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Understanding electromechanical reciprocity and its impact on function and heterogeneity in pathological conditions \u2013 such as (drug\u2010induced) acquired long QT syndrome (aLQTS) \u2013 might lead to novel insights in arrhythmogenesis. Our aim is to investigate how electrical changes impact on mechanical function (EMC) and vice versa (MEC) under physiological conditions and in aLQTS. To measure regional differences in EMC and MEC <jats:italic>in vivo<\/jats:italic>, we used tissue phase mapping cardiac MRI and a 24\u2010lead ECG vest in healthy (control) and <jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub>\u2010blocker E\u20104031\u2010induced aLQTS rabbit hearts. MEC was studied <jats:italic>in vivo<\/jats:italic> by acutely increasing cardiac preload, and <jats:italic>ex vivo<\/jats:italic> by using voltage optical mapping (OM) in beating hearts at different preloads. In aLQTS, electrical repolarization (heart rate corrected RT\u2010interval, RTn370) was prolonged compared to control (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) with increased spatial and temporal RT heterogeneity (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). Changing electrical function (in aLQTS) resulted in significantly reduced diastolic mechanical function and prolonged contraction duration (EMC), causing increased apico\u2010basal mechanical heterogeneity. Increased preload acutely prolonged RTn370 in both control and aLQTS hearts (MEC). This effect was more pronounced in aLQTS (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). Additionally, regional RT\u2010dispersion increased in aLQTS. Motion\u2010correction allowed us to determine APD\u2010prolongation in beating aLQTS hearts, but limited motion correction accuracy upon preload\u2010changes prevented a clear analysis of MEC <jats:italic>ex vivo<\/jats:italic>. Mechano\u2010induced RT\u2010prolongation and increased heterogeneity were more pronounced in aLQTS than in healthy hearts. Acute MEC effects may play an additional role in LQT\u2010related arrhythmogenesis, warranting further mechanistic investigations.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15560-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Electromechanical reciprocity comprising excitation\u2010contraction coupling (EMC) and mechano\u2010electric feedback loops (MEC) is essential for physiological cardiac function.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Alterations in electrical and\/or mechanical heterogeneity are known to have potentially pro\u2010arrhythmic effects.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In this study, we aimed to investigate how electrical changes impact on the mechanical function (EMC) and vice versa (MEC) both under physiological conditions (control) and in acquired long QT syndrome (aLQTS).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We show that changing the electrical function (in aLQTS) results in significantly altered mechanical heterogeneity via EMC and, vice versa, that increasing the preload acutely prolongs repolarization duration and increases electrical heterogeneity, particularly in aLQTS as compared to control.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our results substantiate the hypothesis that LQTS is an \u201belectro\u2010mechanical\u2019, rather than a \u2018purely electrical\u2019, disease and suggest that acute MEC effects may play an additional role in LQT\u2010related arrhythmogenesis.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp284604","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T07:12:40Z","timestamp":1682061160000},"page":"4511-4527","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mechano\u2010electrical interactions and heterogeneities in wild\u2010type and drug\u2010induced long QT syndrome rabbits"],"prefix":"10.1113","volume":"602","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5892-1879","authenticated-orcid":false,"given":"Raphaela D.","family":"Lewetag","sequence":"first","affiliation":[{"name":"Department of Cardiology and Angiology I University Heart Center Freiburg, University Medical Center Freiburg  Freiburg Germany"},{"name":"Institute for Experimental Cardiovascular Medicine University Heart Center Freiburg \u2013 Bad Krozingen and Faculty of Medicine, University of Freiburg  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