Correlation of connexin43 expression and late ventricular potentials in nonischemic dilated cardiomyopathy

Nonischemic dilated cardiomyopathy (DCM) is associated with a high risk of sudden cardiac death. Signal-averaged electrocardiography (SAECG) is a useful clinical tool for detecting late ventricular potentials (LP). Gap junction alterations have recently been shown to be involved in the pathogenesis of ventricular arrhythmias in DCM; however, the possible relationship between gap junctional connexin43 (C x 43) expression and SAECG has not yet been evaluated. In the present study 16 patients (47+/-13 years) with DCM who had undergone SAECG testing were evaluated. In each patient, the expression of C x 43 proteins was qualitatively and quantitatively determined using immunoconfocal microscopy and right ventricular biopsy specimens. The level of expression of C x 43 protein was defined as the proportion of tissue area occupied by C x 43 (percent tissue area) in each test area. The abundance and distribution of the C x 43 signal was assessed in relation to LP. Late ventricular potentials were positive in 5 patients (LP (+) group) and negative in 11 patients (LP (-) group). The incidence of sustained ventricular tachycardia in the LP (+) group was higher than that in the LP (-) group (80% vs 18%, p=0.04). The percent tissue area of C x 43 in the LP (+) group was significantly lower than that in the LP (-) group (p=0.02). Furthermore, C x 43 protein in the LP (+) group was distributed more heterogeneously than that in the LP (-) group (p=0.001). The heterogeneous expression of C x 43 protein may contribute to impaired ventricular conduction, which may be related to the LP detected on SAECG.