Ravi K. Yarlagadda

Reversal of Cardiomyopathy in Patients With Repetitive Monomorphic Ventricular Ectopy Originating From the Right Ventricular Outflow Tract

Background—Tachycardia-induced cardiomyopathy caused by ventricular tachycardia is a well-defined clinical entity. Less well appreciated is whether simple ventricular ectopy can result in cardiomyopathy. We sought to examine a potential causal relationship between repetitive monomorphic ventricular ectopy originating from the right ventricular outflow tract and cardiomyopathy and the role of ablation in reversing this process. Methods and Results—The study consisted of 27 patients (11 men; age, 47±15 years) with repetitive monomorphic ventricular ectopy, including 8 patients (30%) with depressed ventricular function (ejection fraction ≤45%). All patients underwent assessment of cardiac structure and function. The burden of ectopy was quantified through 24-hour Holter monitoring. Patients then underwent ablation guided by 3D mapping. After ablation, patients underwent repeated Holter monitoring and reassessment of cardiac function. Patients with depressed ventricular function were more likely to be older than patients with normal function (58±14 versus 42±18 years; P=0.013). However, the burden of ventricular ectopy was similar in patients with (17 859±13 488 ectopic beats per 24 hours) and without (17 541±11 479 ectopic beats per 24 hours; P=0.800) preserved ventricular function. Successful ablation was performed in 23 patients (85%), including 7 of 8 patients with depressed ventricular function. In this latter group, ventricular function improved in all patients (from 39±6% to 62±6%; P=0.017). Conclusions—Repetitive monomorphic ventricular ectopy (in the absence of sustained ventricular tachycardia) originating from the right ventricular outflow tract is an underappreciated cause of unexplained cardiomyopathy. Successful ablation of the focal source of ventricular ectopy results in normalization of left ventricular function. Patients with ectopy-induced cardiomyopathy are significantly older than patients with preserved ventricular function, which suggests either that older patients are more susceptible to the development of a cardiomyopathy or that the cardiomyopathy has had a longer period of time in which to evolve.

Right and left ventricular outflow tract tachycardias : Evidence for a common electrophysiologic mechanism

Introduction:“Idiopathic” ventricular arrhythmias most often arise from the right ventricular outflow tract (RVOT), although arrhythmias from the left ventricular outflow tract (LVOT) are also observed. While previous work has elucidated the mechanism and electropharmacologic profile of RVOT arrhythmias, it is unclear whether those from the LVOT share these properties. The purpose of this study was to characterize the electropharmacologic properties of RVOT and LVOT arrhythmias.

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

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.