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Over the past decade, advances in early detection and diagnosis have begun to reveal the vast complexity of the primary etiologies that drive pathogenic cardiac remodeling and result in end-stage heart disease; an enduring health burden in the United States and throughout the world. While current treatments focus on the late stages of disease, where morphology, function and outcomes are often highly similar, there is growing evidence that improving patient care and management will require coupling early diagnoses to specific, targeted therapies that alter the natural history of these progressive and often devastating disorders. The development of these targeted therapies will require new ideas, new methodologies and new collaborations between basic and clinical scientists from disparate fields of cardiovascular research.