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Hypertrophic cardiomyopathy (HCM) is underscored by profound phenotypic and genotypic heterogeneity. Echocardiographically, HCM can be categorized in 4 different morphological subtypes: reverse curve-, sigmoidal-, neutral contour-, and apical variant-HCM. Previous studies indicate that reverse curve-HCM is the strongest single predictor of a positive genetic test. Much less is known about the genotypic and phenotypic spectrum associated with apical-HCM.
Between 1999 and 2007, 1053 unrelated patients with the clinical diagnosis of HCM (60% male, age at diagnosis 44.4 ± 19 years) underwent sarcomeric HCM genetic testing. Blinded to the genetic test results, each echocardiogram was scored for septal morphology and phenotyping was performed using the patient's electronic medical record.
Overall, 70 patients (7%) had apical-HCM on echocardiography; 64% of these patients were male with average age at diagnosis of 47.5 ± 15 years and mean left ventricular wall thickness of 19.8 ± 6 mm. As expected, left ventricular outflow tract obstruction was uncommon (7; 10%). Seventeen patients (24%) had a positive genetic test with the majority of mutations found in MYBPC3 (6; 35%) and MYH7 (6; 35%). Two patients (12%) had more than 1 mutation, 2 patients (12%) had a mutation in TNNI3 and 1 (6%) in TNNC1. Compared to patients with reverse curve-HCM, patients with apical-HCM were older at diagnosis (47 ± 15 vs. 36.8 ± 19 years; p<0.001) and were less likely to have a positive family history of HCM (30% vs. 46%; p=0.02) which was reflected in a significantly lower yield of genetic testing for patients with apical-HCM (24%) compared to patients with reverse curve-HCM (59%, p < 0.0001).
In this largest cohort of unrelated patients with genetic testing for clinically diagnosed HCM, <10% exhibited apical variant disease. This least common morphological subtype of HCM was associated with a negative genetic test result over 75% of the time. In contrast to prior publications suggesting a predilection for ACTC1/TPM1 mutations in patients with apical-HCM, the two most common HCM genotypes (MYBPC3- and MYH7-HCM) remained most common among the minority who had a positive genetic test.
Poster Sessions, Expo North
Saturday, March 09, 2013, 10:00 a.m.-10:45 a.m.
Session Title: Hypertrophic Cardiomyopathy: Variants and Outcomes
Abstract Category: 23. Pericardial/Myocardial Disease
Presentation Number: 1122-149
- 2013 American College of Cardiology Foundation