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 Bannon; Ashleigh Philp; Andrew Philp; David M Kaye; Mark Larance; Sean Lal; John F O'Sullivan

doi:10.1016/j.jacbts.2024.01.011

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

JACC Basic Transl Sci. 2024 Mar 20;9(6):733-750. doi: 10.1016/j.jacbts.2024.01.011. eCollection 2024 Jun.

Authors

Yen Chin Koay^{1

2

3}, Ren Ping Liu^{1

2

3}, Bailey McIntosh^{1

2

3}, Niv Vigder^{2

3

4}, Serlin Lauren^{1

2

3}, Angela Yu Bai^{1

3

4}, Saki Tomita^{1

3}, Desmond Li⁵, Dylan Harney^{3

4}, Benjamin Hunter^{2

3

6}, Yunwei Zhang^{3

7}, Jean Yang^{3

7}, Paul Bannon^{1

2

3

8

9}, Ashleigh Philp^{10

11}, Andrew Philp^{3

12

13}, David M Kaye^{14

15

16}, Mark Larance^{2

3}, Sean Lal^{1

2

3

6

17}, John F O'Sullivan^{1

2

3

17

18}

Affiliations

¹ Cardiometabolic Medicine Group, The University of Sydney, Sydney, New South Wales, Australia.
² School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
³ Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
⁴ School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, New South Wales, Australia.
⁵ BCAL Diagnostics, National Innovation Centre, Eveleigh, New South Wales, Australia.
⁶ Precision Cardiovascular Laboratory, The University of Sydney, New South Wales, Australia.
⁷ School of Mathematics and Statistics, Faculty of Science, The University of Sydney, Sydney, New South Wales, Australia.
⁸ Central Clinical School, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
⁹ Department of Cardiothoracic Surgery, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
¹⁰ School of Clinical Medicine, UNSW Medicine and Health, St Vincent's Healthcare clinical campus, UNSW, Sydney, New South Wales, Australia.
¹¹ Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW, Australia.
¹² Centre for Healthy Aging, Centenary Institute, Sydney, New South Wales, Australia.
¹³ School of Sport, Exercise and Rehabilitation Sciences, University of Technology Sydney, Ultimo, New South Wales, Australia.
¹⁴ Department of Cardiology, Alfred Hospital, Melbourne, Australia.
¹⁵ Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, Australia.
¹⁶ Faculty of Medicine, Monash University, Melbourne, Australia.
¹⁷ Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
¹⁸ Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.

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.

Keywords: NAD+ repletion; diastolic heart failure; heart failure.