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REVIEW article

Front. Cardiovasc. Med.

Sec. Cardiovascular Metabolism

Volume 12 - 2025 | doi: 10.3389/fcvm.2025.1616677

This article is part of the Research TopicInflammatory Pathways in Cardiometabolic Diseases: Mechanisms, Biomarkers, and Therapeutic InsightsView all 10 articles

Metabolic Perturbations in Cardiomyopathies: Implications for Early Diagnosis and Targeted Interventions

Provisionally accepted
Rula  Al-ShahrabiRula Al-Shahrabi1,2*Ghadeera  AlmansooriGhadeera Almansoori3,4muna  Al-Saffarmuna Al-Saffar3,5Nadia  AkawiNadia Akawi3,6*
  • 1University of Sharjah, Sharjah, United Arab Emirates
  • 2Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
  • 3United Arab Emirates University, Al-Ain, Abu Dhabi, United Arab Emirates
  • 4Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates
  • 5Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States
  • 6Division of Cardiovascular Medicine, Radcliffe Department of Medicine, Medical Sciences Division, University of Oxford, Oxford, England, United Kingdom

The final, formatted version of the article will be published soon.

Cardiomyopathy (CM) is a heterogeneous group of diseases characterized by structural and functional changes in the heart, with the exact cause often remaining unknown. CM can arise from both inherited and acquired metabolic disturbances. Alterations in energy production and substrate utilization impair the heart's contractile function and limit its ability to respond to stress. Given the complexity and dynamic nature of CM, as well as the multiple etiologies involved, we reviewed metabolomic studies employing high-throughput platforms to understand how metabolic pathways shift across CM subtypes and how these perturbations may inform clinical translation. Several recurring disruptions emerge across CM with alterations in amino acid metabolism (valine, leucine, methionine, tryptophan, tyrosine); mitochondrial redox imbalance (NAD/NADH shifts, niacinamide, acylcarnitines); and oxidative stress as central hallmarks. Each subtype, however, displays a different emphasis. For instance, hypertrophic CM is characterized by nucleotide remodeling, particularly in cases involving MYBPC3 mutations; dilated CM shows accumulation of Krebs cycle intermediates and trimethylamine-N-oxide; restrictive CM is associated with amino acid stress related to amyloidosis; tachycardia-induced CM involves fatty acid remodeling and elevated uric acid, while Takotsubo CM is linked to ketone utilization and glutamate excitotoxicity. Overall, a single metabolomic profile cannot capture CM. What emerges from this review is that subtype-specific shifts, and the way they interact, provide meaningful insight into disease mechanisms and highlight pathways with diagnostic, prognostic, and therapeutic relevance. This broader perspective shifts the focus beyond narrow comparisons, making the translational relevance of metabolomics in CM more apparent.

Keywords: Metabolomics, cardiomyopathy, LC-MS, cardiovascular disease, Heart Failure

Received: 23 Apr 2025; Accepted: 30 Sep 2025.

Copyright: © 2025 Al-Shahrabi, Almansoori, Al-Saffar and Akawi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Rula Al-Shahrabi, ralshahrabi@sharjah.ac.ae
Nadia Akawi, nadia.akawi@uaeu.ac.ae

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