...To explore possible alterations of NAD+ homeostasis in the failing heart, we quantified expression of NAD+ biosynthetic enzymes in human failing heart and in the heart of a mouse model of dilated cardiomyopathy (DCM) triggered by SRF transcription factor depletion in the heart (SRFHKO) or of cardiac hypertrophy triggered by transverse aorta constriction (TAC)...We show that NR supplementation in food attenuates the development of heart failure in mice, more robustly in dilated cardiomyopathy, and partially after transverse aorta constriction, by stabilizing myocardial NAD+ levels in the failing heart. NR treatment also robustly increases the myocardial levels of three metabolites, nicotinic acid adenine dinucleotide (NAAD), methyl-NAM and N1-Methyl-4-pyridone-5-carboxamide, which can be used as validation biomarkers for the treatment. The data show that nicotinamide riboside, the most energy-efficient among NAD precursors, could be useful for treatment of HF notably in the context of DCM, a disease with few therapeutic options.