Mechanisms Underlying Epicardial Radiofrequency Ablation to Suppress Arrhythmogenesis in Experimental Models of Brugada Syndrome

Abstract

OBJECTIVES This study sought to test the hypothesis that elimination of sites of abnormal repolarization, via epicardial RFA, suppresses the electrocardiographic and arrhythmic manifestations of BrS. BACKGROUND Brugada syndrome (BrS) is associated with ventricular tachycardia and ventricular fibrillation leading to sudden cardiac death. Nademanee et al. reported that radiofrequency ablation (RFA) of right ventricular outflow tract epicardium significantly reduced the electrocardiogram and arrhythmic manifestations of BrS. These authors concluded that low-voltage fractionated electrogram activity and late potentials are caused by conduction delay within the right ventricular outflow tract and that the ameliorative effect of RFA is caused by elimination of this substrate. Szel et al. recently demonstrated that the abnormal electrogram activity is associated with repolarization defects rather than depolarization or conduction defects. METHODS Action potentials (AP), electrograms, and pseudoelectrocardiogram were simultaneously recorded from coronary-perfused canine right ventricular wedge preparations. Two pharmacological models were used to mimic BrS genotype: combination of INa blocker ajmaline (1 to 10 μM) and IK-ATP agonist pinacidil (1 to 5 μM); or combination of Ito agonist NS5806 (4 to 10 μM) and ICa blocker verapamil (0.5 to 2 μM). After stable induction of abnormal electrograms and arrhythmic activity, the preparation was mapped and epicardial RFA was applied. RESULTS Fractionated low-voltage electrical activity was observed in right ventricular epicardium but not endocardium as a consequence of heterogeneities in the appearance of the second upstroke of the epicardial AP. Discrete late potentials developed as a result of delay of the second upstroke of the AP and of concealed phase 2 re-entry. Epicardial RFA of these abnormalities normalized Brugada pattern and abolished arrhythmic activity, regardless of the pharmacological model used. CONCLUSIONS Our results suggest that epicardial RFA exerts its ameliorative effect in the setting of BrS by destroying the cells with the most prominent AP notch, thus eliminating sites of abnormal repolarization and the substrate for ventricular tachycardia ventricular fibrillation.

J wave syndromes as a cause of malignant cardiac arrhythmias

“…It remained to be explained why ablation of regions of the RVOT exhibiting fractionated electrogram activity and LP are effective in suppressing the ECG and arrhythmic manifestations of BrS. Patocskai et al . demonstrated that ablation was effective because it eliminated the cells in the surface of the RVOT responsible for the repolarizations defects giving rise to the BrS phenotype.…”

Ajmaline-Induced Slowing of Conduction in the Right Ventricular Outflow Tract Cannot Account for ST Elevation in Patients With Type I Brugada ECG

“…The addition of isoproterenol greatly diminished AP notch area and the Brugada syndrome phenotype (JW-area), despite an increase in QRS-duration and transmural conduction time. Importantly, no difference was observed in conduction-dependent parameters (QRS-duration and conduction time) between preparations in which ajmaline induced a Brugada ECG-pattern and those in which ajmaline did not induce a BrS phenotype (inducible vs. non-inducible: p=0.242 and p=0.822 for QRS and CT, respectively), further refuting the hypothesis that conduction delay plays primary role in the development of a Brugada ECG-pattern 11 .…”

Mechanistic subtypes of focal right ventricular tachycardia

“…It is also important to appreciate that channelopathies causing Brugada syndrome can lead to RV structural abnormalities and the substrate for VT and ventricular fibrillation (VF). Specifically, epicardial RVOT interstitial fibrosis and reduced connexin‐43 expression are thought to contribute to the basis of the arrhythmogenic substrate . A new entity identified in high endurance athletes describes pathological RV remodeling and localized subepicardial RVOT scar that serves as the substrate for rapid VT …”

“…Specifically, epicardial RVOT interstitial fibrosis and reduced connexin-43 expression are thought to contribute to the basis of the arrhythmogenic substrate. [5][6][7] A new entity identified in high endurance athletes describes pathological RV remodeling and localized subepicardial RVOT scar that serves as the substrate for rapid VT. 8 This review will focus its attention on the more rarefied spectrum of sustained RV tachycardias that are focal in origin ( Table 2).…”