Dr. Nannika Pradhan presented on pulmonary hypertension (PH). The key points discussed include: 1. PH is defined as a mean pulmonary arterial pressure ≥25 mmHg at rest as assessed by right heart catheterization. 2. PH is classified clinically into 5 groups based on etiology. 3. Clinical features include dyspnea, chest pain, syncope, signs of right heart failure. Diagnosis involves echocardiogram, CT scan, ventilation-perfusion scan and right heart catheterization. 4. Treatment depends on disease severity and involves diuretics, oxygen supplementation, calcium channel blockers, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, prostano

1. Presenter: Dr. Nannika Pradhan
P.GT,Dept.Of General Medicine,NBMC&H
Chairperson:Dr.Spandan Bhadury
Professor,Dept.of General Medicine,NBMC&H
Pulmonary Hypertension

2. Pulmonary Hypertension
 Definition
 Clinical Classification
 WHO Classification
 Classification: New Changes
 Epidemiology
 Clinical Features
 Diagnosis: Different Modalities
 Approach to Treatment
 Management

3. Definition
• Pulmonary hypertension (PH) is defined as an increase in mean
pulmonary arterial pressure (mPAP :supine and at rest) ≥20mmHg as
assessed by right heart catheterization (RHC).
• 2015 ESC guideline defined PH as an increase in mPAP ≥ 25 mm Hg at
rest or >30 mm on exercise as assessed by RHC.
Diagnosis and Management of Pulmonary Hypertension in the Modern Era:
Insights from the 6th World Symposium 2018

4. Definition: Other changes
 Pulmonary Vascular Resistance (PVR)
Proposed to include PVR of ≥3 Wood units in the definition of all forms of pre-capillary PH
associated with mPAP >20 mmHg.
 Combined Pre- and Post-Capillary PH
The cut off of ≥3 Wood units was also proposed to identify the group of patients who have
combined pre- and post-capillary PH in addition to the mandatory pulmonary capillary
wedge pressure (PCWP) of >15 mmHg and mPAP >20 mmHg, which is a prerequisite to be
classified as having any type of post-capillary PH.

5. Updated
Hemodynamic
definition of
PH
Diagnosis and Management
of Pulmonary Hypertension
in the Modern Era: Insights
from the 6th World
Symposium 2018

6. Clinical Classification

7. CLASS WHO
I Pt. with PHT but without resulting limitations of physical activity. Ordinary physical activity
does not cause undue fatigue or dyspnoea, chest pain or syncope
II Pt. with PHT resulting in slight limitations of physical activity. Comfortable at rest. Ordinary
physical activity results in undue fatigue or dysnpnea, chest pain or syncope
III Pt. with PHT resulting in marked limitations of physical activity. Comfortable at rest. Less than
ordinary physical activity results in undue fatigue or dysnpnea, chest pain or syncope.
IV Pt. with PHT resulting in inability to carry on any physical activity without symptoms. These
patients manifest signs of Right heart failure. Dyspnea and or fatigue may be present even at
rest. Discomfort is increased by physical acitvity
WHO Classification

8. Drug and Toxin Induced

9. Classification: New Change
Arterial Hypertension Long-Term Responders to Calcium Channel Blockers
1. These patients were introduced as a distinct group within Group I prognosis
because they have been shown to have significantly better, unique
management, and different pathophysiology.
2. These patients are defined by a reactive vasodilators stress (a reduction of
mPAP ≥10 mmHg to reach an absolute value of mPAP ≤40 mmHg with an
increased or unchanged cardiac output) and a sustained hemodynamic
response a year after being on calcium channel blockers and New York Heart
Association Functional Class I/II.

10. PH: Pathology
In PAH the pathologic lesions involve mainly the distal pulmonary arteries (< 500
µm in diameter) and are characterized by:
1. Medial hypertrophy
2. Intimal proliferation
3. Fibrotic changes (concentric, eccentric)
4. Adventitial thickening with moderate perivascular inflammatory infiltrates
5. Complex lesions (plexiform, dilated lesions), and thrombotic lesions

11. Pathophysiology

12. Epidemiology
1. 5 to 50 cases per million.
2. 5% of patients with hepatosplenic schistosomiasis, making it one of the most
prevalent causes of PAH worldwide.
3. Hereditary transmission of PAH has been reported in approximately 6% to
10% of patients with PAH.
4. PAH in the scleroderma population is around 8% to 12%.
5. Population studies of individuals infected with HIV suggest that the incidence
of PAH is approximately 0.5% and is independent of the CD4+ cell count or
previous opportunistic infections.

13. Physical Examination
Signs reflecting Severe
PHT
1. Increase JVP, a wave
2. Left parasternal heave
3. Accentuated P2
4. RV S4 (in 38%)
5. Early systolic Click
6. Mid systolic ejection click
Signs reflecting Moderate to
severe PHT
1. Ascites, Peripheral Edema
2. Hepatomegaly, Distended JVP
3. Hepatomegaly and pulsatile liver
4. Hepatojugular reflux
5. RV S3
6. Holosystolic murmur which
increases on inspiration

14. Clinical Features

15. Clinical Signs

16. Chest X-Ray
 Central pulmonary
arterial dilatation
 ‘Pruning’ (loss) of
the peripheral
blood vessels.
 Right atrium (RA)
and RV
enlargement may
be seen in more
advanced cases.

17. Radiographic signs of pulmonary hypertension and
concomitant abnormalities

18. Functional Assessment
6 Minute walk test:
 The 6-minute hall walk (6MW) is an important functional test for
quantifying exercise ability.
 It has proved to be a useful prognostic predictor and an important
parameter to include in the clinical assessment of disease progression
and treatment effect.

19. Functional Assessment
Cardio pulmonary exercise testing:
Cardiopulmonary exercise testing offers a more sophisticated means of
assessing exercise capacity and gas exchange.
Poor prognostic indicators during cardiopulmonary exercise testing
includes:
1. A peak systolic blood pressure lower than 120 mm Hg.
2. A peak oxygen uptake of less than 10.4 mL/kg/min

20. PFT & ABG
1. Diffusion capacity can be normal in PAH, most patients have decreased lung diffusion capacity for carbon monoxide
(DLCO).
2. An abnormal low DLCO, defined as < 45% of predicted, is associated with a poor outcome.
The differential diagnosis of a low DLCO in PAH includes
A. PVOD
B. PAH associated with scleroderma
C. Parenchymal lung disease
Arterial blood gases of COPD patients show a decreased PaO2 with normal or increased PaCO2
3.Overnight Oximetry
In addition to the history, overnight oximetry may help identify patients with obstructive sleep apnea.
Formal polysomnography may be indicated in patients with significant nocturnal desaturation.

21. Diagnosis: ECG
ECG abnormalities may include:
1. P pulmonale
2. Right axis deviation
3. RV hypertrophy, RV strain
4. Right bundle branch block
5. QTc prolongation.

22. Echo

23. Echo:TR

24. Ventilation-Perfusion Lung Scintigraphy
 Patients with unexplained dyspnea and PH should be evaluated for CTEPH.
 Ventilation-perfusion lung scintigraphy is considered the most sensitive study for
this purpose.
 If one has a normal- or very low–probability ventilation-perfusion scan, CTEPH
can be excluded.

25. Drug Therapy: Vasoreactivity test
In treatment naïve patients after diagnosis of PAH, acute Vasoreactivity test (AVT)
should be done to identify patients who may respond to CCB.
Patients who are most likely to be vasoactive are:
 Idiopathic PAH (IPAH)
 Heritable PAH
 Drug/toxin induced PAH

26. Drug Therapy: Vasoreactivity test
 AVT involves the administration of a short-acting vasodilator followed by
measurement of the hemodynamic response using a right heart catheter
(RHC).
 Agents commonly used for vasoreactivity testing include inhaled nitric
oxide, epoprostenol, adenosine, and inhaled iloprost.
 Inhaled nitric oxide is the most common agent used and is administered at
10 to 20 ppm. It is selective for the pulmonary vasculature with minimal
systemic effects and is therefore better tolerated than other agents .

27. General Measures
 Basic counselling and education about the disease state are important
components in the care of patients with PAH.
 Low-level graded aerobic exercise such as walking is recommended.
 Patients are advised against heavy physical exertion and isometric
exercise because this may evoke exertional syncope.
 Oxygen supplementation to keep the saturation higher than 92% at rest and
with exertion, sleep, or altitude is advisable.

28. General Measures
• A sodium-restricted diet (<2400 mg/day) for management of the volume
status in those with right ventricular failure. Diuretics are indicated to
manage right ventricular volume overload.
• Routine immunizations, such as those against influenza and pneumococcal
pneumonia, are advised.
• The hemodynamic fluctuations of pregnancy, labor, delivery, and the
postpartum period are potentially life-threatening in patients with PAH,
with a maternal mortality rate of 30% to 50%.
• Current guidelines recommend that pregnancy should be avoided or
terminated early in women with PAH.

29. • Developed by the task force for the diagnosis and treatment of pulmonary hypertension of the
European Society of Cardiology (ESC) and the European Respiratory Society (ERS)
• Endorsed by the International Society for Heart and Lung Transplantation (ISHLT) and the
European Reference Network on rare respiratory diseases (ERN-LUNG)

30. Approach to Treatment

31. Approach to Treatment

32. Drug Therapy
Drug Route of
Administration
Dose range Half life
Epoprostenol Continuous I/V
Infusion
1 to 12 ng/Kg/min initially.
Dose titrated up every 1 to 2 weeks until
therapeutic response or dose limiting
toxicity
3 to 5 mins (Single
dose)
15 mins (continuous
infusion)
Treprostenil 1. Continuous I/V
infusion or
Subcutaneous
infusion
2. Inhaled
1. 0.625 to 1.25 ng/Kg/min initially
Dose titration up every 1 to 2 weeks.
2. One to three inhalations6 to 18
micrograms, four times daily initially .
Maintenance gradually titrated up to 9
inhalations
1. 4 hours
2. 4 hours
Iloprost Inhaled 2.5 to 5 micrograms,6 to 9 times daily 20 to 30 mins
Selexipag Oral 200 to 1600 microgramstwice daily.
Dose titrated up every 1 to 2 weeks.
0.8 to 2.5 hours
(Selexipag)
6.2 to 13.5 hours
(active metabolite)

33. Drug Therapy
Drug Route of
Administration
Dose Range Half life
Bosentan Oral 62.5 mg to 125 mg, twice a day. 5 hours
Ambrisentan Oral 5 to 10 mg daily 9 hours
Macitentan Oral 10 mg per day 14 to 18
hours
Riociguat Oral Initial dose 0.5 to 1 mg three times daily,
titrated up by 0.5 mg three times per day
every two weeks until therapeutic
response or side effects
Maximum dose 2.5 mg three times a day

34. Drug Therapy
Drug Route of
Administration
Dose Range Half life
Sildenafil 1. Oral
2. Intravenous
1. 20 mg three times daily
2. 10 mg three times dialy
1. 4 hours
2. 4 hours
Tadalafil Oral 4o mg dialy 35 hours
Nifedipine Oral Start to 30 mg per day, Increase to
maximum tolerated dose over
days to week
7 hours
Amlodipine Oral Start to 2.5 mg per day. Increase
to maximum tolerated dose over
days to week
30 to 50
hours
Diltiazem extended
release
Oral Start 120 mg per day. Increase to
maximum tolerated dose over
days to weeks
6 to 9 hours

35. Drug Therapy: Non Vasoactive patients
For patients with PAH who are:
1. Typically non-vasoreactive
2. Who have not undergone vasoreactive testing
3. Vasoreactive and have failed CCB therapy
The World Health Organization (WHO) functional classification for
selection of a suitable agent(s), is used.

36. Drug Therapy: Non Vasoactive patients
Recommended Combination therapy and associated Trials:
1. Tadalafil plus Ambrisentan : AMBITON trial
2. Macitentan plus Sildenafil : SERAPHIN trial
3. Tadalafil plus Bosentan: PHIRST trial
4. Riociguat plus bosentan: PATENT 1 trial
5. Selexipag plus ERA and/or PDE5I: GRIPHON trial

37. References
 Diagnosis and Management of Pulmonary Hypertension in the Modern Era: Insights from the 6th
World Symposium 2018.
 ESC 2015 Guideline on Diagnosis and management of Pulmonary hypertension
 Echocardiographic assessment of pulmonary hypertension: a guideline protocol from the British
Society of Echocardiography
 Harrison’s Principle Of Internal Medicine-21st Edition
 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension

38. THANK YOU