Definition of a Nitric Oxide Responder
A nitric oxide responder is defined as a patient with pulmonary arterial hypertension who demonstrates a reduction of mean pulmonary arterial pressure (mPAP) ≥10 mmHg to reach an absolute value of mean PAP ≤40 mmHg with an increased or unchanged cardiac output during acute vasoreactivity testing with inhaled nitric oxide.
Vasoreactivity Testing Protocol
Vasoreactivity testing is performed during right heart catheterization using the following parameters:
- Standard agent: Inhaled nitric oxide at 10-20 parts per million (ppm)
- Alternative agents: IV epoprostenol, IV adenosine, or inhaled iloprost can be used if nitric oxide is unavailable
- Contraindicated agents: Calcium channel blockers, oxygen, phosphodiesterase type 5 inhibitors, or other vasodilators should not be used for acute vasoreactivity testing
Clinical Significance
Identifying nitric oxide responders has important clinical implications:
- Treatment selection: Only about 10% of patients with idiopathic PAH (IPAH) will meet the responder criteria 1
- Therapeutic implications: Responders are candidates for high-dose calcium channel blocker therapy
- Prognostic value: True responders have excellent long-term survival, with one study showing 95% survival at 5 years 1
Indications for Testing
Vasoreactivity testing is recommended only for specific patient populations:
- Idiopathic PAH (IPAH)
- Heritable PAH (HPAH)
- Drug-induced PAH
Testing is not recommended in other forms of PAH or pulmonary hypertension as:
- Results can be misleading
- Responders are rare in these populations
- The clinical utility of testing is limited in these groups
Hemodynamic Parameters and Monitoring
During vasoreactivity testing, several hemodynamic parameters should be monitored:
- Mean pulmonary arterial pressure (mPAP)
- Cardiac output (CO)
- Pulmonary vascular resistance (PVR)
Pitfalls and Caveats
- False positives: Testing in non-indicated populations may lead to inappropriate treatment decisions
- Misinterpretation: Using less stringent criteria may overestimate the number of true responders
- Treatment failure: Not all acute responders will have sustained responses to calcium channel blockers
- Testing conditions: Measurements should be taken at the end of normal expiration for accuracy
- Technical considerations: High-fidelity tracings should be used rather than small moving traces on cardiac monitors
Vasoreactivity testing with nitric oxide represents an important component in the evaluation of patients with pulmonary arterial hypertension, allowing for identification of a small subset of patients who may benefit from specific therapeutic approaches and have a better prognosis.