What is the purpose of a vasoreactivity test in patients with Pulmonary Arterial Hypertension (PAH)?

Purpose of Vasoreactivity Testing in Pulmonary Arterial Hypertension (PAH)

The primary purpose of vasoreactivity testing in PAH is to identify patients who will respond favorably to long-term treatment with high-dose calcium channel blockers (CCBs), which can significantly improve survival in these select patients. 1

Key Aspects of Vasoreactivity Testing

• Vasoreactivity testing is a key component of the initial workup for PAH patients to identify potential responders to CCB therapy 1
• Testing should be performed during diagnostic right heart catheterization (RHC) before initiating any PAH-specific therapy 1
• A positive vasoreactive response is defined as a decrease in mean pulmonary artery pressure (mPAP) by ≥10 mmHg to reach an absolute value of <40 mmHg without a decrease in cardiac output 1
• Only about 10-15% of idiopathic PAH (IPAH) patients demonstrate a positive response, and even fewer exhibit long-term responsiveness to CCBs 1, 2

Recommended Testing Agents

• Inhaled nitric oxide (iNO) is the preferred agent for acute vasoreactivity testing 1
• Alternative agents include intravenous epoprostenol or intravenous adenosine 1
• Inhaled iloprost has also been shown to identify potential CCB responders 1, 3
• The use of oral or intravenous CCBs for acute testing is not recommended due to risk of potentially life-threatening complications 1

Clinical Implications of Test Results

• Patients with a positive vasoreactivity test should be initiated on high-dose CCB therapy (amlodipine, nifedipine, or diltiazem) 1
• A positive vasoreactivity test predicts better long-term survival in PAH, independent of whether CCBs are started 1, 4
• Patients who respond to CCB therapy typically show dramatic clinical improvements within the first few months of treatment 1, 4
• Follow-up assessment at 3-4 months is essential to confirm clinical improvement with CCB therapy 1

Patient Selection for Testing

• Vasoreactivity testing is strongly indicated in patients with idiopathic PAH, heritable PAH, and PAH associated with anorexigen use 1
• Testing may be considered in other types of PAH (e.g., connective tissue disease-associated PAH), though true responders are less common 1, 5
• Contraindications to testing include low systemic blood pressure, low cardiac output, or WHO functional class IV symptoms 1
• Vasoreactivity testing is not recommended in non-PAH pulmonary hypertension groups (groups 2,3,4, and 5) 1

Additional Benefits of Vasoreactivity Testing

• Beyond identifying CCB responders, baseline and follow-up vasoreactivity testing can provide valuable insights into treatment response and potential anti-remodeling effects 1
• Follow-up vasoreactivity testing may help identify high-risk patients who might need more careful monitoring or consideration for lung transplantation 6, 4
• Recent research suggests that pulmonary artery compliance during vasoreactivity testing may help better identify patients likely to have good long-term response to CCBs 4

Common Pitfalls and Caveats

• Misinterpretation of vasoreactivity test results may lead to inappropriate use of CCBs in non-responders, exposing patients to risks without potential benefit 1
• CCBs should not be used empirically to treat PAH without demonstrated acute vasoreactivity 1
• Even among acute responders, only about half will experience long-term benefits with CCBs 1, 4
• Recent data shows heterogeneity within the group of vasoresponders, with a large subset failing to show sustained clinical response to CCBs, highlighting the necessity for comprehensive reassessment during early follow-up 4
• Vasoreactivity testing should only be performed at specialized referral centers with experience in the performance and interpretation of these tests 1