Abstract 16687: A Genetic Contribution to Postoperative Complete Heart Block Following Congenital Heart Surgery
Background: A familial variant of complete heart block (CHB) is described in association with a substitution mutation in Connexin-40 (GJA5 Q58L) resulting in impaired gap junction formation. We sought to identify genomic predictors that may independently predispose children to the development of early postoperative complete atrioventricular (AV) block following congenital heart surgery.
Methods: Subjects undergoing congenital heart surgery at our institution were consecutively recruited and enrolled from September 2007 through December 2014. In addition to DNA, demographic and perioperative clinical data were obtained from all subjects.
Results: Over the course of the study period, there were 1466 subjects enrolled who underwent 1986 operative procedures; DNA was available for analysis in 1756 cases (1424 subjects). The incidence of at least one episode of postoperative complete AV block was 3.7% (n=65). Genotyping of the common missense polymorphism rs10465885 in GJA5 among subjects yielded allele frequencies in Hardy Weinberg equilibrium (p=0.73), and analysis demonstrated a gene-dose effect association between T allele presence and incidence of postoperative complete AV block (linear by linear association, p=0.009). Multivariate logistic regression analysis demonstrates that TT homozygosity is associated with a two-fold increased odds of new onset complete AV block (OR 2.1, 95%CI 1.2-3.5, p=0.006), independent of other significant univariate predictors including patient weight (p<0.001), operative procedure including closure of a ventricular septal defect (p<0.001), chromosomal anomaly (p=0.016), cross clamp time (p<0.001), ionized calcium and serum lactate on admission (both p<0.001), inotrope use on admission (p<0.001), and preoperative digoxin administration (p<0.001).
Conclusions: A common missense single nucleotide polymorphism within a gene encoding Connexin-40 is associated with the development of early postoperative complete heart block, independent of established risk factors. A refined understanding of genotype-phenotype relationships may serve to guide early postoperative care following congenital heart surgery.
Author Disclosures: A.H. Smith: None. E.C. Flack: None. K. Crum: None. P.J. Kannankeril: None.
- © 2015 by American Heart Association, Inc.