Electromechanical dyssynchrony and resynchronization of the failing heart

Jonathan A. Kirk, David A Kass

Research output: Contribution to journalArticle

Abstract

Patients with heart failure and decreased function frequently develop discoordinate contraction because of electric activation delay. Often termed dyssynchrony, this further decreases systolic function and chamber efficiency and worsens morbidity and mortality. In the mid-1990s, a pacemaker-based treatment termed cardiac resynchronization therapy (CRT) was developed to restore mechanical synchrony by electrically activating both right and left sides of the heart. It is a major therapeutic advance for the new millennium. Acute chamber effects of CRT include increased cardiac output and mechanical efficiency and reduced mitral regurgitation, whereas reduction in chamber volumes ensues more chronically. Patient candidates for CRT have a prolonged QRS duration and discoordinate wall motion, although other factors may also be important because ≈30% of such selected subjects do not respond to the treatment. In contrast to existing pharmacological inotropes, CRT both acutely and chronically increases cardiac systolic function and work, yet it also reduces long-term mortality. Recent studies reveal unique molecular and cellular changes from CRT that may also contribute to this success. Heart failure with dyssynchrony displays decreased myocyte and myofilament function, calcium handling, β-adrenergic responsiveness, mitochondrial ATP synthase activity, cell survival signaling, and other changes. CRT reverses many of these abnormalities often by triggering entirely new pathways. In this review, we discuss chamber, circulatory, and basic myocardial effects of dyssynchrony and CRT in the failing heart, and we highlight new research aiming to better target and implement CRT, as well as leverage its molecular effects.

Original languageEnglish (US)
Pages (from-to)765-776
Number of pages12
JournalCirculation Research
Volume113
Issue number6
DOIs
Publication statusPublished - 2013

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Keywords

  • cardiac resynchronization therapy
  • cell physiological phenomena
  • heart failure
  • molecular biology
  • myocyte
  • ventricular function

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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