Mechanistic insight into prolonged electromechanical delay in dyssynchronous heart failure: A computational study

Jason Constantino, Yuxuan Hu, Albert C. Lardo, Natalia A. Trayanova

Research output: Contribution to journalArticle

Abstract

In addition to the left bundle branch block type of electrical activation, there are further remodeling aspects associated with dyssynchronous heart failure (HF) that affect the electromechanical behavior of the heart. Among the most important are altered ventricular structure (both geometry and fiber/sheet orientation), abnormal Ca2+ handling, slowed conduction, and reduced wall stiffness. In dyssynchronous HF, the electromechanical delay (EMD), the time interval between local myocyte depolarization and myofiber shortening onset, is prolonged. However, the contributions of the four major HF remodeling aspects in extending EMD in the dyssynchronous failing heart remain unknown. The goal of this study was to determine the individual and combined contributions of HF-induced remodeling aspects to EMD prolongation. We used MRI-based models of dyssynchronous nonfailing and HF canine electromechanics and constructed additional models in which varying combinations of the four remodeling aspects were represented. A left bundle branch block electrical activation sequence was simulated in all models. The simulation results revealed that deranged Ca2+ handling is the primary culprit in extending EMD in dyssynchronous HF, with the other aspects of remodeling contributing insignificantly. Mechanistically, we found that abnormal Ca2+ handling in dyssynchronous HF slows myofiber shortening velocity at the early-activated septum and depresses both myofiber shortening and stretch rate at the late-activated lateral wall. These changes in myofiber dynamics delay the onset of myofiber shortening, thus giving rise to prolonged EMD in dyssynchronous HF.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume305
Issue number8
DOIs
StatePublished - Oct 15 2013

Keywords

  • Cardiac electromechanics
  • Dyssynchronous heart failure
  • Electromechanical modeling

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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