This document provides an overview of pulmonary hypertension (PH) in heart failure, including definitions, classifications, epidemiology, pathophysiology, clinical features, and management. Some key points include: - PH is defined as a mean pulmonary artery pressure >25 mmHg and is classified into 5 groups including pulmonary arterial hypertension. - Risk factors for PH include left heart disease, lung disease, chronic thromboembolic disease, and unclear/multifactorial causes. - Clinical features include dyspnea, fatigue, chest pain, and signs of right heart failure. Prognosis depends on functional classification and presence of right heart failure. - Diagnostic tests include echocardiogram, ventilation-perfusion scan, right

1. PULMONARY HYPERTENSION
IN HEART FAILURE

2. OUTLINE
• INTRODUCTION
• DEFINITIONS
• EPIDEMIOLOGY
• CLASSIFICATION
• PATHOPHYSIOLOGY
• CLINICAL FEATURES
• MANAGEMENT

3. INTRODUCTION
• Pulmonary hypertension (PH) is an abnormal elevation in pulmonary
artery pressure. It is a feature of advanced disease.
• The pulmonary artery pressure and pulmonary vascular resistance
progressively rises, leading to right heart failure and death.
• Over the years, improvement in understanding the pathogenesis has
resulted in the development of targeted approaches to the treatment
of PH. Survival advantage has also been shown with some of the
pharmacologic agents.

4. DEFINITIONS
• Pulmonary hypertension (PH) is a hemodynamic and
pathophysiological condition defined as mean pulmonary artery
pressure > 25 mmHg at rest by Right heart Catheterization(RHC).
• Pulmonary arterial hypertension (PAH) is a clinical condition
characterized by the presence of pre- capillary PH in the absence of
other causes of pre- capillary PH such as PH due to lung diseases,
chronic thromboembolic PH, or other rare diseases

5. PULMONARY CIRCULATION
• The pulmonary circulation is the vascular system that conducts blood
from the right to left side of the heart through the lungs
• Pulmonary arteries are very thin walled and distensible.
• The pulmonary vascular resistance (PVR) is a measure of the
impedance to flow in the pulmonary vasculature
• PVR depends on pulmonary artery pressure, left atrial pressure and
the cardiac output. Normal pulmonary artery pressure=25/8 mmHg
Normal mean pulmonary artery pressure=15+/-3mmHg

6. EPIDEMIOLOGY
• E. Romberg, German doctor’s published description of autopsy,
showed thickening of the pulmonary artery but no heart or lung
disease.
• In 1951, 39 cases were reported by Dr. D.T. Dresdale in the United
States.
• Between 1967 and 1973, a 10-fold increase in unexplained PH was
reported in central Europe. The rise was subsequently traced to
Aminorex fumarate, an amphetamine-like drug introduced in Europe
in 1965 to control appetite.

7. • In Nigeria, pulmonary hypertension-related heart disease accounts
for:
• 0.6-28% of heart diseases
• 1.4-10.1% of echo registries
• 0.9-17% of autopsy/mortality studies.
• Mortality associated with the disease is high. Over 70% die in less
than 6 months after the onset of symptom (Ogah OS. Pulmonary
hypertension in Nigeria. PVRI Review 2010;2:95)

8. • Valentine et al in 2017 at OAUTH studied 94 SCA subjects who had
echocardiography and 6-minute self-paced walking exercise done. PH
was diagnosed by Doppler echocardiography on finding a tricuspid
regurgitant velocity (TRV) of ≥2.5 m/s in 23.9% of them
• Akintunde A.A reported an 86year old woman with cor triatriatum
with pulmonary hypertension (WHO group 2) during preoperative
evaluation. Akintunde AA ,Singapore Med J. 2011 Oct;52(10):e203-5

9. CLASSIFICATION OF PULMONARY
HYPERTENSION
• First version was proposed in 1973 at the first international
conference on PPH by WHO.
• Second and third world meetings on PAH in 1998 and 2003,
respectively.
• Fourth World meet on PH held in 2008 in Dana Point, California,
adopted new clinical classification

11. • GROUP 1. PULMONAY ARTERIAL
HYPERTENSION
• Key feature: Elevation in PAP with
normal PCWP
• Idiopathic (IPAH)
• Heritable (BMPR2, ALK1, endoglin ,
Unknown)
• Exposure to drugs or toxins
• Persistent pulmonary hypertension
of the newborn
• Associated with (APAH)
• Collagen vascular disease
• Congenital heart diseases
• Portal hypertension
• HIV infection
• Schistosomiasis
• Chronic haemolytic anaemia
• GROUP 1’ Pulmonary veno-occlusive
disease(PVOD) and pulmonary
capillary haemangiomatosis

12. • GROUP 2. Pulmonary venous hypertension
• Key feature: Elevation in PAP with elevation in PCWP
• Includes:
• Systolic dysfunction
• Diastolic dysfunction
• Valvular disease

13. • GROUP 3. PH ASSOCIATED WITH HYPOXEMIC LUNG DISEASE.
• Key feature: chronic hypoxia with mild elevation of PAP, Includes:
• Chronic obstructive lung disease
• Interstitial lung disease
• Sleep-disordered breathing
• Alveolar hypoventilation disorders
• Chronic exposure to high altitude
• Developmental abnormalities

14. • GROUP 4. PH DUE TO CHRONIC THROMBOEMBOLIC DISEASE
• Key feature: elevation of PA pressure with documentation of
pulmonary arterial obstruction for >3 months. Includes:
• Chronic pulmonary thromboembolism

15. • GROUP 5. WITH UNCLEAR AND/OR MULTIFACTORIAL MECHANISMS
• Key feature: elevation in PAP in association with a systemic disease
where a causal relationship is not clearly understood. Includes:
• Haematological disorders: myeloproliferative disorder, splenectomy.
• Systemic disorders : sarcoidosis, pulmonary Langerhans cell
histiocytosis, neurofibromatosis, vasculitis
• Metabolic disorders: Glycogen storage disease, Gaucher disease
Thyroid disorders
• Others: Tumoural obstruction, fibrosing mediastinitis, chronic renal
failure on dialysis

16. PATHOLOGY OF PH
• Different pathological features characterize the diverse clinical PH
groups.
• Group 1 - PAH
• Affect the distal pulmonary arteries (<500 um of diameter) in
particular, are characterized by
• Medial hypertrophy,
• Eccentric and concentric intimal fibrosis
• Recanalized thrombi appearing as fibrous webs
• Plexiform lesions
• Pulmonary veins are classically unaffected

17. • It includes mainly PVOD
• Which involves septal veins and pre-septal venules with occlusive
fibrotic lesions, venous muscularization, capillary proliferation ,
pulmonary edema, occult alveolar hemorrhage, lymphatic dilatation
and lymph node enlargement.
• Distal pulmonary arteries are affected .

18. • Group 2 - PH
• Due to left heart disease: Characterized by enlarged and thickened
pulmonary veins, pulmonary capillary dilatation, interstitial edema,
alveolar hemorrhage, and lymphatic vessel and lymph node
enlargement.
• Distal pulmonary arteries may be affected

19. • Group 3 – PH
• Due to lung diseases and/or hypoxia:
• Include medial hypertrophy and intimal obstructive proliferation of
the distal pulmonary arteries.
• A variable degree of destruction of the vascular bed in
emphysematous or fibrotic areas may also be present.

20. • Group 4 -CTEPH
• Characterized by organized thrombi tightly attached to medial layer
in pulmonary arteries, replacing the normal intima.
• These may completely occlude the lumen or form different grades of
stenosis, webs, and bands.
• Collaterals from the systemic circulation can grow.

21. • Group 5-PH
• unclear and/or multifactorial mechanisms:
• Includes conditions with different pathological pictures
• Aetiology is unclear or multifactorial.

22. PATHPHYSIOLOGY OF PH
• Group 1-
• The exact processes that initiate the pathological changes seen in PAH
are still unknown
• The increase in PVR is related to vasoconstriction, proliferative and
obstructive remodelling of the pulmonary vessel wall, inflammation,
and thrombosis.
• Excessive vasoconstriction related to abnormal function or
expression of potassium dysfunction.

23. • Group 2-
• the mechanisms are multiple and include
• Passive backward transmission of the pressure elevation .
• The elevation of PVR is due to an increase in vasomotor tone of
pulmonary arteries and fixed structural obstructive remodelling
• Vasoconstrictive reflexes arising from stretch receptors in the left
atrium and pulmonary veins, and endothelial dysfunction
• hannels in the smooth muscle cells and endothelial

24. • Group 3-
• mechanisms include
• Hypoxic vasoconstriction, mechanical stress of hyperinflated lungs,
inflammation and toxic effects of cigarette smoke.
• Group 4 –
• Non-resolution of acute embolic masses which later undergo fibrosis
leading to mechanical obstruction of pulmonary arteries
• Pulmonary thromboembolism or in situ thrombosis may be initiated or
aggravated by abnormalities in either the clotting cascade, endothelial
cells, or platelets
• Group 5- PH with unclear and/or multifactorial mechanisms

25. MOLECULAR ABNORMALITIES IN PAH
• Prostacyclin is a potent vasodilator, inhibits platelet activation, and
has antiproliferative properties
• Prostacyclin synthase is decreased in the pulmonary arteries in
PAHEndothelin-1
• Endothelin-1 (ET-1) is a potent vasoconstrictor and stimulates PASMC
proliferation.
• Plasma levels of ET-1 are increased in PAH and clearance is reduced
Nitric Oxide

26. • Nitric oxide (NO) is a vasodilator and inhibitor of platelet activation
and vascular smooth-muscle cell proliferation.
• Once formed, the effects of NO are largely mediated by cGMP which
is rapidly inactivated by PDE, especially the PDE-5 isoenzymes.
• Serotonin (5-HT) is a vasoconstrictor and promotes PASMC
hypertrophy and hyperplasia.
• Vasoactive intestinal peptide (VIP) has a pharmacologic profile
similar to prostacyclins.
• Serum and lung tissue VIP levels are decreased in PAH patients

27. GENETICS OF PAH
• BONE MORPHOGENETIC PROTEIN RECEPTOR 2 GENE(BMPR2)
• BMPR2 gene encodes a type 2 receptor for bone morphogenetic
proteins, which belong to the TGF-b superfamily involved in the
control of vascular cell proliferation
• Mutations are detected in at least 70% of cases PAH occurs in a
familial context.
• Mutations of this gene can also be detected in 11–40% of apparently
sporadic cases.
• Activin receptor-like kinase 1 and endoglin, have been identified in
PAH

28. IDIOPATHIC PAH
• IPAH corresponds to sporadic disease, without any familial history of
PAH or known triggering factor.
• Formerly referred to as primary pulmonary hypertension
• 1-2 cases per million
• Females>males (1.7:1)

29. SIGNS AND SYMPTOMS OF PH
• SYMPTOMS
• Easy fatigability, lethargy
• Exertional chest discomfort
• Syncope with exertion
• Cough
• Hemoptysis
• Hoarseness of voice

30. • SIGNS
• Increased intensity of the pulmonic component of the second heart sound
(P2)
• Systolic ejection murmur from TR S/O Advanced Disease.
• Diastolic murmur of PI in severe PH.
• left parasternal heave
• Prominent ‘a’ wave in jugular venous system.
• Signs of RV failure:
• Jugular venous distension
• Hepatomegaly
• Ascites, and/or peripheral edema

31. WHO CLASSIFICATION OF FUNCTIONAL
STATUS OF PATIENTS WITH PH
• Class Description
• I Patients with PH in whom there is no limitation of usual physical
activity; ordinary physical activity does not cause increased dyspnea,
fatigue, chest pain, or presyncope.
• II Patients with PH who have mild limitation of physical activity. There
is no discomfort at rest, but normal physical activity causes increased
dyspnea, fatigue, chest pain, or presyncope.

32. • III Patients with PH who have a marked limitation of physical activity.
There is no discomfort at rest, but less than ordinary activity causes
increased dyspnea, fatigue, chest pain, or presyncope.
• IV Patients with PH who are unable to perform any physical activity at
rest and who may have signs of right ventricular failure. Dyspnea
and/or fatigues may be present at rest, and symptoms are increased
by almost any physical activity.

33. NATURAL HISTORY AND SURVIVAL
• Median survival 2.8 years, with 1-, 3-, and 5-year survival rates of
68%, 48%, and 34%, respectively.
• Functional class remains a strong predictor of survival
• The prognosis in patients with PAH associated with the scleroderma is
worse than for IPAH.
• CHD have a better prognosis than those with IPAH
• Cause of death is usually RV failure, manifest by progressive
hypoxemia, tachycardia, hypotension, and edema

34. PARAMETERS OF WORSE PROGNOSIS IN PAH
• Presence of RV failure
• Rapid progression of symptoms
• WHO –FC IV
• 6 MWT < 300 m
• Pericardial effusion

35. DIAGNOSTIC TESTS
• ELECTROCARDIOGRAPHY
• ECG has sensitivity(55%) and specificity (70%) detecting significant
PH, may demonstrate
• Right ventricular hypertrophy or strain
• Right axis deviation
• P pulmonale due to right atrial enlargement.
• Ventricular arrhythmias are rare.
• SVT may be present in advanced stages

36. • Electrocardiogram demonstrating the
• Right ventricular hypertrophy with strain
• Right axis deviation ,
• Increased P-wave amplitude in lead II

37. CHEST RADIOGRAPH
• In 90% of patients with IPAH the chest
radiograph is abnormal.
• Findings include central pulmonary
arterial dilatation, which contrasts with
‘pruning’ (loss) of the peripheral blood
vessels.
• Right atrium and RV enlargement may
be seen Enlargement of the central
pulmonary arteries with attenuation of
the peripheral vessels
• Right ventricular enlargement and
seen.

38. ECHOCARDIOGRAPHY
• Is performed to estimate the pulmonary artery systolic pressure and
to assess RV size, thickness, and function.
• In addition, left ventricular systolic and diastolic function, and valve
function, while detecting pericardial effusions and intracardiac
shunts.
• PH may have echocardiographic signs of right ventricular pressure
overload, including paradoxical bulging of the septum into the left
ventricle during systole and hypertrophy of the right ventricular free
wall.
• As the right ventricle fails, there is dilation and hypokinesia, septal
flattening, right atrial dilation, and tricuspid regurgitation

39. • Echocardiography uses Doppler ultrasound to estimate the pulmonary
artery systolic pressure .
• This technique takes advantage of the tricuspid regurgitation that usually
exists.
• The maximum tricuspid regurgitant jet velocity is recorded and the
pulmonary artery systolic pressure (PASP) is then calculated by Bernoulli’s
equation
• PAP systolic = 4 x ( tricuspid jet velocity squared)m/s + RAP
• Theoretically, calculation of mean PAP from PA systolic pressure is possible
mean
• PAP =0.61 X PAP systolic + 2 mmHg.
• A systolic PAP greater than 40 mmHg is suggestive of PH.

40. • Four-chamber echocardiographic
view of a patient who has severe
PAH.
• Note the massively dilated right
ventricle(RV) and right atrium(RA)
that have shifted the septa and
narrowed the left ventricle (LV)
and left atrium (LA).

41. • VENTILATION-PERFUSION SCANNING
• Is used to evaluate patients for thromboembolic disease.
• A normal V/Q scan accurately excludes chronic thromboembolic
disease with a sensitivity of 90 to 100 percent and a specificity of 94
to 100 percent .
• Pulmonary angiography is necessary to confirm the positive V/Q scan
and to define the extent of disease.
• PULMONARY ANGIOGRAM
• Used to measure circulation in the lungs and to visualize clots in the
lung on x-rays

42. • PULMONARY FUNCTION TESTS
• Pulmonary function tests (PFTs) are performed to identify and
characterize underlying lung disease contributing to PH.
• An obstructive pattern is suggestive of COPD,
• Restrictive disease suggests ILD, neuromuscular weakness, or chest
wall disease.
• In most circumstances, PH should not be attributed to lung disease if
the PFTs are only mildly abnormal

43. • LABORATORY TESTS
• HIV serology to screen for HIV-associated PH
• Liver function tests to screen for porto-pulmonary hypertension
Antinuclear antibody (ANA)
• Thyroid function test
• NT-proBNP is the precursor of BNP in right heart failure .
• Anti-centromere antibodies in scleroderma
• Thrombophilia screening including anti-phospholipid antibodies,
lupus anticoagulant, and anti-cardiolipin antibodies should be
performed in CTEPH

44. • OVERNIGHT OXIMETRY
• Nocturnal oxyhemoglobin desaturation can be identified by overnight
oximetry in patients with PH —obstructive sleep apnea-hypopnea
(OSAH) coexists .
• Polysomnography is the gold standard diagnostic test for OSAH.
• ULTRASONOGRAPHY
• Useful in portal hypertension

45. • EXERCISE TESTING
• Exercise testing is most commonly performed using the six minute
walk test (6MWT)
• Provide benchmarks for disease severity, response to therapy, and
progression.
• In addition to distance walked, dyspnoea on exertion and finger O2
saturation are recorded.
• Walking distances , <250 m and O2 desaturation 10% indicate
impaired prognosis in PAH.

46. • RIGHT HEART CATHETERIZATION
• Right heart catheterization is necessary to confirm the diagnosis of
PH . Accurately determine the severity of the hemodynamic
derangements.
• PH is confirmed if the mean pulmonary artery pressure is greater
than 25 mmHg at rest .
• RHC is required to guide therapy
• An additional benefit of RHC is that the presence and/or severity of a
congenital or acquired left-to-right shunt.

47. • VASOREACTIVITY TEST
• Aim: To detect the residual properties of vasodilatation of small pulmonary
arteries and arterioles .
• It is recommended in patients with group 1 PAH .
• This involves the administration of a short-acting vasodilator and then
measurement of the hemodynamic response .
• Agents commonly used for vasoreactivity testing include epoprostenol,
adenosine, and inhaled nitric oxide .
• Epoprostenol is infused at a starting rate of 1 to 2 ng/kg per min and
increased by 2 ng/kg per min every 5 to 10 minutes until a clinically
significant fall in blood pressure, an increase in heart rate, or adverse
symptoms develop .

48. • Test is positive if mPAP decreases at least 10 mmHg and to a value
less than 40 mmHg, with an increased or unchanged cardiac output,
and a minimally reduced or unchanged systemic blood pressure.
• Patients with a positive vasoreactivity test are candidates for a trial of
CCB therapy.
• Negative vasoreactivity test should be treated with an alternative
agent

49. • COMPUTERIZED TOMOGRAPHY
• High-resolution CT provides detailed views of the lung parenchyma
and facilitates the diagnosis of interstitial lung disease and
emphysema.
• High-resolution CT may be very helpful where there is a clinical
suspicion of PVOD
• Contrast CT angiography of the PA is helpful in determining whether
there is evidence of surgically accessible CTEPH.

50. • MAGNETIC RESONANCE IMAGING
• Cardiac MRI may soon supersede this as the gold standard. RV mass
which is difficult to quantify by other methods can be accurately done
by MRI.
• By MRI, it can be shown that right ventricle has a crescent shape and
left ventricle has a more circular shape.
• When the right ventricle pressure is elevated quite the opposite
happens. This can be well demonstrated by MRI.

51. • LUNG BIOPSY
• Is reserved only in an unusual patient in whom PH is not thought to
be the primary disease.
• In such patients, one always finds abnormalities such as lung
infiltrates or other findings such as pulmonary hemangiomatosis or
pulmonary veno occlusive disease.

52. TREATMENT OF PH
• Early identification and treatment PH is generally suggested because
advanced disease may be less responsive to therapy .
• Treatment begins with a baseline assessment of disease severity,
followed by primary therapy.
• Primary therapy is directed at the underlying cause of the PH.
• Some patients progress to advanced therapy, which is therapy
directed at the PH itself, rather than the underlying cause of the PH.
• It includes treatment with prostanoids, endothelin receptor
antagonists, phosphodiesterase 5 inhibitors, or, rarely, certain calcium
channel blockers.

54. • BASELINE ASSESSMENT
• The baseline severity assessment is essential because the response to
therapy will be measured as the change from baseline.
• The functional significance of the PH is determined by measuring exercise
capacity.
• From the exercise capacity, the patients WHO functional class can be
determined .
• Pulmonary artery systolic pressure and right ventricular function can be
estimated by echocardiography, and then used to make a presumptive
diagnosis of PH.
• Right heart catheterization must be performed to accurately measure the
hemodynamic parameters and confirm that PH exists.

55. PRIMARY THERAPY
• Primary therapy refers to treatment that is directed at the underlying
cause of the PH.
• Group 1 PAH -There are no effective primary therapies for most types
advanced therapy is often needed.
• Group 2 PH — Patients with group 2 PH have PH secondary to left
heart diseases. Primary treatment of the underlying heart disease.
• Group 3 PH — Patients with group 3 PH have PH secondary to various
causes of hypoxemia. Treatment of the underlying cause of
hypoxemia and correction of the hypoxemia with supplement of
oxygen

56. • Group 4 PH — Patients with group 4 PH have PH due to
thromboembolic occlusion .Anticoagulation is primary medical
therapy for patients .
• Surgical thromboendarterectomy is primary surgical therapy for
selected patients with thromboembolic obstruction of the proximal
pulmonary arteries .
• Group 5 PH — Group 5 PH is uncommon and includes PH with unclear
multifactorial mechanisms. Primary therapy is directed at the
underlying cause.

57. • GENERAL MEASURES
• All groups — Several therapies should be considered in all patients with PH.
• Diuretics —
• Diuretics are used to treat fluid retention due to PH . Should be
administered with caution to avoid decreased cardiac output , arrhythmias
induced by hypokalemia, and metabolic alkalosis.
• Oxygen therapy —
• Oxygen the cornerstone of therapy in patients with group 3 PH.
• Oxygen is generally administered at 1 to 4 L/min and adjusted to maintain
the oxygen saturation above 90 percent .
• Supplemental oxygen will not significantly improve the oxygen saturation
of patients who have Eisenmenger physiology.

58. • Digoxin —
• Improves the right ventricular ejection fraction of patients with group 3 PH due
to COPD and biventricular failure
• Helps control the heart rate of patients who have SVT associated with RV
dysfunction .
• Anticoagulation —
• increased risk for intrapulmonary thrombosis and thromboembolism, due to
sluggish pulmonary blood flow, dilated right heart chambers, venous stasis, and a
sedentary lifestyle.
• Indicated in patients with IPAH , hereditary PAH , drug- induced PAH , or group 4
PH.
• The anticoagulant of choice is warfarin.
• Goal of an INR of approximately 2.

59. ADVANCED THERAPY
• Advanced therapy is directed at the PH itself, rather than the
underlying cause of the PH.
• It includes treatment with prostanoids, endothelin receptor
antagonists, phosphodiesterase 5 inhibitors, or, rarely, certain calcium
channel blockers.
• Patient selection — Advanced therapy is considered for patients who
have evidence of persistent PH and a World Health Organization WHO
functional class II, III.

60. • CALCIUM CHANNEL BLOCKERS(CCB)
• Patient who may benefit from CCB therapy can be identified by acute
vasodilator response test in PAH.
• The dosages used are quite high; 90–180 mg/day for nifedipine (up to 240
mg/day) and 240–720 mg/day for diltiazem (up to 900 mg/day). or
amlodipine, 20 mg/day
• <20% of patients respond to calcium channel blockers in the long term.
Not effective in patients who are not vasoreactive.
• Patients with BMPR2 receptor mutation do not respond .
• Side effects – constipation, nausea, headache, rash, edema, drowsiness,
dizziness, low blood pressure

61. • PROSTACYCLIN
• The main product of arachidonic acid in the vascular endothelium
causes relaxation of smooth muscle
• Also results in inhibition of growth of smooth muscle cells.
• Successfully used in the treatment of PH resulting from left to right
shunt, portal hypertension and HIV infection.

62. • EPOPROSTENOL
• Potent vasodilator ,Unstable at acidic pH, not taken orally.
• Very short half life,<6 min requires constant Iv administration Initial
dose: 1 – 2 ng/kg/min
• Titrating in increments of 1- 2 ng/kg/min, based upon side effects
and tolerance to reach a “plateau” between 20 – 40 ng/kg/min
• Side effects: Flushing, headache, jaw pain with first bite of food,
diarrhea, nausea, erythematous rash and musculoskeletal pain.

63. • TREPROSTINIL
• Stable prostacyclin analogue. Can be given intravenously or
subcutaneously and Inhalation. Half life of 3 hours.
• Stable at room temperature
• Initially 1.25 ng/kg/min up to maximum of 22.5 ng/kg/min.
• Side effects: Headache, diarrhea, nausea, rash, jaw pain, infusion site
pain, erythema or induration.

64. • LOPROST
• Prostacyclin analogue. Serum half-life of 20 – 25 mins
• For functional class 3 – 4.
• Administered via nebulized aerosol.
• Administered 6 – 9 times a day, each inhalation requires 10 – 15 mins.
• Dose: 2.5 – 5 ug, median inhaled dose of 30 ug/day.
• Side effects: Cough, headache and flushing.

65. • BERAPROST
• First chemically stable and orally active prostacyclin analogue.
• concentration is reached after 30 minutes and elimination half-life is
35 – 40 minutes after oral administration. Median dose of 80 ug PO
daily.

66. • ENDOTHELIN RECEPTOR ANTAGONISTS
• Endothelin-1 is a potent vasoconstrictor and smooth muscle
mitogen.
• High concentrations of endothelin-1 have been recorded in the lungs
of patients with group 1 PAH, including scleroderma and congenital
cardiac shunt lesions .
• Emerged as an initial therapy for group 1 PAH in the late 1990s.

67. • BOSENTAN
• Nonselective endothelin receptor antagonist
• improves hemodynamics and exercise capacity in patients with group
1 PAH.
• Orally active nonpeptide antagonist of both endothelin receptor
subtypes.
• Prevents and even reverses the development of PH, pulmonary
vascular remodelling and right ventricular hypertrophy.
• Initial dose of 62.5 mg bid for first 4 weeks and followed by target
dose of 125 mg bid. Side effects: Hepatotoxicity and teratogenicity.

68. • SITAXSENTAN
• Selective ETA antagonist
• Has oral bioavailability and a long duration of action (t 1/2, 5-7h) .
• Side effects: ↑ INR and PT .

69. • PHOSPHODIESTERASE INHIBITORSSILDENAFIL
• Orally administered cyclic GMP phosphodiesterase 5 (PDE5) inhibitors
that prolong the vasodilatory effect of NO in group 1 PAH.
• Approved dose is 20 mg t.i.d., but the durability of effect up to a up-
titration beyond 20 mg t.i.d. (mainly 40–80 mg t.i.d.) is needed quite
frequently.
• Contraindicated with Nitrates and nicorandil.
• Prevent rebound pulmonary vasoconstrictionTadalafil and vardenafil
also appear to improve outcomes in patients with group 1 PAH

70. • NITRIC OXIDE
• Inhaled form.
• Acts as direct smooth muscle relaxant via activation of the guanylate
cyclase system.
• Short therapeutic half life.
• Ameliorates hypoxemia and lowers PVR by direct pulmonary
vasodilatation.

71. • SURGICAL INTERVENTIONS
• Balloon Atrial Septostomy
• Allow R - L shunting to increase systemic output that
• In spite of fall in the systemic arterial oxygen saturation, will produce an
increase in systemic oxygen transport.
• Shunt at the atrial level would allow decompression of the RA and RV,
alleviating s/s of right heart failure.
• Considered after short term failure of maximal medical therapy.
• Severe IPAH has been the main indication other include PAH associated
with surgically corrected CHD, CTD, distal CTEPH, PVOD, and pulmonary
capillary haemangiomatosis.

72. • HEART / LUNG TRANSPLANTATION
• 1 year survival of 70%.
• 5 year survival of 50%.
• Effective therapy for patients with end stage pulmonary vascular disease.
• Other areas of research for treatment of PH includes
• Gene therapy
• serotonin transporter
• vasoactive intestinal peptide and tyrosine kinase inhibitors. Angiogenic
factors and stem cells .
• Imatinib