Brugada-Type ST Segment Elevation after Sodium
Channel Blockade is Caused by Right Ventricular
Excitation Failure in Discontinuous Myocardium
American Heart Association Scientific Sessions New Orleans, November 2008.
introduction Brugada-type ST segment elevation has been associated with reduced sodium channel function and right-sided structural heart disease. Both depolarizing or repolarizing abnormalities in the right ventricular wall have been described in patients. The underlying mechanism however, is still debated. We determined depolarization and repolarization characteristics in an isolated human heart from a young patient carrying a sodium channel mutation previously described in a family with the Brugada syndrome.
methods and results A 15-year old female patient carrying a loss-of-function mutation (G752R) in the gene coding for the cardiac sodium channel underwent cardiac transplantation for end-stage heart failure in dilated cardiomyopathy. The explanted, Langendorff-perfused heart was submerged in perfusion fluid. We simultaneously recorded an "Einthoven" configuration pseudo-ECG and 194 unipolar electrograms from the endocardium and epicardium of both ventricles. At baseline, a single shortly coupled premature stimulus resulted in more fractionated electrograms in the right than the left ventricle (38 vs 6%, p<0.001, Z-test). After sodium channel blockade by ajmaline, ST segment elevation of 0.3 mV was observed in pseudo-aVR which coincided with the virtual disappearance of the QRS complex in unipolar electrograms at the basal epicardium of the right ventricle followed by monophasic ST segment elevation. The local origin of this phenomenon was demonstrated by calculating Laplacian electrograms. Neither early repolarization nor delayed activation correlated with the ST change. Marked epicardial fatty infiltration was present at sites of local ST-segment elevation from the basal right ventricle, but not elsewhere. Simulations in a bidomain whole-heart computer model showed that sodium current reduction or random replacement of 50% of the right ventricular epicardium by inexcitable tissue alone does not cause ST segment elevation. The combination however, leads to functional conduction block resulting in Brugada-type ST segment elevation.
conclusion Functional conduction block by current-to-load mismatch underlies Brugada-type ST-segment elevation in right-sided structural heart disease after sodium channel blockade.
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