my lecture about pulmonary hypertension

1. P U L M O N ARY H Y P E R T E N S I O N ( P H )
SA MEER SAWA ED , MD
IN TER N A L MED IC IN E D EPA R TMEN T - A
ZIV H OSPITA L 2 0 2 0

2. INTRODUCTION
defined as an elevation in pulmonary arterial pressures
(mean pulmonary artery pressure [PAP] >22 mmHg or
an estimated systolic PAP >36 mmHg).
Symptoms of dyspnea, chest pain, and syncope.
THE MOST COMMON CAUSE OF DEATH
decompensated right heart failure.
frequently misdiagnosed with more common diseases
such as asthma or chronic obstructive pulmonary disease.

3. PATHOBIOLOGY
Vasoconstriction, vascular proliferation, thrombosis,
and inflammation appear to underlie the development of
PAH

4. PATHOBIOLOGY
The outcome is a progressive increase in the right
ventricular afterload or total pulmonary vascular
resistance (PVR), and, thus, right ventricular work.
(CO) is compromised and starts to fall. With a decline in
CO, the PAP will fall.
tachycardia is a compensatory response. Tachycardia
decreases filling time and, thus, preload, and results in a
reduced fraction of stroke volume

5. MOLECULAR PATHWAYS
Abnormalities in multiple molecular pathways and genes
that regulate the pulmonary vascular endothelial and
smooth muscle cells have been identified EX -
• decreased expression of the voltage-regulated
potassium channel, mutations in the bone
morphogenetic protein receptor-2, increased tissue
factor expression, over activation of the serotonin
transporter

6. PHYSICAL EXAMINATION
evidence of right ventricular failure with elevated
jugular venous pressure, lower extremity edema, and
ascites.
a right-sided S3 or S4, and a holosystolic tricuspid
regurgitant murmur.
signs of the diseases that are often concurrent with
PH:
clubbing may be seen in some chronic lung diseases,
sclerodactyly and telangiectasia may signify
scleroderma

7. DIAGNOSIS
most important initial screening test=echocardiogram
with bubble study
• hypertrophied and dilated right ventricle
specific etiologies of PH

8. DIAGNOSIS
invasive hemodynamic monitoring is the gold standard for
diagnosis = right heart catheterization (RHC)
cardiopulmonary exercise test may help to identify a
true physiologic limitation as well as differentiate between
cardiac and pulmonary causes of dyspnea.
• If this test is normal, there is no indication for a RHC.

9. IMAGING
• chest radiograph = enlargement of the central
pulmonary arteries, “vascular pruning,” and
cardiomegaly

10. REPRESENTATIVE COMPUTED TOMOGRAPHIC SCAN OF THE CHEST
DEMONSTRATING ENLARGED MAIN PULMONARY ARTERIES.

11. OTHER INVESTIGATIONS
isolated reduction in diffusing capacity of the lungs for carbon
monoxide (DLCO) is the classic finding in PAH
antinuclear antibodies, rheumatoid factor, and anti-scl-70
antibodies assessed to screen for the most common
rheumatologic diseases associated with PH.
Liver function and hepatitis serology tests are important to
screen for underlying liver disease.
nocturnal oximetry screening
N-terminus of its pro-peptide (NT-proBNP) correlate with right
ventricular (dys)function, hemodynamic severity, and functional
status in PAH.

12. RHC

13. VASODILATOR TESTING
Vasodilators with a short duration of action, such as
inhaled nitric oxide (NO), or inhaled epoprostenol are
preferred for vasodilator testing.
A decrease in mPAP by ≥10 mmHg to an absolute level
≤40 mmHg without a decrease in CO is defined as a
positive pulmonary vasodilator response
and responders are considered for long-term treatment
with calcium channel blockers (CCB).

14. CATEGORIES OF PH
Pulmonary Arterial Hypertension WHO Group I PH
• Idiopathic PAH (IPAH)
average age at diagnosis was 45 years, with only 9% of
patients with IPAH over the age of 60.
associated with HIV, connective tissue disease, and portal
hypertension.

15. PULMONARY HYPERTENSION ASSOCIATED WITH LEFT
HEART DISEASE WHO GROUP II PH
patients with left heart systolic dysfunction, aortic and
mitral valve disease, (HFpEF).
• The hallmark of Group II PH is elevated left atrial
pressure with resulting pulmonary venous hypertension.
• In general, the transpulmonary gradient and PVR remain
normal.

16. PULMONARY HYPERTENSION
ASSOCIATED WITH LUNG DISEASE
chronic obstructive lung disease and interstitial lung
disease , sleep-disordered breathing
pulmonary function tests demonstrating a very low DLCO.

17. PH ASSOCIATED WITH CHRONIC
THROMBOEMBOLIC DISEASE
PH likely increases following recurrent embolism.
pathogenesis of CTEPH is poorly understood

18. OTHER DISORDERS AFFECTING THE
PULMONARY VASCULATURE
Sarcoidosis , Sickle Cell Disease
• Schistosomiasis Studies suggest that inflammation
from the infection triggers the pulmonary vascular
changes that occur.

20. PHARMACOLOGIC TREATMENT OF
PAH
• prostacyclin and prostacyclin analogues and
agonists
• NO pathway enhancers
• endothelin receptor antagonists (ERAs)

22. PROSTANOIDS
Prostacyclin (PGI2) activates cyclic adenosine monophosphate
(cAMP)-dependent pathways that mediate vasodilation. PGI2
also has antiproliferative effects on vascular smooth muscle and
inhibits platelet aggregation.
• Treprostinil has a longer half-life than epoprostenol (~4 hours
vs ~6 minutes)
• inhaled iloprost and treprostinil
• addition of a phosphodiesterase-5 (PDE5) inhibitor, therefore,
augments the pulmonary hemodynamic and functional
capacity benefits of prostanoids in PAH.

23. Selexipag is an oral nonprostanoid derivative that binds
the prostaglandin I2 (IP) receptor with high affinity.
• Selexipeg significantly reduced the risk of hospitalization
and the risk of disease progression by 43%

24. ENDOTHELIN RECEPTOR
ANTAGONISTS
ET-A receptors found on pulmonary artery smooth muscle
cells (PASMC) mediate vasoconstriction.
• bosentan and macitentan, non-selective receptor
antagonists; and ambrisentan, a selective ET-A receptor
antagonist.
•

25. TRIAL COMPARING BOSENTAN OR PLACEBO
DEMONSTRATED IMPROVED SYMPTOMS, 6MWD

26. BOSENTAN TO PLACEBO DEMONSTRATED IM
(EARLY) STUDY COMPARING PROVED PVR AND 6MWD.

27. AMBRISENTAN IMPROVES EXERCISE
TOLERANCE

28. NITRIC OXIDE PATHWAY
Phosphodiesterase type 5 enzymes metabolize cGMP.
Therefore, cGMP phosphodiesterase type 5 (PDE5)
inhibitors prolong the vasodilatory effect of NO
• sildenafil and tadalafil: Both agents have been shown
to improve hemodynamics and 6MWD
• Riociguate is a soluble guanylyl cyclase stimulator
directly stimulating soluble guanylyl cyclase independent
of NO availability. Riociguat significantly improved
exercise capacity, pulmonary hemodynamics, WHO
functional class, and time to clinical worsening in
patients with PAH and CTEPH.

30. COMBINATION THERAPY
• combination therapy with ambrisentan and tadalafil was
associated with a 50% lower risk of clinical worsening
(composite of death, lung transplantation, hospitalization
for PAH worsening, and worsening PAH)