Background-Oxidative stress has been implicated in the pathogenesis of heart failure. However, direct evidence of oxidative stress generation in the human failing myocardium has not been obtained. Furthermore, the effect of carvedilol, a vasodilating ␤-blocker with antioxidant activity, on oxidative stress in human failing hearts has not been assessed. This study was therefore designed to determine whether levels of lipid peroxides are elevated in myocardia of patients with dilated cardiomyopathy (DCM) and whether carvedilol reduces the lipid peroxidation level. Methods and Results-Endomyocardial biopsy samples obtained from 23 patients with DCM and 13 control subjects with normal cardiac function were studied immunohistochemically for the expression of 4-hydroxy-2-nonenal (HNE)-modified protein, which is a major lipid peroxidation product. Expression of HNE-modified protein was found in all myocardial biopsy samples from patients with DCM. Expression was distinct in the cytosol of cardiac myocytes. Myocardial HNE-modified protein levels in patients with DCM were significantly increased compared with the levels in control subjects (PϽ0.0001). Endomyocardial biopsy samples from 11 patients with DCM were examined before and after treatment (mean, 9Ϯ4 months) with carvedilol (5 to 30 mg/d; mean dosage, 22Ϯ8 mg/d). After treatment with carvedilol, myocardial HNE-modified protein levels decreased by 40% (PϽ0.005) along with amelioration of heart failure. Conclusions-Oxidative stress is elevated in myocardia of patients with heart failure. Administration of carvedilol resulted in a decrease in the oxidative stress level together with amelioration of cardiac function.

Atrial vulnerability is increased in patients with Brugada syndrome. Abnormal atrial conduction may be an electrophysiologic basis for induction of AF in patients with Brugada syndrome.

An epicardial electrogram can be recorded from the CB. Recording from the CB enables identification of an epicardial abnormality in patients with the Brugada syndrome. These abnormal electrograms may be related to a myocardial abnormality in the epicardium of patients with the Brugada syndrome.

Combined I(Kr) and I(Ks) block gives rise to inverted, biphasic, and triphasic T wave morphologies, a dramatic increase in TDR, and a high incidence of EADs. The diversity of T wave morphologies derives from a preferential AP prolongation of different transmural layers leading to variation in the predominance of voltage gradients on either side of the M cell region. Our study provides direct evidence linking EADs that arise in ventricular epicardial and M cells to the triggered beats that precipitate polymorphic ventricular tachycardia. Our results also suggest possible guidelines for the estimation of TDR from complex T waves appearing in the precordial leads of the surface ECG.