Recognising Pulmonary Hypertension: Symptoms, Comorbidities and Clinical Signs

Any mean pulmonary artery pressure greater than 20 mmHg combined with a pulmonary vascular resistance greater than 2 Wood units should be started on therapy — at minimum, a PDE5 inhibitor plus an endothelin receptor antagonist as double therapy. If the patient remains symptomatic, we add a prostacyclin analog to complete triple therapy. Escalating beyond triple therapy to sotatercept should only be considered after at least six months to a year of adequate triple therapy without sufficient response.

First, PDE5 inhibition, to promote vascular relaxation via the cGMP pathway. Second, soluble guanylate cyclase stimulation, to address back-pressure and encourage vasodilation. Third, endothelin receptor blockade, to retard smooth muscle cell hypertrophy and reduce pulmonary vascular resistance. Sotatercept adds a fourth, distinct pathway — anti-proliferative inhibition of activin signalling — which addresses the underlying vascular remodelling rather than just haemodynamics.

The right ventricle is a volume-handling ventricle, not designed for pressure overload — you can load it with considerable volume and it won't fail, because volume is its domain. But impose a pressure overload, as in pulmonary hypertension, and it hypertrophies to compensate before eventually failing. The left ventricle is a pressure-handling ventricle, built for exactly that load. That's why pulmonary hypertension causes right heart failure long before it affects the left.

Two mechanisms operate together. Viral proteins cause stiffness in the lung's interstitial tissue, which physically compresses the pulmonary blood vessels. At the same time, the immunocompromised state associated with HIV promotes smooth muscle hyperplasia within the vessel walls, narrowing the lumen from within. It's the combination of external compression and internal luminal narrowing that drives HIV-associated pulmonary hypertension.

The pulmonary valve opens against a high-pressure circuit, so when it closes, it's slammed shut by that elevated pressure — a forceful, rapid closure that produces the loud P2. It isn't the size of the valve that determines the loudness, it's the closing pressure. That's why even in conditions like tetralogy of Fallot, where pulmonary stenosis would normally produce a soft P2, elevated pulmonary arterial pressure from collateral flow can still produce a loud P2 despite the outflow obstruction.

Typical symptoms are dyspnoea, chest pain, palpitations, orthopnoea, pedal oedema, and abdominal distension, the classic picture of right heart failure, with mild cyanosis sometimes present due to reduced cardiac output.

Congenital or valvular heart disease, COPD, connective tissue disorders, interstitial lung disease, chronic hypoxaemia, HIV, haemoglobinopathies, sarcoidosis, venous thromboembolism, immunosuppressive states, and certain drug exposures should all prompt evaluation for pulmonary hypertension.

A detailed family history is essential, with specific attention to any history of sudden cardiac death in relatives, since this can signal hereditary pulmonary arterial hypertension.

A TAPSE greater than 1.8 cm and a tricuspid regurgitation jet velocity of less than 2.8 m/s are generally indicative of mild, treatable pulmonary hypertension with a favourable outcome.

ProBNP has a supporting but limited role. It is commonly used but is non-specific, since it is elevated in many other acute conditions.