Fibrosis in Hypertrophic Cardiomyopathy Patients With and Without Sarcomere Gene Mutations

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) and an identified sarcomere mutation have worse outcomes than those without though the underlying mechanism is incompletely understood. The presence of replacement fibrosis measured by late gadolinium enhancement (LGE) and diffuse fibrosis measured by extracellular volume (ECV) using cardiac magnetic resonance imaging (CMR) are associated with ventricular arrhythmias and cardiac mortality. We aimed to associate these two forms of fibrosis with identified sarcomere mutations. METHODS AND RESULTS: Three hundred and thirty-six (336) patients with HCM underwent CMR at a single quaternary referral centre between January 2012 and February 2017. Genetic testing was performed in 73 of these patients, yielding an identified sarcomeric mutation in 29 (G+), no mutation in 39 (G-), and a variant of unknown significance (VUS) in five. LGE was more prevalent in G+ compared to G- patients (86 vs. 56%, OR 4.3, p=0.01) and was more extensive (7.5±5.5% of left ventricular [LV] mass vs. 3.0±3.0%, p<0.001). Global ECV from myocardial segments excluding LGE was similar among both groups (26.9±2.9 vs. 25.6±2.8%, p=0.46). However, in G+ patients ECV was greater in the hypertrophied regions of the basal anteroseptum (30.2±7.0 vs. 26.8±3.6%, p=0.004) and basal inferoseptum (28.1±4.3 vs. 26.2±2.9%, p=0.005). CONCLUSIONS: Genotyped HCM patients with an identified sarcomere mutation have greater LGE and greater regional, but not global, ECV than HCM patients without an identified mutation. This difference in fibrosis may contribute to worse outcomes in patients with an identified HCM mutation.