Mitochondrial dysfunction has been implicated in heart failure (HF), and is associated with
an imbalance in intracellular ratio of reduced nicotinamide-adenine dinucleotide (NADH) to
oxidized nicotinamide-adenine dinucleotide (NAD), or the NADH/NAD ratio. In mouse models of
HF, we have found that normalization of the NADH/NAD, through supplementation with NAD+
precursors, is associated with improvement in cardiac function. This Study will randomize
participants with systolic HF (ejection fraction ≤40%) to treatment with the NAD precursor,
nicotinamide riboside (NR) or matching placebo, uptitrated to a final oral dose of 1000mg
twice daily, to determine the safety and tolerability of NR in participants with systolic HF.