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

Aims 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.Methods and results This was a single-centre, retrospective study with a median follow-up of 365 days. 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,>= 25 mmHg; and pulmonary arterial wedge pressure (PAWP),>15 mmHg]. No adverse events were observed after NO inhalation. Thirty-four patients with Group 2 PH showed increased PAWP (Delta PAWP: 3.26 +/- 2.22 mmHg), while the remaining 35patients did not (Delta PAWP:-2.11 +/- 2.29 mmHg). Multivariate analysis revealed that increased PAWP was the only significant predictor of all-cause death or hospitalization for heart failure (HF) after 1 year (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.Conclusions Patients with Group 2 PH were tolerant of the inhaled NO test. NO-induced PAWP is a novel prognostic indicator.