title: Arrhythmia mechanisms in the failing heart.
abstract: BACKGROUND
  Heart failure (HF) claims over 200,000 lives annually in the United States alone. Approximately 50% of these deaths are sudden and unexpected, and presumably the consequence of lethal ventricular tachyarrhythmias. Electrical remodeling that occurs at the cellular and tissue network levels predisposes patients with HF to malignant arrhythmias. Our limited understanding of fundamental arrhythmia mechanisms has hampered the development of effective treatment strategies for these patients.
  
  
  CONCLUSIONS
  In this review, we outline recent advances in our understanding of arrhythmia mechanisms in the failing heart, highlighting various aspects of remodeling of ion channels, calcium handling proteins, and gap junction-related molecules. As will be discussed, these changes promote the prolongation of the action potential, the enhancement of spatio-temporal gradients of repolarization, the formation of calcium-mediated triggers and conduction abnormalities, all of which combine to form an electrophysiological substrate that is ripe for the genesis of lethal arrhythmias and sudden cardiac death.
authors.affiliation: Division of Cardiology, Cardiovascular Research Center, Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Jin
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Lyon
authors.forename: Fadi G
authors.initials: FG
authors.lastname: Akar
mesh_terms: D001145:Arrhythmias, Cardiac / Q000150:complications* / Q000503:physiopathology*; D006329:Heart Conduction System / Q000503:physiopathology*; D006333:Heart Failure / Q000150:complications* / Q000503:physiopathology*; D006801:Humans; D008955:Models, Cardiovascular