Define pulmonary hypertension and cor pulmonale. Classify pulmonary hypertension and describe its pathogenesis and morphology.

Definition

• Normal pulmonary artery pressure is about 25/10 mmHg, mean 14 — roughly a sixth of systemic pressure
• The pulmonary circulation is a low-pressure, low-resistance, high-compliance system, which is why the right ventricle is thin-walled and copes badly with a sudden pressure load
• The exclusion of left heart disease is what defines cor pulmonale — right ventricular failure secondary to left ventricular failure is not cor pulmonale, and is in fact its commonest mimic

Clinical Classification

Pathogenesis

The initiating stimulus — hypoxia, loss of vascular bed, high flow, or raised left atrial pressure → hypoxic pulmonary vasoconstriction — unique to the lung, and normally useful because it diverts blood from poorly ventilated areas → When hypoxia is global and sustained, the whole pulmonary bed constricts → Endothelial dysfunction — reduced nitric oxide and prostacyclin, increased endothelin-1 and thromboxane → Smooth muscle proliferation and intimal thickening → vascular remodelling → In situ thrombosis in the small vessels → Fixed rise in pulmonary vascular resistance — no longer reversible with oxygen → Right ventricular pressure overload → hypertrophy → dilatation → failure

• Hypoxic pulmonary vasoconstriction is the opposite of the systemic response, where hypoxia causes vasodilatation. In the lung it improves ventilation–perfusion matching — but applied to the whole lung it becomes the mechanism of disease
• Early pulmonary hypertension is reversible with oxygen; once remodelling is established it is not, which is the argument for treating hypoxaemia early

Morphology

Clinical Features and Investigation

• Symptoms are non-specific and the diagnosis is often late — exertional dyspnoea and fatigue, then exertional chest pain, syncope on effort, and finally features of right heart failure
• Signs of pulmonary hypertension — a loud pulmonary component of the second heart sound, a right ventricular heave, a right-sided fourth heart sound, and the early diastolic murmur of pulmonary regurgitation (Graham Steell)
• Signs of right heart failure — raised jugular venous pressure with a prominent v wave, pansystolic murmur of tricuspid regurgitation, tender pulsatile hepatomegaly, ascites and dependent oedema
• ECG — right axis deviation, P pulmonale (tall peaked P waves), right ventricular hypertrophy with dominant R in V1, right bundle branch block
• Chest radiograph — enlarged central pulmonary arteries with peripheral "pruning", and right ventricular enlargement
• Echocardiography is the screening test of choice, estimating pulmonary artery pressure from the tricuspid regurgitant jet and assessing the right ventricle and the left heart
• Right heart catheterisation is the gold standard, and is the only way to measure pressure directly and to distinguish pre-capillary from post-capillary disease by the wedge pressure

Cor Pulmonale — Acute and Chronic

• The right ventricle tolerates a volume load far better than a pressure load — it is a thin-walled, compliant chamber built to eject into a low-resistance circuit. A sudden rise in afterload dilates and fails it within minutes, which is why a massive embolism kills so quickly
• Chronic hypoxaemia also causes secondary polycythaemia, which raises viscosity and adds further to pulmonary vascular resistance — a vicious cycle
• Cor pulmonale accounts for a substantial share of all heart failure in India, chiefly through COPD from smoking and biomass smoke, and through post-tuberculous lung damage

Applied Aspects

• Treat the cause — in group 3, that means oxygen, treatment of COPD or interstitial disease, and continuous positive airway pressure for sleep apnoea; in group 2 it means treating the left heart
• Long-term oxygen therapy for chronic hypoxaemia reduces pulmonary pressure and prolongs life; it is one of very few treatments in respiratory medicine that improves survival
• Targeted pulmonary vasodilators — endothelin receptor antagonists (bosentan), phosphodiesterase-5 inhibitors (sildenafil) and prostacyclin analogues — are for group 1, and may be harmful in group 2 and group 3, where they worsen ventilation–perfusion matching or precipitate pulmonary oedema
• Chronic thromboembolic disease must be sought, since pulmonary endarterectomy can be curative — the one potentially reversible form
• Obstructive sleep apnoea is common and under-diagnosed, and is a readily treatable cause of cor pulmonale
• Prognosis depends on right ventricular function rather than on the pressure itself — a failing right ventricle may show a falling pressure as it decompensates, which is an ominous rather than a reassuring sign
• Diuretics relieve congestion but must be used cautiously, since the failing right ventricle is preload-dependent and over-diuresis drops cardiac output
• Digoxin and vasodilators are of limited value in cor pulmonale, and systemic vasodilators may cause hypotension without lowering pulmonary pressure
• Venesection is occasionally used for severe secondary polycythaemia with a haematocrit above about 55%
• Pregnancy carries a very high mortality in pulmonary arterial hypertension and is strongly advised against; effective contraception must be discussed
• Screen patients with systemic sclerosis annually by echocardiography, since pulmonary hypertension is now their leading cause of death and early treatment helps
• Distinguishing group 2 from group 3 changes treatment entirely, and the wedge pressure at catheterisation is what settles it — which is why the invasive study cannot always be avoided