{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T08:07:24Z","timestamp":1791014844275,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":11,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union's Horizon 2020 Research and Innovation Program"},{"name":"Marie Sk\u0142odowska-Curie","award":["860745"],"award-info":[{"award-number":["860745"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Previous studies have not examined the role of non-electrical myocardial disease substrates in determining the optimal atrio-ventricular delay (AVD) settings. We conducted virtual patient simulations to evaluate whether myocardial disease substrates influence the acute response to AVD optimization at rest and during exercise.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>The CircAdapt cardiovascular model was used to simulate various left ventricular (LV) remodelling found in cardiac resynchronization therapy candidates. We simulated electrical dyssynchrony, LV dilatation with preserved and reduced contractility, and increased LV passive stiffness. We simulated cardiac resynchronization following biventricular (BiVP) and non-selective LBB pacing (nsLBBP). The paced-AVD ranged from 220 to 40\u2005ms. Cardiac output and heart rate were increased to simulate different levels of exercise. The optimal AVD was the one leading to the highest stroke volume (SV) and the lowest mean left atrial pressure (mLAP). At rest, in simulations with healthy myocardium the gain in SV by AVD optimization was larger compared to those with reduced contractility and stiff myocardium. However, mLAP was comparably decreased by AVD optimization in both healthy and diseased myocardium. During exercise, the optimal AVD shifted to shorter values, and mLAP was more sensitive to AVD, particularly in the presence of hypo-contractile and stiff myocardium.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Simulations show that hypocontractility and stiffness reduce the effect of AVD optimization on SV but enhance its benefit in lowering mLAP. Notably, virtual patients with stiff ventricles experience greater benefits from AVD optimization during exercise compared to resting conditions. Furthermore, nsLBBP provides more favourable improvements in mLAP than BiVP.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/europace\/euaf082","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T04:27:55Z","timestamp":1744086475000},"source":"Crossref","is-referenced-by-count":4,"title":["Impact of myocardial phenotype on optimal atrioventricular delay settings during biventricular and left bundle branch pacing at rest and during exercise: insights from a virtual patient study"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3763-2972","authenticated-orcid":false,"given":"Claudia A","family":"Manetti","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, CARIM School for Cardiovascular Diseases, Maastricht University Medical Center , Universiteitssingel 40, 6229 ERMaastricht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8927-9110","authenticated-orcid":false,"given":"Nick","family":"van Osta","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, CARIM School for Cardiovascular Diseases, Maastricht University Medical Center , Universiteitssingel 40, 6229 ERMaastricht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0517-7000","authenticated-orcid":false,"given":"Ahmed S","family":"Beela","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, CARIM School for Cardiovascular Diseases, Maastricht University Medical Center , Universiteitssingel 40, 6229 ERMaastricht ,","place":["The Netherlands"]},{"name":"Department of Cardiovascular Diseases, Faculty of Medicine, Suez Canal University , Ismailia 41522 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7784-3610","authenticated-orcid":false,"given":"Lieven","family":"Herbots","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hartcentrum Hasselt, Jessa Hospital , Hasselt ,","place":["Belgium"]},{"name":"Faculty of Medicine and Life Sciences, Biomedical Research Institute, Hasselt University , Hasselt ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8917-9032","authenticated-orcid":false,"given":"Frits W","family":"Prinzen","sequence":"additional","affiliation":[{"name":"Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University , Maastricht ,","place":["The 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