Cardiac magnetic resonance findings in two cases of hypertrophic cardiomyopathy with MYH7 and MYBPC3 variants: Limitations of genotype-based phenotypic prediction

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy, usually caused by sarcomeric variants such as MYH7 and MYBPC3. However, genotype–phenotype correlations remain incompletely defined. We report two patients with distinct genetic backgrounds and contrasting clinical and imaging findings. Case 1, a 40-year-old man with an MYH7 variant, was incidentally diagnosed while asymptomatic, showing basal septal hypertrophy with patchy late gadolinium enhancement (LGE) at the right ventricular insertion point. Case 2, a 37-year-old woman with an MYBPC3 variant, progressed from apical HCM diagnosed in adolescence to dilated-phase HCM with extensive LGE and advanced heart failure requiring defibrillator implantation, left ventricular assist device support, and listing for transplantation. These contrasting cases highlight the phenotypic heterogeneity of sarcomeric HCM. In HCM, the predictive value of single-gene variants is inherently limited for risk stratification, and cardiac magnetic resonance imaging plays a central role in comprehensive phenotypic assessment and prognostic evaluation.

Learning objective

To recognize that hypertrophic cardiomyopathy associated with the representative sarcomeric variants MYH7 and MYBPC3 exhibits marked phenotypic heterogeneity, and that the predictive value of single-gene variants is limited in risk stratification, with cardiac magnetic resonance imaging playing a central role in comprehensive phenotypic assessment and prognostic evaluation.