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

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 (2024): Biomarker Periodic Repolarization Dynamics Indicates Enhanced Risk for Arrhythmias and Sudden Cardiac Death in Myocardial Infarction in Pigs. Journal of the American Heart Association, 13 (9). ISSN 2047-9980

Abstract

Biomarker Periodic Repolarization Dynamics Indicates Enhanced Risk for Arrhythmias and Sudden Cardiac Death in Myocardial Infarction in Pigs Julia Bauer Department of Medicine I University Hospital, LMU Munich Munich Germany German Center for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance Munich Germany Institute of Surgical Research at the Walter‐Brendel‐Centre of Experimental Medicine University Hospital, LMU Munich Munich Germany Julia Vlcek Department of Medicine I University Hospital, LMU Munich Munich Germany Institute of Surgical Research at the Walter‐Brendel‐Centre of Experimental Medicine University Hospital, LMU Munich Munich Germany https://orcid.org/0009-0005-4448-4056 Valerie Pauly Department of Medicine I University Hospital, LMU Munich Munich Germany German Center for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance Munich Germany Institute of Surgical Research at the Walter‐Brendel‐Centre of Experimental Medicine University Hospital, LMU Munich Munich Germany Nora Hesse Department of Medicine I University Hospital, LMU Munich Munich Germany German Center for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance Munich Germany Institute of Surgical Research at the Walter‐Brendel‐Centre of Experimental Medicine University Hospital, LMU Munich Munich Germany Ruibing Xia Department of Medicine I University Hospital, LMU Munich Munich Germany German Center for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance Munich Germany Institute of Surgical Research at the Walter‐Brendel‐Centre of Experimental Medicine University Hospital, LMU Munich Munich Germany Li Mo Department of Medicine I University Hospital, LMU Munich Munich Germany German Center for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance Munich Germany Institute of Surgical Research at the Walter‐Brendel‐Centre of Experimental Medicine University Hospital, LMU Munich Munich Germany https://orcid.org/0009-0000-6548-3099 Aparna Sharma Chivukula Department of Medicine I University Hospital, LMU Munich Munich Germany German Center for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance Munich Germany Institute of Surgical Research at the Walter‐Brendel‐Centre of Experimental Medicine University Hospital, LMU Munich Munich Germany https://orcid.org/0000-0002-3386-1654 Hannes Villgrater Department of Medicine I University Hospital, LMU Munich Munich Germany German Center for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance Munich Germany Institute of Surgical Research at the Walter‐Brendel‐Centre of Experimental Medicine University Hospital, LMU Munich Munich Germany https://orcid.org/0009-0005-6796-4482 Marie Dressler Department of Medicine I University Hospital, LMU Munich Munich Germany German Center for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance Munich Germany Institute of Surgical Research at the Walter‐Brendel‐Centre of Experimental Medicine University Hospital, LMU Munich Munich Germany Bianca Hildebrand Department of Medicine I University Hospital, LMU Munich Munich Germany Eckhard Wolf Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich Munich Germany Interfaculty Center for Endocrine and Cardiovascular Disease Network Modelling and Clinical Transfer (ICONLMU), LMU Munich Munich Germany https://orcid.org/0000-0002-0430-9510 Konstantinos D. Rizas Department of Medicine I University Hospital, LMU Munich Munich Germany German Center for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance Munich Germany https://orcid.org/0000-0002-5993-0339 Axel Bauer German Center for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance Munich Germany University Hospital for Internal Medicine III Medical University of Innsbruck Innsbruck Austria https://orcid.org/0000-0001-9201-8555 Stefan Kääb Department of Medicine I University Hospital, LMU Munich Munich Germany German Center for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance Munich Germany Interfaculty Center for Endocrine and Cardiovascular Disease Network Modelling and Clinical Transfer (ICONLMU), LMU Munich Munich Germany https://orcid.org/0000-0001-8824-3581 Philipp Tomsits Department of Medicine I University Hospital, LMU Munich Munich Germany German Center for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance Munich Germany Institute of Surgical Research at the Walter‐Brendel‐Centre of Experimental Medicine University Hospital, LMU Munich Munich Germany https://orcid.org/0000-0002-5842-9083 Dominik Schüttler Department of Medicine I University Hospital, LMU Munich Munich Germany German Center for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance Munich Germany Institute of Surgical Research at the Walter‐Brendel‐Centre of Experimental Medicine University Hospital, LMU Munich Munich Germany https://orcid.org/0000-0002-2546-5862 Sebastian Clauss Department of Medicine I University Hospital, LMU Munich Munich Germany German Center for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance Munich Germany Institute of Surgical Research at the Walter‐Brendel‐Centre of Experimental Medicine University Hospital, LMU Munich Munich Germany Interfaculty Center for Endocrine and Cardiovascular Disease Network Modelling and Clinical Transfer (ICONLMU), LMU Munich Munich Germany https://orcid.org/0000-0002-5675-6128 Background

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.
Methods and Results

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 2 versus 3.29±0.79 deg 2 , P <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 2 versus 3.18±0.53 deg 2 [ P <0.05]; no SCD versus SCD: 1.67±0.32 deg 2 versus 3.91±0.63 deg 2 [ P <0.01]).
Conclusions

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.
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• Dokumententyp: Artikel (Klinikum der LMU)
• Organisationseinheit (Fakultäten): 07 Medizin > Klinikum der LMU München > Medizinische Klinik und Poliklinik I (Kardiologie)
• DFG-Fachsystematik der Wissenschaftsbereiche: Lebenswissenschaften
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892