Brief Communication abstract

Nature Medicine 15, 380 - 383 (2009)
Published online: 29 March 2009 | doi:10.1038/nm.1942

Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans

Hiroshi Watanabe1,5,6, Nagesh Chopra1,6, Derek Laver2,6, Hyun Seok Hwang1, Sean S Davies1, Daniel E Roach3, Henry J Duff3, Dan M Roden1, Arthur A M Wilde4 & Björn C Knollmann1


Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal inherited arrhythmia syndrome in which drug therapy is often ineffective. We discovered that flecainide prevents arrhythmias in a mouse model of CPVT by inhibiting cardiac ryanodine receptor–mediated Ca2+ release and thereby directly targeting the underlying molecular defect. Flecainide completely prevented CPVT in two human subjects who had remained highly symptomatic on conventional drug therapy, indicating that this currently available drug is a promising mechanism-based therapy for CPVT.

  1. Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
  2. School of Biomedical Sciences, University of Newcastle and Hunter Medical Research Institute, Callaghan, Australia.
  3. Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada.
  4. Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
  5. Current address: Division of Cardiology, Niigata University School of Medical and Dental Sciences, Niigata, Japan.
  6. These authors contributed equally to this work.

Correspondence to: Björn C Knollmann1 e-mail:


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