title: Adenosine-insensitive right ventricular tachycardia: novel variant of idiopathic outflow tract tachycardia.
abstract: BACKGROUND
  A hallmark of idiopathic right ventricular outflow tract (RVOT) tachycardia is its sensitivity to adenosine (ADO), which is consistent with a triggered mechanism. We have identified a novel group of patients with ADO-insensitive, non-reentrant RVOT tachycardia.
  
  
  OBJECTIVE
  This study aimed to identify the clinical and electrophysiologic characteristics of ADO-insensitive RVOT tachycardia.
  
  
  METHODS
  The response of ventricular tachycardia (VT) to ADO was evaluated in 46 consecutive patients with inducible sustained idiopathic RVOT tachycardia. The clinical and electrophysiologic characteristics of patients with ADO-insensitive RVOT tachycardia were compared with patients with ADO-sensitive VT and arrhythmogenic right ventricular cardiomyopathy (ARVC) VT.
  
  
  RESULTS
  Sustained RVOT tachycardia terminated with ADO in 41 patients (89%), while 5 patients (11%) had ADO-insensitive VT. The electrophysiology study findings of patients with ADO-sensitive and ADO-insensitive RVOT tachycardia were similar. Compared with a group of 10 patients with ARVC, patients with ADO-insensitive RVOT tachycardia had no ARVC-associated electrocardiographic or right ventricular morphologic findings, as well as fewer inducible VT morphologies. Analysis of myocardial biopsies at VT origin sites from 3 of 5 patients with ADO-insensitive RVOT tachycardia demonstrated somatic mutations in the A1 ADO receptor (R296C) in 1 patient and in the inhibitory G protein (F200L) in another patient, as described previously. These mutations were not identified at remote myocardial sites. Over a median follow-up period of 4.8 years, no patients insensitive to ADO developed an ARVC phenotype.
  
  
  CONCLUSIONS
  Although most forms of idiopathic RVOT tachycardia are characterized by ADO sensitivity, we described a variant of ADO-insensitive VT that, in some cases, can be linked to somatic myocardial mutations involving the A1 ADO receptor-associated cyclic adenosine monophosphate-mediated pathway.
authors.affiliation: Department of Medicine, Division of Cardiology, Weill Cornell Medical College, New York, New York.
authors.forename: Jim W
authors.initials: JW
authors.lastname: Cheung
authors.affiliation: Department of Medicine, Division of Cardiology, Weill Cornell Medical College, New York, New York.
authors.forename: James E
authors.initials: JE
authors.lastname: Ip
authors.affiliation: Department of Medicine, Division of Cardiology, Weill Cornell Medical College, New York, New York.
authors.forename: Ravi K
authors.initials: RK
authors.lastname: Yarlagadda
authors.affiliation: Department of Medicine, Division of Cardiology, Weill Cornell Medical College, New York, New York.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Liu
authors.affiliation: Department of Medicine, Division of Cardiology, Weill Cornell Medical College, New York, New York.
authors.forename: George
authors.initials: G
authors.lastname: Thomas
authors.affiliation: Department of Medicine, Division of Cardiology, Weill Cornell Medical College, New York, New York.
authors.forename: Linna
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Medicine, Division of Cardiology, Weill Cornell Medical College, New York, New York.
authors.forename: David
authors.initials: D
authors.lastname: Wilkes
authors.affiliation: Department of Medicine, Division of Cardiology, Weill Cornell Medical College, New York, New York.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Markowitz
authors.affiliation: Department of Medicine, Division of Cardiology, Weill Cornell Medical College, New York, New York. Electronic address: blerman@med.cornell.edu.
authors.forename: Bruce B
authors.initials: BB
authors.lastname: Lerman
mesh_terms: D000241:Adenosine / Q000627:therapeutic use*; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D017115:Catheter Ablation / Q000379:methods*; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology* / Q000601:surgery; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017180:Tachycardia, Ventricular / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D000241:Adenosine
keywords: Adenosine; Arrhythmogenic right ventricular cardiomyopathy; Catheter ablation; Ventricular tachycardia