%K Arrhythmia, Cardiac strain, Electromechanical coupling, Mechano-electric feedback, Repolarization %T Direct in-vivo assessment of global and regional mechano-electric feedback in the intact human heart %D 2021 %C United States %X BACKGROUND: Inhomogeneity of ventricular contraction is associated with sudden cardiac death, but the underlying mechanisms are unclear. Alterations in cardiac contraction impact electrophysiological parameters through mechano-electric feedback. This has been shown to promote arrhythmias in experimental studies, but its effect in the in-vivo human heart is unclear. OBJECTIVE: The aim of this study was to quantify the impact of regional myocardial deformation provoked by a sudden increase in ventricular loading (aortic occlusion) on human cardiac electrophysiology. METHODS: In ten patients undergoing open-heart cardiac surgery, left ventricular (LV) afterload was modified by transient aortic occlusion. Simultaneous assessment of whole-heart electrophysiology and LV deformation was performed using an epicardial sock (240 electrodes) and speckle-tracking transoesophageal echocardiography. Parameters were matched to six AHA LV model segments. The association between changes in regional myocardial segment length and in the activation-recovery interval (ARI, a conventional surrogate for action potential duration) was studied using mixed-effect models. RESULTS: Increased ventricular loading reduced longitudinal shortening (P=0.01) and shortened the ARI (P=0.02), but changes were heterogeneous between cardiac segments. Increased regional longitudinal shortening was associated with ARI shortening (effect size 0.20, 0.01 - 0.38, ms/% P=0.04) and increased local ARI dispersion (effect size -0.13, -0.23 - -0.03) ms/%, P=0.04). At the whole organ level, increased mechanical dispersion translated into increased dispersion of repolarization (correlation coefficient, r=0.81, P=0.01). CONCLUSIONS: Mechano-electric feedback can establish a potentially pro-arrhythmic substrate in the human heart and should be considered to advance our understanding and prevention of cardiac arrhythmias. %O This is an Open Access article published under a Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). %J Heart Rhythm %A M Orini %A P Taggart %A A Bhuva %A N Roberts %A C Di Salvo %A M Yates %A S Badiani %A S Van Duijvenboden %A G Lloyd %A A Smith %A PD Lambiase %L discovery10127309