Methods: Thirty consecutive patients submitted for mitral valve surgery were investigated. Eleven patients with permanent AF (6 males, 5 females; mean age 57.7±13.1 years; range 36 to 76 years) were considered as the AF group whereas 19 patients who were in sinus rhythm (11 males, 8 females; mean age 64.1±8.4 years; range 48 to 77 years) were selected as control subjects. Mean left atrial diameter determined by echocardiography was 54.8±3.4 mm in the AF group compared to 40.7±4.1 mm in controls (p=0.001). The right atrial appendage tissue samples were excised before extracorporeal circulation in all patients. We assessed the onset of in situ DNA fragmentation by using the TUNEL assay. Furthermore, we examined the expression pattern of anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins using immunohistochemistry.

Results: Bax and Bcl-2 expression were similar between the AF group and control subjects (16.2% versus 15.1%, p=0.73; 14.6% versus 16.1%, p=0.64, respectively). However, when compared with controls, atrial myocyte apoptosis was significantly higher within the AF group (mean apoptotic index, 21.9% versus 11.8% respectively, p=0.002). Atrial tissue from permanent AF-affected individuals had atrial myocyte nuclei that were positive for TUNEL whereas control subjects had either TUNEL negative or low-grade TUNEL positivity.

Conclusion: This pilot study demonstrated a positive correlation between AF and DNA fragmentation, a terminal determinant of apoptosis. The results suggest a potential link between the pathogenesis of permanent AF and atrial myocyte apoptosis. Targeted anti-apoptotic strategies may have a clinical value by preventing atrial remodeling and fibrosis.