Electrical remodeling in the failing heart

Takeshi Aiba, Gordon F. Tomaselli

Research output: Contribution to journalReview article

103 Citations (Scopus)

Abstract

Purpose of Review: We focus on the molecular and cellular basis of excitability, conduction and electrical remodeling in heart failure with dyssynchronous left ventricular contraction (DHF) and its restoration by cardiac resynchronization therapy (CRT) using a canine tachy-pacing heart failure model. Recent Findings: 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 extracellular matrix contribute to heterogeneity of APD and conduction slowing. The changes in cellular and tissue function are regionally heterogeneous, particularly in the DHF. Furthermore, β-adrenergic signaling and modulation of ionic currents is blunted in heart failure. CRT partially reverses the DHF-induced downregulation of K current and improves Na channel gating. CRT significantly improves Ca homeostasis, especially in lateral myocytes, and restores the DHF-induced blunted β-adrenergic receptor responsiveness. CRT abbreviates DHF-induced prolongation of APD in the lateral myocytes, reduces the left ventricular regional gradient of APD and suppresses development of early afterdepolarizations. Summary: CRT partially restores DHF-induced electrophysiological remodeling, abnormal Ca homeostasis, blunted β-adrenergic responsiveness, and regional heterogeneity of APD, and thus may suppress ventricular arrhythmias and contribute to the mortality benefit of CRT as well as improving mechanical performance of the heart.

Original languageEnglish (US)
Pages (from-to)29-36
Number of pages8
JournalCurrent Opinion in Cardiology
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

Fingerprint

Atrial Remodeling
Cardiac Resynchronization Therapy
Action Potentials
Heart Failure
Adrenergic Agents
Muscle Cells
Homeostasis
Down-Regulation
Ion Channels
Adrenergic Receptors
Extracellular Matrix
Canidae
Cardiac Arrhythmias
Animal Models
Mortality

Keywords

  • Action potential
  • Gene expression
  • Heart failure
  • Ion channels
  • Remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Electrical remodeling in the failing heart. / Aiba, Takeshi; Tomaselli, Gordon F.

In: Current Opinion in Cardiology, Vol. 25, No. 1, 01.01.2010, p. 29-36.

Research output: Contribution to journalReview article

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