Abstract
AIMS: Heart failure represents a substantial burden to both patients and healthcare systems worldwide. Nitric oxide (NO) dysregulation may play a key role in patients transitioning from chronic to acute heart failure with a reduced ejection fraction (HFrEF). Plasma nitrite (NO(2) (-)) is highly reflective of local nitric oxide production and has not been studied in acute HFrEF. This study aims to quantify measures of NO biology in patients with acute and chronic HFrEF. METHODS AND RESULTS: We utilized gas-phase chemiluminescence to determine plasma NO(2) (-) concentrations. Plasma asymmetric dimethylarginine (ADMA) and arterial stiffness were also measured. Plasma concentrations of NO(2) (-) and ADMA, in addition to arterial stiffness, were compared in participants with chronic HFrEF (n = 25) and acute HFrEF (n = 24). We observed lower concentrations of plasma NO(2) (-) in patients with acute HFrEF (P = 0.047). We also observed higher plasma concentrations of ADMA in participants with acute HFrEF (P < 0.001). Plasma NO(2) (-) and ADMA also displayed a significant negative correlation in the total cohort (R(s) = -0.38, P = 0.017). There was no significant difference between groups regarding arterial stiffness measures. CONCLUSIONS: We present novel data with regard to plasma NO(2) (-) in both acute and chronic HFrEF. Our results indicate that patients with acute HFrEF have a relative deficiency of plasma NO(2) (-) whilst also displaying a relative increase in ADMA, a modulator of eNOS. Reduced NO bioavailability may therefore relate to impaired NO production in patients with acute decompensation, with implications for both treatment and prevention of episodes.