Heart failure with preserved ejection fraction (HFpEF) is currently the predominant form of heart failure and the leading cause of hospitalization in the elderly. However, limited understanding of the underlying mechanisms of HFpEF has led to a longstanding absence of evidence-based therapies. Growing epidemiological and experimental evidence indicate that excessive body fat and metabolic dysfunction might drive the pathogenesis of HFpEF. In fact, the majority of HFpEF patients are obese and/or diabetic, suggesting that metabolic therapies acting on the heart and peripheral organs are worth considering. In this regard, nicotinamide adenine dinucleotide (NAD+) represents a master regulator of cellular energy metabolism, which can be targeted using available and safe-to-administer precursors in animals and humans. To this end, in our manuscript, published in Science Translational Medicine (2021), we showed for the first time that:
Collectively, our results demonstrate that boosting NAD+ metabolism by nicotinamide or other precursors might become the first evidence-based therapy for HFpEF, which is arguably one of the toughest challenges in cardiovascular medicine.