Medicine chapters
Pulmonary hypertension
Pulmonary hypertension is a raised mean pulmonary artery pressure; this chapter covers the five causal groups, signs, ECG and echo findings, right heart catheter diagnosis and treatment by group.
- Pulmonary hypertension is a mean pulmonary artery pressure above 20 mmHg at rest on right heart catheter (older definition >25 mmHg); causes fall into 5 groups: PAH (idiopathic, heritable BMPR2, drugs, connective tissue disease, HIV, portal hypertension, congenital shunts), left heart disease (commonest), lung disease/hypoxia, CTEPH and multifactorial.
- Signs: exertional breathlessness, syncope, loud P2, RV heave, raised JVP, TR murmur, oedema; ECG: right axis deviation, dominant R in V1 (RVH), P pulmonale, RBBB, RV strain.
- Treat the cause (left heart disease, oxygen for lung disease, anticoagulation and endarterectomy for CTEPH); in PAH use endothelin antagonists (bosentan), PDE5 inhibitors (sildenafil), prostacyclins (epoprostenol) and high-dose calcium-channel blockers only for vasoreactive responders.
On this page
Overview
Pulmonary hypertension (PH) is an abnormally high pressure in the pulmonary arteries. The normal pulmonary circulation is a low-pressure, low-resistance system (normal mean pressure about 14 mmHg), so a raised pressure means disease of the lung vessels, the lungs or the left heart.
Untreated, it leads to right ventricular hypertrophy, dilatation and failure (cor pulmonale) and death.
The TOS asks for aetiology, ECG findings and treatment.
Definition
- Pulmonary hypertension: mean pulmonary artery pressure (mPAP) above 20 mmHg at rest, measured by right heart catheterisation (2022 ESC/ERS definition). Many textbooks, including older editions, still use above 25 mmHg.
- Pre-capillary PH (groups 1, 3, 4): pulmonary artery wedge pressure ≤15 mmHg and raised pulmonary vascular resistance.
- Post-capillary PH (group 2): wedge pressure above 15 mmHg (left heart disease).
- Cor pulmonale: right heart enlargement and failure caused by lung disease or hypoxia.
Aetiology: the five clinical groups
| Group | Name | Examples |
|---|---|---|
| 1 | Pulmonary arterial hypertension (PAH) | Idiopathic; heritable (BMPR2 mutation); drugs and toxins (fenfluramine, dexfenfluramine, amphetamines, dasatinib); connective tissue disease (especially systemic sclerosis, SLE); HIV; portal hypertension (portopulmonary); congenital heart shunts (VSD, ASD, PDA → Eisenmenger syndrome); schistosomiasis. Also veno-occlusive disease and persistent PH of the newborn |
| 2 | Left heart disease (commonest overall) | LV systolic or diastolic failure, mitral stenosis (very common in Pakistan from rheumatic heart disease), mitral regurgitation, aortic valve disease |
| 3 | Lung disease and/or hypoxia | COPD, interstitial lung disease, obstructive sleep apnoea, obesity hypoventilation, kyphoscoliosis, chronic high altitude |
| 4 | Chronic thromboembolic PH (CTEPH) | Unresolved organised clots after PE |
| 5 | Unclear or multifactorial | Sickle cell disease and other chronic haemolytic anaemias, myeloproliferative disease, splenectomy, sarcoidosis, chronic kidney failure on dialysis, thyroid disease |
Left heart disease is the commonest cause of PH; among lung causes, COPD is the commonest. Idiopathic PAH is rare and typically affects young women.
The groups run "Vessels, Left heart, Lungs, Clots, Others" (1 to 5).
Pathophysiology in brief
- In PAH there is vasoconstriction, endothelial dysfunction (too much endothelin-1, too little nitric oxide and prostacyclin), smooth muscle proliferation, plexiform lesions and in-situ thrombosis.
- In lung disease, hypoxic pulmonary vasoconstriction and loss of the vascular bed raise resistance.
- The right ventricle hypertrophies, then dilates; tricuspid regurgitation develops; cardiac output falls, causing exertional syncope.
These three pathways (endothelin, nitric oxide, prostacyclin) are the targets of the specific drugs.
Clinical features
Symptoms
- Progressive exertional breathlessness and fatigue (earliest and commonest).
- Exertional chest pain (RV ischaemia) and exertional syncope (fixed cardiac output): bad signs.
- Ankle swelling, abdominal distension (right heart failure).
- Hoarseness from compression of the left recurrent laryngeal nerve by a dilated pulmonary artery (Ortner syndrome, rare).
Signs
- Loud pulmonary component of the second heart sound (P2), best in the left second intercostal space; narrow or single S2.
- Left parasternal (right ventricular) heave; palpable P2.
- Raised JVP with a prominent a wave (stiff RV) and, with tricuspid regurgitation, large v waves.
- Pansystolic murmur of tricuspid regurgitation (louder on inspiration).
- Early diastolic Graham Steell murmur of pulmonary regurgitation.
- Right-sided S4 or S3; hepatomegaly (may be pulsatile), ascites, peripheral oedema.
- Look for the cause: clubbing (ILD, cyanotic heart disease), sclerodactyly and telangiectasia (systemic sclerosis), signs of liver disease, mitral stenosis.
Investigations
ECG findings (a favourite exam topic)
| Finding | What it reflects |
|---|---|
| Right axis deviation | RV hypertrophy |
| Dominant R wave in V1 (R:S ratio >1), deep S in V5–V6 | Right ventricular hypertrophy |
| P pulmonale: tall, peaked P waves (>2.5 mm in lead II) | Right atrial enlargement |
| Right bundle branch block (complete or incomplete) | RV dilatation and conduction delay |
| RV strain: ST depression and T-wave inversion in V1–V3 and the inferior leads | RV pressure overload |
| Sinus tachycardia; atrial flutter or fibrillation in late disease | Atrial stretch |
The classic ECG triad of PH is right axis deviation + dominant R in V1 (RVH) + P pulmonale. A normal ECG does not exclude early PH.
P mitrale (broad, notched P wave) means left atrial enlargement (mitral stenosis); P pulmonale (tall, peaked P) means right atrial enlargement.
Other tests
- Chest X-ray: enlarged proximal pulmonary arteries with pruning of peripheral vessels, enlarged right heart; clues to lung or left heart disease.
- Echocardiography (key screening test): estimates pulmonary artery systolic pressure from the tricuspid regurgitation velocity (simplified Bernoulli equation); shows RV dilatation and hypertrophy, septal flattening, left heart and valve disease, shunts.
- Right heart catheterisation (gold standard): confirms the diagnosis, measures wedge pressure and resistance, and includes a vasoreactivity test in idiopathic, heritable and drug-related PAH.
- Lung function and HRCT (lung disease), overnight oximetry or sleep study.
- V/Q scan to screen for CTEPH (more sensitive than CTPA for chronic clots); then CT or conventional pulmonary angiography.
- Blood tests: BNP (prognosis), autoantibodies (ANA, anti-centromere, anti-Scl-70), HIV, liver tests, thyroid tests, FBC (haemolysis).
- Six-minute walk test and WHO functional class to track severity.
Tricuspid regurgitation peak velocity 3.5 m/s; estimated right atrial pressure 5 mmHg
PA systolic pressure = 4 × v² + RAP = 4 × 3.5² + 5 = 4 × 12.25 + 5 = 54 mmHg
Approximate mean PAP = 0.61 × 54 + 2 ≈ 35 mmHg → above 20 (and 25) → PH likely; confirm by right heart cathete
Treatment
General measures (all groups)
- Treat the cause where possible.
- Diuretics for right heart failure and oedema; oxygen if hypoxaemic.
- Avoid pregnancy: maternal mortality is very high; use effective contraception.
- Influenza and pneumococcal vaccines; supervised exercise; avoid heavy exertion.
- Anticoagulation has a role in CTEPH (lifelong) and is considered in idiopathic or heritable PAH.
- Digoxin for atrial arrhythmias or RV failure in selected patients.
Specific therapy for pulmonary arterial hypertension (group 1)
| Pathway | Drugs | Key points |
|---|---|---|
| Calcium-channel blockers (high dose) | Nifedipine, diltiazem, amlodipine | Only for vasoreactive responders (a minority, mostly idiopathic PAH). A positive test is a fall in mPAP of at least 10 mmHg to 40 mmHg or less with unchanged or increased cardiac output. Verapamil is avoided (negative inotrope) |
| Endothelin receptor antagonists | Bosentan, ambrisentan, macitentan | Block endothelin-1 vasoconstriction and proliferation. Liver toxicity (monthly LFTs with bosentan), teratogenic, anaemia, oedema |
| Nitric oxide pathway | PDE5 inhibitors: sildenafil, tadalafil; soluble guanylate cyclase stimulator: riociguat | Raise cGMP → pulmonary vasodilatation. Never with nitrates (severe hypotension). Riociguat is also licensed for inoperable CTEPH |
| Prostacyclin pathway | Epoprostenol (continuous IV), treprostinil, iloprost (inhaled), selexipag (oral receptor agonist) | IV epoprostenol is the most potent and improves survival in severe PAH; line infections, flushing, jaw pain |
- Most patients start combination therapy (e.g. an endothelin antagonist plus a PDE5 inhibitor); severe disease needs a parenteral prostacyclin.
- Balloon atrial septostomy (palliation) and lung or heart–lung transplantation for those who fail medical therapy.
Other groups
- Group 2 (left heart): treat heart failure and valve disease (e.g. mitral valvotomy or replacement for mitral stenosis). PAH drugs are not used and may cause pulmonary oedema.
- Group 3 (lung): treat the lung disease, long-term oxygen for hypoxaemia, CPAP for sleep apnoea.
- Group 4 (CTEPH): lifelong anticoagulation; pulmonary endarterectomy (potentially curative); balloon pulmonary angioplasty or riociguat if inoperable.
- Group 5: treat the underlying disorder (e.g. sickle cell disease).
Vasodilators for PAH are not given in PH due to left heart disease, and calcium-channel blockers are only for proven vasoreactive patients.
Sildenafil for PH is the same drug used for erectile dysfunction; the combination with GTN or nitrates causes profound hypotension.
Complications and prognosis
- Right heart failure, arrhythmias, sudden death.
- Haemoptysis, pulmonary artery dilatation or dissection, thrombosis in situ.
- In congenital shunts, reversal to right-to-left flow gives Eisenmenger syndrome (cyanosis, clubbing, polycythaemia); the shunt can no longer be closed.
- Poor prognostic signs: syncope, WHO functional class IV, short six-minute walk distance, high BNP, pericardial effusion, raised right atrial pressure and low cardiac index.
Expect: the definition (mPAP >20 mmHg now, >25 mmHg in older texts) and right heart catheter as the confirmatory test, the five groups with left heart disease as the commonest cause and COPD the commonest lung cause, BMPR2 in heritable PAH, appetite-suppressant drugs and systemic sclerosis as PAH causes, loud P2, parasternal heave, TR and Graham Steell murmurs, ECG findings (right axis deviation, dominant R in V1, P pulmonale, RBBB, RV strain), echo estimation from TR velocity, vasoreactivity testing before calcium-channel blockers, the mechanisms of bosentan, sildenafil, riociguat and epoprostenol, nitrates with sildenafil, avoidance of pregnancy, and anticoagulation with endarterectomy for CTEPH.
Quick revision
- PH: mPAP >20 mmHg (old >25) at rest on right heart catheter.
- Groups: 1 PAH, 2 left heart (commonest), 3 lung/hypoxia, 4 CTEPH, 5 multifactorial.
- Heritable PAH: BMPR2. Drugs: fenfluramine, amphetamines, dasatinib.
- Signs: loud P2, RV heave, raised JVP, TR murmur, oedema; exertional syncope.
- ECG: right axis deviation, dominant R in V1, P pulmonale, RBBB, RV strain.
- CXR: big proximal pulmonary arteries, peripheral pruning.
- CCBs only for vasoreactive responders.
- Bosentan (endothelin), sildenafil (PDE5), riociguat (sGC), epoprostenol (prostacyclin).
- CTEPH: lifelong anticoagulation + pulmonary endarterectomy.
Written by The House Job from standard references (Kumar and Clark's Clinical Medicine).
FAQ
What is the commonest cause of pulmonary hypertension?
Left heart disease (heart failure and mitral or aortic valve disease); in Pakistan rheumatic mitral stenosis is a frequent example. COPD is the commonest lung cause.
What are the ECG signs of pulmonary hypertension?
Right axis deviation, a dominant R wave in V1 from right ventricular hypertrophy, tall peaked P waves (P pulmonale), right bundle branch block and right ventricular strain changes in V1–V3.
Why is right heart catheterisation needed if echo shows high pressure?
Echo only estimates the pressure; catheterisation measures it directly, separates pre-capillary from post-capillary causes using the wedge pressure, and tests vasoreactivity to guide treatment.
Who should receive calcium-channel blockers for pulmonary hypertension?
Only patients with idiopathic, heritable or drug-related PAH who show a positive acute vasoreactivity test on right heart catheterisation.