Pulmonary Hypertension Diagnosis: Definition, Groups, Tests

Pulmonary hypertension is diagnosed when right heart catheterisation shows a mean pulmonary artery pressure above 20 mmHg at rest, down from the 25 mmHg threshold most doctors were taught. An echocardiogram can raise the suspicion, but it cannot confirm the diagnosis. Classification follows the catheter numbers, into pre-capillary and post-capillary disease, and the cause, into five clinical groups that decide treatment.

Dr. Biswarup Purkayastha, Consultant – Heart & Lung Transplant and Vascular Surgery, Artemis Hospitals, Gurugram, India, built his masterclass for referring doctors around getting these foundations right. His concern is practical: a wrong definition or an echo-only diagnosis sends the wrong patients for the wrong treatment, and sends patients with left-sided heart disease to a pulmonary hypertension clinic when they need their valve treated. This article covers the definition, the haemodynamic and clinical classifications, the work-up, the limits of echocardiography and what low-risk disease looks like. The overview of the condition is in the complete guide to pulmonary hypertension, and treatment is covered in the treatment ladder from tadalafil to sotatercept.

The updated pulmonary hypertension definition: above 20 mmHg

Pulmonary hypertension is now defined as a mean pulmonary artery pressure (mPAP) above 20 mmHg at rest. The earlier definition used 25 mmHg. The lower threshold was proposed at the 6th World Symposium on Pulmonary Hypertension in 2018 and adopted by the 2022 European Society of Cardiology and European Respiratory Society (ESC/ERS) guidelines. It applies across all clinical groups.

Dr. Purkayastha tested his audience on this at the start of the session. A doctor answered with the 25 mmHg figure, measured by catheter on the right side of the heart, which is exactly how he was taught as a trainee. The measurement method is right; the number has moved. The change matters because it brings patients with earlier disease into the diagnosis, when treatment has the most to offer.

Normal pressures across the heart

To read a catheter study, Dr. Purkayastha asks doctors to hold the normal four-chamber pressures in mind:

• right atrium: about 2 to 5 mmHg;
• left atrium: about 5 to 8 mmHg;
• right ventricle: about 25 mmHg systolic;
• left ventricle: about 120 mmHg systolic.

A normal mean pulmonary artery pressure sits at around 15 mmHg.

What the catheter trace shows

The right ventricular pressure trace has no diastolic lift: pressure falls back to a low level in diastole. As the balloon-tipped (Swan-Ganz) catheter passes from the right ventricle into the pulmonary artery, a diastolic pressure appears, because the catheter is now in a vessel that holds a back pressure when the pulmonary valve closes. That diastolic step is how the operator knows the catheter tip has entered the pulmonary artery, where the mean pressure is measured.

Pre-capillary, post-capillary, combined and exercise pulmonary hypertension

The haemodynamic classification has changed little. It has four categories:

1. Pre-capillary pulmonary hypertension, with a raised pulmonary vascular resistance (PVR). The obstruction lies in the arteries before the capillaries: pulmonary arterial hypertension, lung disease, CTEPH or other obstructions of the pulmonary arteries.
2. Post-capillary pulmonary hypertension, without a raised PVR. The pressure is transmitted backwards from the left side of the heart, from valve stenosis, severe valve regurgitation or other left heart disease.
3. Combined pre-capillary and post-capillary pulmonary hypertension, in which left heart disease and a raised PVR coexist.
4. Exercise pulmonary hypertension, defined by how pressure rises with flow during exertion.

Dr. Purkayastha's advice is to avoid getting lost in wedge-pressure terminology and remember one rule: pre-capillary disease has a raised PVR; post-capillary disease does not. In the 2022 ESC/ERS definitions, a raised PVR means more than 2 Wood units (the unit in which pulmonary vascular resistance is expressed), and post-capillary disease is defined by a pulmonary arterial wedge pressure, a catheter reading that reflects pressure in the left atrium, above 15 mmHg.

Why does post-capillary disease leave the resistance normal? The pulmonary veins behave as capacitance vessels, not resistance vessels. They can accommodate the regurgitant volume from a leaking mitral valve, or the volume that cannot drain into the left heart past a stenotic mitral valve, without the resistance rising.

Exercise pulmonary hypertension is a separate concept. It is defined by the slope of mean pulmonary artery pressure against cardiac output during exercise: a slope above 3 mmHg per litre per minute indicates exertional pulmonary hypertension.

The five WHO groups of pulmonary hypertension

The World Health Organization (WHO) clinical classification sorts pulmonary hypertension by cause. Dr. Purkayastha's shorthand: group 1 is isolated, group 2 is left heart, group 3 is lung, group 4 is vascular and group 5 is mixed.

• Group 1: pulmonary arterial hypertension. Far less common than groups 2 and 3. It includes idiopathic and hereditary disease, disease associated with connective tissue disorders and congenital heart disease, drug-induced disease and persistent pulmonary hypertension of the newborn. It was historically the hardest group to treat.
• Group 2: left heart disease. Among the most common, particularly where unmanaged mitral stenosis or severe mitral regurgitation from preventable valvular heart disease is widespread.
• Group 3: lung disease and hypoxia. Idiopathic pulmonary fibrosis, interstitial lung disease, chronic obstructive pulmonary disease, destroyed lung and obstructive sleep apnoea all stiffen the lung or lower oxygen levels, which raises pulmonary pressure.
• Group 4: pulmonary artery obstruction. Chiefly chronic thromboembolic pulmonary hypertension (CTEPH), in which organised clot from earlier emboli narrows the pulmonary arteries, together with other obstructions of the pulmonary arteries, such as sarcoma and other tumours, arteritis and congenital pulmonary artery stenoses. Group 4 is the group in which surgery, pulmonary endarterectomy, can be curative.
• Group 5: multifactorial. Haematological, systemic and metabolic disorders and chronic kidney disease, in which several mechanisms combine.

Groups 2 and 3 are the ones Dr. Purkayastha sees most. In his framing, the secondary and mixed forms tend to improve when the root cause is treated, which is why identifying the group comes before choosing a drug.

Pulmonary hypertension symptoms and clinical signs

The presenting symptoms of pulmonary hypertension are those of a struggling right heart:

• breathlessness on exertion and, later, at rest;
• chest pain;
• fatigue and generalised weakness;
• palpitations;
• orthopnoea;
• pedal oedema, abdominal swelling and a raised jugular venous pressure;
• syncope in more advanced disease.

On examination, a loud P2 (the pulmonary component of the second heart sound) and a prominent split second sound point towards raised pulmonary pressure, and some patients have mild cyanosis because blood flow through the lungs is reduced. The reason the right ventricle, rather than the left, gives way first is explained in the complete guide.

Comorbidities that should raise suspicion

The conditions that either cause pulmonary hypertension or add to it include:

• left heart disease;
• chronic obstructive pulmonary disease and interstitial lung disease;
• connective tissue disorders;
• chronic hypoxaemia, including from obstructive sleep apnoea;
• venous thromboembolism;
• haemoglobinopathies;
• sarcoidosis;
• HIV and other immunosuppressive states;
• schistosomiasis, a recognised cause of pulmonary arterial hypertension in regions where the infection is endemic;
• chronic kidney disease.

Dr. Purkayastha maps them onto the groups: heart disease classically produces group 2, lung disease and chronic hypoxaemia produce group 3, while connective tissue disorders and kidney disease can produce mixed pictures.

How pulmonary hypertension is diagnosed: the work-up

The work-up for suspected pulmonary hypertension combines a careful history, echocardiography, NT-proBNP, a ventilation perfusion scan and lung function tests, and right heart catheterisation then confirms or excludes the diagnosis. In the history, Dr. Purkayastha stresses three elements: the comorbidities above, a detailed family history (hereditary pulmonary arterial hypertension exists) and specifically any family history of sudden cardiac death.

Echocardiography. Two values are worth remembering. A tricuspid annular plane systolic excursion (TAPSE), a measure of how far the base of the right ventricle moves with each beat, of more than 1.8 cm, and a tricuspid regurgitant jet velocity of less than 2.8 metres per second, together generally indicate a favourable outcome. In Dr. Purkayastha's experience, when both hold, the pulmonary hypertension is almost always mild and readily treatable.

NT-proBNP. This natriuretic peptide, a blood marker released when the heart is under strain, is widely used, but Dr. Purkayastha is "not a huge fan" because it rises in many other acute illnesses, which limits its specificity.

Ventilation perfusion (V/Q) scan. Though less used today, he describes it as a cornerstone investigation. A V/Q scan showing mismatched perfusion defects points to chronic thromboembolic disease, and it remains the recommended screening test for CTEPH because a normal scan effectively excludes it.

Lung function tests. Spirometry and full lung function testing distinguish obstructive from restrictive physiology and intrathoracic from extrathoracic airway obstruction. Their role in pulmonary hypertension itself is limited, though they may show a mild mixed obstructive and restrictive pattern, and they help identify group 3 disease.

Why echocardiography cannot diagnose pulmonary hypertension

Echocardiography cannot diagnose pulmonary hypertension because it estimates the pressure indirectly and because tricuspid regurgitation has causes other than pulmonary hypertension; only right heart catheterisation confirms it. This is the point Dr. Purkayastha makes most forcefully. The diagnosis is not a tricuspid regurgitant jet above 2.8 metres per second. It is not pulmonary regurgitation on echo. It is not a TAPSE below 1.7 cm. The one finding necessary to confirm pulmonary hypertension is a right heart catheterisation. Diagnoses made on echocardiography alone are, in his words, "so wrong".

The reasoning is straightforward:

• Severe tricuspid regurgitation can come from isolated right ventricular failure, without pulmonary hypertension.
• It can come from organic disease of the tricuspid valve itself.
• Every patient with pulmonary hypertension will have tricuspid regurgitation, but not every patient with tricuspid regurgitation has pulmonary hypertension.

Echo laboratories estimate pulmonary artery systolic pressure from the tricuspid jet using the simplified Bernoulli equation, four times the jet velocity squared plus the right atrial pressure. Dr. Purkayastha calls using that estimate to diagnose pulmonary hypertension "probably the wrongest possible thing to do under the sun". The estimate is an indirect calculation from a single jet and an assumed atrial pressure; the catheter measures the pressure directly.

Echo still has a job: selecting patients for referral. The patient to send on, in his description, has a large tricuspid regurgitant jet above 3 metres per second without gross right ventricular dilatation or obvious structural disease of the tricuspid valve.

Right heart catheterisation: the confirmatory test

Right heart catheterisation, in which a catheter is passed through a vein into the right side of the heart and the pulmonary artery, is the test that confirms pulmonary hypertension. It measures the mean pulmonary artery pressure, the wedge pressure and cardiac output directly, and from them the pulmonary vascular resistance is calculated. It separates pre-capillary from post-capillary disease, which echo cannot do reliably, and so decides whether targeted pulmonary arterial hypertension drugs are appropriate.

Dr. Purkayastha adds a second reason: the catheter study is where the team learns whether the pulmonary vascular resistance is vasoreactive. An acute vasoreactivity test, usually with inhaled nitric oxide, identifies the minority of patients with idiopathic, heritable or drug-induced pulmonary arterial hypertension who respond to high-dose calcium channel blockers. In his experience, patients who show early reactivity, with a fall in pulmonary artery pressure once drugs such as macitentan or tadalafil are started, tend to have a better course.

Few centres in the referral regions can perform high-quality right heart catheterisation, which is why he asks referring doctors to use echo as a filter and send suspected cases to a dedicated pulmonary hypertension clinic. His earlier masterclass on heart transplantation covers the same test from another angle, in what referring doctors should test before sending a patient for an LVAD.

Risk stratification: what low-risk pulmonary hypertension looks like

Once the diagnosis is confirmed, risk stratification guides how aggressively to treat. Dr. Purkayastha describes the low-risk patient, whose disease is neither severe nor life threatening, as one with:

• no syncope;
• no progression of clinical manifestations;
• no symptoms of right heart failure;
• a six-minute walk distance of more than 440 metres;
• a cardiac index of more than 2.5 litres per minute per square metre.

The 2022 ESC/ERS risk model adds imaging and haemodynamic markers of a low-risk state: a right atrial area below 18 cm², a TAPSE to pulmonary artery systolic pressure ratio above 0.32 mm/mmHg, a right atrial pressure below 8 mmHg and a stroke volume index above 38 mL/m². Most of these markers describe the right ventricle and right atrium, which is consistent with the physiology: in pulmonary hypertension, the right heart sets the prognosis.

The questions discussed during the session, including the PVR threshold for starting treatment, are collected in the Live Discussion.