Beyond hypertrophy: unmasking sarcomeric hypertrophic cardiomyopath in a patient with wild-type ATTR amyloidosis

A 72-year-old male presented with new-onset heart failure. Initial evaluation showed low-voltage complexes on the electrocardiogram and left ventricular hypertrophy on transthoracic echocardiography (A). Given the suspicion of amyloidosis bone scintigraphy was performed, revealing myocardial tracer uptake (Perugini grade 3)(B). Further testing excluded the presence of monoclonal protein conforming the diagnosis of transthyretin amyloidosis (ATTR).
Further phenotyping using cardiovascular magnetic resonance (CMR) imaging showed diffuse late gadolinium enhancement of the left and right ventricle and interatrial septum consistent with amyloidosis (C). However, there were also hallmark features of sarcomeric hypertrophic cardiomyopathy (HCM), including reverse septal curvature, myocardial crypts, muscular band and an irregular wall pattern (D, E). Subsequently, DNA analysis was performed including the TTR gene but also the genes involving HCM, and identified a pathogenic variant in the MYBPC3 gene. No pathogenic variants were found in the TTR gene.