Abstract 12350: Detection of Preclinical Hypertrophic Cardiomyopathy Mutations With Advanced Imaging: The Hypertrophic Cardiomyopathy Network (HCMNet) Study
Background: Myocardial fibrosis is associated with worse clinical outcomes in hypertrophic cardiomyopathy (HCM) mutation carriers with overt left ventricular hypertrophy (LVH). However, hypertrophic cardiomyopathy (HCM) sarcomere mutation carriers may have only subtle, subclinical phenotypes until early adulthood, and the onset of LVH begets widely heterogeneous clinical sequelae. The aim of establishing this multicenter network was to identify reliable phenotypes and potential surrogate endpoints to monitor treatment response in HCM mutation carriers without LVH, or "preclinical HCM". Cardiac magnetic resonance (CMR) imaging was one of the tools used for phenotypic characterization.
Methods and Results: Contrast CMR was performed in 12 participating centers on a subset of sarcomere mutation carriers with LVH (G+/LVH+, n=48) and without LVH (G+/LVH-, n=35), as well as healthy related controls (G-/LVH-, n=25). Three-dimensional CMR modeling was used to assess left ventricular structure, systolic and diastolic function. Focal fibrosis was quantified using late gadolinium enhancement. Preclinical and overt HCM mutation carriers demonstrated step-wise decreases in both end-systolic volume (ESV) and end-diastolic volume (EDV), with detectable differences between healthy controls and preclinical HCM (ESV= 59.2±2.3 and 49.3±1.9; EDV= 145±4.0 and 130±3.1 with p=0.001 respectively). Late gadolinium enhancement (LGE) was present in 43% of overt HCM patients, but absent in preclinical HCM and controls. T1 values remote from regions of LGE did not differ between the three subgroups.
Conclusions: Sarcomere mutation carriers had smaller LV volumes, with the smallest volumes present in those with overt HCM. Focal fibrosis is a common finding that was not associated with T1 values in areas remote from focal myocardial scar.
- © 2013 by American Heart Association, Inc.