What laboratory tests and imaging studies are recommended for the initial work‑up of pulmonary hypertension?

Laboratory and Imaging Work-Up for Pulmonary Hypertension

Begin with transthoracic Doppler echocardiography as your first-line screening test, followed by a comprehensive laboratory panel, high-resolution chest CT, pulmonary function tests, and ventilation/perfusion scanning—culminating in right heart catheterization for definitive hemodynamic confirmation in all patients with suspected pulmonary arterial hypertension. 1, 2

Initial Laboratory Testing

All patients require a comprehensive blood work-up to identify associated conditions and exclude secondary causes:

• Complete blood count to detect myeloproliferative disorders or anemia 3, 1
• Comprehensive metabolic panel including renal and liver function tests 1, 4
• Thyroid function tests (TSH, free T4) to exclude thyroid disorders 3, 1, 4
• Immunology screening including antinuclear antibodies (ANA), anti-Scl-70, anti-centromere, anti-ribonucleoprotein, and rheumatoid factor to detect connective tissue disease 3, 1
• HIV serology in all patients with unexplained pulmonary arterial hypertension 3, 1
• Hepatitis B and C serology 3, 1
• Brain natriuretic peptide (BNP) or NT-proBNP for prognostic assessment and disease severity 2

Essential Imaging Studies

Transthoracic Doppler Echocardiography (First-Line Test)

Echocardiography is the mandatory initial screening tool and should assess:

• Right ventricular systolic pressure estimation 3, 1
• Right atrial and right ventricular size and function, including tricuspid annular plane systolic excursion (TAPSE) 3, 2
• Left ventricular systolic and diastolic function to exclude left heart disease 3
• Valvular abnormalities, particularly mitral and aortic valve disease 3
• Pericardial effusion presence 3, 2
• Intracardiac shunting using contrast echocardiography 3

Ventilation/Perfusion (V/Q) Lung Scan (Mandatory)

A V/Q scan is required in every patient with unexplained pulmonary hypertension to exclude chronic thromboembolic pulmonary hypertension (CTEPH):

• A normal V/Q scan effectively excludes CTEPH 3, 1
• Multiple segmental perfusion defects indicate probable CTEPH and require CT pulmonary angiography and selective pulmonary angiography 3, 1
• Do not substitute CT angiography alone for V/Q scanning—CT is less sensitive and may miss CTEPH 3, 1

High-Resolution Computed Tomography (HRCT) of the Chest

HRCT should be performed in all patients to:

• Identify interstitial lung disease and emphysema 3, 1
• Detect pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis 3
• Assess for parenchymal lung abnormalities that may cause Group 3 pulmonary hypertension 1, 2

Additional Imaging as Indicated

• Abdominal ultrasound to screen for liver cirrhosis and portal hypertension 3, 1, 2
• CT pulmonary angiography when CTEPH is suspected based on abnormal V/Q scan 1, 2
• Cardiac MRI may provide additional assessment of right ventricular function and morphology 5

Pulmonary Function Testing

Obtain complete pulmonary function tests with diffusing capacity:

• Spirometry with lung volumes to assess for obstructive or restrictive lung disease 3, 1
• Diffusing capacity of the lung for carbon monoxide (DLCO) is essential—reduced DLCO may indicate pulmonary vascular disease or interstitial lung disease 3, 1
• Arterial blood gas analysis to evaluate oxygenation and exclude hypoxemia-related pulmonary hypertension 3, 1

Right Heart Catheterization (Gold Standard for Diagnosis)

Right heart catheterization is mandatory for definitive diagnosis in all patients with suspected pulmonary arterial hypertension:

• Required to confirm the diagnosis, establish specific hemodynamic classification, assess severity, and guide therapy 3, 1, 2
• Must measure and record in triplicate:
  • Mean pulmonary arterial pressure (diagnostic threshold ≥25 mmHg at rest) 3, 2
  • Pulmonary capillary wedge pressure (≤15 mmHg defines precapillary pulmonary hypertension) 1, 2
  • Right atrial pressure 3, 2
  • Cardiac output (preferably by thermodilution or Fick method) 3, 2
  • Pulmonary vascular resistance (>3 Wood units required for pulmonary arterial hypertension) 1, 2
• Vasoreactivity testing should be performed during catheterization in appropriate patients 3

Specialized Testing Based on Clinical Suspicion

• Genetic testing for BMPR2, ACVRL1 (ALK-1), and ENG mutations in patients with suspected heritable pulmonary arterial hypertension or positive family history 3, 1, 2
• Overnight oximetry or polysomnography if sleep-disordered breathing is suspected 1
• Exercise testing with 6-minute walk test and Borg dyspnea score for functional assessment and prognosis 3, 2

Critical Pitfalls to Avoid

• Never rely on chest radiography alone—it is insensitive for mild disease and a normal film does not exclude pulmonary hypertension 2
• Do not skip the V/Q scan—failure to perform it can miss treatable CTEPH, which has specific surgical therapy 3, 1, 2
• Do not use CT pulmonary angiography or MRI as the sole test to exclude CTEPH—V/Q scanning is more sensitive 3
• Avoid open or thoracoscopic lung biopsy in patients with pulmonary arterial hypertension due to high risk and limited diagnostic yield 3, 2
• Do not delay right heart catheterization—echocardiography alone cannot definitively diagnose or classify pulmonary hypertension 3, 2

Algorithmic Approach Based on Echocardiographic Probability

When echocardiography shows HIGH probability of pulmonary hypertension:

• Evaluate for left heart disease (ECG, clinical assessment) and lung disease (PFTs, HRCT, arterial blood gases) 1, 2
• Perform V/Q scan to exclude CTEPH 1, 2
• Proceed to right heart catheterization for definitive diagnosis 1, 2

When echocardiography shows INTERMEDIATE probability:

• If symptomatic with risk factors (connective tissue disease, family history, portal hypertension, congenital heart disease, HIV): consider right heart catheterization 2
• If symptomatic without risk factors: evaluate alternative diagnoses; if symptoms are moderate-to-severe, proceed to catheterization 2

When echocardiography shows LOW probability:

• If asymptomatic: no further work-up needed 2
• If symptomatic with risk factors: repeat echocardiography for surveillance 2
• If symptomatic without risk factors: investigate alternative causes 2