Decreased endogenous nitric oxide production in acute decompensated heart failure with a reduced ejection fraction

Abstract

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 (NO2−) 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 NO2− concentrations. Plasma asymmetric dimethylarginine (ADMA) and arterial stiffness were also measured. Plasma concentrations of NO2− 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 NO2− 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 NO2− and ADMA also displayed a significant negative correlation in the total cohort (Rs = −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 NO2− in both acute and chronic HFrEF. Our results indicate that patients with acute HFrEF have a relative deficiency of plasma NO2− 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.

Keywords

• Nitric oxide
• Plasma nitrite
• Heart failure with a reduced ejection fraction
• Asymmetric dimethylarginine