New insights into the pathology of inherited cardiomyopathy

Cardiomyopathies are defined as diseases of the myocardium, which cause cardiac dysfunction with heart failure, arrhythmia, and sudden death. Cardiomyopathies represent a major cause of morbidity and mortality in both children and adults and are a frequent indication for cardiac transplantation. In 1995, the World Health Organization (WHO)/International Society and Federation of Cardiology (ISFC) task force recommended that the cardiomyopathies be classified into two main groups: specific cardiomyopathies, and primary cardiomyopathies.1 The specific cardiomyopathies include heart muscle disease associated with myocarditis, specific cardiac disease or general systemic disease. In contrast, the primary cardiomyopathies are diseases intrinsic to the myocardium itself and are classified pathophysiologically. This group includes dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and unclassified cardiomyopathy. Idiopathic dilated cardiomyopathy (DCM) is the most common cause of congestive heart failure in the young with an estimated prevalence of at least 36.5 per 100 000 persons in the USA.w1 DCM is characterised by an increase in myocardial mass and a reduction in ventricular wall thickness. The heart assumes a globular shape and there is pronounced ventricular chamber dilatation, diffuse endocardial thickening, and atrial enlargement often with thrombi in the appendages. The histological changes associated with DCM are frequently non-specific and not all features may be present. These include the constellation of myocyte attenuation, interstitial fibrosis, myocyte nuclear hypertrophy, and pleomorphism. There is often an increase in interstitial T lymphocytes as well as focal accumulations of macrophages associated with individual myocyte death. Frequently there is extensive myofibrillary loss, imparting an empty or vacuolated appearance to myocytes. Although the aetiology of these cases is largely unknown, up to 35% of individuals with idiopathic DCM have familial disease.w2 This has been shown by detailed pedigree analyses of relatives of index patients with DCM coupled …