Abstract Body (Do not enter title and authors here): Background: Vascular remodeling, both neovascularization and lymphangiogenesis, associated with myocardial fibrosis following ischemic injury is well recognized. The presence of vascular remodeling in non-ischemic heart diseases is unclear, especially in idiopathic, i.e. primary myocardial fibrosis (PMF) leading to sudden cardiac death (SCD).

Purpose: As part of comprehensive histopathological characterization of PMF, we aimed to evaluate whether we could identify vascular remodeling in PMF, and would it differ according to etiology and the type of fibrosis.

Methods: The PMF subjects were derived from the FinGesture cohort, consisting of autopsy verified consecutive victims of SCD in Northern Finland between years 1998-2017 (n=5,869). Total of 24 PMF, eight ischemic and seven accidental/intoxication related death subjects were included in the study. To visualize the location and the type of fibrosis, myocardial samples of the left ventricle were stained with hematoxylin-eosin and Masson’s-Trichrome. Evaluation of vasculature structures was performed with alpha-smooth muscle actin (a-SMA), vimentin, CD34 and podoplanin. Digitalized samples were evaluated with digital microscope software.

Results: Neovascularization, and a-SMA positive pericytes, were observed only in the replacement fibrosis of ischemic and PMF subjects. Lymphatic vessels were especially observed in the ischemic group, not only in replacement fibrosis but also in the interstitial fibrosis. Although lymphatic vessels in PMF were observed in replacement fibrosis, the areas with interstitial fibrosis were rarely associated with lymphatic vessels.

Conclusions: a-SMA positive pericytes, neovascularization and lymphangiogenesis were associated with replacement fibrosis independent of the underlying etiology of fibrosis. Pathogenesis of interstitial fibrosis seem to differ according to etiology.