Abstract
Hypertrophic cardiomyopathy (HCM) is often characterized by augmented cardiac contractility, which frequently remains undetectable in its early stages. Emerging evidence suggests that hypercontractility is linked to mitochondrial defects that develop early in HCM progression. However, imaging markers for identifying these early alterations in myocardial function are lacking. We used cardiac magnetic resonance feature tracking (CMR-FT) to assess myocardial strain in a Mybpc3-knockin (KI) mouse model that mimicked human HCM. While homozygous (HOM) mice exhibited cardiac hypertrophy, heterozygous (HET) mice represented an early, asymptomatic stage of HCM. To explore mitochondrial contributions to hypercontractility, we evaluated mitochondrial integrity via scanning electron microscopy (SEM) and correlated these findings with strain abnormalities. Young HET female, but not male mice exhibited significant torsion abnormalities (p = 0.02), reduced left ventricular global longitudinal strain (LVGLS, p = 0.009), and impaired right ventricular global longitudinal strain (RVGLS, p = 0.035) compared to the controls. Strain abnormalities correlated strongly with mitochondrial morphological alterations, including changes in volume and area distribution (R > 0.7). Abnormal myocardial strain patterns, including torsion and GLS, serve as early markers of HCM and are closely associated with underlying mitochondrial dysfunction. The HET Mybpc3-KI HCM model provides important insights into the initial stages of HCM progression, highlighting strain abnormalities and sex-specific differences to enhance early diagnosis and therapeutic strategies.