The article is based on work presented in the Distinguished Achievement Award lecture at the Society for Cardiovascular Pathology meeting in Seattle, WA, in March 2016. It reviews our current understanding of mechanisms responsible for a highly arrhythmogenic, nonischemic cardiomyopathy. It highlights the armamentarium of powerful methods available to the experimental pathologist in efforts to define how complex cardiovascular diseases work. It concludes with acknowledgment of the need for a far more detailed approach as to how we categorize human disease, a task for which pathologists are especially well positioned.
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