What non-invasive diagnostic tests, aside from echocardiography, can be used to diagnose pulmonary hypertension in patients with varying demographics and medical histories, such as young adults with connective tissue disease or older adults with chronic obstructive pulmonary disease (COPD)?

Non-Invasive Diagnostic Tests for Pulmonary Hypertension Beyond Echocardiography

Ventilation/perfusion (V/Q) lung scanning is the primary non-invasive test recommended after echocardiography for diagnosing pulmonary hypertension, particularly to distinguish chronic thromboembolic pulmonary hypertension (CTEPH) from other forms of PH. 1

Primary Recommended Tests

Ventilation/Perfusion (V/Q) Lung Scan

• V/Q scanning is recommended as a Class I, Level C diagnostic test in all patients with unexplained PH to exclude CTEPH 1
• The planar V/Q lung scan carries 96-97% sensitivity and 90-95% specificity for diagnosing CTEPH 1
• V/Q scanning shows mismatched perfusion defects in CTEPH, while in idiopathic PAH and pulmonary veno-occlusive disease, perfusion scans typically show non-segmental defects or are normal 1
• This test should be performed early in the diagnostic algorithm after echocardiography suggests intermediate or high probability of PH 1

Computed Tomography (CT) Imaging

CT Pulmonary Angiography

• Contrast CT angiography of the pulmonary artery is recommended (Class I, Level C) in the workup of patients with CTEPH 1
• Modern CT pulmonary angiography demonstrates excellent diagnostic efficacy with 96.1% sensitivity, 95.2% specificity, and 95.6% accuracy for detecting CTEPH 1
• CT can identify specific CTEPH findings including complete obstruction, bands and webs, intimal irregularities, ring-like stenoses, and chronic total occlusions 1
• Important caveat: CT pulmonary angiography alone cannot exclude CTEPH and should not replace V/Q scanning as the initial screening test 1

High-Resolution CT (HRCT)

• High-resolution CT should be considered (Class IIa, Level C) in all patients with PH 1
• HRCT provides detailed lung parenchymal views to identify interstitial lung disease, emphysema, and bronchial disease 1
• CT can suggest PH by showing pulmonary artery diameter ≥29 mm and pulmonary artery:ascending aorta diameter ratio ≥1.0 1
• A segmental artery:bronchus ratio >1:1 in three or four lobes has high specificity for PH 1
• HRCT is particularly valuable for identifying pulmonary veno-occlusive disease, showing characteristic ground-glass opacification and interlobular septal thickening 1

Cardiac Magnetic Resonance Imaging (CMR)

• CMR is accurate and reproducible for assessing right ventricular size, morphology, and function 1
• In patients with suspected PH, the presence of late gadolinium enhancement, reduced pulmonary arterial distensibility, and retrograde flow have high predictive value for identifying PH 1
• No single CMR measurement can exclude PH, but it provides comprehensive hemodynamic assessment 1
• CMR provides useful prognostic information at baseline and follow-up 1
• In connective tissue disease patients with suspected PAH, CMR shows superior diagnostic utility compared to CT, with ventricular mass index ≥0.45 demonstrating 85% sensitivity and 82% specificity 2
• MR angiography is particularly valuable in pregnant women, young patients, or when iodine-based contrast is contraindicated 1
• Recent research demonstrates MRI can achieve 100% sensitivity and 96.8% specificity for diagnosing CTEPH, and 92% overall diagnostic accuracy for PH when combining multiple MRI-derived parameters 3, 4

Ancillary Non-Invasive Tests

Pulmonary Function Tests

• Lung function testing with diffusing capacity for carbon monoxide (DLCO) is recommended (Class I, Level C) in the initial evaluation of all patients with PH 1
• These tests help identify underlying lung disease contributing to PH 1

Blood Tests and Biomarkers

• Routine biochemistry, haematology, immunology, HIV testing, and thyroid function tests are recommended (Class I, Level C) in all patients with PAH 1
• N-terminal pro-brain natriuretic peptide (NT-proBNP) may be elevated and serves as an independent risk predictor 1
• Serological testing detects underlying connective tissue disease, with up to 40% of idiopathic PAH patients having elevated antinuclear antibodies 1
• Thrombophilia screening including antiphospholipid antibodies, anticardiolipin antibodies, and lupus anticoagulant is required in CTEPH patients 1

Abdominal Ultrasound

• Abdominal ultrasound is recommended (Class I, Level C) for screening portal hypertension 1
• This test identifies portopulmonary hypertension as a specific PAH-associated condition 1

Diagnostic Algorithm Considerations

For COPD or Lung Disease Patients

• After echocardiography suggests PH, perform pulmonary function tests with DLCO and HRCT to characterize lung disease severity 1
• If signs of severe PH or right ventricular dysfunction are present despite lung disease, proceed with V/Q scanning to exclude CTEPH 1
• Right heart catheterization is NOT recommended unless therapeutic consequences are expected (lung transplantation, alternative diagnoses, clinical trial enrollment) 1

For Connective Tissue Disease Patients

• After echocardiography, obtain comprehensive serological testing and consider CMR for superior diagnostic accuracy over CT 2
• V/Q scanning remains essential to exclude CTEPH 1
• CMR ventricular mass index ≥0.45 provides excellent diagnostic performance in this population 2

Critical Pitfalls to Avoid

• Never rely on CT pulmonary angiography alone to exclude CTEPH—V/Q scanning must be performed first as CT can miss the diagnosis 1
• Do not skip V/Q scanning even if CT appears normal, as V/Q has higher sensitivity for CTEPH 1
• Blood tests alone cannot diagnose PH but are essential for identifying underlying etiologies and associated conditions 1
• While CMR shows promise with high diagnostic accuracy in research settings, it requires expertise and may not be readily available in all centers 3, 4