Abstract WP244: Increased Cardiac Fibrosis In Aged Female Mice May Increase The Risk Of Atrial Arrhythmogenesis And Stroke

Abstract

Introduction: Atrial fibrillation (AF) is an arrhythmia that leads to intracardiac clot formation and cardioembolic strokes. Female sex is an independent risk factor for AF related stroke. This is reflected in the CHA 2 DS 2 -VASc score which is used to stratify AF patients with high, intermediate and low risk of embolism; female sex is an automatic point. The underlying etiology for this sexual dichotomy is unclear. Our laboratory has demonstrated sex differences in atrial tachycardia in aged wild type mice. It is now increasingly recognized that atrial substrate remodeling may lead to increased arrhythmogenesis. We hypothesized that aged females have increased atrial fibrosis leading to enhanced conduction abnormalities and atrial arrhythmias. Methods: C57BL6/J wild type aged 20-24 months old male and female mice underwent Echocardiogram (using vevo 3100 imaging system) to measure cardiac output, ejection fraction, stroke volume and left atrial diameter. All mice were sacrificed and cardiac tissue was used for immunohistochemistry. Cardiac sections were stained with masson trichrome stain and Image J was used for quantification of fibrosis. Data was analyzed using two sample t-test on GraphPad PRISM. Results: On Echocardiogram, we found no significant difference in cardiac output, ejection fraction and stroke volume in aged male and female mice, p>0.5. We also measured the left atrial diameter in aged male (4.5 ± 0.2mm, n=4) and female mice (3.9± 0.2mm, n=6) and found no significant differences, p>0.05. This demonstrates no baseline cardiac function abnormalities in aged males and females. On masson trichrome staining of the cardiac tissue, there was increased cardiac fibrosis in aged females, fibrotic area 2.3±0.19, n=3, as compared to males, 0.74±0.03, n=8/gp, p=0.02. Conclusion: Our results indicate that aged females have increased cardiac fibrosis as compared to aged males, despite having similar and normal cardiac function on echocardiogram. This fibrosis/ atrial substrate remodeling may lead to conduction abnormalities and arrhythmias in aged females. Ongoing studies in our laboratory are evaluating the role of aging and loss of estradiol (at menopause) in atrial substrate remodeling, atrial arrhythmogenesis and stroke risk in aged females.