{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:22:26Z","timestamp":1789647746512,"version":"4.0.0"},"reference-count":14,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000445"],"award-info":[{"award-number":["UL1TR000445"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Aims<\/jats:title>\n<jats:p>Arrhythmia mechanisms in hypertrophic cardiomyopathy remain uncertain. Preclinical models suggest hypertrophic cardiomyopathy-linked mutations perturb sarcomere length-dependent activation, alter cardiac repolarization in rate-dependent fashion and potentiate triggered electrical activity. This study was designed to assess rate-dependence of clinical surrogates of contractility and repolarization in humans with hypertrophic cardiomyopathy.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>All participants had a cardiac implantable device capable of atrial pacing. Cases had clinical diagnosis of hypertrophic cardiomyopathy, controls were age-matched. Continuous electrocardiogram and blood pressure were recorded during and immediately after 30 second pacing trains delivered at increasing rates.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Nine hypertrophic cardiomyopathy patients and 10 controls were enrolled (47% female, median 55 years), with similar baseline QRS duration, QT interval and blood pressure. Median septal thickness in hypertrophic cardiomyopathy patients was 18mm; 33% of hypertrophic cardiomyopathy patients had peak sub-aortic velocity &gt;50mmHg. Ventricular ectopy occurred during or immediately after pacing trains in 4\/9 hypertrophic cardiomyopathy patients and 0\/10 controls (P = 0.03). During delivery of steady rate pacing across a range of cycle lengths, the QT-RR relationship was not statistically different between HCM and control groups; no differences were seen in subgroup analysis of patients with or without intact AV node conduction. Similarly, there was no difference between groups in the QT interval of the first post-pause recovery beat after pacing trains. No statistically significant differences were seen in surrogate measures for cardiac contractility.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Rapid pacing trains triggered ventricular ectopy in hypertrophic cardiomyopathy patients, but not controls. This finding aligns with pre-clinical descriptions of excessive cardiomyocyte calcium loading during rapid pacing, increased post-pause sarcoplasmic reticulum calcium release, and subsequent calcium-triggered activity. Normal contractility at all diastolic intervals argues against clinical significance of altered length-dependent myofilament activation.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0246768","type":"journal-article","created":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T23:02:31Z","timestamp":1613084551000},"page":"e0246768","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Assessment of dynamic cardiac repolarization and contractility in patients with hypertrophic cardiomyopathy"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2360-3552","authenticated-orcid":true,"given":"Andrew E.","family":"Radbill","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy Y.","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachin 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sensitization causes susceptibility to cardiac arrhythmia in mice","volume":"118","author":"F Baudenbacher","year":"2008","journal-title":"J Clin Invest"},{"key":"pone.0246768.ref011","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.yjmcc.2010.01.011","article-title":"Increased myofilament Ca2+-sensitivity and arrhythmia susceptibility","volume":"48","author":"S Huke","year":"2010","journal-title":"J Mol Cell Cardiol"},{"key":"pone.0246768.ref012","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/jce.13194","article-title":"Ventricular Tachyarrhythmias in Patients With Hypertrophic Cardiomyopathy and Defibrillators: Triggers, Treatment, and Implications","volume":"28","author":"MS Link","year":"2017","journal-title":"J Cardiovasc Electrophysiol"},{"issue":"20","key":"pone.0246768.ref013","first-page":"30764","article-title":"Primary prevention implantable cardioverter-defibrillators in hypertrophic cardiomyopathy-Are there predictors of appropriate therapy?","volume":"S1547-5271","author":"A Weissler-Snir","year":"2020","journal-title":"Heart Rhythm"},{"key":"pone.0246768.ref014","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.yjmcc.2009.12.017","article-title":"Myofilament length dependent activation","volume":"48","author":"PP de Tombe","year":"2010","journal-title":"J Mol Cell Cardiol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0246768","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T23:02:47Z","timestamp":1613084567000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0246768"}},"subtitle":[],"editor":[{"given":"Elena 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