Addition of the CSM to an MVR procedure can decrease the risk of stroke or death and high sinus rhythm at 1 year without increasing the operative risk. CSM is a safe and effective approach to treating AF associated with RMVD.

Herein, we conceptualized a transient mediator approach that has the capability of para-selective C-H functionalization of monosubstituted aromatics. This approach is enabled by in situ generation of a versatile sulfonium salt via highly electrophilic phenoxathiine or thianthrene dication intermediate which can be readily generated from its sulfoxide with trifluoromethanesulfonic anhydride. Preliminary mechanistic study implied that the remarkable para selectivity might be related to the incredible electrophilicity of thianthrene dication intermediate. The versatility of this approach was demonstrated via para-borylation of various monosubstituted simple aromatics combining the sulfonium salt formation with further photocatalyzed transformation. 4 Scheme 4. Transformation of Aryl Boron Conditions: a) CH=CHCO2Et, Pd(OAc)2 (10 mol %), Na2CO3 (2.0 equiv), DMF, 50 o C, O2, 3 h; b) PhBr (1.0 equiv), Pd(dppf)Cl2 (5 mol %), K3PO4 (3.0 equiv), H2O (5.0 equiv), THF, 70 o C, 3 h; c) KI (1.5 equiv), CuI (10 mol %), 1,10-phenanthroline (20 mol %), MeOH/H2O (4:1), 80 o C, 20 h; d) MeOH, Cu(OAc)2 (1.0 equiv), DMAP (2.0 equiv), 4 Å MS, rt, air, 24 h; e) morpholine (2.0 equiv), Cu(OAc)2 (1.0 equiv), Et3N (2.0 equiv), 4 Å MS, CH3CN, 80 o C, air, 24 h. In summary, para-borylation of monosubstituted benzenes has been demonstrated using phenoxathiine or thianthrene as the transient mediator. Preliminary mechanistic study indicated that the key to the remarkable para-selectivity might be the use of highly electrophilic phenoxathiine or thianthrene dication species. Detailed mechanistic study and the application of this transient mediator approach for site-selective functionalization are ongoing projects in our laboratory. Experimental procedures, complete characterization data, copies of

The success rate of catheter ablation in atrial fibrillation (AF) is known to be lower in females than in males. However, while the exact mechanism for this phenomenon remains to be elucidated, tissue fibrosis may play an important role in this regard. It has been shown that fibrosis promotes AF and its recurrence, thereby substantially reducing the efficacy of catheter ablation in AF patients. Thus, we hypothesized that fibrosis may contribute to gender differences in the outcomes of AF catheter ablation.Here we systematically assessed pulmonary vein sleeves obtained from 166 patients with and without long-standing persistent-AF (LSP-AF) in order to identify gender-specific mechanistic differences in fibrosis remodeling of AF patients.Histological analysis revealed that the female LSP-AF group, rather than its male counterpart, had a higher degree of fibrosis when compared to the NON-AF group. Further analysis using microarray, immunohistochemistry and Western Blot displayed that gender differences in fibrosis remodeling of LSP-AF were mainly due to the inherent differential expression of fibrosis-related genes (n=32) and proteins (n=6). Especially, those related to the TGFβ/Smad3 pathway appeared to be up-regulated in the female LSP-AF group thus promoting an aggravation of fibrosis remodeling. In summary, our data suggest that the aggravation of fibrosis remodeling in women may be an important reason for the low success rate of AF catheter ablation when compared to men. Therefore, inhibiting the TGFβ/Smad3 pathway-mediated fibrosis could represent an interesting target for future therapeutic concepts to improve the success rate of AF catheter ablation in women.

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