Abnormal Cardiac Formation in Hypertrophic Cardiomyopathy

Abstract

Background— Mutations in genes coding for sarcomeric proteins cause hypertrophic cardiomyopathy. Subtle abnormalities of the myocardium may be present in mutation carriers without left ventricular hypertrophy (G+LVH−) but are difficult to quantify. Fractal analysis has been used to define trabeculae in left ventricular noncompaction and to identify normal racial variations. We hypothesized that trabeculae measured by fractal analysis of cardiovascular magnetic resonance images are abnormal in G+LVH− patients, providing a preclinical marker of disease in hypertrophic cardiomyopathy. Methods and Results— Cardiovascular magnetic resonance was performed on 40 G+LVH− patients (33±15 years, 38% men), 67 patients with a clinical diagnosis of hypertrophic cardiomyopathy (53±15 years, 76% men; 31 with a pathogenic mutation [G+LVH+]), and 69 matched healthy volunteers (44±15 years, 57% men). Trabeculae were quantified by fractal analysis of cine slices to calculate the fractal dimension, a unitless index of endocardial complexity calculated from endocardial contours after segmentation. In G+LVH− patients, apical left ventricular trabeculation was increased compared with controls (maximal apical fractal dimension, 1.249±0.07 versus 1.199±0.05; P =0.001). In G+LVH+ and G−LVH+ cohorts, maximal apical fractal dimension was greater than in controls ( P <0.0001) irrespective of gene status (G+LVH+: 1.370±0.08; G−LVH+: 1.380±0.09). Compared with controls, G+LVH− patients also had a higher frequency of clefts (28% versus 8%; P =0.02), longer anterior mitral valve leaflets (23.5±3.0 versus 19.7±3.1 mm; P <0.0001), greater septal systolic wall thickness (12.6±3.2 versus 11.2±2.1 mm; P =0.03), higher ejection fraction (71±4% versus 69±4%; P =0.03), and smaller end-systolic volumes (38±9 versus 43±12 mL; P =0.03). Conclusions— Increased myocardial trabecular complexity is one of several preclinical abnormalities in hypertrophic cardiomyopathy sarcomere gene mutation carriers without LVH.