The Efficacy of Risk Factor Modification Compared to NAD⁺ Repletion in Diastolic Heart Failure

Area of Science:

• Cardiology
• Biochemistry
• Metabolic Diseases

Background:

• Heart failure (HF) with left ventricular diastolic dysfunction is a significant global health issue.
• Myocardial nicotinamide adenine dinucleotide (NAD+) depletion is implicated in diastolic HF pathophysiology.
• Understanding NAD+ metabolism is crucial for developing novel therapeutic interventions.

Purpose of the Study:

• To evaluate myocardial NAD+ levels in human systolic and diastolic HF.
• To investigate the therapeutic potential of NAD+ repletion using nicotinamide riboside (NR).
• To assess the efficacy of NR in a murine model of HF with preserved ejection fraction.

Main Methods:

• Quantification of myocardial NAD+ and nicotinamide phosphoribosyltransferase (NAMPT) levels in human HF patients.
• Administration of NR to human myocardial tissue samples and a murine HF model.
• Assessment of metabolic and antioxidant profiles in the murine model.

Main Results:

• Significant depletion of NAD+ and NAMPT observed in human diastolic HF myocardium.
• NR treatment successfully restored myocardial NAD+ levels in human samples.
• In murine HF with preserved ejection fraction, NR improved metabolic and antioxidant parameters, both preventively and therapeutically.

Conclusions:

• Myocardial NAD+ depletion is a key feature of diastolic HF.
• NAD+ repletion via NR demonstrates therapeutic potential for diastolic HF.
• NR warrants further investigation as a treatment for heart failure with preserved ejection fraction.