Biomarker Periodic Repolarization Dynamics Indicates Enhanced Risk for Arrhythmias and Sudden Cardiac Death in Myocardial Infarction in Pigs

Periodic repolarization dynamics (PRD) is an electrocardiographic biomarker that captures repolarization instability in the low frequency spectrum and is believed to estimate the sympathetic effect on the ventricular myocardium. High PRD indicates an increased risk for postischemic sudden cardiac de...

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Bibliographic Details
Published in:	Journal of the American Heart Association Vol. 13; no. 9; p. e032405
Main Authors:	Bauer, Julia, Vlcek, Julia, Pauly, Valerie, Hesse, Nora, Xia, Ruibing, Mo, Li, Chivukula, Aparna Sharma, Villgrater, Hannes, Dressler, Marie, Hildebrand, Bianca, Wolf, Eckhard, Rizas, Konstantinos D, Bauer, Axel, Kääb, Stefan, Tomsits, Philipp, Schüttler, Dominik, Clauss, Sebastian
Format:	Journal Article
Language:	English
Published:	England John Wiley and Sons Inc 07-05-2024 Wiley
Subjects:	Action Potentials Animals Arrhythmias, Cardiac - etiology Arrhythmias, Cardiac - physiopathology Autonomic Nervous System - physiopathology autonomic remodeling Biomarkers - blood Death, Sudden, Cardiac - etiology Disease Models, Animal Electrocardiography Heart Rate - physiology ischemic heart failure Male Myocardial Infarction - complications Myocardial Infarction - physiopathology Original Research periodic repolarization dynamics pig model Risk Factors sudden cardiac death Swine Sympathetic Nervous System - physiopathology Ventricular Fibrillation - etiology Ventricular Fibrillation - physiopathology Ventricular Remodeling periodic repolarization dynamics autonomic remodeling pig model sudden cardiac death ischemic heart failure
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Summary:	Periodic repolarization dynamics (PRD) is an electrocardiographic biomarker that captures repolarization instability in the low frequency spectrum and is believed to estimate the sympathetic effect on the ventricular myocardium. High PRD indicates an increased risk for postischemic sudden cardiac death (SCD). However, a direct link between PRD and proarrhythmogenic autonomic remodeling has not yet been shown. We investigated autonomic remodeling in pigs with myocardial infarction (MI)-related ischemic heart failure induced by balloon occlusion of the left anterior descending artery (n=17) compared with pigs without MI (n=11). Thirty days after MI, pigs demonstrated enhanced sympathetic innervation in the infarct area, border zone, and remote left ventricle paralleled by altered expression of autonomic marker genes/proteins. PRD was enhanced 30 days after MI compared with baseline (pre-MI versus post-MI: 1.75±0.30 deg versus 3.29±0.79 deg , <0.05) reflecting pronounced autonomic alterations on the level of the ventricular myocardium. Pigs with MI-related ventricular fibrillation and SCD had significantly higher pre-MI PRD than pigs without tachyarrhythmias, suggesting a potential role for PRD as a predictive biomarker for ischemia-related arrhythmias (no ventricular fibrillation versus ventricular fibrillation: 1.50±0.39 deg versus 3.18±0.53 deg [ <0.05]; no SCD versus SCD: 1.67±0.32 deg versus 3.91±0.63 deg [ <0.01]). We demonstrate that ischemic heart failure leads to significant proarrhythmogenic autonomic remodeling. The concomitant elevation of PRD levels in pigs with ischemic heart failure and pigs with MI-related ventricular fibrillation/SCD suggests PRD as a biomarker for autonomic remodeling and as a potential predictive biomarker for ventricular arrhythmias/survival in the context of MI.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 This article was sent to Barry London, MD, PhD, Senior Guest Editor, for review by expert referees, editorial decision, and final disposition. For Sources of Funding and Disclosures, see page 14. P. Tomsits, D. Schüttler, and S. Clauss contributed equally. Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/JAHA.123.032405
ISSN:	2047-9980 2047-9980
DOI:	10.1161/JAHA.123.032405