Sudden Death From Genetic and Acquired Cardiomyopathies

From the Aphorisms of Hippocrates to the sports fields of the twenty-first century, by both the lay public and the medical community, the cardiomyopathies have been recognized as causes of sudden cardiac death (SCD). Prevention of SCD in the cardiomyopathies is a 2-fold challenge. First, and central to clinical practice, is the need for reliable prognostication in individuals with established disease, and effective therapies to prevent or terminate events in those at risk. The second is the need for public health measures to preempt individuals with undiagnosed, asymptomatic disease from presenting with SCD: a not uncommon phenomenon in the cardiomyopathies. This review seeks to address the demographics and burden of SCD due to cardiomyopathy, its underlying mechanisms and determinants, and current approaches to risk prediction and management. Both genetic and acquired cardiomyopathies are discussed, with the former encompassing hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC), all of which demonstrate Mendelian inheritance. By expert consensus, the umbrella term “cardiomyopathy” is not applicable to myocardial dysfunction secondary to ischemic heart disease, valvular dysfunction, or congenital anomalies. Heart muscle disorders resulting from systemic, metabolic, or other identifiable causes are included if arrhythmia and SCD are prominent components of the phenotype.1 Burden of SCD From CardiomyopathyThe cardiomyopathies differ in the relative contribution of SCD to overall mortality, with ARVC ranking the highest, followed by HCM and then DCM, in which heart failure is the leading cause of death (Figure).2–7 In evaluating the burden of SCD related to cardiomyopathy, 3 distinct questions need to be addressed. First, what is the annual incidence of SCD among individuals with an established diagnosis of cardiomyopathy? Second, to what extent do cardiomyopathies account for SCD from undiagnosed cardiovascular disease—unexpected SCD—in the general population? A third and more involved issue is whether current medical …