The Efficacy of Risk Factor Modification Compared to NAD+ Repletion in Diastolic Heart Failure
Yen Chin Koay, Ren Ping Liu, Bailey McIntosh, Niv Vigder, Serlin Lauren, Angela Yu Bai, Saki Tomita, Desmond Li, Dylan Harney, Benjamin Hunter, Yunwei Zhang, Jean Yang, Paul G. Bannon, Ashleigh M. Philp, Andrew Philp, David M. Kaye, Mark Larance, Sean Lal, John O’Sullivan
Abstract
Heart failure (HF) with left ventricular diastolic dysfunction is a growing global concern. This study evaluated myocardial oxidized nicotinamide adenine dinucleotide (NAD+) levels in human systolic and diastolic HF and in a murine model of HF with preserved ejection fraction, exploring NAD+ repletion as therapy. We quantified myocardial NAD+ and nicotinamide phosphoribosyltransferase levels, assessing restoration with nicotinamide riboside (NR). Findings show significant NAD+ and nicotinamide phosphoribosyltransferase depletion in human diastolic HF myocardium, but NR successfully restored NAD+ levels. In murine HF with preserved ejection fraction, NR as preventive and therapeutic intervention improved metabolic and antioxidant profiles. This study underscores NAD+ repletion’s potential in diastolic HF management.