Tailored therapeutics for cardiomyopathies

The term cardiomyopathy is used to describe a large family of complex heart muscle disorders of diverse aetiology and pathophysiology. For decades, the management of individual cardiomyopathy subtypes has focused primarily on the management of symptoms and the prevention of disease-related complications, such as heart failure and sudden cardiac death. Treatment of progressive myocardial dysfunction has relied on conventional evidence-based heart failure therapies, with variable success. In contrast to other areas of medicine, cardiology is characterized by few aetiology-targeted therapies, but cardiomyopathies offer an ideal model for innovation because, in many individuals, the disorder has a monogenic cause, the expression of which is modified by complex genetic mechanisms, comorbidities and lifestyle. Elucidation of the complex cellular and molecular pathways that result in downstream tissue phenotypes has led to the investigation of new or repurposed pharmacological agents and, in parallel, therapies that modify or mitigate the effects of causative genetic variants, offering the prospect of targeting the disease at its source. In this Review, we describe some of the most promising therapeutic approaches in cardiomyopathy and discuss their potential effect on the lives of patients and relatives.