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Metabolomics Profiling Predicts Ventricular Arrhythmia in Patients with an Implantable Cardioverter Defibrillator

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Abstract

Implantable cardioverter defibrillators (ICDs) reduce sudden cardiac death (SCD) when patients experience life-threatening ventricular arrhythmias (LTVA). However, current strategies determining ICD patient selection and risk stratification are inefficient. We used metabolomics to assess whether dysregulated metabolites are associated with LTVA and identify potential biomarkers. Baseline plasma samples were collected from 72 patients receiving ICDs. Over a median follow-up of 524.0 days (range 239.0–705.5), LTVA occurred in 23 (31.9%) patients (22 effective ICD treatments and 1 SCD). After confounding risk factors adjustment for age, smoking, secondary prevention, and creatine kinase MB, 23 metabolites were significantly associated with LTVA. Pathway analysis revealed LTVA associations with disrupted metabolism of glycine, serine, threonine, and branched chain amino acids. Pathway enrichment analysis identified a panel of 6 metabolites that potentially predicted LTVA, with an area under the receiver operating characteristic curve of 0.8. Future studies are necessary on biological mechanisms and potential clinical use.

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Abbreviations

AF:

Atrial fibrillation

AST:

Aspartate aminotransferase

BUN:

Blood urea nitrogen

CABG:

Coronary artery bypass grafting

ESI:

Electrospray ionization

FAHFA:

Fatty acid esters of hydroxy fatty acids

HR:

Hazard ratios

ICD:

Implantable cardioverter defibrillator

ICM:

Ischemic cardiomyopathy

LASSO:

Least absolute shrinkage and selection operator

LDL:

Low-density lipoprotein

LPG:

Lysophosphatidylglycerol

LTVA:

Life-threatening ventricular arrhythmia

LVEDD:

Left ventricular end diastolic diameter

LVEF:

Left ventricular ejection fraction

LysoPG:

Lysophosphatidylglycerol

MI:

Myocardial infarction

NICM:

Non-ischemic cardiomyopathy

NYHA:

New York Heart Association

PA:

Phosphatidic acid

PI:

Phosphatidylinositol

ROC:

Receiver operating characteristic

SCD:

Sudden cardiac death

SM:

Sphingomyelin

TC:

Total cholesterol

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Acknowledgements

We appreciate the work of our clinical colleagues who performed clinical data collection and all individuals who participated in this study.

Funding

This research was funded by Shengwen Yang of the Beijing Chaoyang Hospital Golden Seeds Foundation (CYJZ202103), Wei Hua of the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2017-I2M-1-009), and the National Natural Science Foundation of China (81570370).

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Authors and Affiliations

  1. Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

    Shengwen Yang

  2. Arrhythmia Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Junhan Zhao, Jing Wang, Min Gu, Chi Cai, Hongxia Niu & Wei Hua

  3. Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, China National Clinical Research Center for Interventional Medicine, Shanghai, China

    Xi Liu

  4. Department of Cardiac surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Liang Chen

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  1. Shengwen Yang
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  2. Junhan Zhao
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  3. Xi Liu
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  9. Wei Hua
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Contributions

Conceptualization, Shengwen Yang and Junhan Zhao; methodology, Hongxia Niu; software, Xi Liu; validation, Chi Cai and Jing Wang; formal analysis, Shengwen Yang; investigation, Shengwen Yang; resources, Xi Liu and Min Gu; data curation, Junhan Zhao; writing, original draft preparation, Junhan Zhao; writing, review and editing, Liang Chen; visualization, Junhan Zhao; supervision, Wei Hua and Liang Chen; project administration, Junhan Zhao; funding acquisition, Shengwen Yang and Wei Hua. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Wei Hua.

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Ethics Approval and Consent to Participate

The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Fuwai. Informed consent was obtained from all participants in the study.

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The authors declare no competing interests.

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Associate Editor Yihua Bei oversaw the review of this article

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Yang, S., Zhao, J., Liu, X. et al. Metabolomics Profiling Predicts Ventricular Arrhythmia in Patients with an Implantable Cardioverter Defibrillator. J. of Cardiovasc. Trans. Res. 17, 91–101 (2024). https://doi.org/10.1007/s12265-023-10413-6

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