What are the steps to diagnose pulmonary arterial hypertension (PAH)?

Diagnostic Algorithm for Pulmonary Arterial Hypertension (PAH)

The diagnosis of pulmonary arterial hypertension (PAH) requires a systematic approach beginning with echocardiography as the initial screening tool, followed by exclusion of secondary causes, and ultimately confirmation with right heart catheterization, which remains the gold standard for definitive diagnosis. 1

Initial Evaluation for Suspected PAH

• Doppler echocardiography is the recommended primary non-invasive screening test to detect elevated pulmonary arterial pressure and should be performed in all patients with suspected PAH 1
• Right ventricular systolic pressure (RVSP) can be estimated using the modified Bernoulli equation: RVSP = 4v² + RAP, where v is the tricuspid regurgitation jet velocity and RAP is the estimated right atrial pressure 2
• An RVSP of >30 mmHg is considered abnormal, with values >96mmHg strongly suggesting severe pulmonary hypertension 3
• Echocardiography should also assess for associated abnormalities including right atrial enlargement, right ventricular enlargement, and pericardial effusion 1
• ECG should be performed to screen for cardiac abnormalities and arrhythmias, recognizing it has limited sensitivity but provides prognostic information 1
• Chest radiograph (CXR) should be obtained to identify features supportive of PAH diagnosis and potential underlying diseases 1

Testing for Secondary Causes

• Ventilation-perfusion (V/Q) scanning is essential to rule out chronic thromboembolic pulmonary hypertension (CTEPH); a normal scan effectively excludes CTEPH 1
• Comprehensive pulmonary function tests should be performed to assess for underlying lung disease 3
• Testing for connective tissue diseases and HIV infection is recommended in patients with unexplained PAH 1
• Non-contrast CT scan of the chest or CT angiogram should be considered if thromboembolic disease is suspected 3
• Screening for sleep apnea should be performed as it can contribute to pulmonary hypertension 3
• Echocardiography with bubble study should be considered if there is suspicion of intracardiac shunts 3

Confirmatory Testing

• Right heart catheterization is mandatory in all patients with suspected PAH to confirm the diagnosis, establish the specific diagnosis, determine disease severity, and guide therapy 1, 4
• PAH is hemodynamically defined by:
  • Mean pulmonary artery pressure >20 mm Hg 4, 5
  • Pulmonary artery wedge pressure ≤15 mm Hg 4, 5
  • Pulmonary vascular resistance ≥3 Wood units 4 or >2 Wood units 5
• Acute vasoreactivity testing should be performed during right heart catheterization to identify potential responders to calcium channel blockers 1
• A positive acute response is defined as a decrease in mean pulmonary arterial pressure of at least 10 mmHg to ≤40 mmHg with unchanged or increased cardiac output 1

Assessment of Disease Severity

• WHO functional class determination should be performed to establish disease severity 1
• Six-minute walk test should be conducted to establish functional capacity baseline and for prognostic assessment 1, 3
• BNP/NT-proBNP levels should be measured as they correlate with disease severity and prognosis 1
• Parameters that predict worse prognosis include:
  • Clinical evidence of right ventricular failure 1
  • Rapid progression of symptoms 1
  • Presence of syncope 1
  • WHO functional class III-IV 1
  • Short 6-minute walk distance (<300m) 1
  • Elevated BNP/NT-proBNP levels 1
  • Presence of pericardial effusion on echocardiography 1
  • Elevated right atrial pressure or reduced cardiac index 1

Follow-up Assessments

• Serial assessments should be performed at baseline, every 3-6 months, with initiation or changes in therapy, and in case of clinical worsening 1
• Follow-up evaluations should include clinical assessment, WHO functional class determination, ECG, 6-minute walk test, BNP/NT-proBNP measurement, and echocardiography 1

Important Caveats and Pitfalls

• Echocardiography may be imprecise in determining actual pressures compared to invasive evaluation, potentially underestimating sPAP by a mean of 11 mm Hg 1, 2
• The discordance between estimated and true pulmonary artery pressure is greatest when sPAP exceeds 100 mm Hg 2
• In cases of severe tricuspid regurgitation, tricuspid regurgitation velocity may be significantly underestimated and cannot be used to exclude PH 2
• Lung biopsy for PAH diagnosis should be avoided due to significant risks unless specific questions can only be answered by tissue examination 1
• When tricuspid regurgitation and pulmonic valve regurgitation jets are not present or quantifiable, right ventricular outflow patterns and time intervals can be used as alternative approaches 2