, seen com-
thematosus, Loeffler’s eosinophillic endocarditis and monly in intravenous drug users. Fungi (Histoplasma,
carcinoid syndrome. Candida, Aspergillus) and Brucella species also affect
After successful antibiotic therapy, vegetation drug abusers, alcoholics and prosthetic valves. S. bo-
may resolve completely or remain contracted in size vis related IE is particularly common in colonic dis-
and persist indefinitely as a sterile mass adherent to ease. Rickettsia like Coxiella burnetii infection spread
valve tissue (healed vegetation). With treatment and from animals to man. The acronym HACEK is used
healing capillaries and fibroblasts appear inside the for a group of fastidious organisms (Haemophilus, Ac-
vegetations. tinobacillus, Cardiobacterium, Eikenella and Kingella
Vegetations are mostly formed in downstream species) which are responsible for 5 to 10 percent
of the regurgitant lesions, i.e. on the ventricular side of cases of IE. In some cases Streptococcus pyogenes,
of the semilunar valves and the atrial side of the AV Neisseria and Pseudomonas may produce IE. Staphy-
valves. Jet lesions from regurgitant valves or intracar- lococcus epidermidis is the most common pathogen
diac shunts may also damage endothelium and veg- for early PVE, besides S. aureus and gram negative
etations may be formed on such sites of injury, e.g. bacteria. Microbiology of late PVE resembles NVE.
mitral chordae in aortic regurgitation, posterior left Common sources of bacteremia for endocarditis
atrial wall in mitral regurgitation and on septal leaf- are:
let of tricuspid valve in ventricular septal defect. De- • Skin infections of any etiology.
gree of mechanical stress as reflected by the pressure • Surgical sources include any surgical procedure
gradient across the valves is also a crucial factor for (minor or major), burn injury, trauma and par-
development of IE. Therefore affection of mitral valve ticularly dental surgical procedures.
• Although very low risk exists for patients having insidious without identifiable predisposing factors. The
pre-existing heart disease with normal pregnancy, clinical manifestations occur within weeks to months
during delivery and puerperium, perinatal infec- in case of native valve endocarditis due to streptococ-
tions and septic abortions are potential sources for cal infection. In case of Staphylococcus aureus infection,
IE. Common organisms are E. faecalis and gram the onset is very rapid and signs and symptoms become
negative bacteria. florid within two to three days (Acute IE).
• Intracardiac and extracardiac surgery and con-
tamination of blood present in pump oxygenator
Constitutional Symptoms
(Common bacterias are Staphylococcus epider-
midis). • Fever is the most common presenting feature. It
• Nosocomial sources are during intracardiac cath- may be low grade or intermittent type persisting
eter manipulation, pacemaker implantation, car- for a long period or it may be continuous and hec-
diac biopsy, intravenous or intra-arterial catheters tic type (high grade fever). It is one of the common
and intratracheal airway catheter procedures. causes of pyrexia of unknown origin. In some cases
• Hemodialysis, creation of AV shunts for dialysis is fever is absent (afebrile) particularly in setting of
a potential source. severe congestive heart failure, immunocompro-
• Urinary tract and GI tract sources. mised patients, cases on prior antibiotics or elderly
• Intravenous drug abuse (right sided endocarditis patients. Chest pain, cough and confusion may be
is common). associated symptoms of high fever.
The prosthetic valves are more prone to infec- • Other constitutional symptoms and signs are ane-
tive endocarditis (PVE). Mechanical valves are more mia (mild to severe), generalized malaise, ano-
prone for early (within 60 days of surgery) as com- rexia, nausea, vomiting, headache, abdominal
pared to bio-prosthetic valves which are more prone pain and loss of weight. Splenomegaly is seen in
for late PVE (after 60 days of surgery). long standing infection (in >50% of cases).
Clinical Features Cardiac Symptoms and Signs

The various pathophysiology involved in clinical • Congestive heart failure (CHF): It is usually due to
manifestations of infective endocarditis are: growth of vegetation causing valve apparatus dam-
1. Cytokine mediated constitutional symptoms, age in form of perforation or rupture of chordae
occur due to persistent bacteremia. tendinae. Sometimes infection may extend to sur-
2. Local destructive effects of intracardiac structures rounding structure like valve ring and aortic wall
resulting in damage of valve apparatus including resulting in periaortic abscess, diverticulum and
perforation and rupture, which ultimately leads to aneurysm. Rupture of such aneurysm produce fis-
congestive heart failure. tula between major vessels and between cardiac
3. Embolization of fragments of vegetations and chambers that also results in CHF. Sometimes dif-
hematogenous seedling at remote sites giving rise fuse myocarditis may produce CHF in addition to
to infective embolism to almost any organ. coronary vasculitis, embolism, and immune com-
4. Host antibody response to the infecting organism plex deposition.
(circulating immune complexes and other immu- • Appearance of new murmurs or changing murmur:
nopathologic factors). New regurgitant murmurs (commonly mitral or
Clinical presentation of infective endocarditis (IE) may be aortic) are mainly audible. There may be
is therefore highly variable and peculiar in that most change in intensity and duration of pre-exist-
of its clinical manifestations can be enrolled under its ing murmurs during the course of the disease.
complications. In about 50 percent of cases the onset is Large vegetations may cause functional valvular
obstruction (mitral inflow or left ventricular out- pathognomonic of IE and are commonly found in
flow obstruction), giving rise to new murmur. SLE, hemolytic anemia and gonococcal infections.
• Conduction defect: High grade AV block (in 2–4% • Clubbing: It takes some days to appear mainly in
of cases) occurs due to periannular abscess from setting of subacute cases of IE. Hypertrophic oste-
extension of infection to paravalvular tissue. It may oarthropathy is rare.
be transient or persistent. It is more common in
aortic than mitral affection, commonly seen with
Ophthalmic Manifestations
PVE. Supraventricular and ventricular arrhyth-
mias may be present due to myocarditis. • Conjunctival hemorrhage: In setting of fever and car-
• Pericarditis: It gives rise to dull aching or acute diac murmur if conjunctival splinter hemorrhage is
chest pain more marked during deep inspiration. present infective endocarditis is most probable.
Auscultation reveals a pericardial rub (scratchy • Roth spots: These are oval shaped hemorrhage with
superficial murmur). It may be associated with pale center close to the optic disk (due to micro
high grade fever when purulent pericarditis is pre- infarction of retinal vessels). They are not specific
sent. of IE, may be seen in anemia, leukemia and SLE.
• Flame shaped hemorrhage: These are also seen in
the retina.
Extracardiac Manifestations
• Sudden loss of vision: It is due to embolism in reti-
Cutaneous Manifestations nal artery or due to optic neuritis or choreo-reti-
nitis. Panopthalmitis may occur in acute IE.
• Petechial hemorrhages: These are often seen over
trunk and feet and in oropharynx. It is nonblanch- Renal Manifestations
ing and has a pale center. It is due to microembo-
lization to the small vessels (seen in long standing Diffuse proliferative glomerulonephritis and inter-
cases). In fulminating cases it is sometimes due stitial nephritis due to deposition of circulating im-
to disseminated intravascular coagulation. They mune complexes can cause microscopic hematuria
appear in crops fading in 2 to 3 days. Petechiae and proteinuria. The flea bitten kidney of acute stage
may be produced by vasculitis. Ischemia of distal is due to multiple small red hemorrhagic spots.
lower extremity due to embolization may cause
Blue toe syndrome. Musculoskeletal Manifestations
• Splinter hemorrhage: These are linear red or brown
streaks (1–2 mm) seen on the finger nails or toe Arthralgia involving multiple joints is common.
nails. It is seen in about one-third cases of long Oligo or mono articular arthralgia, myalgia, back-
standing IE. It is due to microembolization to lin- aches are common features.
ear capillary under nail beds.
• Janeway lesions: They are small (1–4 mm), pain- Neurological Manifestations
less (nontender), erythematous macules, blanches
on pressure, present over palms and soles seen It includes toxic encephalopathy, meningoencepha-
in cases of IE with prolonged duration and are litis, cerebral abscess, cranial nerve palsy, motor sen-
thought to be embolic. sory deficit or some form of psychiatric symptoms.
• Osler’s node: It appears as peas to an almond sized Mycotic aneurysm of cerebral arteries occurs mainly
(2–15 mm) subcutaneous papule over palms due to Streptococcus viridans and is found usually in
and soles and are very tender and indurated. the middle cerebral artery territory. Mechanism in-
They are seen on distal phalanges and disappear volves metastatic infective seedlings occluding the
within 1 to 5 days of therapy. Osler’s nodes are not vasa vasorum causing infarction of the arterial wall.
The aneurysm formed can produce pressure symp- 3. Rheumatoid factor and serum VDRL test: These
toms like focal deficit, epilepsy, headache and later on may be positive due to immunological phenom-
intracerebral hemorrhage due to its rupture. ena known as ‘false positive’ in setting of IE.
4. Blood culture: It is the corner stone for diagnosis
of IE. Care should be taken during venipuncture
Major Embolic Events
to avoid skin contamination. Three to four sets
Septic emboli are seen in 20 to 45 percent of patients (no more than 2 bottles per venipuncture) of cul-
of IE. It may involve any target organs (brain, coro- tures should be obtained in first 24 hours and the
nary arteries, retinal artery, mesenteric arteries, kid- samples are inoculated minimum 10 ml/bottle for
ney and spleen, besides pulmonary embolism due to the optimal pickup rate. Separate bottles for aero-
tricuspid IE). Forty percent of patients who have had bic and anaerobic culture medium must be used.
an embolic event may have another embolic attack. Typical microorganisms for IE from two separate
Hypermobile large vegetations of initial days prior to blood cultures in the absence of a primary focus
antibiotic therapy have high-risk of embolizations. or persistently positive blood culture diagnose the
Embolism affecting the limbs commonly occurs in condition. When two or more samples are posi-
fungal endocarditis. Right sided endocarditis of the tive drawn at 12 hours interval or three or more
tricuspid valve (usually in IV drug abusers or patients samples are positive drawn at least 1 hour apart
on pacemakers, defibrillators or right heart catheteri- or when 70 percent of more than four samples are
zation) may present with chest pain, dyspnea, hemop- positive, it is taken as a positive result for a micro-
tysis and fever due to pulmonary embolization. biological diagnosis. Prolonged period of culture
is necessary for IV drug users and when fun-
gal infection is suspected. One should wait for 3
Investigation
days to 1 week after discontinuation of antibiotics
depending on short or long-acting antibiotic usage
Hematological Investigation
before blood is drawn for culture. Swab should be
1. Peripheral blood examination: Hemoglobin esti- taken from any potential site of infection (skin
mation is done to assess the severity of anemia lesion) for culture and sensitivity. Streptococci (in
which is usually present with a characteristic of subacute IE) and staphylococci (in acute IE) are
anemia of chronic disease (normochromic/nor- responsible for 80 percent of infective endocardi-
mocytic). Total leukocyte count and the number tis. Culture negative endocarditis contributes to
of polymorphonuclear leukocyte are increased one-third to half of all cases of IE in India.
in acute IE. Buffy coat smear examination shows 5. Serological tests: If blood culture is negative in case
intracellular Staphylococcus if present (in acute of suspected IE, specific serological tests are done
IE). Blood urea and creatinine are raised in against Aspergillus precipitous, Candida anti-
immune complex glomerulonephritis with renal bodies (rise in titer), Q fever (Coxiella burnetii),
failure (Needs continuous monitoring). LFT may Chlamydia (complement fixation test), Brucella
be deranged, especially with an increase in ALP agglutinins; Legionella antibodies, and Bartonella
and gamma GT. species on routine basis to isolate the particular
2. Acute phase reactants—ESR: It is markedly organism responsible for endocarditis and its sen-
increased (60–100 mm/hr) in almost all cases sitivity to antibiotics.
(90%) of IE (particularly subacute IE) and gradu- 6. New techniques: Recently newer techniques like
ally comes down to normal (3–6 months after anti- molecular methods (to identify DNA sequences)
biotic therapy). CRP is also raised in IE but comes and marker of bacterial infection (serum procal-
down to normal earlier as compared to ESR. citonin) are also used in diagnosis of IE.
Urine Examination genic and oscillating pedunculated mass attached to

valve apparatus (Figs 17.1A and B) with independent
In most of the cases of IE including acute IE there motion from the valve. If the vegetation is a fixed one
is microscopic hematuria and mild proteinuria. In or ill defined but attached to the leaflets, it is known
some cases frank hematuria is present indicating as possible vegetation, may or may not be due to IE.
renal infarction. Vegetations are termed large if size when more than
10 mm (Fig. 17.1C). Perivalvular or periannular ab-
scess are easily seen by 2D echo as echo free spaces
Electrocardiogram
adjacent to valve annulus (Fig. 17.1E). Valve perfo-
Electrocardiogram (ECG) changes are mainly asso- ration can also be detected by color Doppler show-
ciated with underlying complications. In some cases ing regurgitation through the perforation. Chordal
AV block or other conduction abnormalities may be rupture is diagnosed when chordal tissue is seen
present over a previously normal ECG indicating fo- prolapsing to LA in systole (Fig. 17.1D) with appear-
cal myocarditis or abscess formation. ECG changes ance of new mitral regurgitation or increased severity
of myocardial infarction may be present due to coro- of previous regurgitation. In prosthetic valve endo-
nary embolism. carditis, dehiscence of prosthetic valve may be seen
apart from vegetation. TEE is also more sensitive for
evaluation of prosthetic valve endocarditis. However,
Roentgenography
a normal echo does not exclude the diagnosis of IE.
Chest X-ray may be normal. Signs of pulmonary ede- Repeat TEE is indicated in 3 to 5 days if clinical sus-
ma or multiple patchy opacities or infarcted areas of picion remains high.
septic emboli indicating right sided (tricuspid valve) Echocardiography also helps in assessing
endocarditis can be seen. All patients should have an the predisposing condition in the heart, valve
OPG (Orthopentamogram—a panoramic dental X- function, associated lesions and determining other
ray) and dental opinion. Fluoroscopy can demonstrate hemodynamic parameters including ventricular
abnormal motion of prosthetic valve dehiscence. function.
Vegetations should be differentiated from nor-
mal variants like Chiari network and Eustachian
Echocardiography
valve seen in right atrium of healthy persons and
It is an essential and specific noninvasive investiga- also from myxomatous mitral valve with significant
tion to diagnose IE which is included in major diag- redundancy of leaflets. Vegetations should not be
nostic criteria. confused with cardiac tumors and thrombi. Maran-
Infective endocarditis (IE) vegetation can be seen tic endocarditis of advanced cancer, Libman–Sacks
in all modalities of echocardiography. Initially veg- endocarditis of systemic lupus erythemotosus and
etation was detected by M-mode echocardiography. antiphospholipid antibody syndrome shows large
Subsequently with advent of transthoracic echocar- vegetations.
diography (TTE) and transesophageal echocardiog- Vegetations of acute rheumatic fever are small
raphy (TEE) with color Doppler facility, vegetations and sessile and have no independent motion from
and other complications of IE could be detected the valve where it is attached. Sclerosis and calcific
accurately. Vegetation > 2 mm are detected by TTE nodules of degenerated valves in elderly many a
where as small vegetations < 0.5 mm can be detected times mimic vegetation.
by TEE. TEE is definitely superior to TTE for detect-
ing vegetations. The sensitivity of TTE for vegetation
Magnetic Resonance Imaging (MRI)
detection is 65 percent, for intracardial abscess is 30
percent. For TEE this amounts to more than 95 per- It is useful in case of neurological complication of IE
cent. Vegetation are characterized by distinct, echo- to detect the type of lesions like cerebral infarction
A B C
D E
Figs 17.1A to E: Echocardiography in infective endocarditis. (A) Vegetation in mitral valve on the left atrial side of anterior
leaflet (arrow) seen in parasternal long axis; (B) Large vegetation seen on aortic valve (arrow) occupying the outflow tract
in apical long axis; (C) A large tricuspid valve vegetation (arrow) in apical 4 chamber view; (D) Aortic valve vegetation
(arrow) with ruptured chordae to anterior leaflet, chordal tissue seen prolapsing to LA in systole (open arrow); (E) Aortic
root abscess, note in short axis the echo free space adjacent to aortic root on anteromedial aspect (arrow). Abbreviations:
AV—Aortic valve; Ao—Aorta; LA—Left atrium; LV—Left ventricle; RV—Right ventricle
or brain abscess. Aortic root aneurysm, periannular done in elderly patients to exclude associated coro-
abscess and fistulae may also be detected by thoracic nary artery disease before valve surgery.
MRI.
Diagnosis
V/Q Scan
In the first half of the twentieth century there was
In case where right sided endocarditis is suspected, no criteria to diagnose IE, physicians were waiting
this may show multiple mismatched defects indicat- for traditional signs like continued fever, clubbing,
ing pulmonary embolism. splinter hemorrhage or Osler nodule to develop for
diagnosis of IE, which is nowadays highly inexcus-
able. Because the clinical pictures are highly variable
the diagnosis of IE remained difficult. In other words
It is indicated only on rare occasion like in some con- as the clinical features are nonspecific, it is difficult
genital heart disease, coarctation of aorta (COA) and to differentiate IE from other bacteremic conditions.
valvular lesions when echo did not give adequate in- Therefore certain criteria are laid down for early di-
formation for surgery. Coronary angiogram is mostly agnosis in mid seventies.
The first criteria was established by Pellitier and For definite diagnosis of IE, it requires two major
Petersdorf in 1977, then another set of criteria was criteria or one major and three minor criteria or five
published by Von Reyn et al in 1982 (Beth Israel cri- minor criteria. When there is only one major plus
teria) and subsequently Durack and coworkers from one minor criteria or only three minor criteria there
Duke University in 1994 laid down a comprehensive is possibility of IE (possible IE) and they should be
criteria for diagnosis of IE known as Duke’s criteria followed up and investigated further either to meet
incorporating echocardiographic evidence of IE. The criteria for definite diagnosis or for alternate diagno-
recent American College of Cardiology and Ameri- sis. When alternative diagnosis is made or substantial
can Heart Association (ACC/AHA) guidelines rec- resolution of clinical features occurs within four days
ommended the use of modified Dukes criteria as a of antibiotic therapy or no pathological evidence is
primary scheme for the diagnosis of IE. It is highly detected in specimens after surgery, IE is ruled out
specific (99%) and sensitive (92%) depending on (Rejected IE).
both positive blood culture and echo.
In modified Duke Criteria demonstration of
Prevention
microorganism by culture or histological examina-
tion from a vegetation or intracardiac abscess makes It is now clear that endocarditis is more likely to result
a diagnosis of IE. Otherwise clinical and labora- from bacteremia of daily activities than after a surgi-
tory features are combined for diagnosis. Depending cal or interventional procedure. Antibiotic prophy-
upon their specificity and sensitivity they are divided laxis prevents only a very small number of cases.
into major and minor criteria. Hence antibiotic prophylaxis is needed only in cardi-
The major criteria are: ac conditions likely to develop highest risk of adverse
1. Positive blood culture (see section on blood culture). outcome if endocarditis is superadded. Maintenance
2. Evidence of endocardial involvement either clini- of proper oral hygiene is more important than routine
cally by appearance of new regurgitant murmur antibiotic prophylaxis. Generally IE is highest in inva-
or by echocardiographic demonstration of vegeta- sive dental and oral procedures where oral mucosa is
tion, abscess, valve perforation, prosthetic valve penetrated and that require manipulation of gingival
dehiscence or new valve regurgitation (see section tissue, tonsillectomy, esophageal surgery, gallbladder
on echocardiography). surgery, cystoscopy, urinary tract surgery including
The minor criteria are: lithotripsy and gynecological surgery in presence of
1. Predisposing heart condition (MVP, bicuspid infection.
aortic valve, rheumatic heart disease, congenital Conditions that require IE prophylaxis are:
heart disease, pacemaker, AV fistula in patients • Chronic rheumatic heart disease and other
for hemodialysis) or IV drug users. acquired valvular disease
2. Fever > 38°C. • Mitral valve prolapse with mitral regurgitation
3. Vascular phenomena: Major arterial emboli, septic • Prosthetic cardiac valves
pulmonary infarct, mycotic aneurysm, intra • History of endocarditis
cranial and conjunctival hemorrhage and Janeway • Acyanotic congenital heart disease (CHD) includ-
lesions. ing bicuspid aortic valve (except isolated secun-
4. Immunologic phenomena: Glomerulonephritis, dum atrial septal defect)
Osler’s node, Roth’s spot, positive rheumatoid factor. • Unrepaired cyanotic CHD, including palliative
5. Microbiologic evidence: Positive blood cultures but shunts and conduits
not meeting major criteria or serologic evidence • CHD repaired with prosthetic material within
of organism consistent with IE. first 6 months of the procedure
6. Echo consistent with IE but not meeting major • Repaired CHD with residual defect
criteria. • Hypertrophic cardiomyopathy.
Drugs recommended for prophylaxis of dental, oral, 7. Detection of in vitro minimum inhibitory concen-
esophageal and respiratory procedures: tration (MIC) for penicillin in case Streptococcus
The usual drug used is amoxicillin as a single dose of is isolated.
2 gm in adult or 50 mg/kg in children 1 hour prior There are recommendations by European So-
to the procedure. In penicillin allergy clindamycin ciety of Cardiology (ESC guideline for prevention,
(600 mg) is used. Alternatively cephalexin or cephad- diagnosis and treatment of Infective Endocarditis,
roxil 2 gm in adult or 50 mg/kg in children is used. 2004) and American College of Cardiology/Ameri-
Azithromycin or clarithromycin 500 mg in adult or can Heart Association (guideline update on valvular
15 mg/kg in children can also be used. For those un- heart disease: Focused update on Infective Endocar-
able to take orally ampicillin 2 gm IV in adults or 50 ditis: 2008).
mg/kg in children or ceftriaxone 1 gm in adult or 25
mg/kg in children are used IM or IV 30 minutes prior
Therapy for Streptococci
to the procedure.
Drugs recommended for prophylaxis of genitor-uri- For Streptococcus viridans, Streptococcus bovis and
nary and gastrointestinal procedures: other non-enterococcal streptococci the MIC for
Ampicillin 2 gm IV plus gentamycin 1.5 mg/kg IV is penicillin is determined. When MIC is ≤ 0.12 mcg/
given half to one hour before the procedure and then ml, they are highly susceptible to penicillin and
ampicillin 1 gm IV or oral is repeated 6 hours later. In treated with penicillin G 12 to 18 million U/day IV
penicillin allergy vancomycin 20 mg/kg or in adults either continuously or in 4 to 6 doses or ceftriaxone
1.0 gm IV is given 1 hour before the procedure. In 2 gm/day IV/IM in a single dose for 4 weeks. Alter-
very high-risk group gentamycin in the above men- natively cephazoline may be given. Combining gen-
tioned dose may be combined with vancomycin. tamycin 3 mg/kg/day IV/IM in 3 divided doses for 2
weeks gives a high cure rate. Vancomycin 30 mg/kg/
day IV in 2 divided doses (not exceeding 2 gm/day)
Treatment of Infective Endocarditis
is used in penicillin allergy. When MIC is between
Timely intervention with suitable antibiotics immedi- 0.12 and 0.5 mcg/ml combination of penicillin G
ately after blood culture is the single most important (for 4 weeks) and gentamycin (for 2 weeks) is recom-
step in the management of suspected or proven IE. mended in the above mentioned doses. When MIC
Sensitive organisms with low MIC respond to shorter is > 0.5 mg/ml the regimen as for penicillin resistant
course of antibiotics. However evidence has shown staphylococci are used.
that combination therapy is more effective than single For streptococcal prosthetic Valve endocarditis
chemotherapeutic agent. Antibiotic therapy has im- with MIC <0.12 µg/ml above regimen is used for six
proved survival by 70 to 80 percent. weeks.
Certain principles are required to guide therapy
like Therapy for Staphylococci
1. Bactericidal antibiotics should be chosen.
2. Parenteral antibiotics are given. Majority of staphylococci are penicillin resistant.
3. Prolonged course of treatment is required for Therefore nafcillin or oxacillin 12 gm/day IV in 4
eradication of the organisms that are sequestrated or 6 divided doses for 6 weeks is used. Flucloxacillin
inside the vegetation. (8 gm/day in 6 divided doses) is also used. Alterna-
4. Synergistic combinations are used for better bac- tively first generation cephalosporin such as cepha-
tericidal activity. zolin 6 gm/day IV in 3 divided doses for 6 weeks is
5. Patients should be hospitalized to monitor ther- used preferably in combination with an aminogly-
apy and to deal with possible complication. coside like gentamycin. However in methicillin re-
6. Identification of causative organism and its antibi- sistant Staphylococcus aureus vancomycin 30 mg/kg/
otic sensitivity. day IV in 2 divided doses (not exceeding 2 gm/day)
is the drug of choice given for 4 weeks in NVE and 6 When Staphylococcus is likely nafcillin or cephalo-
weeks in PVE. Gentamycin 3 mg/kg/day IV/IM in 2 sporin replaces penicillin.
or 3 divided doses is added for initial 3 to 5 days to Sometimes therapy is started empirically before
up to 2 weeks. In PVE oral rifampicin is also added culture report is available on clinical decision. Here
in a dose of 300 to 450 mg 8 hourly for 4 to 6 weeks. a combination of nafcillin plus gentamycin is chosen
when Staphylococcus or penicillin resistant Strepto-
Therapy for Enterococci coccus is suspected. In penicillin allergy vancomycin
plus gentamycin are used.
Enterococci are difficult to eradicate organisms.
Always high dose of synergistic combination are used. Summary
Here ampicillin 12 gm/day IV in 6 divided doses for
4 to 6 weeks may be used in place of penicillin com-
1. Native Valve Endocarditis (NVE)
bined with gentamycin 3 mg/kg/day IV/IM in 3 di-
vided doses for 4 to 6 weeks. Vancomycin in above Common organisms are Streptococcus viridans in 70
mentioned dose plus gentamycin is also effective percent cases and streptococcal fecalis in 15 percent
when MIC is high. Longer duration of therapy may be cases. The conventional management is penicillin
required in case of relatively resistant strain or PVE. 2 million units every 4 hourly IV with gentamycin.
(1 mg/kg) IV every 8 hourly until other organism de-
fined and sensitivity and minimum inhibitory con-
Therapy for Gram Negative Organism
centration (MIC) of drug against the isolated organ-
For HACEK organism third generation cephalospor- ism is known.
in like ceftriaxone and cephotaxime are the drug of
choice given for 3 to 4 weeks for NVE and 6 weeks 2. Prosthetic Valve Endocarditis (PVE)
for PVE. For Pseudomonas aeruginosa high dose of
piperacillin along with high dose of aminoglycoside Common organisms are in early PVE Streptococcus
like tobramycin is used for 6 weeks. Alternatively epidermidis and Staphylococcus aureus, in this situa-
imipenem plus aminoglycoside with a quinolone tion cephalosporin such as cephazolin 6 gm/day IV
may be used. in 3 divided doses in combination with gentamycin
3 mg/kg/day IV/IM in 2 or 3 divided doses is used.
Alternatively vancomycin 30 mg/kg/day IV in 2 di-
Therapy for Fungal Endocarditis
vided doses (not exceeding 2 gm/day) is used. Oral
Liposomal amphotericin B is infused in 5 percent rifampicin is also used in a dose of 300 to 450 mg
dextrose over 2 to 4 hours at a dose of 0.7 to 1 mg/kg/ 8 hourly. Duration therapy is for 6 weeks in PVE.
day, larger doses is used (1–1.5 mg/kg/day) for man- Treatment of late PVE is similar to NVE.
agement for PVE by Aspergillus species. Other drugs
used are 5-Fluorocytosine or other fungicidal drugs 3. Right Sided Endocarditis
like fluconazole often in combination with surgery to
remove the vegetation or replace the valve. It is seen in IV drug users and congenital heart dis-
eases. Tricuspid valve is commonly affected. Systemic
embolism is not a feature. Common organisms are
Culture Negative Cases and Empirical Therapy
Staphylococcus aureus, gram negative organisms like
In culture negative cases the therapy is directed Pseudomonas and Fungus. The vegetation is bigger
against Staphylococcus, Streptococcus and HACEK in size and may not be amenable to medical therapy,
group of organism. A combination of penicillin or therefore often requires surgical removal. Treatment
ampicillin plus gentamycin plus ceftriaxone is given. is as above for staphylococcal infection, for gram
negative organism imipenem plus aminoglycoside Elective Indications

with a quinolone may be used. IV anti-fungal drugs
like amphotericin B are used in cases of fungal infec- • Recurrent emboli and persistent or increasing size
tion. of vegetation despite appropriate antibiotic treat-
ment.
• Surgery may be considered in mobile, large (>10
4. Infective Endocarditis in Children
mm) vegetation with or without emboli.
Community acquired IE is rare below 2 years of age, • Evidence of paravalvular prosthetic leak.
although nosocomial IE may occur in neonatal and
pediatric ICU settings. In children it often involves Prognosis
cases of RHD and CHD. Viridans group A Strepto-
coccus is responsible in majority case of IE in RHD. Overall mortality from analysis of Chuetal et al amongst
Enterococcal endocarditis is less common in children. cases of definite IE is approximately 20 percent. Bad
Treatment with antimicrobial agents is similar to that prognostic factors include advanced age, female gen-
of adults except for dose consideration according to der, diabetes mellitus, moderate to severe heart failure,
body weight. Hydration and nutrition are important periannular abscess formation, vegetation size >10
aspects to maintain in children during treatment of IE. mm, serum creatinine >2 mg/dL elevated leukocyte
count, lower serum albumin and virulent organism.
Surgical Treatment
Future Perspectives
There are many categories of recommendations for
surgery for example by American College of Cardi- The significant mortality and morbidity associated
ology/American Heart Association (ACC/AHA) as with infective endocarditis is quite challenging and
Class I, Class IIa and IIb indications (see level of evi- stimulates ongoing effort to improve preventive,
dence in Chapter 9, Section 2). Others have catego- diagnostic and therapeutic strategies. New molecu-
rized as major indication and minor indication, and lar diagnostic methods, bacterial vaccines, antimi-
other group categorizes as emergency indications, crobial agents (e.g. daptomycin for S. aureus IE) and
urgent indications and elective indications. colonization resistant biomaterial are under constant
development. There is ongoing research on disrup-
tion of microbial bio-film production as a means to
Emergency Indications
prevent infection of intravascular devices. Novel an-
• Progressive or refractory heart failure timicrobial strategies targeted towards drug resistant
• Acute AR or acute MR. staphylococcal and enterococcal species are essential.
Definitive studies of infective endocarditis are ex-
tremely challenging because of low incidence of dis-
Urgent Indications
ease at any one center and the heterogeneous charac-
• Valvular obstruction teristics of both the host and causative organisms. To
• Echo evidence of valve dehiscence address some of these limitations the international
• Perivalvular abscess collaboration on endocarditis (ICE) was formed and is
• Leaflet or septal perforation or fistula collecting prospective data from a large cohort of IE
• IE caused by fungal or highly resistant organisms patients at multiple international centers.
—blood culture remains positive after 1 week of Although the prognosis of IE has improved due
antibiotic therapy or one or more embolic event to improvement in quality of management over past
during first 2 weeks of therapy three decades yet in many occasions it baffles the
• Rupture of mycotic aneurysm. treating physician.
further reading utilization of specific echocardiographic findings:

1. A George Koshy. Infective endocarditis: Indian Duke Endocarditis Service. Am J Med. 1994;96:200-9.
Scenario, CSI, Cardiology Update 2008, (Ed) VK Bahl. 6. Gould FK, Elliott TS, Foweraker J, Fulford M, Perry
2. Bansal RC. Infective endocarditis. Med Clin North JD, Roberts GJ, Sandoe JA, Watkin RW. Working
Am. 1995;79:1205-40. Party of the British Society for Antimicrobial
3. Baddour LM, Wilson WR, Bayer AS, Fowler VG Jr, Chemotherapy. Guidelines for the prevention of
Bolger AF, Levison ME, et al. Infective endocarditis endocarditis: report of the Working Party of the
diagnosis, antimicrobial therapy, and management of British Society for Antimicrobial Chemotherapy. J
complications. Circulation. 2005; 111: 3167-84. Antimicrob Chemother. 2006;57:1035-42.
4. Dajani AS, Taubert KA, Wilson W, et al. Prevention 7. Li JS, Sexton DJ, Mick N, et al. Proposed modifica-
of bacterial endocarditis: recommendations by tions to the Duke criteria for the diagnosis of infective
the American Heart Association. Circulation. endocarditis. Clin Infect Dis. 2000;30:633-8.
1997;96:358-66. 8. Strom BL, Abrutyn E, Berlin JA, et al. Risk factors for
5. Durack DT, Lukes AS, Bright DK. New cri- infective endocarditis: oral hygiene and nondental
teria for diagnosis of infective endocarditis: exposures. Circulation. 2000;102:2842-8.
CHAPTER 18
Natural History of Rheumatic Fever
M Satpathy, Bharati Das, JP Das
Introduction There is no well planned community based large

Natural history of any disease means “its evolution epidemiological studies to find out accurate statis-
in the absence of treatment”. It gives proper idea tics regarding its incidence, prevalence and to study
about the whole disease process including its clinical the natural course of rheumatic fever and rheumatic
manifestations, pathophysiology, complications and heart diseases. Some of the studies reported are small
sequelae. It also gives insight to develop new strategy and confined to local places, so the conclusion may
for management. not reflect the correct picture of the country. Our
Rheumatic fever (RF) and rheumatic heart disease opinion and observation is based on 40 years of per-
(RHD) are the consequence of group A beta hemolyt- sonal experience on large number of cases but it is
icus streptococcus infection of the pharynx. RF is very not based on a well planned statistical evaluation.
peculiar in sense; that there is no single symptom or
sign or laboratory test finding which is characteristic Historical Aspect
feature to diagnose rheumatic fever. Similarly its eti-
ology and pathogenesis are not yet fully understood Going back to the history Guillaume de Baillou
and so also there is no unanimous opinion regarding (1538–1616I) the “Father of Rheumatism”, first used
management schedule, although recently national the term rheumatism to mean; a distinct clinical
consensus meeting of Indian Academy of Pediatric entity of arthritis, to differentiate from gout. Rheu-
in Vision 2007 has laid down a specific schedule. The matic fever and rheumatic heart disease got recog-
natural course of the disease is also widely variable. nition during the industrial revolution in early 19th
It is worth mentioning that when RF and RHD were century in England and other European countries
rampant in temperate climate (developed countries) after Charles Wells lecture in 1810 who described
and also tropical climate (developing countries); the it as a separate clinical entity. The earliest report in
natural course reported was highly variable. As for India dated back to 1835 but it was not recognized till
example rheumatic valvular lesions were mostly pre- Basu, Kutumbiah, Hughes, Md Yusuf and many oth-
sent in third and fourth decade of life in developed ers reported authentic evidences from the year 1920.
countries after the initial attack of rheumatic fever Later on it was established that RF and RHD are ram-
as compared to its early manifestation that is within pant in India (for detail information refer chapter 2).
20 years of age in developing countries.
India and some other developing countries are
Magnitude of the Problem
best places to study the natural course of rheumatic
heart disease because more than 50 percent of pa- In 1994, it was estimated that 12 million individu-
tients live as such even without proper medical ad- als suffer from RF and RHD worldwide. Recent esti-
vice what to speak of surgical management. mation suggests that 15.6 million people suffer from
RHD and nearly 0.47 million new patients acquire means primary prophylaxis (by penicillin) is the an-
this disease annually all over the world. The annual swer to prevention of rheumatic fever.
death is around 0.233 million globally.
WHO has estimated 0.13 million death annually
Natural Course of Rheumatic Fever
from RF and RHD in South East Asia including In-
dia (compared to 10,000 death in USA). Considering It is an established fact that RF occurs mostly in
a median incidence of 0.5/1000; it appears 131,000 childhood period. Early diagnostic workup of strep-
patients suffer from RF every year in India. At least tococcal pharyngitis and rheumatic fever is still be-
one-third of them suffer from chronic valvular heart yond the reach of a large number of people, as a con-
disease that is nearly 44,000 patients per year are sequence full fledged valvular lesions develop during
added. Considering the lowest and highest reported adolescence period or later. Besides many times we
prevalence of RHD in the population of 5 to 15 years have seen that RHD for the first time being detected
the number of RHD population, ranges from 0.44 to during medical check-up when they join their job
3.37 million in India (S Ramakrishnan et al. Cardiol- and in case of ladies during their pregnancy when
ogy update 2008). The mortality rate in the WHO re- they become symptomatic.
gion including India is 7.6/100,000. So the mortality There are many reasons why rheumatic fever
rate is very high in younger age group. goes unnoticed during its initial period of affection.
These data are based on the population of In- • It affects preferentially the poor, who have no bio-
dia of 2001 census when it was 1027 million, but graphic (proper acess to medical care).
in recent census 2011 the population of India is • It is a disease of children, traditionally less impor-
1210 million. This indicates the magnitude of the tance given to their complaints than adult and often
problem of RHD has become many fold in spite of goes unnoticed unless there is severe arthritis.
patchy decline in incidence. The exact magnitude • Initial attack is for a short period, therefore, com-
of the problem that is accurate incidence of RF and monly ignored and it subsides without treatment.
RHD is difficult to estimate because of lack of large • Rheumatic heart disease manifest decades after
number of hard epidemiological surveys from dif- the initial attack (by the time initial attack is for-
ferent parts of India. gotten.
From the natural course of pharyngeal infection
it is observed that the incidence of RF following
Evolution of Rheumatic Fever (Birth of RF)
untreated epidemic of streptococcal pharyngitis is
Rheumatogenic (M type) Group A beta hemolytic 3 percent; where as attack rate of RF following
Streptococcus (GABHS) is the agent (equivalent to sporadic streptococcal pharyngitis is much lower,
the embryo for RF). It forms a nidus in the pharynx only 0.3 percent. Surveys have shown 24.11 percent
by way of pharyngeal infection, the host (compared of rural school children clinically suffer from throat
to mother’s womb where it develops). This infection infection which includes tonsillitis and pharyngitis.
takes three to four weeks to manifest clinically i.e. la- All the children suffering from streptococcal
tent period [which is equivalent to conception period pharyngitis are not affected, only the susceptible one
and the baby (RF) is growing normally]. When the (susceptible host) suffer from rheumatic fever. Chil-
pharyngeal infection is not treated (environmental dren belonging to 5 to 15 years of age with peak inci-
factor unsuitable in checking this process) after this dence of 9 years, are mostly affected. Rheumatic fever
latent period the different manifestations of the RF is uncommon below 5 years and above 40 years even in
are seen; that means RF has taken birth in form of developing countries. It is also observed that genetics
arthritis and carditis. In other words if suitable medi- play some role in pathogenesis; that is persons having
cal care and antibiotics for the pharyngeal infection HLA-DR1, DR2, DR3, DR4, DR7, DRW53 and specific
could have been given properly, the RF (the baby) B-cell alloantigen (D8/17antigen) are prone for
could have been aborted before its manifestations. It developing RF.
Natural History of Rheumatic Fever and Rheumatic Heart Disease 149
Environmental factors play a definite role to con- very few variations in their percentage. RF and RHD
trol the streptococcal infection; thereby indirectly have already been extinct from developed countries
help in protecting from an attack of rheumatic fever. since last six decades, so natural course of the disease
The important factors responsible are: remains as a part of history for present day
• Improvement in living standards. physicians. But although 100 years have passed RF
• Improved access to medical care. and RHD still remain as major problems in India and
• Use of antibiotics. other developing countries. The clinical manifesta-
• Natural changes in streptococcal strain. tions projected by various Indian authors are men-
There is direct evidence that treatment of strep- tioned (Table 18.1).
tococcal pharyngitis decrease the incidence of ini- There is no sex or race predilection, both sexes
tial attacks and the primary prophylaxis by penicillin are equally predisposed to develop RF, except cho-
terminate epidemics of RF. Rheumatic Fever is an rea which is uncommon in post pubertal male. RF
excellent example in which agent, host, and environ- may remain silent for many years till the patients are
ment (components of epidemiologic triad) interact symptomatic in form of chronic valvular disease, so
together to result in, development of the disease, RF it is not surprising that in some patients the disease
and subsequently RHD. is diagnosed for the first time in their 4th or 5th dec-
Previously the initial problem causing delay in ade. This leads to the speculation that probably in
recognizing rheumatic fever and RHD was because some cases rheumatic fever manifest late in life in a
of its varieties of manifestations confusing whether it modified way or initial attack occurs at later age. It
is a single disease or a syndrome complex. Ultimately has come to our observation that a few cases at their
all controversies were over when Duckett Jones in age 30 to 40 years presented with recent attack of
1944 comprehensively described a criteria (manifes- arthritis with high ESR and ASO titer and subse-
tations grouping as per their clinical importance) for quently develop valvular lesions.
diagnosis of rheumatic fever, known as Jones criteria
(elaborate description in chapter 5). In the mean time
Natural History of Rheumatic
it has undergone several modifications. The speci-
Manifestations
ficity of Jones criteria is 97 percent and sensitivity
77 percent for the diagnosis of RF. Carditis
It was observed that clinical manifestations of
rheumatic fever (not RHD) were almost uniformly The natural history of carditis is unpredictable var-
present throughout the globe when it was rampant ies from patient to patient. Not all patients with acute
in developed countries, that is before 1920, with rheumatic fever develop carditis. Carditis is seen in 30
Table 18.1: Percentage of different manifestations in rheumatic fever in India

Manifestations Padmavati*, 1962, Sanyal et al**, 1973, Sharma et al***, Routray****, 2003,
New Delhi New Delhi 1999, New Delhi Cuttack
Arthritis – 56.6 61.8 44.2
Arthralgia 60.1 – 13.6 43.1
Carditis 30.9 33.3 81.2 76.6
Chorea 8.8 20 9.4 5.2
Subcutaneous nodules 1.5 1.9 20.4 11.1
Erythema marginatum – 1.9 1.0 0
*Padmavati S Circulation Vol XXV, April, 1062, 703-10. ** Sanyal KS Circulation, Vol XIIX, Jan, 1974.***Sharma M et al,
Ind HJ (Abstract), 1990, ****Routray et al, Ind HJ, 2003;55(2):1952-7.
to 80 percent of cases RF (Table 18.1), mainly in teen 50 years it is seen only in developing countries and
age. As age progresses the incidence of carditis de- still continues as a major cause of morbidity and
creases but reverse happens in case of arthritis. Valve mortality in young adults.
lesion and cardiac murmur (valvulitis) initially disap-
pear in one-third of patients when carditis subsided.
Determinant of Disappearance of Murmur
Those patients who develop carditis in the initial
attack, it tends to recur in subsequent recurrence of RF. • Disappearance of murmur depends on severity of
Mitral and aortic valves are commonly involved in car- initial attack of carditis, type of valve involved and
ditis. Mitral valve is involved in about 90 to 95 percent its severity. Murmurs commonly disappear in mild
of cases; and combined with aortic valve lesion in 20 carditis (no cardiomegaly/congestive heart fail-
to 25 percent cases. Isolated aortic valve involvement is ure), mitral systolic murmur that is MR murmur
seen in 5 to 8 percent of cases where as tricuspid valve usually disappears, but aortic regurgitation mur-
is less commonly involved. Pulmonary valve involve- mur tends to persist. Chance of disappearance of
ment only in acute RF has not been reported in India. murmur is more when only one valve is affected.
The natural history of carditis in developing • Presence/absence of recurrence.
countries which is not seen developed countries re- • Institution of Penicillin prophylaxis.
veals that it gives rise to valvular heart lesion very • The time elapsed since the episode of rheumatic
early in teen ages and also to its subsequent complica- carditis and initiation of treatment.
tions. Carditis remain clinically silent, so not detected
at initial stage in about 40 to 50 percent of cases till
Recurrence
it manifests with valvulur lesions. Adequate rest is
necessary even if the carditis subsides (if tachycar- The period of 1 year following RF is the most vulner-
dia and mild carditis persists) otherwise there is fair able period for recurrence. After the first episode of
chance that some of these patients may go for con- RF, if a patient gets fresh streptococcal pharyngeal in-
gestive heart failure. Recurrent carditis occurs in high fection, rheumatic fever recurs in 50 percent of cases.
frequency in subsequent attacks of RF. The different ASO titre also correlates with recurrence of RF. More
modes of presentation of carditis are as follows: the ASO titer, more is the recurrence rate. It is said
• An episode of acute carditis resolves over a period that “Rheumatic recurrence begets recurrence”. More
of 12 weeks in 80 percent of the patient and may severe the valve lesion in initial carditis, chance of
sometimes extended up to15 weeks. recurrence is also more. Patients above 35 years are
• In pre-penicillin era 10 percent cases were devel- at very low-risk of recurrent attack. The US-UK co-
oping fulminating carditis but now days it is rare. operative trial showed patient with RF without recur-
• In 5 percent of cases when carditis persists for rence, incidence of RHD is 34 percent after 10 years
more than 6 months it is known as chronic rheu- and with recurrence, incidence of RHD is 60 percent.
matic carditis. These patients remain symptomatic It also depends on the number of recurrences.
for a long period. In the pre-penicillin era, recurrent carditis was
• In another 5 percent cases, severe MR develop responsible for chronic RHD in 60 to 90 percent of
and remain symptomatic with congestive heart cases. But in penicillin era it has been reduced to
failure (CHF). To clarify further although pancar- 35 to 65 percent. After the initial attack of RF without
ditis occurs in ARF it is valvulitis, not myocarditis carditis the number of cases of valvular heart disease
which is responsible for severe MR and CHF. (VHD) varies from 0 to 44 percent in pre-penicillin
• Till early twentieth century RF and RHD was era to 0 to 8 percent in penicillin era. The study done
the leading cause of death in 5 to 20 years of by Lue et al, from South East Asia in 1970 showed
age and second leading cause in age group of 20 79 percent of RF patient developed RHD, in part
to 40 years, throughout the globe. But since last related to inadequate penicillin prophylaxis. Recur-
rence of rheumatic fever reported in 10 percent of The concomitant occurrence of carditis in these pa-
cases who miss penicillin prophylaxis. We have also tients varies widely that is from 3 to 73 percent, both
observed the rate of recurrence is high in patients at initial and recurrent attacks of RF. On long-term
missing or irregularly taking penicillin prophylaxis. follow up of cases of chorea in various series it is re-
ported that chronic valvular heart disease (VHD) de-
Fulminant Rheumatic Carditis velop in 20 to 34 percent of cases.
It is a very severe form of carditis known as malig- Subcutaneous Nodule

nant or fulminating carditis, was commonly seen in
pre-penicillin era even up to 1970 and mainly chil- It is also a late manifestation occurs in 10 to 16 per-
dren having severe mitral regurgitation give rise to cent of cases after the first attack of rheumatic fever.
acute pulmonary edema. Acute MR (following cardi- Presence of subcutaneous nodule suggests underly-
tis) due to leaflet prolapse, rupture of chordae tendi- ing carditis. In this setting most of the cases of cardi-
nae and annular dilation do occur in some of these tis subsequently give rise to valvular heart lesion. It
cases. It is life threatening unless urgent surgical in- occurs in crops that is appear and disappear sponta-
tervention is advised. neously within 2 to 3 weeks leaving no scar. We have
observed that subcutaneous nodules associated with
severe form of carditis (with severe MR) in some
Arthritis
cases, occur in crops (i.e. after the first appearance).
Rheumatic arthritis is a migratory poly arthritis,
involving large joints mainly in lower limbs that Erythema Marginatum
resolve within 3 weeks of time even when untreated.
It heals without any evidence of residual sign. RF It is much less seen in India and other developing
licks the joint but bites the heart. Jaccoud’s arthritis is countries. The incidence varies from 1 to 10 percent
a rare post rheumatic arthropathy which is character- in different series. It occurs with carditis and may
ized by periarticular fibrosis of the metacarpophalan- continue for months. It may recur with carditis or
geal joints which occurs predominantly in patients arthritis. We have seen one case of recurrence of ery-
with multiple arthritic episodes. thema marginatum with carditis and arthritis recently
Migratory arthritis is seen in about 50 to 60 (Ref. Chapter 5).
percent of cases and associate with carditis in about
75 percent of cases. Carditis may remain silent in Natural History of Rheumatic Heart
some cases and manifest later on as valvular heart
Disease
disease. Our observation is that once polyarthritis
subsides and the patients are under regular penicil- It is our observation that the natural course of rheu-
lin prophylaxis, most of them do not develop cardiac matic heart disease (RHD) is very peculiar and un-
lesions. predictable in India and also other developing coun-
tries as compared to the course of the disease seen
about five decades back in developed countries.
Chorea
Rheumatic fever occurs much earlier in India,
Chorea is a late feature, may occur after 1 to 6 months about 40 percent of cases of RHD seen below 14 years
of latent period. It occurs as an isolated manifesta- of age. The peculiarity of RF in our country is that it
tion in about 10 percent of cases. It subsides in leads to established rheumatic heart disease within
75 percent of cases within 6 months. Recurrence oc- 6 months to 6 years in majority of cases. This is in
curs in one-third cases and persists for 1 to 2 years. great contrast to what happened in developed coun-
tries. Why it occurs earlier in India and some tropical countries like India up to 25 percent of patients with
countries the causative organism being one and same severe MS belong to less than 20 years of age.
is still not known. The postulations are: The stenotic lesions as compared to regurgitant
• Is it variance of virulence of some of these strain of lesions develop late. For example mitral regurgitation
GABHS? develop in 50 percent of cases of ARF along with car-
• Is this due to endemicity of the streptococcal ditis but mitral stenosis develop relatively late after
pharyngitis? the arthritis or associated carditis subsided. It is ob-
• Is it due to exuberant immune response to anti- served that most of the stenotic lesions (mitral steno-
genic stimulus producing tissue injury in RF? sis) develop minimum 6 months to 6 years after the
• Is it due to high prevalence of HLA type in RHD? initial attack. This is the reason why symptomatic ju-
Persistent and progressive valvular damage re- venile mitral stenosis (below 20 years) is seen in large
sulting from initial and or recurrent rheumatic number.
fever associated with carditis give rise to valvular Olsen reported 271 cases of mitral stenosis with
heart disease (VHD). The natural history of VHD average age of 42 years among which 86 percent were
mainly refers to the course and complication of un- symptomatic. Similarly Rowe reported 250 patients
treated diseases. of mitral stenosis who were asymptomatic at an aver-
Morbidity and mortality from VHD depends age age of 28 years in western countries.
upon the severity of valve damage, number of Arthur Selzer described that mitral valve surgery
valves involved and the type of complications. The was performed below 20 years in 0.5 to 1 percent in
prognosis depends upon the severity of hemody- USA and 3 to 5 percent in European countries but in
namic burden of either stenotic or regurgitant or 27 percent of cases in India. All these indicate that
combined lesions and their complications. The rheumatic heart disease occurs much earlier and
common complications which interfere in the nat- become severe in developing countries as compared
ural course of the valvular lesions are: to developed countries.
• Congestive cardiac failure. To re-emphasise 500 patients of MS below 20
• Pulmonary artery hypertension. years of age were operated between 1958–72 by Stan-
• Atrial fibrillation. ley John (J Thoracic CV Surgery,1969) and he report-
• Thromboembolism. ed re-stenosis after 10 years in 11 percent of cases.
• Infective endocarditis. Closed mitral valvotomy (CMV) was done in 25
• Other associated situations like VHD with preg- percent cases of juvenile MS up to the year 2000 till
nancy or VHD with congenital heart disease (CHD). BMV started as routine procedure at Cuttack (per-
sonal communication from NK patnaik, SCB Medi-
Stenotic Lesions cal College).
The hemodynamic burden of severe stenotic
Mitral Stenosis lesion, not well tolerated, that is the patient becomes
early symptomatic. In case of mitral stenosis when the
It is observed that; RHD frequently seen below lesion is severe (MVA less than 1 cm2) intervention
20 years of age in India and other developing countries is mandatory, not related to age factor. Therefore, ju-
and was first reported under the heading of “juvenile venile mitral stenosis possesses a problem for cardi-
heart disease” in 1939 (Lancet, editorial). Juvenile ologists and cardiothoracic surgeons. Recently BMV
rheumatism in South India was reported by S Vaish- below 20 years of age have been reported from many
nava below 12 years of age from Vellore (Ind J Child cardiac centers in India. Side by side it is restenosis
Health 9:290, 1960). Later on the term “juvenile mitral after CMV has emerged as a problem for cardiologists
stenosis” was coined by SB Roy in 1962. In developing and for surgeons, because of surgery done at early age.
Aortic Stenosis servation is that prognosis of symptomatic patients

having severe rheumatic AS become worse and death
It is observed that aortic stenosis develop much occurs much earlier if not surgically corrected.
later age as compared to mitral stenosis. Rheumat-
ic AS usually occurs above 20 years and remains Tricuspid Stenosis
asymptomatic for a long period even severe aor-
tic stenosis develop in the mean time. Patients of It is well known that life expectancy of patients
severe AS usually become symptomatic after with tricuspid valve disease is relatively long with
30 years of age, in form of accustomed dyspnea, syn- variable degrees of disability. In true sense prog-
cope and chest pain (angina). Rheumatic aortic stenosis depends on severity of associated mitral or
nosis like rheumatic MS occurs much earlier in In- aortic valve diseases. Our long clinical observation
dian patients then western patients (Vijayraghavan is that some patients with mild-to-moderate TS
et al, Bri HJ, 1977;39:294). But angina pain often oc- along with mild-to-moderate MS carry their work
curs in AS of degenerative or bicuspid valve origin, for pretty long time up to 5th decade with class
specifically after fourth decade, but not so often in II to III symptoms. But patients having severe TS,
rheumatic AS. even if the mitral commissurotomy is done does not
Incidence of isolated rheumatic AS is varies from show satisfactory improvement and remain with class
2 to 5.9 percent of all RHD and in 25 percent of cases III to IV symptoms with restricted physical activities.
when it is associated with other valvular lesions in In these cases prognosis is poor unless tricuspid valve
our country. Balloon aortic valvotomy (BAV) is surgery is simultaneously done.
sometime done in cases of severe AS but majority of
them are non-rheumatic origin. BAV is advised par-
Regurgitant Lesions
ticularly with combind condition and/or LV dysfunc-
tion as a bridge to surgery. Recently BAV is reported Mitral regurgitation is the most common valvular
from our country in cases of rheumatic AS. In devel- lesion develops in about 60 to 70 percent of cases
oped countries lone rheumatic AS is practically non- along with or just after rheumatic carditis subsided.
existent. All cases are of degenerative or congenital Carditis preferably occurs at younger age, most of
bicuspid aortic valve origin. It is observed that when these children below 10 years develop MR. Rheu-
patient of aortic stenosis become symptomatic and matic MR alone in all ages is seen in 21.2 percent of
develop heart failure the prognosis is worse and life cases (Adarsh Kumar et al, Ind HJ, 2009;61:19-23).
span is limited within five years in most of the cases The natural course of MR depends upon the degree
without surgical intervention. In case of symptomatic of MR (mild, moderate, severe) and with associated
AS as mentioned death occur within 3 years after an- lesions. Patients of mild-to-moderate MR remain
gina, 2 years after dyspnea (CHF) and 1.5 to 2 years asymptomatic for a long period, till they gradu-
for syncope and the average age of death is 60 years. ally develop severe MR or develop complications.
All these prognostic data mains hold good for severe Patients of severe MR also remain asymptomatic or
AS due to bicuspid valve origin not for severe rheu- with class I/II (NYHA) symptom for a pretty long
matic aortic stenosis. Hemodynamical study shows time till suddenly become symptomatic due to some
when there is average rate of progression in jet veloc- precipitating cause like undue physical exertion,
ity of 0.3 m/s per year and decrease in valve area of arrhythmias (AF), infective endocarditis. Sudden
0.1 cm2 per year, the prognosis is bad. Sudden death death do occur in this group besides common mode
do occur with significant hemodynamic changes due of death like acute pulmonary edema, low cardiac
to any cause, even if AS is moderately severe. Our ob- output state or thromboembolic episodes.
The hemodynamic burden of regurgitant lesions nary artery hypertension. Our observation is most
is well tolerated but if the lesion progress rapidly of the patients having moderate-to-severe TR with
decompensation starts early in about 50 percent of close mitral valvotomy done, although remain
cases of even below 30 years of age. These patients ful- symptomatic (class II-III, NYHA) but survive for
fill the clinical and echocardiographic criteria for sur- 15 to 20 years more without further surgical inter-
gical intervention; mitral valve replacement (MVR) at vention. The prognosis of TR depends upon the se-
an early age. MVR was done (based on catheter data) verity of disease. In general the prognosis is good.
in 220 cases out of which 55 were below 20 years and When TR is due to idiopathic PAH and Cor-pulmo-
110 were below 30 years of age (Stanley Jhones, Anna nale, the outlook is poor with limited life expectan-
thoracic surgery, 25; 316:1978). But about 90 percent cy. Death eventually occurs due to progressive right
of these patients of our country cannot afford for heart failure, arrhythmias, pulmonary embolism
MVR because of poor socioeconomic status so fully and pulmonary infarction. However, organic TR of
dependant on medical advice. It is observed that most rheumatic origin could lead to rapid deterioration
of these severe MR (class IV, NYHA) survive maxi- with congestive failure and ascitis.
mum up to fourth to fifth decade.
Combined Lesions
Aortic Regurgitation
Multivalvular lesions are commonly seen in clinical
The incidence of isolated rheumatic AR was report- practice. It is reported by different authors at differ-
ed in 9.7 percent of cases of all age group (Adarsh ent times from India. One of the series reported that
Kumar) and our observation is that it is 2.4 percent MS with MR in 15.3 percent, MS with AR 26.7 per-
below 20 years of age. cent of cases (Routray et al). Another series based on
As it is mentioned the regurgitant lesions are echocardiographic study shows MS MR in 12.9 per-
well tolerated for a long time, cases of mild-to-mod- cent, MS AR in 13.9 percent, AS AR in 4.4 percent, MS
erate lone AR remain asymptomatic or with class MR AR in 2.0 percent, MS MR AR in 2.1 percent and
I or II symptoms even up to fourth decade. When MS MR TR in 8.02 percent (Patnaik AN, NIMS, Hy-
these lesions progress rapidly or some complications derabad, 2002). Combined lesions like MS, TS and AS,
occur in-between they become rapidly symptomat- although valvotomy successfully done at some centers
ic. Chronic severe AR once become symptomatic in our country a long-term prognosis is not rewarding.
develop a rapid downhill course and without surgi- Our long observation concludes that the prog-
cal intervention life expectancy is short may be within nosis is very unpredictable as there is hemodynamic
5 years. Rappaport reported three-fourth of patients instability in these patients of combined lesions.
with significant AR survive for 5 years and 55 percent It is the dominant lesion plays important role as
have shown to live for 10 years after diagnosis. But our regards clinical course is concerned. Only in cases of
observation on isolated AR (mild-to-moderate) who balanced lesion without hemodynamic compromise
were below 20 years live with class II-III symptoms till the prognosis is much better, otherwise in combined
about fifth decade in absence of complications. Once lesions it is always worse. Once patients become class
common complications like physical exertion induced IV symptomatic survival period is limited. The surgi-
arrhythmias, chest infection and in a few cases infec- cal results are also not very rewarding in combined
tive endocarditis occur, the life span becomes limited. lesions.
Tricuspid Regurgitation Natural Problems Emerging

Tricuspid regurgitation is mostly associated with Cases of RHD both stenotic and regurgitant lesions
mitral stenosis or due to functional causes pulmo- progress recentlessly that cardiologist and the cardio-
thoracic surgeons are to intervene at relatively earlier adequate for large number of poor socioeconomic
age of the patients because delay in surgery definitely group of people. The proper medical treatment
compromise the long-term benefit. Interventions and specialized valve surgery is still remote for
done at early age before 20 years for mitral stenosis the majority of patients in India. The cost of valve
(either BMV or CMV) before 30 years of age for MR replacement, anticoagulant therapy and follow-up
(for MV repair or MVR). These patients after 2 to 3 is affordable to only a few patients. In recent years
decade, i.e. now pose a new problem of restenosis (or balloon valvuloplasty made a great contribution and
re-restenosis) or redo surgery. At present about 40 large number of patients (even during pregnancy)
percent of patients having CMV done 25 to 30 years are benefited from this procedure. Closed mitral
back are coming with class III or IV symptoms and commissurotomy still remains a significant mode
restenosis and similarly prosthetic valve problems are of surgical treatment for mitral stenosis and is less
emerging after 20 to 25 years of valve replacement expensive. Adequate health and hygienic measure
(MVR was done in 220 cases out of which 55 were and awareness for early detection of RF and RHD will
below 20 years by Stanley Johns et al, in 1978 have result in remarkable decline of disease. Prophylaxis
become symptomatic). for rheumatic fever with benzathine penicillin should
The average age of these patient who have under- be widely available at all health centers. Anaphylactic
gone surgery at early age will pose problem at around reaction with benzathine penicillin has limited its
45 to 50 years of their age. But the natural course of use in many private health centers and allergy test
RHD (when it was rampart) was different in Europe- for penicillin is still not properly practiced. The
an countries or other developed countries. Majority availability of adequate treatment mainly depends
of the valve lesions occurred and diagnosed at about upon health planning which also covers health
40 years of age and the lesion progressed slowly re- insurance for all. It is also mentioned resurgence of
quiring surgery at later age. (Rapaport E Am J Card RF is a problem in developed countries but not for
1975;35:221-7 and Olesen KH in BMJ 1962;24:349- developing countries where rheumatic fever is still
57). Once surgery is done at 40 to 50 years of age, widely prevalent.
patient remain asymptomatic for 15 to 20 years with Although large number of cardiac and cardiotho-
medical care that is up to their sixth to seventh dec- racic centers have come up in recent years still it is
ade of life. So resurgery problem was practically non- meager to cater the service for the number of patients
existent in developed countries. having RHD standing on queue. It is apprehended
At present the number of patients waiting for that restenosis and redo surgery will emerge as a new
CMV or BMV or for other valve surgery out numbers problem for cardiologists and cardiothoracic sur-
the number of patients who have undergone surgery. geons during mid to late twenty-first century in India
It indicates RHD still prevalent significantly in India. and also for other developing countries.
Our observation is that RHD still remains a com-
mon disease in India and other developing countries,
Conclusion representing three-fourth of world’s population. The
It is observed that the clinical course of rheumatic natural course of RHD is widely variable. Hence, it
heart disease is widely variable, even patients to is difficult to stereotype the various manifestations
patients having same lesion with same severity. So, and prognosis of the diseases into specific groups. It
it is very difficult to group the patients into specific is the common cause of morbidity and mortality in
categories and to predict the natural course of the younger age group in our country. The aim should be
disease. to eradicate completely to get rid off the menance of
As of today the facilities for early diagnosis rheumatic fever and rheumatic heart disease. The only
and treatment of rheumatic heart disease are not way to achieve this goal is primary prophylaxis (not
secondary) and a potent vaccine which should be eas- 2. Sanyal K Shyamal, et al. The initial attack of ARF, dur-
ily available to one and all. ing childhood in North India, a prospective study,
Circulation; Vol XIIX, Jan, 1974.
3. SN Routray. Has the prevalence of Rheumatic Fever
Further reading and Rheumatic Heart disease really changed? A hos-
1. Cardiology chapter of Indian Academy of Pediatrics: pital based study. Ind HJ. 2003;55:152-7.
Consensus meeting on pediatric rheumatic fever and 4. Anil Grover et al. Burden of Rheumatic and Congenital
rheumatic heart disease. Vision, 2007. Heart Disease in India. Ind HJ. 2002;54:104.
Index
Page numbers followed by f refer to figure and t refer to table
A Arrhythmias 57 index 55
Arterioarterial shunt 134 magnetic resonance 80
Acquired valvular disease 142 Arthralgia 28, 51 right atrial myxoma 106
Acute Arthritis 25, 27f, 34, 51, 151 Cardioselective beta blockers 57
aortic regurgitation 95, 96, 99 Atrial Carditis 22, 27f, 34, 37
arthritis 36 fibrillation 58, 69, 70, 81, 152 Carey Coombs murmur 69
bacterial endocarditis 135 natriuretic factor 61 Carotid pulse tracing 87f
inferior myocardial infarction 113 Auscultatory findings Carvallo’s sign 63, 109, 127
MR 77 in severe MR 77f Causes of
rheumatic of severe AR 99f acute MR 75
arthritis 36 Austin flint murmur 69, 99t pulmonary
fever 1, 14, 27f, 29, 34, 36, 47,
regurgitation 121
60, 75
stenosis 120
Acyanotic congenital heart disease 42 b
Central nervous system 21
Adjacent right atrial wall 107 Bactericidal antibiotics 143 Chest
Amyloidosis 60, 74 Balloon pain 51
Anatomy of aortic X-ray in
aortic valve 84, 85f valvotomy 153
mitral valve 59 MR 79
valvuloplasty 93
pulmonary valve 120, 120f MS 65f
mitral valvotomy 69, 70, 71f
tricuspid valve 107 Chordae tendinae 60, 107
Basic hemodynamic parameters 53
Ancillary therapy 57 Chorea 26, 34, 35, 38, 151
Becker's sign 98
Anemia of chronic disease 139 Choreoathetoid movements 38
Behcet’s syndrome 95
Aneurysm of sinus of valsalva 121 Chronic
Bicuspid aortic valve 38
Angina pectoris 81 constrictive pericarditis 112
Bisferiens pulse 98
Angiocardiography 111 rheumatic heart disease 142
Bolloon mitral valvotomy 70
Angiotensin Borrelia burgdorferi 37 valvular heart disease 151
converting enzyme inhibitors 57 Bernoulli’s equation 117 Closed mitral valvotomy 152
receptor blockers 57 Coarctation of aorta 90, 141
Ankylosing spondylitis 74, 95 Collapsing pulse 97
c Colored vision 57
Anterior mitral leaflet 60f
Anterolateral papillary muscle 60f Carcinoid Combined
Anti-Parkinsonian drug 113 heart disease 106, 121 aortic regurgitation 127f, 130f
Aortic syndrome 74, 113 and mitral regurgitation 129t
component of second heart sound Cardiac and mitral stenosis 128t
77 catheterization 111, 117, 141 aortic stenosis 133f
regurgitation 95, 96, 154 and angiocardiography 68, 80, and aortic regurgitation 125t
root diseases 95 89, 101 mitral stenosis and
stenosis 81, 84, 87, 92, 153 cirrhosis 114 aortic stenosis 126t
valve replacement 93, 94, 96 glycosides 57 mitral regurgitation 124t
158 Rheumatic Fever and Rheumatic Heart Disease
tricuspid stenosis and mitral in carditis 32f Glomerulonephritis 142

stenosis 132t in infective endocarditis 141 Gorlin method 68
valvular lesions 123 in tricuspid stenosis 110f Grading of dyspnea 55f
Community acquired IE 135 Edema feet 51 Graham Steell murmur 63, 103, 121
Congenital Egg cell calcification 100 Griffith classification 15
heart disease 38, 141 Ehlers-Danlos syndrome 74
mitral stenosis 68 Ejection systolic murmur 86f, 99f
h
Congestive Electrocardiography 31, 64, 99, 115
cardiac failure 152 End-diastolic pressure 53 Hemodynamics in mitral stenosis 61f
heart failure 30, 52, 55, 69, 112, Endocarditis 134 Hemoptysis and winter bronchitis 69
137, 150 Endocardium 20 Henoch-Schonlein’s purpura 36, 37
Conjunctival hemorrhage 138 Endomyocardial Hill’s sign 98
Connective tissue disorders 36, 74 biopsy 33 Human
Coronary artery disease 53, 74 fibrosis 74, 113 immunodeficiency virus 135
Corrigan’s Endothelial infection 135 leukocytes antigens 17
pulse 97 Enterococcus faecalis 136 Huntington’s
sign 98 Erythema marginatum 27, 27f, 34, chorea 38
Coxiella burnetii 136, 139 35, 39, 151 disease 38
Erythrocyte sedimentation rate 30 Hurler’s syndrome 74
Escherichia coli 47 Hypereosinophilic syndrome 74
d
Etiopathogenesis of rheumatic fever Hypertrophic obstructive cardio
De Musset’s sign 98 14 myopathy 81, 90, 92
Degenerative Evolution of rheumatic fever 148
aortic valve disease 95 Extracardiac sarcoma 106 i
valves 85
Determinant of disappearance of Idiopathic
f
murmur 150 dilatation of aorta 95
Disorder of Fabry’s disease 60 rupture of chordae 74
chordae tendineae 75 Father of rheumatic heart disease 7 Immunologic phenomena 142
leaflets and valves 75 Felty’s syndrome 39 Infection of arteriovenous shunts 134
mitral annulus 75 Femoral artery 71 Infectious arthritis 36, 37
papillary muscles 75 Fenfluramine 113 Infective endocarditis 36, 38, 74, 75,
Dissecting aortic aneurysm 95 Fever 27, 34, 35, 51 81, 87, 113, 134, 135, 137, 140, 152
Doppler mitral regurgitation 51 Fick’s principle 90 in children 145
Double right cardiac border 65f Flame shaped hemorrhage 138 of fungal origin 106
Duroziez’s sign 98 Flash pulmonary edema 62 Inferior vena cava 107
Dyspnea 51, 52 Fulminant rheumatic carditis 151 Infiltrative disease 74
Functional Intervention for atrial fibrillation 72
basal murmur 90 Intracerebral tumors 38
e
classification of dyspnea 52 Ischemia of mitral valve apparatus 74
Early diastolic murmur 98 pulmonary regurgitation 121 Ischemic MR 74
Ebstein’s anomaly 113 tricuspid regurgitation 62
ECG in chronic severe AR 100f
j
Echo evidence of valve dehiscence
g
145 Jomiva balloon catheter 71
Echocardiography 31, 65, 79, 89, 101, Gerhardt's sign 98 Jones criteria 23t
110, 115, 121, 140 Giant cell arteritis 95 Jugular venous pulse 56f
Index 159
Juvenile anatomy 60f Pathogenesis of rheumatic fever 14

heart disease 152 apparatus 74 Pathology of
mitral stenosis 64, 152 prolapse 74, 75 acute rheumatic fever 19
rheumatoid arthritis 36, 37, 39 replacement 72 infective endocarditis 135
valvotomy 71 Pathophysiology of mitral stenosis
Modified Jones criteria 34 62f
k
Morphology of group beta hemolytic Peak right ventricular 54
Katz-Wachtel phenomenon 81 Streptococcus 15f Peculiar observation of acute
Knee joints 27f Mucopolysaccharidosis 60 rheumatic fever 36
Müller sign 98 Pediatric autoimmune neuro
l Myocardial disease 52, 74 psychiatric disorders 38
Myocarditis 38 Percutaneous
Landolfi’s sign 98 Myocardium 19 aortic valve replacement 93
Left transvenous mitral
atrial myxoma 68 commissurotomy 70
n
ventricular Pericardial constriction 106
ejection fraction 55 Native valve endocarditis 135, 144 Pericarditis 38
end-diastolic pressure 96, 98, Nonbacterial thrombotic endocarditis Pericardium 19
103 136 Perivalvular abscess 145
end-diastolic volume 103 Noninvasive tests 31 Petechial hemorrhages 138
outflow tract 101 Nonrheumatic origin 95 Phentermine 113
Leukemia 36 Non-steroidal anti-inflammatory Pistol short 98
Leukocyte count 30 drugs 25 Platypnea 52
Leukocytosis 34 Normal valve areas 55 Polyarthralgia 34, 35
Loeffler’s endocarditis 106 Polyarthritis 34
Lungs 21 Positive C-reactive protein 34
o
Lutembacher’s syndrome 68, 112 Posterior mitral leaflet 60f
Lyme disease 36, 37 Oliver-Cardarelli’s sign 98 Posteromedial papillary muscle 60f
Open Post-stenotic dilatation of aorta 90f
commissurotomy 93 Poststreptococcal reactive arthritis 36
m
mitral Primary myocardial disease 74
MacCallum’s patch 20f commissurotomy 130 Prosthetic valve endocarditis 135, 144
Magnetic resonance imaging 101, 140 valvotomy 72 Pseudomonas aeruginosa 144
Malignant carcinoid 60 Orthopentamogram 140 Psoriatic arthritis 95
Marfan’s syndrome 74, 95, 113 Orthopnea 52 Pulmonary
Methysergide 113 Osler’s node 138, 142 arterial
therapy 60 diastolic pressure 53
Microinfarction of retinal vessels 138 dilatation 109f
p
Mid-diastolic murmur 63, 77f hypertension 107
of mitral stenosis 99t Palfrey’s sign 98 narrowing 62
Minervini’s sign 98 Palmar click 98 artery 56f, 120f, 121
Mitral Pansystolic murmur 77f hypertension 152
annular calcification 60 Papillary muscles 60, 107 systolic pressure 117
annulus 59, 60f, 74 Parenteral antibiotics 143 capillary wedge pressure 53
regurgitation 74, 103, 123, 130f Paroxysmal nocturnal dyspnea 52, component of second heart sound
stenosis 59, 63, 106, 127f, 152 111 77f
valve 59, 71 Patent ductus arteriosus 103 edema 81
160 Rheumatic Fever and Rheumatic Heart Disease
regurgitation 69, 103 Scleroderma 113 Therapy for

stenosis 120 Septicemia 36 enterococci 144
valve disease 120 Serological tests 139 fungal endocarditis 144
vascular resistance 55 Serum gram negative organism 144
vein 55f C-reactive protein 30 staphylococci 143
venous sickness 36 streptococci 143
hypertension 61, 65f, 89 Severe Thermodilution method 90
pressure 53 aortic stenosis 91f Throat swab culture 30
pulmonary arterial hypertension 62 Ticks disorder 38
q Severity of tricuspid stenosis 108t Transesophageal echocardiography
Sickle cell disease 36 68, 89, 110, 135, 140
Quincke’s pulse 98 Sodium nitroprusside 104 Transthoracic echocardiography 140
Sokolsky-Bouillard disease 7 Traube’s sound 98
r Splinter hemorrhage 138 Treatment of infective endocarditis
Restenosis 72 Staphylococcus 143
Rheumatic aureus 135, 136, 137, 143, 144 Tricuspid
aortic stenosis 84 epidermidis 136, 137 aortic valve 102
carditis 23, 35 Sternocostal joint 27f regurgitation 51, 69, 77, 81, 113,
fever 4, 5, 7, 17, 22, 27, 34, 51, 59, Still’s disease 37, 39 154
68, 148 Streptococcal stenosis 106, 108f, 109f, 153
and rheumatic heart disease bacterial morphology 14 valve 107
7, 147 infections 38 anatomy 107f
heart disease 3-5, 7, 9, 14, 47, 49, Streptococcus disease 106
51, 59, 74, 95, 120, 123, 130, bovis 143 prolapse 117
147, 151 epidermidis 144 surgery 118
mitral valvulitis 69 pyogenes 136 Troponin test 31
MR 74 viridans 135, 136, 138, 143 Tuberculosis 36
nodule 4 Streptozyme test 29
Subacute bacterial endocarditis 135
origin 113 v
recurrence begets recurrence 150 Subcutaneous nodules 26, 34, 35, 39,
151 Valvular
Rheumatogenic strain 15
Sudden loss of vision 138 calcification 89
Rheumatoid arthritis 36, 37, 60, 74, 95
Superior vena cava 107 heart disease 150, 152
Right
Surgical valvotomy 71 obstruction 145
atrial myxoma 112
Sydenham’s chorea 26 pulmonary stenosis 52
atrial thrombus 106
Syphilitic aortitis 95 Valvulitis 150
pulmonary artery 55f
Systemic Vascular phenomena 142
ventricular hypertrophy 64
embolism 81 Vegetation obstruct tricuspid orifice
ventricular wall 107
lupus erythematosus 36, 37, 60, 106
Roentgenography 31, 64, 89, 100,
74, 113f Ventricular septal defect 81, 90, 92
110, 115, 121, 140
Rosenbach's sign 98 vascular resistance 55
Roth’s spot 138, 142 Systolic pressure 117 w
Water hammer pulse 97
s t
Whipple’s disease 60, 95
School surveys for prevalence of RHD Tachypnea 52 Wilkins-Weyman’s score 68
11t Tapering of vascular shadows 65 Wilson’s disease 38

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Rheumatic Fever

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Rheumatic Fever and Rheumatic Heart Disease

Section 1: Acute Rheumatic Fever

1. Historical Aspect of Rheumatic Fever and Rheumatic Heart Disease...............................................3

2. Epidemiology of Rheumatic Fever and Rheumatic Heart Disease....................................................7

3. Etiopathogenesis of Rheumatic Fever...............................................................................................14

4. Pathology of Acute Rheumatic Fever................................................................................................19

5. Clinical Manifestations of Rheumatic Fever....................................................................................22

6. Laboratory Diagnosis of Acute Rheumatic Fever.............................................................................29

7. Diagnosis and Differential Diagnosis of Rheumatic Fever..............................................................34

8. Management of Rheumatic Fever.....................................................................................................40

– Prophylaxis of Rheumatic Fever 44

Section 2: Rheumatic Heart Diseases

9. Approach to Diagnosis of Rheumatic Heart Disease.......................................................................51

10. Mitral Stenosis................................................................................................................................... 59

11. Mitral Regurgitation.........................................................................................................................74

12. Rheumatic Aortic Stenosis................................................................................................................84

13. Aortic Regurgitation.........................................................................................................................95

14. Tricuspid Valve Disease...................................................................................................................106

15. Pulmonary Valve Disease................................................................................................................120

16. Combined Valvular Lesions............................................................................................................123

17. Infective Endocarditis.....................................................................................................................134

18. Natural History of Rheumatic Fever and Rheumatic Heart Disease.............................................147

Index .......................................................................................................................................... 157

The history of medicine is vital and inspiring. It gives Egyptian Medicine

Introduction “A peculiar disease of the heart” which made clear that

Table 2.8: School surveys for prevalence of RHD (1981–2010)

Table 2.9: Incidence of Changing Pattern of RHD (1950–2010)

Introduction the research workers. To explain the etiopathogenesis

Summary Further Reading

introduction fever is one of the common causes of acute pericar-

over bony prominences. The histological picture is Kidneys

Lungs Further Reading

Table 5.1: Year-wise modification of Jones criteria

our country it is rare. These are small, pink colored,

Erythema Marginatum Fever

activity. Fever subsides without treatment, but if Further Reading

Introduction There are two types of streptolysin; one is oxygen

Throat Swab Culture Acute Phase Reactants

Diagnosis of acute rheumatic fever (ARF) depends Lab Tests

Less common clinical lesions are:

1. Innocent murmur (anemia and physiological Pericarditis

Introduction when there is congestive heart failure or severe ar-

Table 8.1: Drugs for control of inflammation in acute rheumatic fever

use of steroids result in faster resolution of inflamma- Note:

Table 8.2: Drugs and dosages for heart failure

Resistance cases are treated with plasmapheresis Primary Prophylaxis

Note a mucosal stimulant for the production of protective

Introduction 1. History taking.

For academic interest: Any step-up or step-down in Remember

Normal Valve Areas

Level of Evidence of Treatment/

Definition Anatomy of Mitral Valve

or recurrent carditis which may or may not mani-

Narrowing of mitral valve orifice in diastole impedes Mild 1.6–2.0

ease that is increased pressure at precapillary pul-

2D echo is the basis for diagnosing MS. The fol-

4. Multivalvular lesions In our series of 900 cases (M 310, F 509, AF 20.6

Definition 3. Ischemic MR (Coronary artery disease causing

Aortic Stenosis Complications

iastolic period thereby increases aortic run off and