Abnormal Cardiac Formation in Hypertrophic Cardiomyopathy - Fractal Analysis of Trabeculae and Preclinical Gene Expression
Background—Mutations in genes coding for sarcomeric proteins cause hypertrophic cardiomyopathy (HCM). Subtle abnormalities of the myocardium may be present in mutation carriers without hypertrophy (G+LVH−) but are difficult to quantify. Fractal analysis has been used to define trabeculae in LV noncompaction and to identify normal racial variations. We hypothesized that trabeculae measured by fractal analysis of cardiovascular magnetic resonance (CMR) images are abnormal in G+LVH− patients providing a preclinical marker of disease in HCM.
Methods and Results—CMR was performed on 40 G+LVH− patients (33±15yrs, 38% men), 67 patients with a clinical diagnosis of HCM (53±15yrs, 76% men; 31 with a pathogenic mutation (G+LVH+)) and 69 matched healthy volunteers (44±15yrs, 57% men). Trabeculae were quantified by fractal analysis of cine slices to calculate the fractal dimension (FD) - a unitless index of endocardial complexity calculated from endocardial contours after segmentation. In G+LVH− patients apical LV trabeculation was increased compared to controls (maximal apical FD, 1.249±0.07 vs 1.199±0.05, P=0.001). In G+LVH+ and G−LVH+ cohorts, maximal apical FD 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 to controls, G+LVH− patients also had a higher frequency of clefts (28 vs 8%, P=0.02), longer anterior mitral valve leaflets (23.5±3.0 vs 19.7±3.1mm, P<0.0001), greater septal systolic wall thickness (12.6±3.2 vs 11.2±2.1mm, P=0.03), higher ejection fraction (71±4 vs 69±4 %, P=0.03) and smaller end-systolic volumes (38±9 vs 43±12mls, P=0.03).
Conclusions—Increased myocardial trabecular complexity is one of several preclinical abnormalities in HCM sarcomere gene mutation carriers without LVH.
- Hypertrophic cardiomyopathy
- cardiac magnetic resonance imaging
- hypertrophic cardiomyopathy
- cardiomyocyte hypertrophy
- left ventricular mass genetics
- Received August 9, 2013.
- Revision received March 17, 2014.
- Accepted March 23, 2014.