Pulmonary

Hypertensi
on

Pulmonary Vascular
Pressures
(8
mmHg)
15/4
4
2

15/
2
Normal

(30mmH
g)
50/20 10
15

50/
15

Pulmonary HTN

Pulmonary Vasculature
Pulmonary
venule

Pulmonary
arteriole

Netter FH. Atlas of Human Anatomy

Pulmonary Circulation
High flow, low resistance
PVR ~1/15 of SVR due to
large cross-sectional area

High capacitance
Accommodate CO

Arterioles offer very little

resistance
Systemic arterioles supply
75% total peripheral
resistance

Pulm VenoOcclusive Dz

ThromboEmbolic Dz

PV

IVC/SVC

LUNGS

Hypoxemia
Related PH

RA

LA

RV

LV

ORGAN SYSTEMS

Cardiac Dysfn
SPHTN

PA
PPHTN

AORTA

Left Heart
Disease
LV dysfunction
Left atrial disease
Valvular disease

Chronic thrombotic and/or embolic

diseases
Chronic thromboembolic disease
Other emboli

Pulmonary
Hypertension

Parenchymal Lung
Disease
and/or chronic
hypoxemia
COPD
ILD
OSA/Hypoventilation

Pulmonary
Arterial
Hypertension

Miscellaneous
Sarcoidosis
Fibrosing Mediastinitis

5th World Symposium on PH:

Modified Classification of PH
1. Pulmonary arterial hypertension
1.1 Idiopathic PAH
1.2 Heritable PAH
1.2.1 BMPR2
1.2.2 ALK1, ENG, SMAD9, CAV1, KCNK3
1.2.3 Unknown
1.3 Drug- and toxin-induced
1.4 Associated with
1.4.1 Connective tissue disease
1.4.2 HIV infection
1.4.3 Portal hypertension
1.4.4 Congenital heart diseases (update)
1.4.5 Schistosomiasis
1. Pulmonary veno-occlusive disease
and/or
pulmonary capillary hemangiomatosis
1. PPHN
2. PH due to LHD
2.1 LV systolic dysfunction
2.2 LV diastolic dysfunction
2.3 Valvular disease
2.4 Congenital/acquired left heart
inflow/outflow tract
obstruction and congenital
cardiomyopathies
Simonneau G et al. JACC. 2013;62:D34-D41.

3. PH due to lung diseases and/or hypoxia

3.1 COPD
3.2 Interstitial lung disease
3.3 Other pulmonary diseases with mixed
restrictive
and obstructive pattern
3.4 Sleep-disordered breathing
3.5 Alveolar hypoventilation disorders
3.6 Chronic exposure to high altitude
3.7 Developmental lung diseases (update)
4. CTEPH
5. PH with unclear multifactorial mechanisms
5.1 Hematological disorders: chronic hemolytic
anemia, myeloproliferative disorders,
splenectomy
5.2 Systemic disorders: sarcoidosis, pulmonary
histiocytosis, lymphangioleiomyomatosis,
5.3 Metabolic disorders: glycogen storage disease,
Gaucher disease, thyroid disorders
5.4 Others: tumoral obstruction, fibrosing
mediastinitis, chronic renal failure, segmental
PH
Pulmonar

PAH

y
hypertens
ion

Definition of Pulmonary HTN

Mean Pulmonary Artery Pressure

pre-capillary hypertension

25 mm Hg (rest)
30 mm Hg (exercise)

Pulmonary Vascular Resistance

3 Woods Units (240 dynes/sec/cm5)

Trans-pulmonary Pressure difference

12 mm Hg

Clinical features
Common symptoms
to right and left
heart failure
Fatigue
Dyspnoea
Palpitations
Weight gain

Clinical features
Left heart failure
Paroxysmal nocturnal dyspnoea
Orthopnoea
Basal lung crackles
Presence of the third heart sound

Clinical features
Pure Right heart failure
Jugular venous distension
Hepatomegaly
Peripheral oedema
NO LUNG CRACkLES

 MANAGEMENT OF CHF

Treatment
Vasodilator therapy
ACE inhibitors
Angiotensin II receptor antagonists
Nitrates
Hydralazine

Treatment
blockers
Metoprolol
Bisoprolol
Carvedilol

Treatment
Diuretics
Loop diuretics
Thiazide diuretics
Potassiumsparing diuretics

Treatment
Digoxin
Dopamine
Dobutamine
Antiarrhythmic drugs

Treatment
Revascularization
Biventricular pacemaker
Cardiac transplantation

Pulmonary Arterial Hypertension

LEADS TO RIGHT HEART FAILURE
Idiopathic Pulmonary Arterial Hypertension (IPAH)
Familial Pulmonary Arterial Hypertension (FPAH)
Associated PAH (APAH)
Drug & Toxins (Anorexigens)

Collagen-Vascular Disease (PSS > MCTD > SLE)

Portal Hypertension
HIV infection
Congenital Systemic to Pulmonary Shunts
Other: HHT, thyroid disorders, hemoglobinopathies

PAH in conjunction with Significant Venous or Capillary

Involvement
3rd World Symposium on PAH (Venice 2003)

Survival in PAH

Adapted from McLaughlin VV. Chest; 2004:126; 78S

 HISTORY

Diagnosis
Signs & Symptoms

Dyspnea (>95% long term)

Fatigue (25%)
Syncope (10%)
Hemoptysis
Raynauds (10%)
Angina (20%)
Medication use

PHYSICAL EXAM
JVD
Pulm S2
a wave
RV S3 (50%)
Hepatomegaly Cyanosis
TR murmur (70%)
Edema

Symptoms of PAH
Initial symptoms reported
by patients in the NIH
Registry
Dyspnea in 60%
Fatigue in 19%
Chest pain in 7%
Near syncope in 5%
Palpitations in 5%
Leg edema in 3%

Rich S ,et al. Ann Intern Med 1987;107:216-23.

By time of diagnosis &

enrollment in NIH
Registry
Dyspnea in 98%
Fatigue in 73%
Chest pain in 47%
Near syncope in 41%
Syncope in 36%
Edema in 37%
Palpitations in 33%

Pathophysiology
Increasing PVR

Level

Preclinical

Symptomatic /
stable

Cardiac
output at
peak
exercise

Progressive /
declining
Pulmonary
pressure

Cardiac
output
at rest

Time

Physical Findings
Right Heart Failure
elevated jugular venous distention
tricuspid regurgitation
pulmonary insufficiency (Graham-Steel
murmur)
accentuated S2 (P2)
S3 gallop
peripheral edema
hepatomegaly, pulsatile liver, ascites

Electrocardiogram
Not sensitive enough to be a screening tool
Notable findings1
RVH 87% of PH cases
RAD 79% of PH cases
RAE P wave > 2.5 mm
in II, III, aVF

Rich S, et al. Ann Intern

Med 1987;107:216-23

Roentgenogram findings
Enlargement of
central
pulmonary
arteries
Reduced caliber
of peripheral
vessels (pruning)

Roentgenogram findings
Enlargement of
right & left
pulmonary
arteries
Cardiomegaly
with right
ventricular
enlargement

Echocardiography
PASP (TR jet velocity)
PRV PRA = 4v2
RV hypertrophy
Flattened IV septum
Small LV dimension
Pericardial Effusion
Sensitivity: 80 - 100%
Specificity: 60 - 100%
Correlation: 0.6 - 0.9

4 Chamber view
Right ventricle

Right atrium

Left ventricle

Left
atrium

Short-axis view
Right ventricle

Left
ventricle

Chronic Thromboembolic Disease

Webbing
Webbing

Pulmonary Angiography
Webs
Irregular
lumen
Truncated
vessel
Abnormal
blush
Courtesy J. Gould

Right Heart Catheterization

Gold Standard

confirm diagnosis
survey for left-sided disease (PAWP or LVEDP)
rule out L to R intracardiac shunt
acute vasodilator challenge
prognostic information
mPAP, mRAP, CI
acute vasodilator challenge

Goals of Therapy
Abolish Right Heart Failure
Improve CO/CI, MVO2, and mean RAP

Symptomatic Improvement
6MW Distance, Peak VO2, Functional Clas
Reverse Vascular Remodeling
Improve PAP and PVR

Pulmonary Arterial
Hypertension:
Goals of Therapy
Improve hemodynamics

Improve exercise capacity

Improve functional class
Prevent clinical worsening
Improve survival

Chronic Adjuvant Therapies in

PAH
Oxygen

Use to prevent hypoxic vasoconstriction

Consider exercise, sleep, altitude
Aim for target saturation of 92%
Diuretics
Most patients need
Low systemic BP and elevated Cr often not a
contraindication
Anticoagulation
Recommended in IPAH
Warfarin with INR 1.5 2.5 range (can go off for
procedures): other Rx not studied
Newer agents such as dabigatran, rivaroxaban and
apixaban not studied for IPAH
Dietary
Sodium and fluid restriction often necessary for RV
dysfunction and fluid retention
Exercise Training
Supervised exercise training studied in PAH and useful
to increase exercise capacity

PAH Therapy
(+) Vasodilator Response
Calcium channel blockers
() Vasodilator Response or Non-sustained
Vasodilator Response
Endothelin receptor antagonists
Phosphodiesterase-5 inhibitors
SCG stimulator
Prostanoids
McLaughlin VV et al. J Am Coll Cardiol. 2009;53:1573-1619.

Available Therapies

Diuretics
Digitalis
Warfarin
Oxygen
Inotropes
Vasoactive
Agents

Atrial Septostomy
Transplantation

Thromboendarterectom
y

Vasoactive Agents
Calcium-channel blockers
Endothelial receptor antagonists (ERAs)
Phosphodiesterase-5 Inhibitors (PDE5-I)
Prostanoids

Treatment Pathways
Endothelin pathway
Endothelin
cells

Nitric oxide pathway

Vessel
lumen

Arachidonic acid
Prostaglandin I2

Pre-proendothelin
Proendothelin
L-arginine Lcitrulline

Endothelin
receptor A
Endothelin
1

Prostacyclin
(prostaglandin I2)

Nitric oxide

Endotheli
+ Exogenou
n
Endotheli
cGMP
s nitric
receptor
n receptor
oxide
antagonis Vasodilation andB
Phosphodiesteras
Vasodilation and
ts
proliferation
e type 5
antiproliferation

Smooth
muscle cells

Prostacyclin pathway

Phosphodiester
ase type 5
inhibitor

Humbert M. N Engl J Med 2004;351:1425-36

cAMP

Prostacycli
n
derivatives

Vasodilation and
antiproliferation

Simplicity
Efficacy

Route

Indicatio
Drawback
n
(WHO)

Bosentan,
PO
Ambrisentan

II-IV

Cost / yr
$
thousands

Hepatotoxicit
$35
y

Sildenafil

PO

I-IV

Adequate
Dosing

$10

Iloprost

IH

III-IV

Fluctuating
levels

$75

Treprostinil

SQ
IV

II-IV

Site pain
Catheterrelated

$50-150

III-IV

Catheterrelated

$50-100

Epoprostenol IV

Conclusions
Evaluation of chronic pulmonary hypertension should
focus on identifying its origin
Most common causes of PH are underlying cardiac or
pulmonary conditions with treatment geared
towards underlying condition
PAH is a group of diverse diseases linked by
pathophysiology & histopathology with a natural
history of right heart failure
Existing therapies offer symptom relief and delay
progression of disease but are not curative

Cor Pulmonale
.
Dept. of Pulmonary and Critical Care
Medicine

Cor Pulmonale
Right Sided Heart Disease, secondarily
caused by abnormalities of lung
parenchyme, airways, thorax, or
respiratory control mechanisms.
Noevidence of other heart conditions,
Acute vs. Chronic

Pathophysiology
pulmonary hypertension that is sufficient
to lead to RV dilation, with or without the
development of concomitant RV
hypertrophy
Right ventricle: thin walled, compliant
Better suited for high volumes than
high pressure
Sustained pressure overload (pulm HPN)
and increased vascular resistance causes
RV to fail

Etiology of Cor Pulmonale ( I )

Lung and
Airways
COPD
Asthma
Bronchiectasis
DILD
Pulmonary
tuberculosis

Etiology of Cor Pulmonale ( II )

Thoracic Cage
Kyphosis > 100 o
Scoliosis > 120 o
Thoracoplasty
Pleural fibrosis

N-M Disease
Polio Myelitis
Myasthenia Gravis
ALS
Muscular
Dystrophy

Etiology of Cor Pulmonale ( III )

Abnormal Respiratory Control

Idiopathic hypoventilation Syndrome
Obesity hypoventilation syndrome (PickWickian syndrome)
Cerebrovascular disease

Hypercapnea
H

Hypoxia

Acidemia
A

Increased
Viscosity
Acidosis

Anatomic changes

Pulmonary Vessel
Restriction
Increased C.O.
C

Chronic Cor Pulmonale

Rt. Ventricular Failure

Pathologic Features
Lung : consistent with Specific diseases
Common Features: hypertrophy of
microvasculatures
Hallmark : Rt. Ventricular Hypertrophy
60g 200g, > 0.5 CM, RV/LV <2.5
Lt. Ventricular Hypertrophy
Hypertrophy of Carotid Body

Natural History
Several months to years to develop
All ages from child to old people
Repeated infections aggravate RV strain into
RV failure
Initilly respondes well to therapy but
progressively becomes refractory

Prevalence

Emphysema : less frequent

Cronic bronchitis : more common
US : 6-7 % of Heart failure
Delhi : 16%
Sheffield in UK : 30 40%
Autopsy in Chronic Bronchitis : 50%
More prevalent in pollution area or smokers

Factors that determine severity

hypoxia secondary to alterations in

gas exchange
Hypercapnia
Acidosis
alterations in RV volume overload
that are affected by:
exercise, heart rate, polycythemia, or increased salt
and retention because of a fall in cardiac output

Clinical presentation
Symptoms:
Dyspnea, the most common symptom
usually the result of the increased work of
breathing secondary to changes in elastic recoil of
the lung (fibrosing lung diseases) or altered
respiratory mechanics

Orthopnea and paroxysmal nocturnal

dyspnea are rarely symptoms of isolated
right HF
reflect the increased work of breathing in the
supine position that results from compromised
excursion of the diaphragm

Clinical presentation
Symptoms:
Tussive or effort-related syncope
because of the inability of the RV to deliver
blood adequately to the left side of the heart

Abdominal pain and ascites

Due to right heart failure

Lower extremity edema

secondary to neurohormonal activation, elevated
RV filling pressures, or increased levels of
carbon dioxide and hypoxia,

Clinical presentation
Signs

tachypnea
elevated jugular venous pressures
hepatomegaly
lower-extremity edema
Cyanosis is a late finding

Lab. Findings
X-Ray : Prominent pulmonary hilum
pulmonary artery dilatation
Rt MPA diameter> 20 mm
EKG : P- pulmonale, RAD, RVH
Echocardiography : RVH, TR, Pulm. Hypertension
ABG : Hypoxemia, Hypercapnea, Respiratory
acidosis
CBC : polycythemia
Cardiac catheterization

Treatment
Treat Underlying Disease : COPD Tx, Steroid,
Infection control, theophylline,
Continuous O2 : < 2-3L/min
Diuretics
Phlebotomy
Digoxin : controversial
Beta adrenergic agents
Reduce Ventilation/Perfusion imbalance
:CPAP/BIPAP

Treatment
Primary goal: target the underlying
pulmonary disease
decrease in pulmonary vascular resistance and relieve
the pressure overload on the RV

General principles:
decreasing the work of breathing using noninvasive
mechanical ventilation, bronchodilation, and steroids
treating any underlying infection

Adequate oxygenation (oxygen

saturation 9092%) will also decrease
pulmonary vascular resistance and
reduce the demands on the RV
Diuretics