Mechano-electrical coupling as framework for understanding functional remodeling during LBBB and CRT

Am J Physiol Heart Circ Physiol. 2014 Jun 15;306(12):H1644-59. doi: 10.1152/ajpheart.00689.2013. Epub 2014 Apr 18.


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.

Keywords: cardiac resynchronization therapy; excitation-contraction coupling; left bundle-branch block; mechano-electrical coupling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomechanical Phenomena
  • Bundle-Branch Block / physiopathology*
  • Bundle-Branch Block / therapy*
  • Calcium Channels, L-Type / physiology
  • Cardiac Resynchronization Therapy*
  • Electrophysiological Phenomena
  • Humans
  • Models, Biological*
  • Stroke Volume / physiology
  • Treatment Outcome
  • Ventricular Remodeling / physiology*


  • Calcium Channels, L-Type