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. CONCLUSION: 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.
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. CONCLUSION: 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: James E Ip; Linna Xu; Jie Dai; Clemens Steegborn; Fabrice Jaffré; Todd Evans; Jim W Cheung; Craig T Basson; Gianina Panaghie; Trine Krogh-Madsen; Geoffrey W Abbott; Bruce B Lerman Journal: Circ Arrhythm Electrophysiol Date: 2021-09-30