A common angiotensin-converting enzyme polymorphism and preoperative angiotensin-converting enzyme inhibition modify risk of tachyarrhythmias after congenital heart surgery.

BACKGROUND: The angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphism is described in association with numerous phenotypes, including arrhythmias, and may provide predictive value among pediatric patients undergoing congenital heart surgery. OBJECTIVE: The purpose of this study was to examine the role of a common polymorphism on postoperative tachyarrhythmias in a large cohort of pediatric patients undergoing congenital heart surgery with cardiopulmonary bypass (CPB). METHODS: Subjects undergoing congenital heart surgery with CPB at our institution were consecutively enrolled from September 2007 to December 2012. In addition to DNA, perioperative clinical data were obtained from subjects. RESULTS: Postoperative tachyarrhythmias were documented in 45% of 886 enrollees and were associated with prolonged mechanical ventilation (P <.001) and intensive care unit length of stay (P <.001). ACE I/D was in Hardy-Weinberg equilibrium (19% I/I, 49% I/D, 32% D/D). I/D or D/D genotypes were independently associated with a 60% increase in odds of new tachyarrhythmia (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.1-2.3, P = .02). Preoperative ACE inhibitor administration was independently associated with a 47% reduction in odds of postoperative tachyarrhythmia in the entire cohort (OR 0.53, 95% CI 0.32-0.88, P = .01), driven by a 5-fold reduction in tachyarrhythmias among I/I genotype patients (OR 0.19, 95% CI 0.04-0.88, P = .02). CONCLUSION: The risk of tachyarrhythmias after congenital heart surgery is independently affected by the ACE I/D polymorphism. Preoperative ACE inhibition is associated with a lower risk of postoperative tachyarrhythmias, an antiarrhythmic effect that appears genotype dependent. An understanding of genotype variation may play an important role in the perioperative management of congenital heart surgery.

A genetic contribution to risk for postoperative junctional ectopic tachycardia in children undergoing surgery for congenital heart disease.

BACKGROUND: Junctional ectopic tachycardia (JET) is a common arrhythmia complicating pediatric cardiac surgery, with many identifiable clinical risk factors but no genetic risk factors to date. OBJECTIVE: To test the hypothesis that the angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphism associates with postoperative JET. METHODS: DNA samples were collected from children undergoing the Norwood procedure; arterial switch operation; and repairs of Tetralogy of Fallot, balanced atrioventricular septal defect, and ventricular septal defect at a single center. The incidence of postoperative JET was associated with previously identified clinical risk factors and ACE I/D genotype. RESULTS: Of the 174 children who underwent the above-mentioned surgeries, 21% developed JET. Postoperative JET developed in 31% of children with the D/D genotype but only in 16% of those with the I/I genotype or the I/D genotype (P = .02). Clinical predictors of JET were selected a priori and included age, inotrope score, cardiopulmonary bypass time, and cross-clamp time. Multivariable logistic regression identified a significant correlation between the D/D genotype and postoperative JET independent of these predictors (odds ratio = 2.4; 95% confidence interval, 1.04-5.34; P = .04). A gene-dose effect was apparent in the homogeneous subset of subjects with atrioventricular septal defect (58% JET in D/D subjects, 12% JET in I/D subjects, and 0% JET in I/I subjects; P <.01). CONCLUSION: The common ACE deletion polymorphism is associated with a greater than 2-fold increase in the odds of developing JET in children undergoing surgical repair of atrioventricular septal defect, Tetralogy of Fallot, ventricular septal defect or the Norwood and arterial switch procedures. These findings may support the potential role of the renin-angiotensin-aldosterone system in the etiology of JET.