Circulation Research. 2004;95:754-763
doi: 10.1161/01.RES.0000145047.14691.db
doi: 10.1161/01.RES.0000145047.14691.db
© 2004 American Heart Association, Inc.
Reviews |
What Causes Sudden Death in Heart Failure?
From the Department of Medicine (G.F.T.), Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Md; and the Department of Medicine (D.P.Z.), Krannert Institute of Cardiology, the Indiana University School of Medicine, Indianapolis.
Correspondence to Gordon F. Tomaselli, MD, Division of Cardiology, Johns Hopkins University, 720 N Rutland Ave, Ross 844 Baltimore, MD 21287-2196. E-mail gtomasel{at}jhmi.edu
This Review is part of a thematic series on Unanswered Questions in Heart Failure, which includes the following articles:
Is Depressed Contractility Centrally Involved in Heart Failure?
What is the Role of ß-Adrenergic Signaling in Heart Failure?
What Mechanisms Underlie Diastolic Dysfunction in Heart Failure?
Is the Failing Heart Energy Starved?
What Causes Sudden Death in Heart Failure?
Is Abnormal Cell Growth and Hypertrophy the Cause of Heart Failure?
Steven Houser Guest Editor
Patients with heart failure experience a number of changes in the electrical function of the heart that predispose to potentially lethal cardiac arrhythmias. Action potential prolongation, the result of functional downregulation of K currents, and aberrant Ca2+ handling is a recurrent theme. Significant alterations in conduction and activation of a number of initially adaptive but ultimately maladaptive signaling cascades contribute to the generation of a highly arrhythmogenic substrate. We review the changes in active and passive membrane properties, neurohumoral signaling, and genetic determinants that predispose to sudden arrhythmic death in patients with heart failure and highlight the critical unanswered questions that are ripe for future investigation.
Key Words: arrhythmia • Ca2+ handling • cardiac electrophysiology • heart failure • ionic remodeling
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