11th May 2025

Diagnosis

Definitive diagnosis of PH is at right cardiac catheterisation where pulmonary pressures can be measured. PH is defined by a mean pulmonary artery pressure of greater than 20 mmHg at rest. Clinical history, examination and investigations should be utilised to review secondary causes of PH. IPAH is a diagnosis of exclusion once secondary causes of PH have been excluded.

Clinical Manifestations

Most commonly, PH affects females between 20 and 50 years. Presentation may be precipitated by use of stimulants such as cocaine. PH presents with progressive dyspnoea and fatigue on exertion. Other exertional symptoms include cardiac chest pain and presyncope/syncope, which may not appear until the onset of right sided heart failure. Given that the symptoms of PH are not specific, diagnosis is often delayed. 

Symptoms can be classified by WHO functional status. This is useful for marking severity, prognosis and outcome to therapies.

Table 1: WHO functional classification of PH

Examination signs are absent or subtle in early disease and again generally occur after onset of right sided cardiac failure.  

Examination findings include: 

• Cyanosis
• Right ventricular heave – indicating right heart hypertrophy
• Loud P2 – accentuated pulmonary component of second heart sound 
• Holosystolic murmur – functional tricuspid regurgitation
• Signs of right heart failure: raised JVP, peripheral oedema, hepatomegaly, ascites. 
• Note that the lungs remain clear on auscultation (unless underlying lung disease)

In secondary PH, additional clinical features will depend on the underlying aetiology. When related to systemic sclerosis, one may expect to see sclerodactyly, Reynaud’s, polyarthralgia, telangiectasia, dysphagia and additional rheumatological manifestations associated with this condition. In the presence of left sided cardiac failure, signs of pulmonary congestion may be present, such as coarse bi-basal crackles, orthopnoea and paroxysmal nocturnal dyspnoea. Interstitial lung disease may reveal fine inspiratory bi-basal crackles. 

This illustrates the importance of a thorough history and examination in guiding the clinician towards the cause of suspected PH.

Investigations

PH investigations usually begin when the patient presents with dyspnoea and includes chest x-ray, transthoracic echocardiogram, and possibly pulmonary function tests at this stage (Table 2 describes findings related to PH and its associated conditions). Echocardiogram estimates systolic pulmonary artery pressures and so is useful in raising clinical suspicion but is not considered diagnostic. All patients should go on to have right cardiac catheterisation to accurately measure pulmonary pressures and provide definitive diagnosis. Right heart catheterisation also allows for measurement of haemodynamic parameters (such as cardiac output/index atrial pressures, pulmonary vascular resistance and pulmonary artery saturations) which are important prognostic markers.

Blood tests performed in the initial patient work-up are aimed at alternative causes of dyspnoea and eventually to investigate secondary causes of PH. Labs include full blood count, liver function tests, clotting studies, thyroid function tests, autoantibodies (anti-nuclear, anti-dsDNA, anti-centromere), HIV serology, BNP (B-type natriuretic peptide) or NT-proBNP (N-terminal proBNP). BNP correlates to the severity of right cardiac dysfunction and is used as a marker of prognosis and mortality in patients with PAH.

If obstructive sleep apnoea (OSA) is suspected, overnight oximetry should be performed. 

If no secondary aetiologies are identified, a diagnosis of idiopathic PAH is made.

Table 2: Clinical findings of PH and its associated conditions

In PAH (WHO Group 1), vasodilator testing can be used to identify a small subset of patients who may benefit from treatment with calcium-channel blockers (CCB’s). Pulmonary pressures are measured before and after administration of vasodilators (inhaled nitric oxide, intravenous epoprostenol, or intravenous adenosine). If the patient has already progressed to right heart failure, vasodilator testing should not be performed.

A 6-minute-walk-test (6MWT) is performed in all patients with PH and is used to track management and guide prognosis. This test assesses how far the patient can walk in 6-minutes and has an inverse correlation with the functional class of the patient.