Characterization of right ventricular outflow tract fat infiltrations in the healthy porcine and human heart

Introduction We recently found the presence of a pro-arrhythmic electrophysiological substrate with increased collagen content and slow conduction in the healthy right ventricular outflow tract (RVOT). An epicardial layer of fat is commonly found in the RVOT but whether fat penetrates in the myocardium and regulates RVOT structure and electrophysiology remains unknown. Objective To assess the presence and localization of fat infiltrations (FI) in the healthy RVOT. Methods The presence of FI was assessed histologically in Massonu0027s trichrome and Oil-Red-O stained sections from young healthy pigs ( n  = 4) and human donor hearts with no cardiac disease history ( n  = 5). High resolution MRI (9.4 T Bruker Biospin) was used to localize fat in formaldehyde-fixed human RVOTs. The expression of selected targets was assessed by qPCR and Western Blot in the subepicardial layer (EPI) of the RV free wall (RVFW) and RVOT of healthy pigs. Results Sporadic FIs could be observed in the pig RVOT but were absent in the RVFW. In human hearts, FIs were present in the RVFW, LV free wall but were larger in the RVOT. High resolution MRI showed the presence of 3 layers in the human RVOT wall with a thick epicardial fat layer, a transition layer composed of myocardial fibers and fat (up to 50% of wall thickness) and a muscular endocardial layer. Intramyocardial fat content increased with age. The mRNA expression of perilipin (PLIN1) and the adipogenic hormone adiponectin (ADIPOQ) was significantly higher in the RVOT EPI compared to the RVFW ( P P P Conclusion FIs are in direct contact with the adjacent myocardium in the healthy porcine and human RVOT. Activin-A is likely to contribute to the higher collagen content found in the healthy RVOT as observed in the atria. Thus, these infiltrations are likely to participate to RVOT slower conduction and arrhythmogenesis.