Approach

Because IPAH is a diagnosis of exclusion, there is no definitive diagnostic test, but there are a number of laboratory and imaging tests that should be used to rule out other types of pulmonary hypertension (PH). The 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines advise a three-step approach to diagnosis of PH: first suspicion by first-line physicians, then detection by echocardiography, and finally confirmation in PH centres.[3]​ If PAH is suspected at any time in the patient evaluation, fast-track referral to a centre with expertise in its diagnosis and management is recommended.[3][35][36]​​​​​

History

Symptoms are non-specific and mainly related to right heart dysfunction.[3][36]​ Early symptoms include progressive dyspnoea on exertion, fatigue and rapid exhaustion, palpitations, chest discomfort, and lightheadedness. Syncope is a less common but worrisome symptom. Patients may have syncope or near syncope as cardiac output becomes fixed and eventually falls.[37] Other historical clues are the presence of pulmonary hypertension in a first-degree relative and prior use of stimulants. There may also be a history of blood clots or splenectomy. 

Physical examination

Physical examination is often normal in early stages. Lungs are clear to auscultation. Positive signs include a prominent jugular V wave on the neck, a palpable left parasternal heave, an accentuated pulmonic component to the second heart sound (P2), and a high-pitched holosystolic murmur best heard at the left sternal border. In more advanced cases, there are signs of right heart failure such as jugular venous distension, hepatomegaly, ascites, and peripheral oedema.

Tests

Initial tests include a chest x-ray, an ECG, and a transthoracic echocardiogram.[17][38]​​ Right heart catheterisation is required to confirm the diagnosis of pulmonary arterial hypertension, determine the type of pulmonary hypertension (pre-capillary, post-capillary, or combined), and assess pulmonary haemodynamics and cardiac output to calculate pulmonary vascular resistance.[3][36]​ Additional tests are performed to rule out known causes of pulmonary hypertension. These include antinuclear antibodies, HIV serology, full blood count, liver function tests, thyroid function tests, pulmonary function studies, arterial blood gas, overnight oximetry, and ventilation perfusion scan. Depending on the clinical suspicion, polysomnography, high-resolution computed tomography (CT) scan of the chest, cardiac magnetic resonance imaging (MRI), and pulmonary angiography could be indicated as well. If the complete evaluation is unrevealing, the diagnosis of IPAH is made. B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) levels should be obtained. These are elevated in right ventricular pressure overload and correlate with severity of right ventricular dysfunction and mortality in IPAH.[3] A 6-minute walk test should be done as it provides an estimation of exercise capacity and disease severity, as well as response to therapy and progression.[3]

Vasodilator testing (with inhaled nitric oxide, inhaled iloprost, or intravenous epoprostenol) may help identify a subset of IPAH patients who might be treated with oral calcium-channel blockers. Testing is not indicated in unstable patients or those who are in right heart failure.[35]

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