Possible mechanism for disposal of degenerative cardiomyocytes in human failing hearts: phagocytosis by a neighbour

Abstract

The index case was a 51‐year‐old woman suffering from doxorubicin cardiomyopathy. In her endomyocardial biopsy specimen, we observed under electron microscopy six scenes in which degenerative cardiomyocytes were engulfed by neighbouring cardiomyocytes. The enclosed cardiomyocytes appeared more degenerative than the enclosing ones in every pair: the myofibrils were more severely damaged. At more degenerative stages, some desmosomes of the intercalated discs on the enclosed cardiomyocyte had disappeared. The membranes between the cardiomyocytes were occasionally disrupted, and there appeared to be sharing of cellular contents between the cells. One pair of such a phagocytosis‐like figure was observed in one case with 5‐fluorouracil cardiomyopathy (a 68‐year‐old man) among eight other chemotherapy‐induced cardiomyopathies but none among 30 non‐drug‐induced dilated cardiomyopathies. The findings suggest a mechanism for disposal of degenerative cardiomyocytes in human failing hearts: phagocytosis by a neighbour, although alternative interpretations remain (e.g. giant autophagic vacuoles or two cardiomyocytes with degenerative intercalated discs).

Myocardial ultrastructure can augment genetic testing for sporadic dilated cardiomyopathy with initial heart failure

“…18 Diffuse myofilament lysis has previously been recognized in acute myocarditis due to Coxsackie virus infection 19 and in doxorubicin-induced cardiomyopathy. 20 It was considered to be a non-specific change due to various causes rather than as a result of the spread of focal myofilament derangement. We identified diffuse myofilament lysis in DCM associated with non-sarcomere-related gene variants, such as TMEM43 and DSP.…”