Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure ≥25 mm Hg at rest, measured during right heart catheterization. There is still insufficient evidence to add an exercise criterion to this definition. The term pulmonary arterial hypertension (PAH) describes a subpopulation of patients with PH characterized hemodynamically by the presence of pre-capillary PH including an end-expiratory pulmonary artery wedge pressure (PAWP) ≤15 mm Hg and a pulmonary vascular resistance >3 Wood units. Right heart catheterization remains essential for a diagnosis of PH or PAH. This procedure requires further standardization, including uniformity of the pressure transducer zero level at the midthoracic line, which is at the level of the left atrium. One of the most common problems in the diagnostic workup of patients with PH is the distinction between PAH and PH due to left heart failure with preserved ejection fraction (HFpEF). A normal PAWP does not rule out the presence of HFpEF. Volume or exercise challenge during right heart catheterization may be useful to unmask the presence of left heart disease, but both tools require further evaluation before their use in general practice can be recommended. Early diagnosis of PAH remains difficult, and screening programs in asymptomatic patients are feasible only in high-risk populations, particularly in patients with systemic sclerosis, for whom recent data suggest that a combination of clinical assessment and pulmonary function testing including diffusion capacity for carbon monoxide, biomarkers, and echocardiography has a higher predictive value than echocardiography alone.

1. DIAGNOSIS & MANAGEMENT OF
PULMONARY HYPERTENSION
Dr Kamal Bharathi. S
Department of Pulmonary Medicine
Sri Manakula Vinayagar Medical college and Hospital

2. DIAGNOSTIC STUDIES
• Identify the etiology
• Assess severity and prognosis
• Evaluate the functional and haemodynamic
impairment
• Help guide appropriate therapy

3. Detection of pulmonary hypertension
Detailed history and physical examination Suspicion of pulmonary hypertension and
possible causes/ associations
Electrocardiogram Exclude other causes of cardiopulmonary
symptoms
Chest radiograph
Echocardiogram (at rest. to consider
repeat with exertion)
Evaluate for presence of pulmonary
hypertension, assess chamber sizes and
function, valvular abnormalities, contrast
(bubble) study to evaluate possible shunt

4. Essential testing
Pulmonary function testing Exclude intrinsic lung disease
Lung (V/Q) scan Exclude thromboembolism
Overnight oximetry Screen for sleep-disordered breathing
Blood serologies (e.g., CBC. liver function,
renal function, HIV, ANA, antiphospholipid
antibodies)
Exclude collagen vascular disease, liver
disease, infection, and other possible
causes of pulmonary hypertension
Oxygen desaturation study Assess need for supplemental oxygen
6-Minute walk test Establish baseline
Right cardiac catheterization Confirm diagnosis, assess other cardiac
causes (shunt); consider left heart
catheterization

5. Contingent testing
Transesophageal echocardiogram Assess patent foramen ovale (PFO)
Characterize valvular function
Computed tomogram of chest Assess interstitial lung disease,
adenopathy
Polysomnogram Diagnosis and treatment of sleep-
disordered breathing
Pulmonary angiogram
Blood studies (BNP, clotting studies,
genetic testing)
Assess presence and location of organized
thromboemboli and suitability for
pulmonary thromboendarterectomy
Lung biopsy Exclude subtle interstitial lung disease
vasculitis and other uncommon diseases
(PVOD, PCH) to assist planning

6. Chest Radiograph
Features include:
• elevated cardiac apex due to right ventricular
hypertrophy
• enlarged right atrium
• prominent pulmonary outflow tract
• enlarged pulmonary arteries
• pruning of peripheral pulmonary vessels

8. CHEST X RAY

9. ECG
• RV hypertrophy with strain pattern (increased
R-wave amplitude with ST-segment
depression and T-wave inversion in the
precordial leads)
• Right atrial enlargement (increased P-wave
amplitude in leads II and V1)

11. Echocardiogram
• Suspicion- first test to assess if PHT is present.
• Modified Bernoulli equation:
RVSP = 4v2 + right atrial pressure;
v = tricuspid jet velocity in meters per second
• assumed equal to the PA systolic pressure
when the pulmonic valve is normal.
• Normal RVSP has been reported as 28 ± 5 mm
Hg.

12. Echocardiogram
• Reveals important anatomical and functional information-
identifying the cause.
• Conditions that Predispose to Pulmonary Hypertension
• Congenital or acquired valvular disease (MR, MS, AS, prosthetic
valve dysfunction)
• Left ventricular systolic dysfunction
• Impaired left ventricular diastolic function (hypertensive heart
disease, HCM, Fabry disease, infiltrative cardiomyopathies)
• Other obstructive lesions (aortic coarctation, supravalvular AS,
subaortic membrane, cor triatriatum)
• Congenital disease with shunt (ASD, VSD, coronary fistula, patent
ductus arteriosus, anomalous pulmonary venous return)
• Pulmonary embolus (thrombus in IVC, right-sided cardiac chamber,
or PA; tricuspid or pulmonic valve vegetation)
• Pulmonary vein thrombosis/stenosis

13. Echocardiogram Findings
• TR
• Right atrial and ventricular hypertrophy
• Flattening of interventricular septum
• Small LV dimension
• Dilated PA
• Pericardial effusion- Poor prognostic sign
 RA pressure so high it impedes normal drainage
from pericardium
 Do not drain, usually does not induce tamponade
since RV under high-pressure and non-collapsible

14. Four-chamber view. Right atrial (RA) enlargement, right
ventricular
(RV) enlargement. The left atrium (LA) and left ventricle (LV) are
small and underfilled.

15. Short axis view. RV enlargement is present. Flattening of the
intraventricular septum (IVS) results from pressure and volume
overload of the RV

18. SIX-MINUTE WALK DISTANCE
• The 6-minute walk test (6MWT) is the most commonly
employed measure of exercise capacity in patients with
PH.
• In addition to the distance walked, the degree of
dyspnea (Borg score) and oxygen saturation are also
measured.
• A 6-minute walk distance of < 332 m and a drop in
oxygen saturation by > 10% are suggestive of poor
prognosis.
• It is also measured on routine follow-ups and can be
indicative of clinical deterioration.
• It may also be used to assess the response to therapy.

19. • PFT and ABG:
Identify the contribution of underlying airway
or parenchymal lung disease.
• Ventilation/Perfusion lung scan:
should be performed in patients with PH to
look for potentially treatable CTEPH

20. • 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
• Blood tests and immunology Routine biochemistry,
haematology, and thyroid function tests are required in all
patients. Serological testing is important to detect
underlying CTD, HIV, and hepatitis.
• Abdominal ultrasound scan Liver cirrhosis and/or portal
hypertension can be reliably excluded by the use of
abdominal ultrasound.

21. Cardiac Catheterization
• Right heart cardiac catheterization is required to
confirm the diagnosis of pulmonary hypertension.
• to assess the severity of the haemodynamic
impairment.
right atrial pressure
mean PAP
pulmonary artery occlusion pressure (PAOP)
cardiac output (CO)
pulmonary vascular resistance (mPAP-PAOP)/CO
Transpulmonary gradient (mPAP-PAOP)
• to test the vasoreactivity of the pulmonary circulation

22. • Usually, the RAP and PCWP also increase,
implying RV failure and left ventricular (LV)
diastolic dysfunction, respectively.
• The latter is the consequence of ventricular
interdependence and abnormal compliance of
the left ventricle produced by an enlarged
right ventricle.

23. Diagnosis of PAH
• requires a mean pulmonary artery pressure
greater than or equal to 25 mm Hg,
• an adequately measured PAWP or a directly
recorded LVEDP of less than or equal to 15
mm Hg;
• An elevated PVR >3 Wood units is also seen
and required in some published diagnostic
criteria for PAH.

24. Vasodilator testing
• to identify those few patients in whom a trial of
treatment with oral calcium channel antagonists is
appropriate.
• Agents commonly used include inhaled nitric oxide,
intravenous adenosine, or epoprostenol administered
by either route.
• the definition has varied, a decrease in the mPAP of
at least 10 mm Hg to a value less than 40 mm Hg,
together with a CO that is unchanged or increased
(but not decreased) is generally considered a
“positive” acute vasodilator response

25. THERAPY FOR PAH
• Therapy must be driven by an appropriately
established diagnosis

26. Exercise and the Avoidance of
Deconditioning
• Regardless of the cause, patients with
pulmonary hypertension and cor pulmonale
should be encouraged to maintain as active a
lifestyle as possible.
• Regular, steady aerobic exercise should be
encouraged, and is often best initiated under
guidance of a pulmonary or cardiac
rehabilitation program.

27. Oxygen Therapy
• To avoid acute hypoxia- as hypoxic pulmonary
vasoconstriction will add to the burden on the
right ventricle.
• Oxygen relieves hypoxic pulmonary
vasoconstriction, thus decreasing vascular
resistance and improving CO.
• Levels of arterial oxygen saturation < 90% -
supplemental oxygen.

28. Immunizations
• against influenza and pneumococcal
pneumonia are important preventive
measures in all patients with pulmonary
hypertension and cor pulmonale.

29. Fluid Management and Diuretics
• to avoid fluid overload is central to the
management of cor pulmonale.
• dietary habits and to restrict sodium intake.
• Spironolactone is often used to manage mild
fluid retention.

30. Anticoagulation
• In the absence of contraindications,
anticoagulation with warfarin is
recommended.
• The generally recommended target INR for
warfarin therapy in patients with PAH is 1.5 to
2.5.

31. Contraception and Pregnancy
• Pregnancy in women with IPAH is associated
with a high mortality, on the order of 30% to
50%.
• pregnancy should be avoided, and early
termination recommended on account of the
high maternal mortality.

32. PAH-SPECIFIC PHARMACOTHERAPY
• Treatment of PAH aims to decrease PVR, thereby
improving CO.
• Calcium Channel Antagonists
• Endothelin Receptor Antagonists- Bosentan,
Sitaxsentan, Ambrisentan
• Phosphodiesterase Inhibitors- Sildenafil,
Tadalafil, Vardenafil.
• Prostenoid Therapies- Epoprostenol, Treprostinil,
Iloprost.
• Guanylate cyclase stimulant- Riociguat

34. Calcium Channel Antagonists
• Use only when demonstrated vasoreactivity in
RHC (about 10% or less of patients)
• Diltiazem or nifedipine preferred.
• Titrate up to maximum tolerated dose.
• Systemic hypotension may prohibit use
• Only 50% of patients maintain response to CCB.
• Not in FC IV patients or severe right heart failure

35. Endothelin Receptor Antagonists
• Targets relative excess of endothelin-1 by
blocking receptors on endothelium and vascular
smooth muscle
• Bosentan, Ambrisentan, Sitaxentan, Macitentan
• Ambrisentan is ET-A selective.
• Both show improvement in 6MWD and time to
clinical worsening.
• Monthly transaminase monitoring required for
both
• Annual cost is high

36. • Potential for serious liver injury (including very rare cases
of unexplained hepatic cirrhosis after prolonged
treatment)
• Oral dosing
 Initiate at 62.5 mg BID for first 4 weeks
 Increase to maintenance dose of 125 mg BID thereafter
 Initiation and maintenance dose of 62.5 mg BID
recommended for patients >12 years of age with body
weight >40kg
• No dose adjustment required in patients with renal
impairment
• No predetermined dose adjustments required for
concomitant warfarin administration.

37. Ambrisentan
• 5 or 10 mg once daily
• Much less risk of transaminase elevation
(about 1%), but monthly monitoring still
required
• No dose adjustment of warfarin needed.

38. Macitentan
- able to achieve enhanced tissue penetration,
- long-lasting pharmacologically active metabolites,
- an increased receptor affinity and
- more sustained receptor binding
• These properties allow a once-a-day regimen with lower
doses and optimised safety profile, and with no effect on liver
enzymes in phase II trials

39. PDE-5 inhibitors

40. Sildenafil
• Safety
– Side effects: headaches, epistaxis, and
hypotension (transient)
– Sudden hearing loss
– Drug interaction with nitrates
– FDA approved dose is 20 mg TID
– Tadalafil 40mg OD
– Vardenafil 5mg OD

41. Prostacyclin analogues
• Epoprostenol- continuous IV
• Treprostinil- continuous subcutaneous,
continuous IV, intermittent inhaled, and oral.
• Iloprost- intermittent inhaled
Benefits
– Vasodilation
– Platelet inhibition
– Anti-proliferative effects
– Inotropic effects

42. Epoprostenol
• First PAH specific therapy
available in the mid
1990’s
• Lack of acute vasodilator
response does not correlate
well with epoprostenol
unresponsiveness.
• Very short half life = 2
minutes
• Delivered via continuous
infusion

43. • Side effects: headache, jaw pain, flushing,
diarrhea, nausea and vomiting, flu-like
symptoms, and anxiety/nervousness
• Complex daily preparation
• Individualized dosing
• Catheter complications
– Dislodgement/malfunction
– Catastrophic deterioration
– Embolization
– Infection (3% deaths)

44. Treprostinil (Remodulin)
• Continuous subcutaneous
infusion or IV infusion
• Longer t1/2 = 4 hours
• Less risk of rapid fatal
deterioriation if infusion stops
• Intravenous treprostinil
– Hemodynamic improvements and
6MWT improvements
– No site pain
– Risk of catheter related
bloodstream infection and embolic
phenomenon
– Recent concerns about increased
gram-negative bloodstream
infections.

45. Iloprost
• Inhaled prostacyclin
• Administered 6-9 times
daily via special
nebulizer
• Reported risk of
morning syncope
• Improvements in 6MW,
functional class and
hemodynamics
observed

46. • Safety and side effects
– Potential for increased hypotensive effect with
antihypertensives
– Increased risk of bleeding, especially with co-
administration of anticoagulants
– Flushing, increased cough, headache, insomnia
– Nausea, vomiting, flu-like syndrome
– Increased liver enzymes

47. Guanylate cyclase stimulant
• Stimulators of the nitric oxide receptor.
• Dual mode of action.
• They increase the sensitivity of sGC to
endogenous nitric oxide (NO)
• Directly stimulate the receptor to mimic the
action of NO.
• Riociguat is an oral sGC stimulant that has
reported benefit in patients with inoperable and
persistent chronic thromboembolic pulmonary
hypertension (CTEPH)

49. ATRIAL SEPTOSTOMY
• patients with RV failure and associated PH in whom medical
therapy has failed.
• This approach has been proposed by some experienced centers
to improve peripheral oxygen delivery, despite a fall in
systemic arterial saturation due to a compensatory rise in
cardiac output.
• It is recommended not to perform AS in patients with
(1) severe RV failure on cardiorespiratory support,
(2) mean right atrial pressure (mRAP) >20mmHg,
(3) room-air resting O2 saturation <90%,
(4) left ventricular end diastolic pressure (LVEDP) >18mm
Hg

51. Pott’s shunt
• An alternative method of right
ventricular decompression is via
the creation of an anastomosis
between the descending aorta and
left pulmonary artery or Potts
shunt.
• In the setting of suprasystemic
PAP, a theoretical advantage of
Potts shunt over septostomy is the
sparing of the cerebral and
coronary circulation from
deoxygenated blood.

52. Pulmonary Artery Denervation
• pulmonary artery denervation is a novel
nonmedical therapy for PAH and the
presumed mechanism of action is via the
abolishment of sympathetic nerve supply to
the pulmonary circulation.

53. Lung Transplantation
• Lung transplantation remains a destination therapy for a
significant number of patients despite targeted PAH
therapy.
• Because of limited organ availability and the high mortality
rates of PAH patients awaiting transplantation, eligible
patients for whom first-line treatment strategies have failed
should be referred early for transplantation assessment.
• Double-lung transplantation is the preferred option for PAH,
but heart-lung transplantation remains necessary for some
patients in the context of complex Eisenmenger physiology
and is also adopted by some centers for patients with
refractory right heart failure

54. Failure of Medical Therapy:
Indications for Lung Transplant

55. • Thank You…!!!