AAV8-LDLr gene therapy in C57BL/6 LDLr-/- mice with only a mild degree of hypercholesterolemia enhances survival, counteracts left ventricular hypertrophy, attenuates metabolic remodelling, and improves heart function in a model of non-ischemic cardiomyopathy. Here, LDLR is linked to familial hypercholesterolemia.