Hypertrophic cardiomyopathy (HCM) caused by autosomal-dominant mutations in genes that code for the structural proteins of the sarcomere, is the most common inherited heart disease. HCM is associated with progressive myocardial hypertrophy and fibrosis, ventricular dysfunction, and arrhythmias. Disease onset during childhood and adolescence carries the risk of morbidity and sudden cardiac death. This study evaluates the impact of the R-enantiomer of pioglitazone on the proteome of myocardial tissue using the α-MHC719/+ HCM mouse model.