Background: Arrhythmogenic cardiomyopathy (AC) is a genetically determined heart muscle disease characterized by progressive myocardial atrophy with fibro-fatty substitution. Originally reported as a disease of the right ventricle (RV), in the recent years a biventricular (BiV) involvement with even dominant or isolated left ventricular (LV) variants (so called “left dominant” AC, LDAC have been reported.
Purpose: To assess the whole pathologic spectrum either macroscopic or histologic of AC and the mode of death/failure by reviewing our heart specimens archive.
Methods: We reviewed the AC heart specimens and histologic slides of three series: a) juvenile SD (<40 years, total N. 723); b) cardiac transplantation – CT, (total N. 912); and c) general autopsy archives – extra cases (total N. 1996). For each case, we looked for the mode of death or failure (congestive heart failure or arrhythmias); type of involvement (RV, BiV or LDAC) and other gross and histological features, including aneurysms or thrombosis, the transmural extent of fibro-fatty replacement and the presence of inflammatory cells, necrosis and “cardiomyopathic” changes.
Results: A total N of 129 AC heart specimens have been enrolled, including 73 juvenile SD cases, 33 CT cases and 23 extra cases.
In the SD group (49 M, mean age 26 years), the AC phenotype is RV in 8 (11%), BiV in 42 (58%) and LDAC in 18 (25%). RV aneurysms were detected in 19 (26%), in the absence of endocavitary thrombosis or LV aneuryms.
In the CT group (18 M, mean age 45 years), the AC phenotype is RV in 2 (6%), BiV in 29 (88%) and LDAC in 2 (6%). RV aneurysms were detected in 26 (79%), endocavitary thrombosis in 10 (30%) and LV aneurysms in 6 (18%). A “spongy-like” appearance was present in 5 cases (15%).
In the AC extra group (20 M, mean age 42), the phenotype is BiV in 16 (70%) and LDAC in 6 (26%). The AC phenotype was absent in two mutation carriers who died in adolescence (“pre-phenotypic stage”); the cause of death was extracardiac in one and ventricular fibrillation with a myocarditis picture in the other.
At histology, the fibro-fatty replacement of the RV was transmural in 68% of SD, 91% of CT (p SD vs CT <0,01) and 52% of AC extra (p CT vs extra <0,01). The fibro-fatty or fibrous replacement of the LV free wall was transmural in 9% of SD, 27% of CT and 9% of AC extra (p SD vs CT <0,01). Inflammation and cardiac myocyte necrosis were detected in 95% of SD, 67% of CT and 91% of AC extra cases.
Conclusions: The phenotypic spectrum of the disease is wider than it was thought in the past. BiV variants prevail with the highest frequency in the CT series, whereas the LDAC variant reaches the highest prevalence in the juvenile SD group. RV aneurysms are a common finding in CT at difference from the SD hearts. Fibro-fatty replacement is not necessarily transmural, being frequently confined to the sub-epicardial or midmural layers not only in the LV free wall, but even in the RV free wall.