Cardiovascular disease is the world’s no. 1 killer responsible for premature death and disability affecting all stages of life. Sudden cardiac death accounts for approximately half of all heart disease related deaths and structural heart disease such as familial hypertrophic cardiomyopathy is the leading cause of death in people under the age of 30. Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic heart disease that affects approximately1:500 of the general population. Pathogenic features include ventricular hypertrophy, myocardial fibrosis, and diastolic dysfunction. At the level of the myocyte there is cytoskeletal disarray, hypercontractility and altered mitochondrial function. Mitochondrial dysfunction is considered to be a key driver in HCM pathology. The recently FDA approved cardiac myosin small molecule inhibitor mavacamten has demonstrated effective improvement in symptoms associated with severe outflow tract obstruction. Calcium channel antagonists are prescribed for the treatment of the symptoms of hypertrophic cardiomyopathy and the prevention of arrhythmias. However, there is no treatment that prevents the hypertrophy. Identifying therapeutic strategies to prevent the development of HCM is a significant clinical need. We previously demonstrated that the L-type Ca2+ channel plays a role in the development of HCM facilitated by a structural-functional communication between the channel and mitochondria involving the auxiliary beta subunit. We have designed peptides that interfere with the binding of the auxiliary β2 subunit to the α1C subunit causing immobilisation of the β2 subunit and decreasing mitochondrial metabolic activity. The peptides significantly improve contractility and prevent the development of the hypertrophy in murine models of HCM, providing evidence for an effective and safe first in class preventative therapy.