Pulmonary Hypertension: A Multidisciplinary Approach

Pulmonary hypertension is raised blood pressure in the arteries of the lungs, now defined as a mean pulmonary artery pressure above 20 mmHg at rest, measured by right heart catheterisation. It strains the right ventricle until it fails. Managed well, it is no longer the death sentence it once was: care depends on finding the cause, confirming the diagnosis with a catheter and combining drugs, surgery and counselling across specialties.

That is the case made by Dr. Biswarup Purkayastha, Consultant – Heart & Lung Transplant and Vascular Surgery, Artemis Hospitals, Gurugram, India, who trained first in paediatric cardiac surgery and works within a dedicated pulmonary hypertension clinic team. His teaching to referring doctors across Africa rests on three ideas: the threshold has moved, the echocardiogram is a screening tool and not a diagnosis, and the drug arsenal has changed so much that no patient should be written off before combination therapy has been tried properly.

This guide sets out the physiology and the clinical judgement behind that approach. Two companion articles go deeper: the updated definition, the five groups and how the diagnosis is confirmed, and the treatment ladder from tadalafil to sotatercept and surgery.

What pulmonary hypertension means in practice

Pulmonary hypertension today means a mean pulmonary artery pressure above 20 mmHg, not the 25 mmHg that doctors were taught for years. The lower threshold brings patients into the diagnosis earlier and makes earlier treatment possible. Dr. Purkayastha opened his masterclass by asking the audience for the definition, and the first answer was exactly that textbook figure of 25 mmHg. It is, he noted, how he too was taught as a trainee.

Officially the condition is called pulmonary hypertension (PH). Pulmonary arterial hypertension (PAH) is the narrower term for group 1 disease, in which the problem lies in the small pulmonary arteries themselves. Dr. Purkayastha admits he still "lovingly" calls it pulmonary arterial hypertension, a habit from his paediatric cardiac surgical training, but the distinction matters for treatment, because the targeted drugs were developed for group 1.

Pulmonary hypertension is not one disease. It is a haemodynamic state with five broad families of cause, and the cause decides the treatment:

• Left heart disease (group 2), such as untreated mitral stenosis or severe mitral regurgitation.
• Lung disease and low oxygen (group 3), such as idiopathic pulmonary fibrosis, interstitial lung disease and obstructive sleep apnoea.
• Obstruction of the pulmonary arteries (group 4), chiefly chronic thromboembolic pulmonary hypertension (CTEPH).
• Mixed or multifactorial causes (group 5), including blood and kidney disorders.
• Group 1 pulmonary arterial hypertension, far less common than groups 2 and 3: idiopathic, hereditary, linked to connective tissue disease or congenital heart disease, or drug induced.

In the developing world, Dr. Purkayastha sees groups 2 and 3 most often, driven by preventable valvular heart disease that has gone unmanaged and by chronic lung disease. In his framing, most of these secondary and mixed forms improve once the root cause is resolved. Group 1 is different: before modern therapy, the answer in idiopathic or hereditary disease was, in his words, "an untimely death, young age death".

Pulmonary hypertension prognosis: from a death sentence to a treatable disease

In Dr. Purkayastha's account, multidisciplinary care has completely changed the outlook in group 1 pulmonary hypertension. When he was training, it meant death within a few years. Care was little more than palliation: leave the patient to die in peace with friends and family. The drug classes have multiplied, so that clinicians can now act on several biological pathways at once rather than one, and an antiproliferative drug, sotatercept, has arrived, which he calls "the magic drug" because it acts on the thickened vessel wall rather than simply dilating the vessel. The trial evidence behind it is set out in the treatment article.

The practical consequence for a referring doctor is a change of posture. A patient with severe pulmonary arterial hypertension is no longer someone to be kept comfortable. Dr. Purkayastha's rule is that double and then triple combination therapy must be tried in every patient before anyone says the disease is "just not going to improve".

Why pulmonary hypertension causes right heart failure first

Pulmonary hypertension causes right heart failure long before it troubles the left ventricle because it is a pressure overload, and the right ventricle is built to handle volume, not pressure. For a generalist this is the single most useful piece of physiology, and Dr. Purkayastha answered it directly in the Live Discussion.

The pressure overload sharply raises the afterload on the right ventricle, the resistance the ventricle must pump against. The two ventricles are built for different jobs:

• The right ventricle is a volume-handling chamber. It is thin walled and crescent shaped, wrapped around the left ventricle, a design that can accept a great deal of preload (incoming volume) without failing. Load it with volume and it simply stretches to accommodate it.
• The left ventricle is a pressure-handling chamber. It is thick walled, so a rise in pressure does not kill it. It may hypertrophy, but it copes.

Under a sustained pressure load, the right ventricle hypertrophies up to a point. Beyond that point, in Dr. Purkayastha's words, "it'll just fail". That is why the clinical picture of advancing pulmonary hypertension is the picture of right heart failure: a raised jugular venous pressure, ankle and leg oedema, abdominal swelling, fatigue and breathlessness. It is also why the prognostic measures that matter most, discussed in the diagnosis article, are measures of right ventricular function.

Why P2 is loud in pulmonary hypertension

A loud pulmonary component of the second heart sound (P2) is one of the classic bedside signs. Asked why P2 is loud, Dr. Purkayastha explained that the pulmonary valve is opening into a high-pressure circuit. A normal pulmonary valve opens and closes gently, so P2 is soft. When pressure in the pulmonary artery is high, the valve does not close gently: it slaps shut, and the forceful closure is what the clinician hears. However small the valve, if it slaps shut, P2 will be loud.

He used the question to make a teaching point about pattern recognition. Tetralogy of Fallot is usually associated with a soft P2, because the narrowed right ventricular outflow limits flow into the lungs. Yet in his board finals he examined an adult with tetralogy and a loud P2. The explanation is a rare but real physiology: pulmonary stenosis does not always mean low pulmonary blood flow. Collateral vessels can deliver high flow to the lungs, raise pulmonary arterial pressure and produce pulmonary hypertension, so that despite the tetralogy and the outflow obstruction, P2 is loud. The lesson for the examining doctor is to reason from the haemodynamics rather than from the label.

Pulmonary hypertension in HIV

HIV is among the recognised comorbidities that should raise suspicion of pulmonary hypertension, and it matters for doctors practising where HIV is common. Answering a question from the audience, Dr. Purkayastha described smooth muscle hyperplasia in the vessel wall, which narrows the lumen. HIV-associated pulmonary arterial hypertension is a disease of the small pulmonary arteries themselves: viral proteins such as Nef, Tat and gp120, together with chronic inflammation, injure the endothelium and drive the proliferation of smooth muscle and endothelial cells. Stiffening of the lung interstitium is not part of the mechanism.

HIV-associated pulmonary arterial hypertension is classified within group 1, which means it falls within the scope of the targeted therapies described in the treatment article. For a clinician managing HIV, unexplained breathlessness or signs of right heart strain warrant an echocardiogram and a low threshold for referral. The vessels are narrowed from within and crushed from outside. HIV-associated pulmonary arterial hypertension is classified within group 1, which means it falls within the scope of the targeted therapies described in the treatment article. For a clinician managing HIV, unexplained breathlessness or signs of right heart strain warrant an echocardiogram and a low threshold for referral.

Hypertension and pulmonary hypertension in pregnancy

Amlodipine is reasonably safe in pregnancy after the first trimester, in Dr. Purkayastha's answer to an audience question on blood pressure treatment; his short answer was "yes and no". For systemic hypertension and pre-eclampsia in pregnancy, the established first-line agents are labetalol, nifedipine and methyldopa.

Pulmonary arterial hypertension itself is a different and more serious matter in pregnancy. The European Society of Cardiology advises women with pulmonary arterial hypertension against pregnancy because of the high maternal risk, and endothelin receptor antagonists and riociguat, two of the drug classes used to treat it, are contraindicated in pregnancy because they can harm the fetus. Any woman with pulmonary hypertension who is pregnant or planning pregnancy needs specialist care from the outset.

When to refer suspected pulmonary hypertension

Dr. Purkayastha's instruction to referring doctors is to use the echocardiogram to select patients for a dedicated pulmonary hypertension clinic, not to diagnose them. He is realistic about the referring doctor's tools: in peripheral settings the echocardiogram is the most accessible investigation, and few centres can perform a high-quality right heart catheterisation.

The patient to pick up is one who presents with:

• fatigue and easy tiring;
• prominent right heart failure symptoms, such as pedal oedema and a raised jugular venous pressure;
• breathlessness, sometimes with mild cyanosis because of reduced blood flow through the lungs;
• and an echocardiogram showing a large amount of tricuspid regurgitation with a jet velocity above 3 metres per second, without gross right ventricular dilatation and without primary disease of the tricuspid valve.

That patient should go to a dedicated pulmonary hypertension clinic for confirmation and targeted treatment. Equally, the purpose of getting the definition and the groups right, he told the audience, is so that referrers stop sending left-sided heart disease as though it were pulmonary arterial hypertension. A patient whose pulmonary pressure is raised by mitral valve disease needs the valve treated; Dr. Purkayastha's earlier masterclass on valvular heart disease in emerging countries covers that pathway.

What a multidisciplinary approach to pulmonary hypertension involves

The title of the masterclass was "A Multidisciplinary Approach", and the content shows why one specialty cannot carry the condition alone:

• Diagnosis depends on a catheter laboratory able to perform right heart catheterisation and vasoreactivity testing, supported by echocardiography, ventilation perfusion scanning and lung function testing.
• Cause-specific treatment draws on cardiology and cardiac surgery for valve disease, respiratory medicine for interstitial lung disease and sleep apnoea, and infectious disease care for HIV.
• Targeted drug therapy in group 1 disease is a specialist discipline in its own right, with careful dose titration and escalation from double to triple therapy.
• Surgery has a defined place: pulmonary endarterectomy for CTEPH is, in Dr. Purkayastha's description, "an absolute surgeon's joy" that "will nearly break your back". His session on vascular surgical problems covers how pulmonary embolism leads to it.
• Counselling is part of the treatment. Phosphodiesterase 5 inhibitors can cause prolonged erections, and Dr. Purkayastha's practice is to have younger men counselled by a clinical psychologist so that they understand the effect is expected and tolerable.

The questions from attending doctors, on the right ventricle, the loud P2, HIV and pregnancy, are collected in the Live Discussion. Related cardiology content sits on the cardiology specialty page.

The series at a glance

• Pulmonary hypertension diagnosis: definition, groups and tests covers the 20 mmHg threshold, pre-capillary and post-capillary disease, the five groups, the work-up, why the echo cannot confirm the diagnosis and what low-risk disease looks like.
• Pulmonary hypertension treatment: from tadalafil to sotatercept covers when to start therapy, Dr. Purkayastha's weight-based starting doses, side-effect counselling, triple therapy, sotatercept and pulmonary endarterectomy.