Nature reviews. Cardiology
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Arrhythmogenic cardiomyopathy (AC) is a clinically and genetically heterogeneous disorder of heart muscle that is associated with ventricular arrhythmias and risk of sudden cardiac death, particularly in the young and athletes. Mutations in five genes that encode major components of the desmosomes, namely junction plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, and desmocollin-2, have been identified in approximately half of affected probands. AC is, therefore, commonly considered a 'desmosomal' disease. ⋯ Caution in the interpretation of screening results is highly recommended because a 'pathogenic' mutation is difficult to define. Experimental data confirm that this genetically determined cardiomyopathy develops after birth because of progressive myocardial dystrophy, and is initiated by cardiomyocyte necrosis; cellular and animal models are necessary to gain insight into the cascade of underlying molecular events. Crosstalk from the desmosome to the nucleus, gap junctions, and ion channels is under investigation, to move from symptomatic to targeted therapy, with the ultimate aim to stop disease onset and progression.
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This Review explores contemporary circulatory support in profound postinfarction cardiogenic shock. Frequently, death is the only alternative to implantation of a blood pump, so prospective randomized trials of device versus medical treatment are unacceptable and evidence is derived from clinical experience. Irrespective of ACC/AHA and European guidelines, no study has shown survival benefit for the intra-aortic balloon pump in patients with established shock. ⋯ Effective ventricular unloading is best achieved by surgical implantation of a temporary rotary or volume-displacement pump. After cardiopulmonary resuscitation, hemodynamic stabilization allows assessment of cerebral injury and prognosis. Published series demonstrate that 50-75% of patients with profound shock can be salvaged either through native heart recovery, urgent transplantation, or switch to a long-term pump.