Pulmonary Hypertension

and its management

Presented by:
Under the guidance of:
Goyal Sir

Mohit Goyal
Dr. V. K.

Pulmonary hypertension (PH) is an

abnormal elevation in pulmonary artery
pressure, as a result of left heart
failure,
pulmonary
parenchymal
or
vascular disease, thromboembolism, or
a combination
of these factors.
Pulmonary Hypertension and its management

Pulmonary Hypertension and its management

Salient features of Pulmonary circulation: It is a low resistance circuit

Pulmonary BP is about 1/8th of systemic blood
pressure
PH occurs when Pulmonary BP reaches 1/4th of
systemic levels

Pulmonary Hypertension and its management

Genesis of PH: Increased pulmonary blood flow

Increased pulmonary vascular resistance
Increased left heart resistance to blood flow

Pulmonary Hypertension and its management

Right Ventricular Output

Ventricular Systolic Pressure

Right
Pulmonary

Vascular Resistance

Pulmonary Hypertension and its management

Adaptability of Right Ventricle

vascular resistance depends upon:-

to

increased

Age of the patient

Rapidity of development of Pulmonary Hypertension

Pulmonary Hypertension and its management

Conditions leading to PH (Secondary PH): Those with elevated PAP and normal PCWP
E.g. Idiopathic, Familial, in Collagen disorders, in L
to R shunts,
drugs, toxins, persistent PH of newborn
Those with elevated PAP and PCWP
E.g. Left side valve disease, Pulmonary
venoocclusion
Those associated with chronic hypoxia
E.g. COLD, ILD, Sleep apnoea
Elevated PAP with Pulmonary arterial obstruction >
3 months
Pulmonary Hypertension and its management

Connective tissue diseases e.g. Systemic

sclerosis
Intimal fibrosis, Medial hypertrophy

Reduced functional cross sectional area

Increased pulmonary vascular resistance

Increased pulmonary arterial pressure

Pulmonary Hypertension and its management

Heart Diseases
Mitral stenosis

Increased left atrial pressure

Increased pulmonary venous pressure

Increased pulmonary arterial pressure

Pulmonary Hypertension and its management

COLD/ILD
Destruction of lung parenchyma

Fewer alveolar capillaries

Increased pulmonary arterial resistance

Increased pulmonary arterial pressure

Pulmonary Hypertension and its management

Pulmonary thromboembolism
Pulmonary emboli

Reduced functional cross sectional area

Increased pulmonary vascular resistance

Increased pulmonary arterial pressure

Pulmonary Hypertension and its management

Pulmonary embolism
Chronic thromboembolism

Pulmonary Hypertension and its management

Miscellaneous substances found to cause

PH

Crotolaria spectabilis tropical leguminous

plant
Aminorex Appetite depressant
Adulterated olive oil
Fenfluramine, Phentermine anti-obesity drugs
They are postulated to act through effects on
serotonin transporter expression or activity.
Pulmonary Hypertension and its management

Underlying mechanisms in Secondary PH

Shear and mechanical injury in left to right
shunts
Biochemical
injury
thromboembolism

by

fibrin

in

Pulmonary vasoconstriction by decreased

prostacyclin, decreased nitric oxide and
increased endothelin
Promotion of platelet activation and adhesion
by decreased prostacyclin and nitric oxide
Pulmonary Hypertension and its management

Idiopathic Pulmonary Hypertension

Uncommon form encountered sporadically in
patients whom all known causes of Pulmonary
hypertension are excluded.

Pulmonary Hypertension and its management

Familial Pulmonary Hypertension

Least common form having autosomal dominant
inheritance
with
incomplete
penetrance,
consequently only 10-20% family members
developing overt disease.

Pulmonary Hypertension and its management

BMPR2 is a cell surface protein belonging to the

TGF- receptor superfamily, which binds a variety
of
cytokines,
including
TGF-,
bone
morphogenetic protein (BMP), activin, and
inhibin.
Apart from its role in bone growth, BMP-BMPR2
signalling is now known to be important for
embryogenesis, apoptosis, and cell proliferation
and differentiation.

Pulmonary Hypertension and its management

Inactivating germline mutations in the BMPR2

gene are found in 50% of the familial cases of
pulmonary arterial hypertension and 25% of
sporadic cases.
In many families, even without mutations in the
coding regions of the BMPR2 gene, linkage to the
BMPR2 locus on chromosome 2q33 can be
established, thus indicating that other possible
lesions such as gene rearrangements, large
deletions, or insertions could be involved.
Pulmonary Hypertension and its management

Unanswered questions
Topics of researches
First, how does loss of a single allele of the
BMPR2 gene lead to complete loss of signalling?
Either the mutation might act as a dominant
negative or
A secondary loss of the normal allele might
occur in the vascular wall via e.g. microsatellite
instability, thus leading to a homozygous loss
of BMPR2.
Pulmonary Hypertension and its management

Why the phenotypic disease occurs only in 10%

to 20% of individuals with BMPR2 mutations?
Existence of modifier genes like endothelin,
prostacyclin synthetase, and angiotensin
converting enzymes.
Environmental triggers which affect vascular
tone.

Pulmonary Hypertension and its management

Thus, a two-hit model has been proposed whereby a

genetically susceptible individual with a BMPR2
mutation requires additional genetic or
environmental insults to develop the disease.
Pulmonary Hypertension and its management

Vasospastic component in PH
Some individuals with PH have a vasospastic
component; in such patients, pulmonary vascular
resistance can be rapidly decreased with
vasodilators. Exact mechanism is not known.
It appears that even in cases with very advanced
primary pulmonary hypertension there is a
vasospastic component which can be influenced
by vasodilators e.g. Phentolamine.

Heinrich U, Angehrn W, Steinbrunn W. (1983). Therapy of primary pulmonary

hypertension
with Hypertension
phentolamine,
113(4):145-8.
Retrieved
from
Pulmonary
and its management

Morphology
All forms of PH have some common pathologic features
Medial hypertrophy of muscular and elastic arteries
Atheromas of pulmonary artery and its major branches
Right ventricular hypertrophy
Pulmonary embolism - organizing or recanalized
Coexistence of diffuse pulmonary fibrosis, or severe
emphysema and chronic bronchitis, points to chronic
hypoxia as the initiating event
Pulmonary Hypertension and its management

Gross
appearance of
atheroma
formation

Marked medial
hypertrophy
Plexiform lesions
in PH due to
drugs, HIV

Pulmonary Hypertension and its management

Symptoms
Exertional dyspnoea
Fatigue
Angina pectoris
Syncope, near syncope
Peripheral oedema

Pulmonary Hypertension and its management

Signs
Raised JVP
Reduced carotid pulse
Increased component of P2 in S2
Right Sided S4
Tricuspid regurgitation
Peripheral cyanosis and oedema in late stage
Pulmonary Hypertension and its management

Clas
s

NYHA

WHO

1/I

No
symptoms
with Patients with PH but without resulting
ordinary
physical limitation of physical activity. Ordinary
activity.
physical activity does not cause undue
dyspnoea or fatigue, chest pain, or near
syncope.

2/II

Symptoms
with Patients with PH resulting in slight limitation
ordinary activity. Slight of physical activity. They are comfortable at
limitation of activity.
rest. Ordinary physical activity causes
undue dyspnoea or fatigue, chest pain, or
near syncope.

3/III

Symptoms with less

than ordinary activity.
Marked limitation of
activity.

4/IV

Symptoms with any Patients with PH with inability to carry

activity or even at rest. out any physical activity without
symptoms. These patients manifest signs
of right-heartand
failure.
Dyspnoea and/or
Pulmonary Hypertension
its management

Patients with PH resulting in marked

limitation of physical activity. They are
comfortable at rest. Less than ordinary
activity causes undue dyspnoea or
fatigue, chest pain, or near syncope.

Investigations
Chest Radiography
Electrocardiogram
Echocardiography
Lung function testing
Ventilation-perfusion scanning
HRCT scanning
Pulmonary angiography
Cardiac catheterization
Exercise testing
Pulmonary Hypertension and its management

Chest Radiograph
Enlargement of pulmonary trunk
Pruning of peripheral pulmonary arterial tree
Right ventricular enlargement
Findings corresponding to condition leading to
PH

Pulmonary Hypertension and its management

Pulmonary Hypertension and its management

Electrocardiogram
RAD
Right Ventricular Enlargement

Pulmonary Hypertension and its management

Echocardiogram and Continuous Wave Colour

Doppler
Thickened right ventricle
Regurgitant flow across the tricuspid valve
Regurgitant flow across the pulmonic valve

Pulmonary Hypertension and its management

Pulmonary Hypertension and its management

Pulmonary Hypertension and its management

Cardiac catheterization

Pulmonary Hypertension and its management

Cardiac catheterization
Determination of: Right atrial pressure
Right ventricular pressure
PAP
PCWP
Pulmonary blood flow (cardiac output)
Vasoreactivity
Pulmonary Hypertension and its management

Pulmonary Hypertension and its management

Other Investigations
Lung function testing
Ventilation-perfusion scanning
HRCT scanning
Lung biopsy
Pulmonary angiography
Exercise testing

Pulmonary Hypertension and its management

Echocardiogr
am
Dilated
RV
PF
T
Obstructi
ve

Restricti
ve

COLD

HRCT

ILD

Left heart disease

Valvular heart
disease
Congenital
anomaly
Cardiac
Catheterization

Pulmonary
Normal or
thromboembolis
enlarged
m
pulmonary
Lab tests:arteries
CBC, ANA, HIV,
TSH, LFTs

Exercise testing, Catheterization,

Vasodilator testing

Pulmonary Hypertension and its management

Management options
Drug therapy
Atrial septostomy
Lung transplantation

Pulmonary Hypertension and its management

Drug options
Calcium channel blockers
Endothelin receptor antagonists
Phosphodiesterase-5 inhibitors
Prostacyclin analogues

Pulmonary Hypertension and its management

Pulmonary Hypertension and its management

Principles of drug treatment

Patients should undergo cardiac catheterization before initiating therapy.
Obtain baseline assessments of the disease to know whether treatments
are effective.
Test Vasoreactivity.
Reactive patients should be treated with calcium channel blockers.
Nonreactive patients should be offered other therapies.
Reassess at 8 weeks; patients who dont respond are unlikely to respond
with longer exposure.
Ineffective treatments should be substituted rather than new added.
Patients who fail
transplantation.

all

treatments

should

be

considered

for

lung

Only the addition of sildenafil to epoprostenol has been shown to be

Pulmonary Hypertension and its management
efficacious.

Calcium channel blockers

Indicated in patients who respond to vasodilators during
catheterization
Mean PAP<40 mm of Hg and fall > or = 10 mm of Hg
High doses required e.g. nifedipine 240 mg/d, or amlodipine,
20 mg/d
Dramatic reductions in PAP, resistance associated with
improved symptoms
Regression of RV hypertrophy
Improved survival now documented to exceed 20 years
However <20% patients respond to calcium channel blockers
Hypertension and its management
in the longPulmonary
term

Endothelin receptor antagonists

Bosentan and ambrisentan are approved treatments of PAH
Both improved exercise tolerance in RCTs
Bosentan initiated at 62.5 mg BD for first month and
increased to 125 mg BD
Ambrisentan initiated as 5 mg OD and can be increased to 10
mg daily
Liver function be monitored monthly throughout the duration
of use
Contraindicated in patients on cyclosporine or glyburide
Pulmonary Hypertension and its management

Phosphodiesterase-5 inhibitors
Approved for the treatment of PAH
Phosphodiesterase-5 is responsible for the hydrolysis of cyclic
GMP
Sildenafil and tadalafil improve exercise tolerance
Effective dose for sildenafil is 2080 mg TID
The effective dose for tadalafil is 40 mg OD
The most common side effect is headache
Neither drug should be given to patients who are taking
nitrovasodilators
Pulmonary Hypertension and its management

Prostacyclin analogues
Iloprost
Approved via inhalation for PAH
Improves a composite measure of symptoms and exercise
tolerance by 10%
Given at either 2.5 or 5 g per inhalation treatment via a
dedicated nebulizer
Most common side effects are flushing and cough
Very short half-life of <30 min
Recommended to be administered as often as every 2 h
Pulmonary Hypertension and its management

Prostacyclin analogues
Epoprostenol
Approved as a chronic IV treatment of PAH
Improvement in symptoms, exercise tolerance, and survival
Administration requires placement of a permanent central
venous catheter
Infusion done through an ambulatory infusion pump system
Cause vasodilation and platelet inhibition
Also inhibition of vascular smooth muscle growth and
inotropic effects
Side effects include flushing, jaw pain, and diarrhoea
Doses of
epoprostenol
range from
25its
tomanagement
40 ng/kg per min
Pulmonary
Hypertension
and

Prostacyclin analogues
Treprostinil
Analogue of epoprostenol, approved for PAH
May be given intravenously, subcutaneously, or via inhalation
Clinical trials have demonstrated
symptoms with exercise
Local pain at
administration

the

infusion

site

an

improvement

with

in

subcutaneous

Doses of treprostinil range from 75 to 150 ng/kg per min

Pulmonary Hypertension and its management

Atrial Septostomy
Blade-balloon atrial septostomy is performed
In patients with severe refractory RV pressure and volume
overload
Decompresses overloaded right heart
Improves systemic output of the underfilled left ventricle
Increased venous admixture
Worsening hypoxaemia is expected over time
Pulmonary Hypertension and its management

Lung transplantation
Only 1/3rd patients
vasodilators

of

primary

PH

are

responsive

to

oral

Indicated in patients on IV prostacyclin, who continue to manifest

right heart failure
Handicapped by shortage of lung donors
Single/double lung transplantation has largely replaced heart-lung
transplantation
Median survival after transplantation is 3 years
Rejection phenomena e.g. Bronchiolitis obliterans are limiting
factors Pulmonary Hypertension and its management

What we can do
High index of suspicion
Electrocardiography,
Echocardiography, Lung function
Angiography, Exercise testing

Radiography,
testing, HRCT,

Easily available CCBs, Sildenafil

Educate suitable candidates about catheterization

Pulmonary Hypertension and its management

THANK YOU
Bibliography

HAVE A GOOD
DAY

Rich, S., 2012. Pulmonary Hypertension. In: D. Longo, A. Fauci, D. Kasper, S.

Hauser, J. Jameson, J. Loscalzo, ed. 2012 Harrisons Principles of Internal Medicine.
USA: McGraw-Hill. pp.2076-2082.
Rubin, L.J., 2001. Pulmonary Hypertension. In: R.A. ORourke, V. Fuster, R.W.
Alexander, R. Roberts, S.B. King III, H.J.J. Wellens, eds. 2001. Hurst's The Heart :
Manual of Cardiology. USA: McGraw-Hill. Ch.19.
Husain, A.N., 2010. The Lung. In: V. Kumar, A.K. Abbas, N. Fausto, J.C. Aster, eds.
2010. Robbins and Cotran Pathologic Basis of Disease. USA: Saunders. Ch.15.

Pulmonary Hypertension and its management