Adenosine-insensitive right ventricular tachycardia: Novel variant of idiopathic outflow tract tachycardia

BackgroundA 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.ObjectiveThis study aimed to identify the clinical and electrophysiologic characteristics of ADO-insensitive RVOT tachycardia.MethodsThe 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.ResultsSustained 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.ConclusionAlthough 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.