Sudden cardiac death in younger adults: autopsy diagnosis as a tool for preventive medicine

Sudden death in children and younger adults can be caused by potentially heritable cardiovascular disorders, and the fatal outcome is often the first symptom in apparently healthy subjects. In these cases, a careful autopsy becomes the sole diagnostic tool to guide the clinical screening of the families. The aims of the present study were (1) to assess the pathological substrate of sudden cardiac death in children and younger adults (age, 1-40 years) in a large prospective series using strict morphological criteria; and (2) to perform cardiological assessment of the relatives of the deceased subjects with cardiomyopathies or structurally normal hearts, potentially consistent with a heritable cardiac disease. We studied 100 consecutive cases. Autopsy findings included coronary artery disease (30%, atherosclerotic in the majority of cases), cardiomyopathies (22%), and various cardiac abnormalities (28%). In the remaining 20% of cases, the presence of significant morphological abnormalities of the heart was ruled out. Twenty of 42 families in which the heart of the proband was either affected by a cardiomyopathy or failed to show significant structural abnormalities could be contacted and provided informed consent to cardiological assessment. A potentially inherited cardiac disease was diagnosed in 4 (20%). Molecular genetic analysis was restricted to 3 of these families and revealed a mutation in the ryanodine receptor type 2 gene (RyR2) in 1. Our results underline the implication of autopsy findings for relatives and the importance of cardiological screening of family members to uncover familial cardiomyopathies or genetic arrhythmias and to adopt the proper therapeutic and preventive strategies. Genetic testing is still time consuming and costly: accordingly, it should be restricted only to selected cases.