Pulmonary Hypertension

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.

After the first trimester, amlodipine and other calcium channel blockers are reasonably safe. For eclampsia or hypertension specifically during pregnancy, the preferred agent is a direct alpha agonist, such as prazosin.

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 threshold is a mean pulmonary artery pressure (MPAP) above 20 mmHg, measured by right heart catheterisation. This replaces the older definition, which required an MPAP above 25 mmHg.

Group 2, caused by left heart disease, is the most common group encountered in the developing world, largely driven by unmanaged mitral stenosis or severe mitral regurgitation.

No. Echocardiography can raise suspicion, but only right heart catheterisation confirms the diagnosis, measures pulmonary vascular resistance, and determines whether the disease will respond to vasodilator therapy.

Once the diagnosis is confirmed, patients are risk-stratified into low-risk and high-risk categories based on symptoms, exercise capacity, and haemodynamic measurements, and this classification guides how aggressively treatment is escalated.

For CTEPH, pulmonary endarterectomy offers the prospect of a surgical cure, unlike the medical management used for most other forms of pulmonary hypertension.