What is the recommended diagnostic workup for a patient with suspected pulmonary arterial hypertension (PAH)?

Diagnostic Workup of Pulmonary Arterial Hypertension

Begin with transthoracic Doppler echocardiography as your first-line screening tool, then proceed to right heart catheterization for hemodynamic confirmation in all patients with suspected PAH—this two-step approach is mandatory and non-negotiable. 1, 2

Initial Clinical Assessment

Key Historical Red Flags

Look specifically for these presenting features that should trigger your workup:

• Unexplained exertional dyspnea disproportionate to known disease is the most common presenting symptom 3, 4
• Syncope or presyncope occurs in approximately 40% of patients and demands urgent evaluation 1
• Fatigue, weakness, and chest pain each affect roughly 40% of patients 1
• Unexplained exercise intolerance warrants screening 1

Critical Risk Factors Requiring Systematic Screening

• Connective tissue disease—particularly scleroderma spectrum disorders—carries poor prognosis and requires echocardiographic screening even when symptomatic 1, 2
• Portal hypertension (especially liver transplant candidates) 1, 2
• Congenital heart disease 1
• HIV infection 1
• Family history of PAH or BMPR2 mutation warrants periodic screening even in asymptomatic individuals 1
• Prior venous thromboembolism raises suspicion for chronic thromboembolic PH 1
• Exposure to appetite suppressants or chemotherapy (mitomycin-C, carmustine, etoposide, cyclophosphamide, bleomycin) 1

Physical Examination Findings

• Accentuated pulmonary component of S2 at the apex is present in ~90% of idiopathic PAH patients 1
• Left parasternal lift reflecting right ventricular hypertrophy 1
• Right ventricular S4 gallop (present in ~38% of patients) 1
• Prominent jugular "a" waves indicating elevated right atrial pressure 1
• Advanced disease signs: pulmonary regurgitation murmur, peripheral edema, hepatomegaly, ascites 1

Echocardiography-Based Diagnostic Algorithm

When Echocardiography Shows "PH Unlikely"

• No symptoms: No additional workup needed 2
• Symptoms present WITH risk factors for PAH: Perform echocardiographic follow-up 2
• Symptoms present WITHOUT risk factors: Evaluate other causes for symptoms 2

When Echocardiography Shows "PH Possible"

• No symptoms and no risk factors: Echocardiographic follow-up 2
• Symptoms WITH risk factors: Consider right heart catheterization 2
• Symptoms WITHOUT risk factors: Consider alternative diagnosis and echocardiographic follow-up; if symptoms are at least moderate, consider RHC 2

When Echocardiography Shows "PH Likely"

• With symptoms (regardless of risk factors): Right heart catheterization is mandatory 2
• Without symptoms (regardless of risk factors): Right heart catheterization should be considered 2

Mandatory Diagnostic Tests

Right Heart Catheterization (Gold Standard)

Right heart catheterization is required at baseline for ALL patients in whom PAH is suspected to confirm diagnosis, assess prognosis, and guide therapy. 1, 2 This is non-negotiable.

Record these variables during RHC:

• Pulmonary artery pressure (systolic, diastolic, mean) 2
• Right atrial pressure 2
• Pulmonary capillary wedge pressure (PCWP) 2
• Right ventricular pressure 2
• Cardiac output measured in triplicate (preferably thermodilution or Fick method) 2

Hemodynamic diagnostic criteria:

• Mean pulmonary artery pressure ≥25 mmHg at rest 1
• PCWP ≤15 mmHg (confirms precapillary PH) 1
• Pulmonary vascular resistance >3 Wood units 1

Imaging Studies

• Ventilation/perfusion lung scan is mandatory in ALL patients with unexplained PH to exclude chronic thromboembolic PH—this is a critical step to avoid missing treatable disease 2, 1
• Contrast CT angiography of the pulmonary arteries is indicated in the workup of suspected CTEPH 2
• High-resolution CT should be considered in all PH patients 2
• Chest radiography may show enlarged central pulmonary arteries (right interlobar artery >15 mm in women, >16 mm in men), but a normal film does NOT exclude PH, particularly in early disease 1

Laboratory Evaluation

Obtain these tests in ALL patients to identify associated conditions: 2, 1

• Routine biochemistry and hematology
• Thyroid function tests
• Immunology panel (ANA, anti-Scl-70, anti-centromere for connective tissue disease)
• Liver function tests
• HIV serology
• Abdominal ultrasound for portal hypertension screening 2

Pulmonary Function Testing

• Pulmonary function tests and arterial blood gases are essential to evaluate for underlying lung disease 1

Critical Pitfalls to Avoid

• Do NOT rely solely on chest radiography—a normal film cannot exclude PH, especially in early disease 1
• Do NOT skip the ventilation/perfusion scan—you will miss treatable chronic thromboembolic disease 2, 1
• Do NOT perform open or thoracoscopic lung biopsy in PAH patients—it is not recommended 2
• Do NOT initiate PAH-specific therapy empirically without right heart catheterization confirmation 3

Urgent Referral Indications

Refer immediately to a specialized pulmonary hypertension center for: 1

• Syncope or rapid symptom progression
• Overt right heart failure
• Suspected PAH or chronic thromboembolic PH
• Unexplained PH of uncertain etiology

Prognostic Assessment at Diagnosis

Document these adverse prognostic markers:

• WHO functional class III-IV 1
• 6-minute walk distance <440 meters 1
• Elevated BNP/NT-proBNP 1
• Elevated right atrial pressure 1
• Significant right ventricular dysfunction on imaging 1
• Approximately 15% of patients die within one year despite modern therapy 1