{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:37:49Z","timestamp":1791862669789,"version":"4.3.4"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T00:00:00Z","timestamp":1724025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["303178"],"award-info":[{"award-number":["303178"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The electrophysiological mechanism connecting mitral valve prolapse (MVP), premature ventricular complexes and life-threatening ventricular arrhythmia is unknown. A common hypothesis is that stretch activated channels (SACs) play a significant role. SACs can trigger depolarizations or shorten repolarization times in response to myocardial stretch. Through these mechanisms, pathological traction of the papillary muscle (PM), as has been observed in patients with MVP, may induce irregular electrical activity and result in reentrant arrhythmia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Based on a patient with MVP and mitral annulus disjunction, we modeled the effect of excessive PM traction in a detailed medical image-derived ventricular model by activating SACs in the PM insertion region. By systematically varying the onset of SAC activation following sinus pacing, we identified vulnerability windows for reentry with 1 ms resolution. We explored how reentry was affected by the SAC reversal potential <jats:inline-formula><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"m1\"><mml:mrow><mml:mo stretchy=\"false\">(<\/mml:mo><mml:mrow><mml:msub><mml:mrow><mml:mi>E<\/mml:mi><\/mml:mrow><mml:mrow><mml:mtext>SAC<\/mml:mtext><\/mml:mrow><\/mml:msub><\/mml:mrow><mml:mo stretchy=\"false\">)<\/mml:mo><\/mml:mrow><\/mml:math><\/jats:inline-formula> and the size of the region with simulated stretch (SAC region). Finally, the effect of global or focal fibrosis, modeled as reduction in tissue conductivity or mesh splitting (fibrotic microstructure), was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In models with healthy tissue or fibrosis modeled solely as CV slowing, we observed two vulnerable periods of reentry: For <jats:inline-formula><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"m2\"><mml:msub><mml:mrow><mml:mi>E<\/mml:mi><\/mml:mrow><mml:mrow><mml:mtext>SAC<\/mml:mtext><\/mml:mrow><\/mml:msub><\/mml:math><\/jats:inline-formula> of \u221210 and \u221230 mV, SAC activated during the T-wave could cause depolarization of the SAC region which lead to reentry. For <jats:inline-formula><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"m3\"><mml:msub><mml:mrow><mml:mi>E<\/mml:mi><\/mml:mrow><mml:mrow><mml:mtext>SAC<\/mml:mtext><\/mml:mrow><\/mml:msub><\/mml:math><\/jats:inline-formula> of \u221240 and \u221270 mV, SAC activated during the QRS complex could result in early repolarization of the SAC region and subsequent reentry. In models with fibrotic microstructure in the SAC region, we observed micro-reentries and a larger variability in which times of SAC activation triggered reentry. In these models, 86% of reentries were triggered during the QRS complex or T-wave. We only observed reentry for sufficiently large SAC regions (<jats:inline-formula><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"m4\"><mml:mo>&gt;<\/mml:mo><mml:mo>=<\/mml:mo><\/mml:math><\/jats:inline-formula> 8 mm radius in models with healthy tissue).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Stretch of the PM insertion region following sinus activation may initiate ventricular reentry in patients with MVP, with or without fibrosis. Depending on the SAC reversal potential and timing of stretch, reentry may be triggered by ectopy due to SAC-induced depolarizations or by early repolarization within the SAC region.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphys.2024.1447938","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T04:40:18Z","timestamp":1724042418000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Stretch of the papillary insertion triggers reentrant arrhythmia: an in silico patient study"],"prefix":"10.3389","volume":"15","author":[{"given":"Lena","family":"Myklebust","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Monopoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Balaban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eivind Westrum","family":"Aabel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margareth","family":"Ribe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Isotta","family":"Castrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina Eide","family":"Hasselberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilie","family":"Bugge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Five","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Haugaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"Maleckar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermenegild","family":"Arevalo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1016\/j.jcmg.2021.01.028","article-title":"Tricuspid annulus disjunction: novel findings by cardiac magnetic resonance in patients with mitral annulus disjunction","volume":"14","author":"Aabel","year":"2021","journal-title":"Cardiovasc. 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