What causes sudden death in heart failure?
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.
Tomaselli
Gordon F
GF
Department of Medicine , Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-2196, USA. gtomasel@jhmi.edu
Zipes
Douglas P
DP
D000200:Action Potentials; D000818:Animals; D001161:Arteriosclerosis / Q000150:complications; D002118:Calcium / Q000378:metabolism; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D005355:Fibrosis; D020022:Genetic Predisposition to Disease; D006329:Heart Conduction System / Q000503:physiopathology*; D006333:Heart Failure / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D017136:Ion Transport; D051379:Mice; D008822:Mice, Transgenic; D017202:Myocardial Ischemia / Q000150:complications / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000502:physiology; D009431:Neural Conduction; D011188:Potassium / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D015398:Signal Transduction; D013564:Sympathetic Nervous System / Q000503:physiopathology; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000503:physiopathology
D011188:Potassium; D002118:Calcium