Dietary Inorganic Nitrate Supplementation And Ventilatory Threshold In Patients With Reduced Ejection Fraction Heart Failure

Abstract

Patients with chronic heart failure (HF) are characterized by exercise intolerance. Maximal oxygen consumption (VO2peak) is predictive of health outcomes, but is often influenced by early onset fatigue or external factors. Oxygen consumption at the ventilatory threshold (VO2AT) is a submaximal marker of sustainable oxygen uptake and has been shown to predict 6 month mortality in HF. An intervention that increases VO2AT in HF would likely produce beneficial clinical and quality of life outcomes. Nitric oxide (NO) bioavailability is a mediator of skeletal muscle perfusion, mitochondrial function and contractile efficiency during exercise. Heart Failure with reduced ejection fraction (HFrEF) is characterized by a reduction in endothelial function and bioavailable NO. Dietary inorganic nitrate supplementation has been shown to increase NO bioavailability and exercise tolerance in patients with other cardiovascular diseases and HFpEF. PURPOSE: To determine the effect of dietary inorganic nitrate supplementation on VO2AT in patients with HFrEF. METHODS: Sixteen patients with HFrEF (15 men, 63 ± 4 y, BMI: 31.8 ± 2.1 kg·m-2) participated in a randomized, double-blind, crossover design study. Participants consumed either beetroot juice (BRJ - 16mmol nitrate/day), or a nitrate-depleted placebo (PL) for five days prior to completing a cardiopulmonary exercise test (CPX). RESULTS: Following BRJ supplementation plasma nitrite increased significantly compared to placebo (511.5 ± 461.0nM vs. 195.0 ± 176.8nM; p<0.05). No differences were observed for the onset of VT (BRJ: 611.0 ± 119.7s; PL: 611.0 ± 142.3s; p=0.9) or VO2AT (BRJ: 1159.7 ± 207.8ml·min-1; PL: 1132.4 ± 221.0ml·min-1; p=0.53). CONCLUSIONS: Dietary nitrate supplementation, despite significant increase in circulating nitrite, produced no changes time to anaerobic threshold or sustainable sub-maximal oxygen uptake. Supported by Australian Heart Foundation Vanguard Award 101389 to Jason D. Allen