What is the term for pulmonary hypertension that is responsive to calcium channel blockers, such as nifedipine (generic name) or diltiazem (generic name), and diagnosed through right heart catheterization (RHC)?

Vasoreactive Pulmonary Arterial Hypertension

Pulmonary arterial hypertension that responds to calcium channel blockers during vasoreactivity testing is termed "vasoreactive pulmonary arterial hypertension" or "calcium channel blocker-responsive pulmonary arterial hypertension." 1, 2

Vasoreactivity Testing and Definition

Vasoreactivity testing is a critical procedure performed during right heart catheterization to identify patients with pulmonary arterial hypertension (PAH) who may benefit from calcium channel blocker (CCB) therapy. The process involves:

• Testing is indicated only in patients with idiopathic PAH (IPAH), heritable PAH (HPAH), and PAH associated with drug use 1
• Testing must be performed in specialized centers 1, 2
• A positive response is defined as:
  • Reduction in mean pulmonary arterial pressure (mPAP) ≥10 mmHg
  • Reaching an absolute value of mPAP ≤40 mmHg
  • With increased or unchanged cardiac output 1, 2

Vasodilators Used for Testing

The preferred agents for vasoreactivity testing are:

1. Nitric oxide (recommended as first-line) 1, 2
2. Intravenous epoprostenol (recommended alternative) 1
3. Adenosine (should be considered as alternative) 1
4. Inhaled iloprost (may be considered) 1

Important: CCBs themselves should never be used for acute vasoreactivity testing 1, 2

Clinical Significance

Only 10-15% of patients with idiopathic PAH demonstrate a positive vasoreactive response during testing 1, 2. These "vasoreactive" or "CCB-responsive" patients have:

• Better long-term survival compared to non-responders 1
• Potential for substantial clinical improvement with CCB therapy alone 1
• Been recently re-introduced as a distinct subgroup of idiopathic PAH in the clinical classification of pulmonary hypertension 3

CCB Treatment in Vasoreactive Patients

For patients with a positive vasoreactivity test:

• Preferred CCBs: nifedipine, diltiazem, and amlodipine 1
• Selection based on heart rate:
  • Relative bradycardia: nifedipine or amlodipine
  • Relative tachycardia: diltiazem 1
• Dosing:
  • Start with lower doses and increase gradually
  • Target doses: nifedipine 120-240 mg/day, diltiazem 240-720 mg/day, amlodipine up to 20 mg/day 1, 2
• Follow-up:
  • Reassessment after 3-4 months including repeat right heart catheterization
  • Adequate response defined as WHO functional class I or II with marked hemodynamic improvement 1, 2

Cautions and Contraindications

CCB therapy has important limitations:

• Contraindicated in non-PAH pulmonary hypertension (groups 2,3,4, and 5) 1, 2
• Contraindicated in patients with right heart failure due to negative inotropic effects 2
• May cause systemic hypotension and peripheral edema 1, 2
• Rare but serious complication: pulmonary edema 4

Clinical Pearls

• Some patients may have a specific CCB-sensitive PAH phenotype that is refractory to other pulmonary vasodilators 5
• Long-term CCB responders have been recognized as a distinct clinical entity with better prognosis 3
• Even among initial responders, only about half will show sustained long-term response to CCB therapy 1
• If inadequate response or clinical deterioration occurs, additional PAH-specific therapy should be initiated 1, 2

Understanding vasoreactive pulmonary arterial hypertension is crucial for appropriate patient selection for CCB therapy, which can significantly improve outcomes in this specific subset of PAH patients.