Heart failure, female sex and atrial fibrillation are the main drivers of atrial cardiomyopathy in cardiac surgery patients: results from the CATCH ME consortium

FUNDING ACKNOWLEDGEMENTS: Type of funding sources: Public grant(s) – EU funding. Main funding source(s): CATCH ME: Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly BACKGROUND: Atrial cardiomyopathy is emerging as independent prognostic factor in cardiovascular disease. Fibrotic remodeling, cardiomyocyte hypertrophy and a reduction in capillary density are histological hallmarks of atrial cardiomyopathy. The contribution of etiological factors to atrial cardiomyopathy has not been robustly quantified. PURPOSE: To quantify the relation between histological features of atrial cardiomyopathy and the clinical profile of patients. METHODS: We examined left (LA, n=91) and right (RA, n=75) atrial appendages sampled from a European cohort of patients undergoing cardiac surgery. Quantification of histological cardiomyopathy features was performed a recently developed and validated imaging analysis algorithm following myocardial triple staining with wheat germ agglutinin (WGA), CD31 and vimentin. The contributions of AF, heart failure (HF), sex, age, and 4 principal components accounting for confounding clinical characteristics to over-all and endomysial fibrosis were determined in a multivariate model. K-means clustering of 6 atrial histological features was performed to identify different types of remodeling. RESULTS: LA samples showed less fibrosis (p<0.001), a higher capillary density (p<0.05), a smaller capillary size (p<0.05), and larger cardiomyocytes (p<0.01) than RA samples. In both LA and RA, persistent AF was associated with endomysial fibrosis, while over-all fibrosis was not. Men had larger cardiomyocytes (LAA), while women had a higher degree of endomysial fibrosis (LA). Heart failure patients had more endomysial and over-all fibrosis (LA), a higher capillary density (LA) and capillary size (LA/RA). Samples clustered into 2 distinct clusters. One cluster showed fibrotic cardiomyopathy, with more endomysial (p<0.001) and overall fibrosis (p<0.001), more fibroblasts (p<0,001) and a higher capillary density (p<0.001). The other cluster showed hypertrophic cardiomyopathy, with hypertrophic cardiomyocytes (p<0.001). Patients with fibrotic cardiomyopathy were more often female (LA and RA, p<0.003) and had more often persistent AF (LA, p=0.031) or heart failure (LA, p<0.001). Patients with hypertrophic cardiomyopathy were more often male (LA and RA, p<0.003). CONCLUSIONS: Fibrotic cardiomyopathy is associated with female sex, persistent AF and heart failure while hypertrophic cardiomyopathy more often occurs in men. More research is needed to establish whether treatment of AF and heart failure prevents the development of atrial cardiomyopathy.