Sex differences in the substrate of atrial fibrillation and the outcome of thoracoscopic ablation

Abstract Background Women with atrial fibrillation (AF) suffer more from AF symptoms, a lower quality of life, and have an enhanced risk of stroke. The AF recurrence after ablation is higher in women than in men. We hypothesize that sex specific differences in the atrial fibrotic substrate underlie these differences in clinical outcome. Here, we sought to characterize atrial fibrosis and fibrosis formation in the left atrial appendage (LAA) of women and men undergoing thoracoscopic ablation of AF. Methods We used the excised LAA of 30 female and 30 male patients with persistent AF undergoing thoracoscopic AF ablation. Patients were matched for age. In addition propensity score matching was also conducted for adjusting intermediary variables such as AF duration, Age ≥ 75, Body mass index (BMI), and CHA2DS2-VASc score ≥ 4. LAAs were stained with picrosirius red to quantify collagen and with vimentin for fibroblasts. Images were analyzed automatically (Image J version 1.50i) using color deconvolution to identify the area fraction of collagen and fibroblast. Results Women had similar age as men (66.4±7.76 vs 66.1 ±7.57, P= 0.85) but had a trend toward more cardiovascular risk factors [CHA2DS2-VASc score ≥ 4, (23.3 vs 6.7)%, P=0.07]. The total percentage of fibroblasts was larger in women 14.98 (9.79-24.95) % than men 13 (5.85-17.46) %, P=.018. In addition, in women fibroblasts were located more in epicardially and endocardially than in the interstitium.[women 8.18 (5.06-13.36) % vs men 6.49 (2.73-9.92) % , P=0.005].There was not a remarkable differences in total amount of collagen between the groups [women 16.03 (9.67-26.98) % vs men 15.50 (9.50-20.90) %, P=0.57 ], but there was a trend towards more epicardial and endocardial collagen in women than men [11.81(5.75-22.11)% vs 10.24 (6.06-15.10) % , P=0.06]. Conclusion We demonstrate more epicardial and endocardial fibroblasts in the LAA of women compared to men with persistent AF. There was similarly a trend towards more epicardia and endocardial but not interstitial collagen deposition. These findings may –at least in part- underlie sex specific differences in AF pathophysiology and ablation outcome.