Cardiac Resynchronization and Electrophysiological Reverse-Remodeling in the Failing Heart

Takeshi Aiba, Ikutaro Nakajima, Takashi Noda, Hideo Okamura, Yuko Yamada, Koji Miyamoto, Kazuhiro Satomi, Naohiko Aihara, Shiro Kamakura, Wataru Shimizu, David Kass, Gordon Tomaselli

Research output: Contribution to journalArticlepeer-review


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 Ca2+ 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, <-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 Ca2+ homeostasis especially in myocytes from late-activated, lateral wall, and restores the DHF-induced blunted <-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 the DHF-induced ion channel remodeling, abnormal Ca2+ homeostasis, blunted <-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.

Original languageEnglish (US)
JournalJournal of Arrhythmia
StatePublished - 2011
Externally publishedYes


  • heart failure
  • ion channels
  • resynchronization

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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