Abstract 16944: Ablation of the LV Endocardial Surface Reveals Origin of Ventricular Arrhythmias in a Murine CPVT Model
Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disorder caused by spontaneous Ca releases from the sarcoplasmic reticulum. Cellular studies suggest that both purkinje cells and ventricular myocytes from CPVT mouse models can trigger spontaneous beats, but the precise origin of CPVT within the heart is still unknown.
Methods: ECG and optical maps from isolated Casq2KO hearts were recorded at baseline and after LV endocardial ablation using Lugol's solution. The ablation was considered successful when the left ventricle breakthrough activation disappeared and the ECG showed a QRS morphology consistent with a complete left bundle branch block. The extent of the LV endocardial ablation was evaluated with TTC staining. Ventricular tachyarrhythmias were triggered with a bolus of isoproterenol after reducing the intrinsic sinus rate with carbachol. The origin of ventricular beats (VBs) was classified into 6 anatomical regions: right ventricular outflow track (RVOT), mid/lateral RV (RVM), RV apex (RVA), left ventricular base (LVB), mid/lateral LV (LVM), LV apex (LVA).
Results: A total of 4334 VBs were analyzed from 16 hearts. In control conditions, 66% of VBs arose from the RV (19% RVOT, 33% RVM, 14% RVA) and 34% from the LV (11% LVB, 11% LVM, 12% LVA). LV endocardial ablation almost completely abolished VBs originating from the LV, but did not significantly change the number of RV beats (Figure). TTC staining demonstrated that ablation was restricted to <20% of LV wall thickness.
Conclusions: The endocardial surface plays a central role in the initiation of arrhythmias in CPVT, suggesting that Purkinje fibers are the most likely culprit for the ectopic events and they should be considered as a target for both pharmacological and gene therapy.
- © 2011 by American Heart Association, Inc.