Late Gadolinium Enhancement and Extracellular Volume Fraction Between Sarcomeric Mutation Positive and Negative Hypertrophic Cardiomyopathy

Abstract

Introduction Hypertrophic cardiomyopathy (HCM) is a genetic disorder with an autosomal dominant pattern of inheritance and variable expression and penetrance. Traditional genetic testing has a yield of approximately 60%, due in part to a lack of identified causal genes. Patients with an identified sarcomeric mutation have worse outcomes with a higher incidence of sudden cardiac death though the underlying mechanism behind this is incompletely understood. Cardiac MRI has emerged as a modality to detect fibrosis, and HCM patients with focal/replacement fibrosis measured by late gadolinium enhancement (LGE) have a higher incidence of malignant ventricular arrhythmias and may develop systolic heart failure. Few studies exist investigating patterns of LGE between gene mutation positive (G+) and gene mutation negative HCM patients (G−). And to date, no study has compared diffuse fibrosis measured by extracellular volume (ECV) between these two groups in HCM. Hypothesis HCM patients with an identified gene mutation will have more focal/replacement fibrosis (measured by LGE) and diffuse fibrosis (measured by ECV) than HCM patients without an identified mutation. Methods and Results A total of 336 patients with a diagnosis of HCM underwent a cardiac MRI at our institution between 4/2012 and 2/2017. Genetic testing was performed on 73 (mean age 49.6, 66% male) of these patients (29 G+, 39 G−, 5 variant of unknown significance or VUS). LGE was more commonly seen in G+ compared to G− patients (86 vs. 56%, OR 4.3, p = 0.01) and LGE measured as percentage of LV mass was significantly higher in G+ patients (7.5 ± 5.5 vs. 3.0 ± 3.0%, p Figure 1 ]. ECV from myocardial segments excluding LGE was similar among all groups (26.9 ± 2.9, 25.6 ± 3.0, and 25.9 ± 1.2%, p = 0.28) for G+, G-, and VUS cases respectively [ Figure 2 ]. Conclusion Genotyped HCM patients with an identified sarcomeric mutation have more focal/replacement fibrosis, but not diffuse fibrosis measured by ECV when compared to HCM patients without an identified mutation.