Inhaled nitric oxide testing in predicting prognosis in pulmonary hypertension due to left-sided heart diseases.

Abstract

The pathophysiology of pulmonary hypertension (PH) due to left-sided heart disease (Group 2 PH) is distinct from that of other groups of PH, yet there are still no approved therapies that selectively target pulmonary circulation. The increase in pulmonary capillary pressure due to left-sided heart disease is a trigger event for physical and biological alterations of the pulmonary circulation, including the nitric oxide (NO)-soluble guanylate cyclase-cyclic guanosine monophosphate axis. This study investigated inhaled NO vasoreactivity tests for patients with Group 2 PH and hypothesized that these changes may have a prognostic impact. This was a single-centre, retrospective study with a median follow-up of 365days. From January 2011 to December 2015, we studied 69 patients with Group 2 PH [age, 61.5±13.0 (standard deviation) years; male:female, 49:20; left ventricular ejection fraction, 50.1±20.4%; mean pulmonary arterial pressure, ≥25mmHg; and pulmonary arterial wedge pressure (PAWP), >15mmHg]. No adverse events were observed after NO inhalation. Thirty-four patients with Group 2 PH showed increased PAWP (ΔPAWP: 3.26±2.22mmHg), while the remaining 35 patients did not (ΔPAWP: -2.11±2.29mmHg). Multivariate analysis revealed that increased PAWP was the only significant predictor of all-cause death or hospitalization for heart failure (HF) after 1year (hazard ratio 4.35; 95% confidence interval, 1.27-14.83; P=0.019). The acute response of PAWP to NO differed between HF with preserved and reduced ejection fractions. Patients with Group 2 PH were tolerant of the inhaled NO test. NO-induced PAWP is a novel prognostic indicator.