• Heart Rhythm · May 2008

    Repolarization heterogeneity in the right ventricular outflow tract: correlation with ventricular arrhythmias in Brugada patients and in an in vitro canine Brugada model.

    • Hiroshi Morita, Douglas P Zipes, Kengo Fukushima-Kusano, Satoshi Nagase, Kazufumi Nakamura, Shiho T Morita, Tohru Ohe, and Jiashin Wu.
    • Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana, USA. hmorita@cc.okayama-u.ac.jp
    • Heart Rhythm. 2008 May 1; 5 (5): 725-33.

    BackgroundBrugada syndrome (BrS) is characterized by repolarization abnormality with ST-segment elevation in the right ventricular outflow tract (RVOT).ObjectiveAlthough action potential (AP) heterogeneity is associated with induction of ventricular arrhythmias (VA) in BrS, clinical evidence and its experimental correlations are still absent and are the focus of this study.MethodsWe evaluated repolarization heterogeneity in 15 patients with BrS using body surface mapping and in 8 pairs of isolated canine RVOT and right ventricular anteroinferior (RVAI) preparations having drug-induced BrS using optical mapping.ResultsPatients had large J-ST-segment elevation and long QT interval in the RVOT at baseline. Administration of pilsicainide (1 mg/kg) exaggerated J-ST-segment elevation, caused simultaneous long and short QT intervals in the RVOT, and induced polymorphic ventricular tachycardia (VT) and T wave alternans (TWA). Dispersion of QT within the RVOT after pilsicainide was greater in patients that had syncope or ventricular fibrillation than those that did not. Ventricular arrhythmias originated from the RVOT along with local electrocardiogram changes and TWA. Repolarization heterogeneity was much less in areas outside the RVOT. Inducing BrS increased AP heterogeneity (with and without spike-and-dome) within the RVOT epicardium. Phase 2 reentry and TWA originated from the epicardium in 88% and 50% of RVOT preparations, respectively. In contrast, the RVOT endocardium and RVAI had little AP heterogeneity, with neither reentry nor TWA.ConclusionThe instability and heterogeneity of repolarization within the epicardium of the RVOT seem to be associated with arrhythmogenesis in both patients and in the in vitro tissue models of BrS.

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