Gender Difference in the Long-Term Clinical Implications of New-Onset Atrial Fibrillation after Coronary Artery Bypass Grafting

PURPOSE: New-onset postoperative atrial fibrillation (POAF) is associated with poor short- and long-term outcomes after isolated coronary artery bypass graft (CABG) surgery. This study evaluated gender differences in the long-term clinical implications of POAF. MATERIALS AND METHODS: After propensity score matching, a gender-based comparison of long-term (>1 year) newly developed atrial fibrillation (LTAF) and mortality between 1664 (480 females) consecutive patients with (POAF) and without POAF (no-POAF) who had undergone CABG was performed. RESULTS: During a follow-up of 49±28 months, cumulative survival free of LTAF was lower in the POAF group than in the no-POAF group for both males (92.1% vs. 98.2%, p<0.001) and females (84.1% vs. 98.0%, p<0.001). However, female patients with POAF more frequently developed LTAF than male POAF patients (13.9 % vs. 6.9%, p=0.049). In multivariate analysis, POAF was a significant predictor of LTAF among males [hazard ratio (HR) 4.91; 95% confidence interval (CI) 1.22–19.79, p=0.031] and females (HR 16.50; 95% CI 4.79–56.78; p<0.001). POAF was a predictor of long-term mortality among females (adjusted HR 3.96; 95% CI 1.13–13.87, p=0.033), but not among males. CONCLUSION: Although POAF was related to LTAF in both genders, cumulative survival free of LTAF was poorer among females than among males. Additionally, a significant correlation with long-term mortality after CABG was observed among female patients with POAF.

The functional role of the CARM1-SNF5 complex and its associated HMT activity in transcriptional activation by thyroid hormone receptor

We have investigated the function and mechanisms of the CARM1-SNF5 complex in T3-dependent transcriptional activation. Using specific small interfering RNAs (siRNA) to knock down coactivators in HeLa alpha2 cells, we found that coactivator associated arginine methyltransferase 1 (CARM1) and SWI/SNF complex component 5 (SNF5) are important for T3-dependent transcriptional activation. The CARM1- SWI/SNF chromatin remodeling complex serves as a mechanism for the rapid reversal of H3-K9 methylation. Importantly, siRNA treatment against CARM1 and/or SNF5 increased the recruitment of HMTase G9a to the type 1 deiodinase (D1) promoter even with T3. Knocking- down either CARM1 or SNF5 also inhibited the down- regulation of histone macroH2A, which is correlated with transcriptional activation. Finally, knocking down CARM1 and SNF5 by siRNA impaired the association of these coactivators to the D1 promoter, suggesting functional importance of CARM1- SNF5 complex in T3-dependent transcriptional activation.