Layer-specific proteomic analysis of human hearts in patients with sudden cardiac death

Histologically, cardiomyocytes were enlarged in all layers of SCD and CH cases without significant progression of myocardial fibrosis. The proteomic profiles of SCD and CH cases were distinguishable from those of control cases, especially in the inner layer. The levels of mitochondrial and calcium-handling proteins were significantly decreased in SCD hearts. Arrhythmogenic changes, including decreased PKP2 and RYR2 levels, developed in a stepwise manner from control through CH to SCD, most prominently in the inner layer. Immunohistochemical analysis showed reduced levels of PKP2 in intercalated disks and RYR2 in sarcomeres. Because proteomic alterations precede the progression of myocardial fibrosis, their detection may enhance the accuracy of postmortem diagnosis of SCD in middle-aged and older asymptomatic individuals with CH.