What is the diagnostic workup for pulmonary hypertension?

Diagnostic Workup for Pulmonary Hypertension

The diagnostic workup for pulmonary hypertension should begin with echocardiography as the first-line non-invasive investigation, followed by a systematic approach to determine the specific type of PH through specialized tests including ventilation/perfusion scanning, pulmonary function tests, and ultimately right heart catheterization for definitive diagnosis. 1

Initial Evaluation

• Echocardiography is recommended as the first-line non-invasive diagnostic test when PH is suspected 1
• Clinical history, symptoms (breathlessness on exertion, syncope, angina, palpitations, dry cough), signs, ECG, and chest radiograph should be evaluated to identify risk factors and potential causes 1, 2
• Laboratory testing should include complete blood count, renal and liver function tests, thyroid function tests, immunology screening, and HIV testing 1, 2
• Pulmonary function tests with diffusing capacity of the lung for carbon monoxide (DLCO) are essential in the initial evaluation 1
• High-resolution CT of the chest should be considered in all patients with PH to identify underlying lung disease 1

Diagnostic Algorithm Based on Echocardiographic Probability

For High or Intermediate Probability of PH on Echocardiography:

• Evaluate for left heart disease and lung diseases through clinical assessment, ECG, PFTs with DLCO, chest radiograph, HRCT, and arterial blood gases 1
• If left heart or lung disease is confirmed:
  • Treat the underlying condition 1
  • If severe PH or right ventricular dysfunction is present, refer to a PH expert center 1
• If left heart or lung disease is not confirmed:
  • Perform ventilation/perfusion (V/Q) lung scan to exclude CTEPH 1
  • Refer to a PH expert center 1, 3

For Low Probability of PH on Echocardiography:

• If no symptoms are present, no additional investigations are required 1, 3
• If symptoms are present, evaluate for other causes 1, 3

Specialized Testing

• Ventilation/perfusion or perfusion lung scan is mandatory in patients with unexplained PH to exclude CTEPH (CT pulmonary angiography alone may miss the diagnosis) 1
• If V/Q scan shows multiple segmental perfusion defects:
  • CTEPH should be suspected 1
  • Proceed with CT pulmonary angiography, right heart catheterization, and selective pulmonary angiography 1
• If V/Q scan is normal or shows only subsegmental "patchy" perfusion defects:
  • Consider PAH or other rare conditions 1
  • Proceed with right heart catheterization 1
• Abdominal ultrasound is recommended for screening of portal hypertension 1, 3
• Additional specialized testing based on clinical suspicion:
  • Extended laboratory testing including TSH, troponin, uric acid, and iron status 1
  • Genetic testing for BMPR2, ACVRL1, and ENG mutations in cases of suspected heritable PAH 1, 4

Definitive Diagnosis with Right Heart Catheterization

• Right heart catheterization is required for definitive diagnosis of PH 1, 5
• Diagnostic criteria:
  • Mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest 5
  • Pulmonary arterial wedge pressure (PAWP) ≤15 mmHg for pre-capillary PH 5
  • Pulmonary vascular resistance (PVR) >3 Wood units for PAH 1, 5

Important Considerations and Pitfalls

• Open or thoracoscopic lung biopsy is not recommended in patients with PAH 1, 3
• CT pulmonary angiography alone may miss the diagnosis of CTEPH; V/Q scan is more sensitive 1
• Fast-track referral to a PH center is recommended in cases of high probability of severe pulmonary vascular disease, especially with signs of right heart failure 5
• Regular follow-up assessments every 3-6 months are recommended in stable patients once diagnosis is established 1

Classification of PH

• Group 1: Pulmonary arterial hypertension (including idiopathic, heritable, drug-induced, and associated forms) 1, 4
• Group 2: PH due to left heart disease 1, 4
• Group 3: PH due to lung diseases and/or hypoxia 1, 4
• Group 4: Chronic thromboembolic PH 1, 4
• Group 5: PH with unclear/multifactorial mechanisms 1, 4

Accurate classification is crucial as treatment strategies differ significantly between groups, with specialized PAH therapies potentially harmful in certain forms of PH 2, 6.