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Review
. 2024 Jul 31;9(9):1144-1158.
doi: 10.1016/j.jacbts.2024.04.008. eCollection 2024 Sep.

Towards Metabolomic-Based Precision Approaches for Classifying and Treating Heart Failure

Virginia S Hahn  1 , Senthil Selvaraj  2   3 , Kavita Sharma  1 , Svati H Shah  2   3
Affiliations
Review

Towards Metabolomic-Based Precision Approaches for Classifying and Treating Heart Failure

Virginia S Hahn et al. JACC Basic Transl Sci. .

Abstract

Both heart failure and cardiometabolic disease are on the rise, and abnormal cardiac and peripheral metabolism are central to the syndrome of heart failure. Advances in metabolomic profiling have improved our understanding of the heart's metabolic flexibility in patients with and without heart failure. Prior studies have noted patients with heart failure display metabolomic profiles associated with marked abnormalities in the metabolism of fatty acids, branched-chain amino acids, ketones, and glucose compared with control subjects. Metabolomics can highlight specific pathways that are dysregulated; however, other metabolites beyond those related to fuel metabolism may also play a role in precision-medicine approaches. Novel approaches include metabolic flux studies, spatial and single-cell analysis, serial monitoring of treatment response, and integration with other -omics data. The goal of these innovative approaches should be to harness metabolomic technologies to affect precision care for patients with heart failure.

Keywords: heart failure; metabolism; metabolomics; obesity; precision medicine.

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Conflict of interest statement

Dr Hahn has received support from the National Heart, Lung, and Blood Institute 1K23HL166770-01 and Sarnoff Scholar Award 138828. Dr Selvaraj has received support from the National Heart, Lung, and Blood Institute (K23HL161348), Doris Duke Charitable Foundation (#2020061), American Heart Association (#935275), Mandel Foundation, Duke Heart Center Leadership Council, and the Institute for Translational Medicine and Therapeutics; and has served on the advisory board for AstraZeneca. Dr Sharma has served as an advisory board member and consultant to Alleviant, AstraZeneca, Bayer, Edwards Lifesciences, Novartis, Novo Nordisk, and RIVUS. Dr Sharma has received support from the American Heart Association (16SFRN27870000), National Heart, Lung, and Blood Institute (R01:HL61912), and Amgen, Inc. Dr Shah is a co-inventor on 2 patents held by Duke University on related research findings; and has received research funding through sponsored research agreements to Duke University from AstraZeneca, Inc.

Figures

None
Graphical abstract
Central Illustration
Central Illustration
Overview of Study Considerations for Metabolomics Studies in Heart Failure Examples of common metabolomics platforms (including for both targeted and nontargeted assays), locations of sampling, metabolite pathways interrogated, and statistical analysis considerations are provided. ATP = adenosine triphosphate; BCAA = branched-chain amino acid; FADH2 = falvin adenine dinucleotide; NADH = nicotinamide adenine dinucleotide.
Figure 1
Figure 1
Future Proposed Personalized Approach to Metabolomic Phenotyping In Heart Failure Advances in metabolomics technology will improve biological interpretation of metabolomics studies, test the metabolic effect of pharmacologic therapies, identify metabolomic subgroups of heart failure (HF), and contribute understanding of rare etiologies of heart failure. Created with BioRender.com.
See this image and copyright information in PMC

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