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Cardiovascular Drugs and Therapy
Published in: Cardiovascular Drugs and Therapy 6/2023

Open Access 13-10-2022 | Heart Failure | Trial Designs

The HF-AF ENERGY Trial: Nicotinamide Riboside for the Treatment of Atrial Fibrillation in Heart Failure Patients

Authors: Lisa Pool, Paul Knops, Olivier C. Manintveld, Jasper J. Brugts, Dominic A. M. J. Theuns, Bianca J. J. M. Brundel, Natasja M. S. de Groot

Published in: Cardiovascular Drugs and Therapy | Issue 6/2023

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Abstract

Background

The presence of atrial fibrillation (AF) in heart failure (HF) patients with reduced ejection fraction is common and associated with an increased risk of stroke, hospitalization and mortality. Recent research findings indicate that a reduction in nicotinamide adenine dinucleotide (NAD+) levels results in mitochondrial dysfunction, DNA damage and consequently cardiomyocyte impairment in experimental and clinical HF and AF. The HF-AF ENERGY trial aims to investigate the cardioprotective effects of the NAD+ precursor nicotinamide riboside (NR) treatment in ischemic heart disease patients diagnosed with AF.

Study design

The HF-AF ENERGY trial is a prospective intervention study. The study consists of a (retrospective) 4 months observation period and a 4 months intervention period. The cardioprotective effect of NR on AF burden is investigated by remote monitoring software of implantable cardiac defibrillators (ICDs), which enables continuous atrial rhythm monitoring detection. Cardiac dimension and function are examined by echocardiography. Laboratory blood analysis is performed to determine mitochondrial function markers and energy metabolism. All the study parameters are assessed at two fixed time points (pre- and post-treatment). Pre- and post-treatment outcomes are compared to determine the effects of NR treatment on AF burden, mitochondrial function markers and energy metabolism.

Conclusion

The HF-AF ENERGY trial investigates the cardioprotective effects of NR on AF burden and whether NR normalizes blood-based mitochondrial function markers and energy metabolites of the NAD metabolome in ischemic heart disease patients diagnosed with AF. The study outcomes elucidate whether NAD+ metabolism can be used as a future therapy for HF patients with AF.
Literature
1.
Baher A, Marrouche NF. Treatment of atrial fibrillation in patients with co-existing heart failure and reduced ejection fraction: time to revisit the management guidelines? Arrhythmia & electrophysiology review. 2018;7(2):91.CrossRef
2.
Virani SS, Alonso A, Aparicio HJ, et al. Heart disease and stroke statistics—2021 update: a report from the American Heart Association. Circulation. 2021;143(8):e254–743.CrossRefPubMed
3.
James SL, Abate D, Abate KH, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet. 2018;392(10159):1789–858.CrossRef
4.
Zafrir B, Lund LH, Laroche C, et al. Prognostic implications of atrial fibrillation in heart failure with reduced, mid-range, and preserved ejection fraction: a report from 14 964 patients in the European Society of Cardiology Heart Failure Long-Term Registry. Eur Heart J. 2018;39(48):4277–84.CrossRefPubMed
5.
Anter E, Jessup M, Callans DJ. Atrial fibrillation and heart failure: treatment considerations for a dual epidemic. Circulation. 2009;119(18):2516–25.CrossRefPubMed
6.
7.
Belenky P, Bogan KL, Brenner C. NAD+ metabolism in health and disease. Trends Biochem Sci. 2007;32(1):12–9.CrossRefPubMed
8.
Pool L, Wijdeveld LFJM, de Groot N, Brundel BJJM. The role of mitochondrial dysfunction in atrial fibrillation: translation to druggable target and biomarker discovery. Int J Mol Sci. 2021;22(16):8463.CrossRefPubMedPubMedCentral
9.
Zhang D, Hu X, Li J, et al. DNA damage-induced PARP1 activation confers cardiomyocyte dysfunction through NAD(+) depletion in experimental atrial fibrillation. Nat Commun. 2019;10(1):1307.CrossRefPubMedPubMedCentral
10.
11.
Pillai JB, Isbatan A, Imai S, Gupta MP. Poly(ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2alpha deacetylase activity. J Biol Chem. 2005;280(52):43121–30.CrossRefPubMed
12.
Zhang D, Wu C-T, Qi X, et al. Activation of histone deacetylase-6 induces contractile dysfunction through derailment of α-tubulin proteostasis in experimental and human atrial fibrillation. Circulation. 2014;129(3):346–58.CrossRefPubMed
13.
Airhart SE, Shireman LM, Risler LJ, et al. An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers. PLoS ONE. 2017;12(12):e0186459.CrossRefPubMedPubMedCentral
14.
Brundel B, Ai X, Hills MT, Kuipers MF, Lip GYH, de Groot NMS. Atrial fibrillation. Nat Rev Dis Primers. 2022;8(1):21.CrossRefPubMed
15.
Wiersma M, van Marion D, Bouman EJ, et al. Cell-free circulating mitochondrial DNA: a potential blood-based marker for atrial fibrillation. Cells. 2020;9(5):1159.CrossRefPubMedPubMedCentral
16.
Li J, Zhang D, Ramos KS, et al. Blood-based 8-hydroxy-2′-deoxyguanosine level: a potential diagnostic biomarker for atrial fibrillation. Heart Rhythm. 2021;18(2):271–7.CrossRefPubMed
17.
Starreveld R, Ramos KS, Muskens AJQM, Brundel BJJM, de Groot N. Daily supplementation of l-glutamine in atrial fibrillation patients: the effect on heat shock proteins and metabolites. Cells. 2020;9(7):1729.CrossRefPubMedPubMedCentral
18.
Corell P, Gustafsson F, Schou M, Markenvard J, Nielsen T, Hildebrandt P. Prevalence and prognostic significance of atrial fibrillation in outpatients with heart failure due to left ventricular systolic dysfunction. Eur J Heart Fail. 2007;9(3):258–65.CrossRefPubMed
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20.
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Metadata
Title
The HF-AF ENERGY Trial: Nicotinamide Riboside for the Treatment of Atrial Fibrillation in Heart Failure Patients
Authors
Lisa Pool
Paul Knops
Olivier C. Manintveld
Jasper J. Brugts
Dominic A. M. J. Theuns
Bianca J. J. M. Brundel
Natasja M. S. de Groot
Publication date
13-10-2022
Publisher
Springer US
Published in
Cardiovascular Drugs and Therapy / Issue 6/2023
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-022-07382-4

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