title: Mechano-electrical coupling as framework for understanding functional remodeling during LBBB and CRT.
abstract: It is not understood why, after onset of left bundle-branch block (LBBB), acute worsening of cardiac function is followed by a further gradual deterioration of function, whereas most adverse cardiac events lead to compensatory adaptations. We investigated whether mechano-electrical coupling (MEC) can explain long-term remodeling with LBBB and cardiac resynchronization therapy (CRT). To this purpose, we used an integrative modeling approach relating local ventricular electrophysiology, calcium handling, and excitation-contraction coupling to global cardiovascular mechanics and hemodynamics. Each ventricular wall was composed of multiple mechanically and electrically coupled myocardial segments. MEC was incorporated by allowing adaptation of L-type Ca(2+) current aiming at minimal dispersion of local external work, an approach that we previously applied to replicate T-wave memory in a synchronous heart after a period of asynchronous activation. LBBB instantaneously decreased left-ventricular stroke work and increased end-diastolic volume. During sustained LBBB, MEC reduced intraventricular dispersion of mechanical workload and repolarization. However, MEC-induced reduction in contractility in late-activated regions was larger than the contractility increase in early-activated regions, resulting in further decrease of stroke work and increase of end-diastolic volume. Upon the start of CRT, stroke work increased despite a wider dispersion of mechanical workload. During sustained CRT, MEC-induced reduction in dispersion of workload and repolarization coincided with a further reduction in end-diastolic volume. In conclusion, MEC may represent a useful framework for better understanding the long-term changes in cardiac electrophysiology and contraction following LBBB as well as CRT.
authors.affiliation: Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands;
authors.forename: Nico H L
authors.initials: NH
authors.lastname: Kuijpers
authors.affiliation: Department of Radiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands;
authors.forename: Evelien
authors.initials: E
authors.lastname: Hermeling
authors.affiliation: Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands;
authors.forename: Joost
authors.initials: J
authors.lastname: Lumens
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Huub M M
authors.initials: HM
authors.lastname: ten Eikelder
authors.affiliation: Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands; tammo.delhaas@maastrichtuniversity.nl.
authors.forename: Tammo
authors.initials: T
authors.lastname: Delhaas
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands;
authors.forename: Frits W
authors.initials: FW
authors.lastname: Prinzen
mesh_terms: D001696:Biomechanical Phenomena; D002037:Bundle-Branch Block / Q000503:physiopathology* / Q000628:therapy*; D020746:Calcium Channels, L-Type / Q000502:physiology; D058406:Cardiac Resynchronization Therapy; D055724:Electrophysiological Phenomena; D006801:Humans; D008954:Models, Biological; D013318:Stroke Volume / Q000502:physiology; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D020746:Calcium Channels, L-Type
keywords: cardiac resynchronization therapy; excitation-contraction coupling; left bundle-branch block; mechano-electrical coupling