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 (Cx43) 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 Cx43 proteins was qualitatively and quantitatively determined using immunoconfocal microscopy and right ventricular biopsy specimens. The level of expression of Cx43 protein was defined as the proportion of tissue area occupied by Cx43 (percent tissue area) in each test area. The abundance and distribution of the Cx43 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 Cx43 in the LP group was significantly lower than that in the LP (-) group (p=0.02). Furthermore, Cx43 protein in the LP group was distributed more heterogeneously than that in the LP (-) group (p=0.001). The heterogeneous expression of Cx43 protein may contribute to impaired ventricular conduction, which may be related to the LP detected on SAECG.