Abstract 17536: Abnormal Cardiac Formation in Hypertrophic Cardiomyopathy - Fractal Analysis of Trabeculae Detects Pre-Phenotypic Gene Expression
Objectives: To evaluate whether left ventricular (LV) trabeculae are abnormal before overt disease expression in individuals carrying sarcomeric protein mutations that cause hypertrophic cardiomyopathy (HCM).
Background: Mutations of genes encoding for sarcomeric proteins cause HCM. Some HCM hearts are observed to have apparent macroscopic LV structural abnormalities even before hypertrophy -a pre-phenotypic marker in gene-positive hypertrophy-negative mutation carriers(G+LVH-). Fractal analysis (FA) defines trabecular complexity which is elevated in LV noncompaction and it detects trabecular differences in normal subjects with ethnicity. We hypothesized that FA of CMR images would be abnormal in HCM mutation carriers without LVH.
Methods: CMR was performed on 67 LVH+ HCM patients (53 ± 15yrs,76% M) who underwent next generation sequencing genotyping (31 G+LVH+;36 G-LVH+) and on 44 G+LVH- carriers (29 ± 2yrs, 35% M). CMR was performed in an equivalent group of matched healthy volunteers. All G+LVH- had a max. LV wall thickness <13 mm by CMR. Trabeculae were quantified by FA of end-diastolic cine slices in MATLAB to calculate the fractal dimension (FD): a unitless index of endocardial complexity, calculated from the shape of endocardial contours after segmentation using a level set method.
Results: In G+LVH- HCM, LV trabeculation was increased when compared to healthy volunteers (max. apical FD, 1.253±0.083 vs. 1.200±0.048, P=0.001)(mean±sd). In G+LVH+ and G-LVH+ HCM, trabeculation was higher than in normals (P<0.0001), irrespective of gene status (FD: G+LVH+ 1.370±0.084; G-LVH+ 1.380±0.092).
Conclusion: For the first time, trabeculae are shown to be abnormal in sarcomere G+ HCM before any overt phenotypic expression (LVH) by conventional methods. Sarcomeric protein mutations therefore cause abnormalities of LV trabecular architecture that may represent a “fingerprint” of genetic carriage identifying those that will progress onto manifest HCM.
- © 2013 by American Heart Association, Inc.