Comparison of acute hemodynamic effects of inhaled nitric oxide and inhaled epoprostenol in patients with pulmonary hypertension

Inhaled nitric oxide (iNO) is used for acute vasoreactivity testing in pulmonary arterial hypertension (PAH) patients. Inhaled epoprostenol (iPGI(2)) has pulmonary selectivity and is less costly. We sought to compare acute hemodynamic effects of iNO (20 ppm) and iPGI(2) (50 ng/kg/min) and determine whether their combination has additive effects. We conducted a prospective, single center, randomized, cross-over study in 12 patients with PAH and seven with heart failure with preserved ejection fraction (HFpEF). In PAH patients, iNO lowered mean pulmonary artery pressure (mPAP) by 9 +/- 12% and pulmonary vascular resistance (PVR) by 14 +/- 32% (mean +/- SD). iPGI(2) decreased mPAP by 10 +/- 12% and PVR by 12 +/- 36%. Responses to iNO and iPGI(2) in mPAP and PVR were directly correlated (r(2) = 0.68, 0.70, respectively, P < 0.001). In HFpEF patients, mPAP dropped by 4 +/- 7% with each agent, and PVR dropped by 33 +/- 23% with iNO, and by 25 +/- 29% with iPGI(2) (P = NS). Pulmonary artery wedge pressure (PAWP) increased significantly with iPGI(2) versus baseline (20 +/- 3 vs. 17 +/- 2 mmHg, P = 0.02) and trended toward an increase with iNO and the combination (20 +/- 2, 19 +/- 4 mmHg, respectively). There were no additive effects in either group. In PAH patients, the vasodilator effects of iNO and iPGI(2) correlated at the doses used, making iPGI(2) a possible alternative for testing acute vasoreactivity, but their combination lacks additive effect. Exposure of HFpEF patients to inhaled vasodilators worsens the PAWP without hemodynamic benefit.