Logo Logo

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

[thumbnail of bauer-et-al-2024-biomarker-periodic-repolarization-dynamics-indicates-enhanced-risk-for-arrhythmias-and-sudden-cardiac.pdf] Published Article
bauer-et-al-2024-biomarker-periodic-repolarization-dynamics-indicates-enhanced-risk-for-arrhythmias-and-sudden-cardiac.pdf

The publication is available under the license Creative Commons Attribution Non-commercial.

Download (12MB)

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.
05 07 2024 e032405 10.1161/JAHA.123.032405 2 10.1161/crossmarkpolicy www.ahajournals.org true 2023-08-29 2024-03-08 2024-04-19 10.1161/JAHA.123.032405 https://www.ahajournals.org/doi/10.1161/JAHA.123.032405 https://www.ahajournals.org/doi/full/10.1161/JAHA.123.032405 10.1155/2019/8295054 10.1016/s0140-6736(17)32154-2 10.1056/NEJMra000650 10.1016/j.acvd.2021.10.012 10.1161/circulationaha.109.902148 10.1001/jama.2008.553 10.1161/circresaha.116.304521 10.1016/0002-9149(90)91285-e 10.1093/eurheartj/ehac223 10.1161/01.RES.0000145047.14691.db 10.1002/phar.2663 10.1038/s41569-019-0221-2 10.1152/ajpheart.00575.2016 10.1161/circresaha.113.302549 10.1161/circep.115.001359 10.1161/01.cir.101.16.1960 10.1161/circresaha.116.304679 10.1172/jci26381 10.1161/01.RES.0000133678.22968.e3 10.1186/s12872-016-0192-8 10.1155/2015/698368 10.1016/j.hrthm.2007.09.007 10.1016/j.autneu.2007.01.014 10.1161/01.res.86.7.816 10.1172/jci70085 10.1093/eurheartj/ehx161 10.1016/j.hrthm.2019.02.024 10.1016/s0140-6736(19)31996-8 10.1161/circulationaha.121.056464 10.1089/ham.2020.0131 10.1007/s00394-022-02853-8 10.3389/fphys.2020.542183 10.1213/00000539-199402000-00029 10.1371/journal.pone.0232374 10.1038/s41684-021-00909-6 10.1161/01.Cir.0000080327.32573.7c 10.1016/j.hrthm.2006.02.005 10.1046/j.1540-8167.2001.01068.x 10.1093/europace/euq089 10.1161/01.cir.103.1.22 10.1016/0168-0102(96)01042-5 10.1073/pnas.83.10.3537 10.15420/aer.2016:11:2 10.1038/s41569-019-0179-0 10.1161/CIRCRESAHA.120.316366 10.1378/chest.100.1.207 J Am Assoc Lab Anim Sci Lelovas PP 432 53 2014 A comparative anatomic and physiologic overview of the porcine heart Lelovas PP, Kostomitsopoulos NG, Xanthos TT. A comparative anatomic and physiologic overview of the porcine heart. J Am Assoc Lab Anim Sci. 2014;53:432–438. 10.1161/01.res.69.2.429 10.1016/j.jacc.2019.01.056 10.1016/j.abb.2010.12.017 10.1152/ajpheart.00768.2003 10.1161/01.cir.78.4.1008 10.1046/j.1365-2281.2000.00278.x 10.1152/ajpheart.00434.2013 10.1016/j.neulet.2012.12.059 10.1007/s00414-017-1590-x 10.1016/s0002-9149(97)89125-4 10.1073/pnas.74.10.4516 10.1016/1044-7431(91)90027-l 10.1006/dbio.1995.1146 10.1016/S0008-6363(00)00308-4 10.1371/journal.pone.0095106 10.1056/NEJMoa043938 10.1136/emj.2010.095885 10.1023/a:1024463418429 10.1055/a-1152-4662 10.1126/science.6166045 10.1161/01.cir.84.2.482 10.1161/01.cir.101.8.886 10.1111/j.1540-8167.1996.tb00487.x 10.1126/science.2017682 10.1056/nejm199401273300402 10.1161/circulationaha.105.607895 10.1111/j.1540-8167.1997.tb00621.x 10.1093/eurheartj/ehab368 10.1093/eurheartj/ehac262 10.1161/cir.0000000000000549 10.1016/j.hrthm.2013.11.028 10.1016/j.jacep.2017.06.006 10.1249/mss.0000000000001912 10.3389/fcvm.2019.00158 10.1111/apha.12447 10.1016/j.hrthm.2015.02.012

View Item
View Item