What are the steps for testing and diagnosing pulmonary arterial hypertension (PAH)?

Diagnostic Algorithm for Pulmonary Arterial Hypertension (PAH)

The diagnosis of pulmonary arterial hypertension requires a systematic approach with both non-invasive screening tests and confirmatory right heart catheterization, as this methodical workup is essential for both confirming PAH and determining its underlying etiology to guide appropriate treatment. 1

Initial Evaluation for Suspected PAH

• Perform ECG to screen for cardiac abnormalities and arrhythmias, recognizing it has limited sensitivity but provides prognostic information 1
• Obtain chest radiograph (CXR) to identify features supportive of PAH diagnosis and potential underlying diseases 1
• Conduct Doppler echocardiography as the primary non-invasive screening test to detect elevated pulmonary arterial pressure 1
• Evaluate right ventricular systolic pressure and assess for associated abnormalities including right atrial enlargement, right ventricular enlargement, and pericardial effusion 1
• Screen for left ventricular systolic/diastolic dysfunction, chamber enlargement, and valvular disease using Doppler echocardiography 1
• Perform contrast echocardiography to identify potential intracardiac shunting 1

Testing for Secondary Causes

• Test for connective tissue diseases and HIV infection in patients with unexplained PAH 1
• Perform ventilation-perfusion (V/Q) scanning to rule out chronic thromboembolic pulmonary hypertension (CTEPH); a normal scan effectively excludes CTEPH 1
• Note that contrast-enhanced CT or MRI should not be used to exclude CTEPH 1
• If V/Q scan suggests CTEPH, proceed to pulmonary angiography for accurate diagnosis and anatomic definition to assess operability 1
• Conduct pulmonary function testing and arterial blood gas analysis to evaluate for underlying lung disease 1
• In patients with systemic sclerosis, perform pulmonary function testing with DLCO every 6-12 months to improve detection of pulmonary vascular or interstitial disease 1

Confirmatory Testing

• Perform right heart catheterization in all patients with suspected PAH to:
  • Confirm the diagnosis of PAH
  • Establish the specific diagnosis
  • Determine disease severity
  • Guide therapy 1
• Define PAH hemodynamically as mean pulmonary arterial pressure >20 mmHg with pulmonary vascular resistance >2 Wood Units and pulmonary arterial wedge pressure ≤15 mmHg 2
• Conduct acute vasoreactivity testing during catheterization using short-acting agents (IV epoprostenol, adenosine, or inhaled nitric oxide) 1
• Define positive acute response as a decrease in mean pulmonary arterial pressure of at least 10 mmHg to ≤40 mmHg with unchanged or increased cardiac output 1, 3

Genetic Testing Considerations

• Offer genetic testing and professional genetic counseling to relatives of patients with familial PAH 1
• Advise patients with idiopathic PAH about the availability of genetic testing and counseling for their relatives 1
• Consider screening for BMPR2 gene mutations, which are present in approximately 70% of familial PAH cases 4

Assessment of Disease Severity

• Determine functional class and exercise capacity using the 6-minute walk test to establish disease severity, response to therapy, and progression 1
• Monitor parameters that predict worse prognosis:
  • Clinical evidence of right ventricular failure
  • Rapid progression of symptoms
  • Presence of syncope
  • WHO functional class III-IV
  • Short 6-minute walk distance (<300m)
  • Elevated BNP/NT-proBNP levels
  • Presence of pericardial effusion on echocardiography
  • Elevated right atrial pressure or reduced cardiac index 1, 5

Follow-up Assessments

• Perform serial assessments at baseline, every 3-6 months, with initiation or changes in therapy, and in case of clinical worsening 1
• Include clinical assessment, WHO functional class determination, ECG, 6-minute walk test, BNP/NT-proBNP measurement, and echocardiography in follow-up evaluations 1
• Consider cardiopulmonary exercise testing to assess peak oxygen consumption and ventilatory efficiency 1

Important Caveats

• Avoid lung biopsy for PAH diagnosis due to significant risks unless specific questions can only be answered by tissue examination 1
• Recognize that Doppler echocardiography may be imprecise in determining actual pressures compared to invasive evaluation 1
• Be aware that exercise pulmonary hypertension is defined as an abnormal increase in mean PAP during exercise with a mean PAP/cardiac output slope >3 mmHg/L/min 2
• Remember that early diagnosis is critical as most patients are diagnosed late in the disease course when mortality risk is already high 4