doi: 10.1161/01.RES.0000095382.50153.7D
© 2003 American Heart Association, Inc.
Editorials |
A Surprising New Arrhythmia Mechanism in Heart Failure
From the Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tenn.
Correspondence to Dan M. Roden, MD, Professor of Medicine and Pharmacology, Director, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, 532 Medical Research Building I, Nashville, TN 37232. E-mail dan.roden@vanderbilt.edu
Key Words: arrhythmia • heart failure • long QT
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Heart failure is the most common discharge diagnosis in the United States, with a prognosis worse than many cancers.1 Patients with heart failure die for two reasons: advanced circulatory insufficiency or sudden death.2 We know that continuous online monitoring of cardiac rhythm from patients with advanced heart failure is inevitably abnormal and often shows long runs of irregular and/or polymorphic ventricular tachycardia. Unlike patients with ventricular tachycardia due to healed myocardial infarction, those with heart failure rarely have ventricular tachycardia inducible by programmed stimulation, and when it is, its prognostic importance is uncertain. Therapy with conventional antiarrhythmics is no more successful in patients with heart failure than in those with serious ventricular arrhythmias due to healed infarction.
Arrhythmias, Disordered [Ca2+]i Homeostasis, and K+ Current Downregulation in Heart Failure
Given the huge public health impact of the problem and the failure of current pharmacological therapies, one obvious way forward in attacking the problem of sudden death in heart failure is to understand the basic molecular mechanisms underlying arrhythmia susceptibility in this setting. The disordered contractility that characterizes heart failure naturally suggests abnormal intracellular calcium homeostasis, a well-recognized feature of the heart failure phenotype,3,4 as a candidate arrhythmia mechanism, and experimental studies support this idea. Pogwizd and colleagues have used three-dimensional activation mapping in rabbits with volume-overload heart failure to identify focal triggers and repetitive focal activity as a major mechanism underlying VT in this model,5 behaviors that are highly reminiscent of afterdepolarization-related triggering due to intracellular calcium overload. Indeed, their further studies indicated that heart failure–related upregulation of the sodium-calcium exchanger, in
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