Diagnostic Work‑Up for Suspected Pulmonary Hypertension

1. Laboratory Evaluation

• Complete blood count should be obtained in all patients to screen for anemia or myeloproliferative disorders that can mimic or contribute to pulmonary hypertension. 1
• Thyroid function tests (TSH, free T4) are recommended to exclude thyroid disease as a secondary cause of pulmonary hypertension. 1
• Autoimmune serology (ANA, anti‑Scl‑70, anti‑centromere, anti‑RNP, rheumatoid factor) is essential to identify connective‑tissue disease‑associated pulmonary hypertension. 1
• HIV serology must be performed in every patient with unexplained pulmonary arterial hypertension to detect HIV‑related disease. [2][3]
• Hepatitis B and C serology should be included to rule out viral hepatitis‑related pulmonary vascular disease. 1

2. Imaging Evaluation

2.1 Transthoracic Doppler Echocardiography (first‑line)

• Estimate right‑ventricular systolic pressure to gauge the likelihood of pulmonary hypertension. [2][3]
• Assess right‑atrial and right‑ventricular size and function, including TAPSE, for early right‑heart involvement. 2
• Evaluate left‑ventricular systolic and diastolic function to exclude left‑heart disease as the primary driver. [2][3]
• Identify valvular abnormalities (especially mitral and aortic disease) that may cause secondary pulmonary hypertension. [2][3]
• Detect pericardial effusion, which can influence hemodynamics. 2
• Perform contrast echocardiography to uncover intracardiac shunts that could contribute to elevated pulmonary pressures. [2][3]

2.2 Ventilation/Perfusion (V/Q) Scan (mandatory)

• A normal V/Q scan reliably excludes chronic thromboembolic pulmonary hypertension (CTEPH). [2][3]
• Multiple segmental perfusion defects on V/Q suggest probable CTEPH and trigger further evaluation with CT pulmonary angiography and selective pulmonary angiography. 1
• CT pulmonary angiography alone is less sensitive for CTEPH and should not replace the V/Q scan. [2][3]

2.3 High‑Resolution Computed Tomography (HRCT)

• HRCT is required to identify interstitial lung disease and emphysema, which define Group 3 pulmonary hypertension. 1
• It also helps detect pulmonary veno‑occlusive disease or pulmonary capillary hemangiomatosis, rare causes of pulmonary arterial hypertension. 1

2.4 Additional Imaging

• Abdominal ultrasound should be used to screen for liver cirrhosis and portal hypertension, conditions associated with Group 1 pulmonary hypertension. 1

3. Pulmonary Function Testing

• Spirometry with lung volumes is necessary to characterize obstructive or restrictive patterns that may underlie pulmonary hypertension. [2][3]
• Diffusing capacity for carbon monoxide (DLCO) is essential; a reduced DLCO supports a pulmonary vascular or interstitial etiology. [2][3]
• Arterial blood gas analysis evaluates oxygenation and rules out hypoxemia‑driven pulmonary hypertension. [2][3]

4. Hemodynamic Confirmation (Right‑Heart Catheterization)

• Right‑heart catheterization is mandatory to confirm the diagnosis, classify hemodynamic type, assess severity, and guide therapy. [2][3]
• Measurements must be obtained in triplicate, including:
  
  • Mean pulmonary arterial pressure (mPAP) – diagnostic threshold ≥ 25 mmHg at rest. 1
  • Right‑atrial pressure – recorded for completeness of the hemodynamic profile. 1
  • Cardiac output – preferably measured by thermodilution or the Fick method. 1
• Acute vasoreactivity testing should be performed in appropriate patients to identify candidates for calcium‑channel blocker therapy. 1

5. Specialized Testing Based on Clinical Suspicion

• Genetic testing for BMPR2, ACVRL1 (ALK‑1), and ENG mutations is advised in patients with suspected heritable pulmonary arterial hypertension or a positive family history. 1
• Exercise testing (6‑minute walk test with Borg dyspnea score) provides functional assessment and prognostic information. [2][3]

6. Critical Pitfalls to Avoid

• Do not rely on chest radiography alone; a normal film does not exclude pulmonary hypertension. (no citation)
• Never omit the V/Q scan; failure can miss treatable CTEPH, which may be surgically curable. [2][3]
• Do not use CT pulmonary angiography or MRI as the sole test to exclude CTEPH; V/Q scanning remains the most sensitive modality. [2][3]
• Avoid open or thoracoscopic lung biopsy in patients with pulmonary arterial hypertension due to high procedural risk and limited diagnostic yield. [2][3]
• Do not delay right‑heart catheterization; echocardiography alone cannot definitively diagnose or classify pulmonary hypertension. [2][3]

Diagnostic Workup for Pulmonary Hypertension

Initial Evaluation

• The European Society of Cardiology recommends echocardiography as the first-line non-invasive diagnostic test when pulmonary hypertension is suspected 4
• Clinical history, symptoms, signs, ECG, and chest radiograph should be evaluated to identify risk factors and potential causes 5
• Laboratory testing should include complete blood count, renal and liver function tests, thyroid function tests, immunology screening, and HIV testing 4
• Pulmonary function tests with diffusing capacity of the lung for carbon monoxide are essential in the initial evaluation 4, 6
• High-resolution CT of the chest should be considered in all patients with pulmonary hypertension to identify underlying lung disease 4, 5

Diagnostic Algorithm Based on Echocardiographic Probability

• For high or intermediate probability of pulmonary hypertension on echocardiography, evaluate for left heart disease and lung diseases through clinical assessment, ECG, PFTs with DLCO, chest radiograph, HRCT, and arterial blood gases 5, 7
• If left heart or lung disease is confirmed, treat the underlying condition 5
• If severe pulmonary hypertension or right ventricular dysfunction is present, refer to a pulmonary hypertension expert center 5
• If left heart or lung disease is not confirmed, perform ventilation/perfusion lung scan to exclude chronic thromboembolic pulmonary hypertension 4, 5

Specialized Testing

• Ventilation/perfusion or perfusion lung scan is mandatory in patients with unexplained pulmonary hypertension to exclude chronic thromboembolic pulmonary hypertension 4, 5
• If V/Q scan shows multiple segmental perfusion defects, chronic thromboembolic pulmonary hypertension should be suspected 5
• Proceed with CT pulmonary angiography, right heart catheterization, and selective pulmonary angiography if V/Q scan is abnormal 4, 5
• Abdominal ultrasound is recommended for screening of portal hypertension 4
• Additional specialized testing based on clinical suspicion, including extended laboratory testing and genetic testing for BMPR2, ACVRL1, and ENG mutations in cases of suspected heritable pulmonary arterial hypertension 7, 8

Definitive Diagnosis with Right Heart Catheterization

• Right heart catheterization is required for definitive diagnosis of pulmonary hypertension 6
• Diagnostic criteria include mean pulmonary arterial pressure ≥25 mmHg at rest and pulmonary vascular resistance >3 Wood units for pulmonary arterial hypertension 5

Important Considerations and Pitfalls

• Open or thoracoscopic lung biopsy is not recommended in patients with pulmonary arterial hypertension 4
• CT pulmonary angiography alone may miss the diagnosis of chronic thromboembolic pulmonary hypertension; V/Q scan is more sensitive 4, 5
• Regular follow-up assessments every 3-6 months are recommended in stable patients once diagnosis is established 8, 9

Classification of Pulmonary Hypertension

• The European Respiratory Society classifies pulmonary hypertension into five groups, including pulmonary arterial hypertension, pulmonary hypertension due to left heart disease, pulmonary hypertension due to lung diseases and/or hypoxia, chronic thromboembolic pulmonary hypertension, and pulmonary hypertension with unclear/multifactorial mechanisms 10