Pulmonary hypertension

1. PULMONARY HYPERTENSION

2. Definition:
 Mean pulmonary artery pressure >20mmhg at rest
measured by right heart catheterisation
 Previously it was >25mmhg
 Normal pulmonary artery pressure 14+/-2

3. PH vs PAH
 Pulmonary hypertension: mPAP>20 mmhg
 Pulmonary arterial hypertension :
mPAP >20 + PVR >3WU + PCWP<15 + specific vasculopathy
PH
PAH

4. Features of PH
 Low pressure -12-14mmhg
 Low resistance : impedance to flow of blood is less
 High compliance : During exercise , it gets engorged and
can accommodate 3 times its blood volume(high
compliance )

5. Mean Pulmonary pressure = cardiac output Pulmonary
vascular resistance + pulmonary capillary wedge
pressure
Causes of increased mean pulmonary hypertension
 Increased cardiac output
 Increased pulmonary vascular resistance
 Increased pulmonary capillary wedge pressure or left atrial pressure

6. Increased cardiac output
 Congenital heart disease with left to right shunts
 Anemia
 A-V malformation
 Thiamine deficiency
 Thyrotoxicosis
 Cirrhosis and Portal hypertension

7. Increased pulmonary capillary wedge
pressure or left atrial pressure
 Left ventricular failure
 Mitral/aortic valve disease
 Restrictive cardiomyopathy

8. Increased pulmonary vascular resistance
 Destruction /obliteration of pulmonary vascular bed : ILD ,
Emphysema , chronic pulmonary embolism
 Hypoxic vasoconstriction :COPD ,high altitude
 Small pulmonary arteriole vasculopathy : PAH

9. WHO groups

12. Hemodynamics
 Normal values
 mPAP : <20mmhg
 PVR: <3 WU
 PCWP/LA P: <15mmhg
PH mPAP PVR PCWP
Type 1 >20mmhg >3WU <15mmhg
Type 3 >20mmhg >3WU <15mmhg
Type 4 >20mmhg >3WU <15mmhg
Type 2 >20mmhg <3WU >15mmhg

13. Clinical Classification of Pulmonary
hypertension
 Type 1 :Pulmonary arterial hypertension (PAH)
 Type 2:Secondary to left heart disease (Increased
Pulmonary venous hypertension/PVH)
 Type 3: Secondary to Lung diseases and hypoxia
 Type 4: Chronic thromboembolic PH (CTEP)
 Type 5: miscellaneous

14. Type 1 :Pulmonary arterial hypertension
(PAH)
Small vessel vasculopathy:
1.Intense vasoconstriction (more in younger
individuals) Treated with vasodilators
2. Arterial remodeling and inflammation
3.Plexiform lesion : Destruction of endothelial cell
integrity and infiltration of inflammatory cells lead
to obstruction of the lumen
4. Thrombotic lesion(oral anticoagulants )

15. Pathology

16. Type 1 :Pulmonary arterial hypertension
(PAH)
 Idiopathic PAH : Most common type among group I PAH
M:F- 1:2
Average age: 37 years (younger)
 Heriditary type I PAH:
Autosomal dominant
BMPR-2 gene mutation: 1 PAH gene-very bad prognosis
In Younger, sicker and shorter life-span
Associated with 75% of hereditary PAH
Only 20% express PAH (incomplete penetrance)

17.  Drug induced PAH
1. Appetite suppressants that increase Serotonin
(valvulopathy, Regurgitation > Stenosis)
Aminorex
Fenfluramine/dexfenfluramine/benfluorex
2. Tyrosine kinase inhibitors:
Dasatinib
3. drugs: methamphetamine (crystal meth)

18.  Associated PAH:
MC: CTD Scleroderma (mc)Limited PAH >Diffuse PAH,SLE
portal hypertension- splanchnic blood bypass liver
Schistosomiasis
congenital heart disease

19. Pathophysiology

20. Obliteration of retro sternal space

22. Clinical features
 Features of decreased cardiac output
Fatigue
Exercise intolerance
Dyspnea
Syncope
 Features of increased RV afterload
Increased JVP
Hepatomegaly
Ascites
Pedal edema
 RV ischemia: chest pain

23. Management
Idiopathic PAH
General measures:
 Avoid pregnancy : as there is 30-50% maternal mortality
during pregnancy and 15%
fetal mortality. maternal mortality> Fetal
mortality As most of the females

24.  Medical management:
Diuretics (judicious use) as LV preload is less
Anti coagulants: IPАН/СТЕРН
Digoxin (shown to increase RV contraction)
Oxygen: To prevent hypoxemia as Pulmonary circulation reacts to
hypoxia by vasoconstriction.

25. PAH specific therapy

26.  Endothelin Receptor antagonist:
Endothelin receptor antagonists (ERAs) inhibit the
detrimental effect of ET-1, a potent endogenous
vasoconstrictor and vascular smooth muscle mitogen
Oral
Bosentan: Endothelin receptor (ER)-A+B:
62.5mg to 125mg BD
monitor LFT, edema,headache
Ambrisentan ER-A: 10mg OD Edema (liver safe)
Macitentan: ER A+B: Anemia (liver safe)

27.  PDE5 inhibitors:
The PDE-5 inhibitors prevent hydrolysis (inactivation) of cGMP to maximize NO
-dependent vasodilation, serving as the basis for use of this drug class in the treatment of
PH (and erectile dysfunction). The two PDE-5 inhibitors used for the treatment of PAH are
sildenafil and tadalafil
 Oral
Sildenafil /Viagra: 20mg TID monitor LFT
Tadalafil : 40mg OD
Vardenafil
Should not be given with nitrates
 Soluble guanylate cyclase stimulator:
Riociguat : Avoid with PDES inhibitors
Also used in the treatment of CTEPH (only drug approve- for CTEPH

28. Prostanoids
 Prostanoids/PG1 analogues:
Endothelial dysfunction and platelet activation cause an imbalance of arachidonic acid
metabolites with reduced prostacyclin levels and increased thromboxane A2 production.
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.
Epoprostenol:
Continuous IV infusion (Antithrombotic effect),
expensive drug
Treprostinil: S/C,oral, inhaled, Iv
Iloprost: Inhaled
Selexipag: Oral prostacyclin receptor agonist

29. Treatment protocol
 Assessment of risk by:
WHO Functional class
1. Symptoms at more than ordinary physical activity
II. Symptoms at ordinary physical activity
III Symptoms at less than ordinary physical activity
IV. Symptoms at rest
 6 min walk test
1. > 400 meter: Good prognosis
2. <300 meters: Bad prognosis
Treatment protocol:
Single agent for PAH therapy was followed previously.
It is now recommended to start combination therapy.

30. Step-1
 RHC- Is the patient vasoreactive
 mainly for idiopathic, hereditary, drug-induced PAH
 Vasoreactivity testing:
• Inhaled NO (DOC)
• IV Epoprostenol
• Inhaled lloprost
• Oral Sildenafil
• Pure oxygen
 Sitbon criteria, 2005:
A positive acute response is defined as a reduction of mean PAP > 10 mmHg to
reach an absolute value of mean PAP <40 mmHg with an increased or unchanged
cardiac output

31. Vasoreactive
YES
CCB
NO
class1
Class 2,3
Class4
Observation
Treat contributing factors
Combination
therapy
IV Epoprostenol
Ambrisenton+Tadalafil
IV Epoprostenol+
Ambrisenton+tadanafil
IF FAILS
Tripple therapy
Atrial septostomy or lung transplant
Nifedipine :30-240mg
Diltiazem:120-720mg
Amlodipine:2.5-40mg

32.  Type 2 PH /left heart disease
post capillary pulmonary hypertension
Presentations
Dyspnea
volume overload : edema
PAH specific therapy is harmful (so elevation of Pcwp should be
ruled out before the start of PAH specific therapy)

33.  Type 3 PH/Lung disease:
worsens Functional Capacity of lung
Chronic hypoxia Long term oxygen therapy (LTOT)
PAH specific therapy: No benefit, sometimes harmful
 Type 4 PH : CTEPH
2-4% of patients following PE- partially recanalized and causes
a distal vasculopathy
Pulmonary endarterectomy (Curative)
Lifelong anticoagulant
riociguat

34. Take home messages
 PAH is different from PH
 PH remain asymptomatic for longer time , when
RV fails –rapid detioration
 Suspect PH and screening
 Only epoprostenol has mortality benefit
 Oral anticoagulant in type 1,4 PH
 CTEPH-potentially curable

35. THANK YOU