Abstract 2258: Electrocardiographic Analyisis Of Arrhythmias Developing During Exercise In Patients With Catecholaminergic Polymorphic Ventricular Tachycardia: Insights For Mechanisms And Site Of Origin
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare arrhythmogenic disorder characterized by adrenergically mediated polymorphic ventricular tachycardia in the absence of structural heart disease. Mutations in the cardiac ryanodine receptor gene (RyR2) or in the calsequestrin (CASQ2) gene have been identified in CPVT patients. In vivo and in vitro investigations of CPVT arrhythmogenesis have suggested that delayed afterdepolarizations mediated triggered activity in the leading arrhythmogenic mechanisms for CPVT. Recently we reported that in a knock-in model of CPVT arrhythmias predominantly originated from the Purkinje network. Objective of this study was to perform 12-leads ECG analysis of arrhythmias in CPVT to gain insights in the electrophysiological mechanisms of arrhythmias in patients (pts). Sixty-one consecutive pts entered the study before therapy (mean age 23±14 years, female 62 %). Arrhythmias developing during exercise stress test were analyzed. Supraventricular arrhythmias (SVA) occurred in 45 pts (74%): rate of onset of SVA was 72±16 bpm; ventricular arrhythmias (VA) occurred in all pts (bidirectional VT n=25; polymorphic VT n=16; bidirectional and polymorphic VT=11; bidirectional couplets n=9). The rate of onset of VA was faster than that of SVA (107±18 beats/min; p<0.05). In agreement with a triggered aetiology of arrhythmias observed in knock-in models of CPVT, a positive direct correlation between coupling interval of VA and the preceding RR interval was observed (r=0.76 p<0.001). The site of origin of the first beat of the most complex arrhythmic episode in each pts (VT n= 52; couplets n=9) was the right (RVO) or the left (LVO) ventricle outflow tract in 45/61 pts (74%): 57% of RyR2 pts but only 17% of non RyR2 pts had RVOT origin (p<0.05). In summary ECG analysis of VA and SVA in CPVT patients suggest that:
a shorter coupling interval for ventricular beats is observed at faster rates consistent with the data obtained in knock-in animal models that triggered activity is the mechanism underlying arrhythmias in CPVT;
the evidence that the origin of the polymorphic VT is predominantly from RVOT or LVOT suggests that it is unlikely that the Purkinje network is the pivotal site of origin of arrhythmias in CPVT patients.