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A 2025 review in the American Journal of Cardiovascular Drugs identified NAD+ as a fundamental coenzyme whose deficiency impairs sirtuin activity, disrupts mitochondrial biogenesis via PGC-1, compromises ATP synthesis efficiency, attenuates antioxidant defences (via SIRT3-FOXO3/SOD2), disturbs Ca homeostasis, and dysregulates mitophagy collectively driving bioenergetic collapse alongside oxidative stress and adverse cardiac remodelling