Regenerative and plastic insufficiency of cardiomyocytes comprises cell changes resulting from impaired DNA-dependent RNA synthesis and biosynthetic processes. It is accompanied by progressive involution of cytoplasmic structures and causes atrophy and partial elimination of cells without signs of coagulation and colliquative necroses. Segregation and fragmentation of nucleoli in cardiomyocyte nuclei, lysis of myofibrils, and focal degradation of the cytoplasm are ultrastructural signs of impaired protein synthesis. Intracellular cardiomyocyte regeneration is characterized by disorientation of newly formed myofibrils and their excessive elongation, which are related to DNA damages followed by changes in transcription and translation in cardiomyocytes. Calculation of the absolute number of cardiomyocytes is a new approach to evaluation of contractile myocardial insufficiency.