Open AccessElectrophysiological Remodeling in Heart Failure Dyssynchrony vs. Resynchronization
Author(s) -
Aiba Takeshi,
Tomaselli Gordon F.,
Shimizu Wataru
Publication year - 2010
Publication title -
journal of arrhythmia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.463
H-Index - 21
eISSN - 1883-2148
pISSN - 1880-4276
DOI - 10.1016/s1880-4276(10)80011-0
Subject(s) - heart failure , medicine , cardiac resynchronization therapy , cardiology , downregulation and upregulation , homeostasis , myocyte , electrophysiology , depolarization , ion channel , afterdepolarization , endocrinology , receptor , chemistry , repolarization , ejection fraction , biochemistry , gene
The electrophysiological hallmark of cells and tissues isolated from failing hearts is prolongation of action potential duration (APD) and conduction slowing. In human studies and a number of animal models of heart failure, functional downregulation of K currents and alterations in depolarizing Na and Ca currents and transporters are demonstrated. Alterations in intercellular ion channels and matrix contribute to heterogeneity of APD and conduction slowing. The changes in cellular and tissue function are regionally heterogenous particularly in the heart failure with dyssynchronous LV contraction (DHF). Furthermore, β‐adrenergic signaling and modulation of ionic currents is blunted in heart failure. Cardiac resynchronization therapy (CRT) partially reversed the DHF‐induced downregulation of K current and improved Na channel gating. CRT significantly improved Ca homeostasis especially in myocytes from late‐activated, lateral wall, and restores the DHF‐induced blunted β‐adrenergic receptor responsiveness. CRT abbreviated DHF‐induced prolongation of APD in the lateral wall myocytes and reduced the LV regional gradient of APD, and suppressed development of early afterdepolarizations. In conclusion, CRT partially restores DHF‐induced ion channel remodeling, abnormal Ca homeostasis, blunted β‐adrenergic response and regional heterogeneity of APD, thus may suppress ventricular arrhythmias and contribute to the mortality benefit of CRT as well as improve mechanical performance of the heart.