title: Gene therapy to restore electrophysiological function in heart failure.
abstract: BACKGROUND
  Heart failure (HF) is a major public health epidemic and a leading cause of morbidity and mortality in the industrialized world. Existing treatments for patients with HF are often associated with pro-arrhythmic activity and risk of sudden cardiac death. Therefore, development of novel, effective and safe therapeutic options for HF patients is a critical area of unmet need.
  
  
  METHODS
  In this article, we review recent advances in the emerging field of cardiac gene therapy for the treatment of tachy- and bradyarrhythmias in HF. We provide an overview of gene-based approaches that modulate myocardial conduction, repolarization, calcium cycling and adrenergic signaling to restore heart rate and rhythm.
  
  
  CONCLUSIONS
  We highlight major advantages of gene therapy for arrhythmias, including the ability to selectively target specific cell populations and to limit the therapeutic effect to the region that requires modification. We illustrate how advances in our fundamental understanding of the molecular origins of arrhythmogenic disorders are allowing investigators to use targeted gene-based approaches to successfully correct abnormal excitability in the atria, ventricles and conduction system. Translation of various gene therapy approaches to humans may revolutionize our ability to combat lethal arrhythmias in HF patients.
authors: The Cardiovascular Institute, Mount Sinai School of Medicine , One Gustave L. Levy Place, Box 1030, New York, NY 10029 , USA fadi.akar@mssm.edu.
authors: Lukas J
authors: LJ
authors: Motloch
authors: Fadi G
authors: FG
authors: Akar
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D053840:Brugada Syndrome; D000075224:Cardiac Conduction System Disease; D004562:Electrocardiography / Q000379:methods / Q000639:trends; D015316:Genetic Therapy / Q000379:methods / Q000639:trends*; D006329:Heart Conduction System / Q000002:abnormalities / Q000503:physiopathology; D006333:Heart Failure / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D006801:Humans
keywords: arrhythmias; calcium; conduction; gene therapy; heart failure; repolarization