Genotypic and phenotypic predictors of complete heart block and recovery of conduction after surgical repair of congenital heart disease

Abstract

BACKGROUND Complete heart block (CHB) is a major complication that occurs after congenital heart surgery. We hypothesized that genetic and clinical factors are associated with the development of postoperative CHB and recovery of atrioventricular (AV) conduction. OBJECTIVE The purpose of this study was to identify predictors of CHB and recovery after congenital heart surgery. METHODS Patients undergoing congenital heart surgery at our institution from September 2007 through June 2015 were prospectively enrolled in a parent study of postoperative arrhythmias. Patients with onset of CHB within 48 hours postoperatively were included in the study. Daily rhythm assessment was performed until demonstration of 1:1 conduction or pacemaker implantation. RESULTS Of 1199 subjects enrolled, 56 (4.7%) developed post-operative CHB. In multivariate analysis, preoperative digoxin exposure (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.3–4.4), aortic cross-clamp time (OR 1.08, 95% CI 1.04–1.11), ventricular septal defect closure (OR 2.2, 95% CI 1.2–4.1), and a common polymorphism in the gene encoding connexin-40 (GJA5 rs10465885 TT genotype; OR 2.1, 95% CI 1.2–3.8) were independently associated with postoperative CHB. Junctional acceleration (JA) (OR 4.0, 95% CI 1.1–15.1) and intermittent conduction noted during complete AV block (OR 9.1, 95% CI 1.0–80) were independently associated with 1:1 AV conduction recovery. Use of a multivariate model including both JA and intermittent conduction demonstrated good discrimination with a positive predictive value of 86% (95% CI 67%–96%) in predicting 1:1 conduction recovery. CONCLUSION Preoperative factors, including a missense polymorphism in GJA5, are independently associated with increased risk for CHB. JA and intermittent conduction may prove useful in predicting recovery of AV conduction among patients with CHB after congenital heart surgery.

Early postoperative arrhythmias in patients undergoing congenital heart surgery

“…Complete AV block is a hemodynamically important sequela and its incidence decreases to 1 to 5% from 25% with the development of modern surgical techniques and a better understanding of the anatomy of the conducting system. [ 22 - 24 ] In a study, Murray et al,[ 25 ] reported the incidence of complete AV block as 3.7%, Ayyildiz et al[ 26 ] reported as 6.7%.…”

Multiplex ligation dependent probe amplification - A useful, fast and cost-effective method for identification of small supernumerary marker chromosome in children with developmental delay and congenital heart defect

“…Congenital heart disease (CHD) is the most frequent type of congenital malformation with a relative incidence of 6/1000 live births and a small percentage of this CHD is related to chromosomal abnormality described in literature (1,2). An important cause of mortality and morbidity is represented by the malformation itself and by the complications which may occur in the long term (3,4). In the majority of these cases the etiology remains unknown, but among the known causes of congenital heart disease, approximately one third of cases is associated with genetic factors such as chromosomal anomalies identified in about 0.4 -26.8% of all CHD, copy number variants (CNVs), gene mutations (5)(6)(7)(8).…”

Identification of TTN as a novel candidate gene for atrioventricular block in a Chinese pedigree by whole-exome sequencing

“…As reported previously, many gap junction and ion channel genes such as KCNQ1, KCNE1, KCNH2, KCNE2, KCNJ2, SCN5A, CASQ2, ANK2, GJA5 and HCN4 were known to relate with AVB. 10–16 Besides, the structural protein TTN mutation (TTN p.Glu5365Asp;TTN p.Arg3067His; TTN p.Arg8985Cys) was reported previously to be detected among AVB patients. 6 TTN mutation was reported previously to be the genetic cause of cardiomyopathy, 17,18 one of the potential causes of AVB.…”