Abstract 10958: Impact of Combined Abnormalities of Troponin-Gene Mutations and Renin-angiotension System Polymorphisms on Occurrence of Atrial Fibrillation in Hypertrophic Cardiomyopathy: Results From Clinical and Genetic Analyses of Genotyped Patients
Background: Although the occurrence of atrial fibrillation (AF), one of the major complications of hypertrophic cardiomyopathy (HCM), can be determined by disease-causing sarcomere gene mutations and additional genetic factors such as renin-angiotensin system (RAS) polymorphisms, few data exist regarding the relationship between these genetic factors and the occurrence of AF in HCM patients.
Methods and Results: We studied 125 carriers with disease-causing sarcomere gene mutations of HCM namely MYH7, MYBPC3, TNNT2 and TNNI3 from 49 families (63 males, mean age 51±21 years). Relationship between disease-causing gene mutations, RAS polymorphisms (angiotensin-converting enzyme (ACE) insertion/deletion (I/D) and angiotensin II type 1 receptor (AT1-R) A/C1166), echocardiographic parameters and the occurrence of AF were examined. Thirty subjects (24%) had AF. Decreased ejection fraction (EF) and dilated left atrial dimension (LAd) were independent predictors of the occurrence of AF (p<0.05 and p<0.001, respectively). Troponin-gene group (TNNT2 and TNNI3, n=73) exhibited significantly larger LAd than other-gene group (MYH7 and MYBPC3, n=52) (42 mm versus 38 mm, p<0.05). Although the occurrence of AF was not different between Troponin-gene and other-gene groups (26% versus 21%, p=0.53), there was a trend toward early onset of AF in Troponin-gene group (log-rank test, p=0.056). The presence of both the ACE D and AT1-R C1166 alleles (n=9) was accompanied by lower EF than other genotypes (n=116) (48 % versus 59 %, p<0.05). Under these conditions, Troponin-gene with both the ACE D and AT1-R C 1166 alleles (n=7) was a risk factor for the occurrence of AF (57% versus 22%, p<0.05) and the initial onset of AF was significantly earlier in these subjects than other genotypes (n=118) (log-rank test, p<0.05).
Conclusion: These results demonstrate that HCM with Troponin-gene mutations with both the ACE D and AT1-R C1166 alleles could be at high risk for occurrence of AF and can have high possibility of early onset of AF associated with LAd dilatation and left ventricular systolic dysfunction in HCM. We suggest that in addition to screening for disease-causing gene mutations, detection of RAS polymorphisms might contribute to further risk stratification of HCM patients.
- © 2013 by American Heart Association, Inc.