Milrinone reduces the risk of low cardiac output syndrome for some pediatric patients following congenital heart surgery. Data from adults undergoing cardiac surgery suggest an association between milrinone and increased risk for postoperative arrhythmias. We tested the hypothesis that milrinone is an independent risk factor for tachyarrhythmias following congenital heart surgery. Subjects undergoing congenital heart surgery at our institution were consecutively enrolled for 38 months, through September 2010. Data was prospectively collected, including review of full-disclosure telemetry and the medical record. Over 38 months, 603 enrolled subjects underwent 724 operative procedures. The median age was 5.5 months (0.0–426), weight was 6.0 kg (0.7–108), and the cohort was 45% female. Overall arrhythmia incidence was 50%, most commonly monomorphic ventricular tachycardia (n=85, 12%), junctional ectopic tachycardia (n=69, 10%), accelerated junctional rhythm (n=58, 8%), and atrial tachyarrhythmias (including atrial fibrillation, atrial flutter, and ectopic or chaotic atrial tachycardia, n=58, 8%). Multivariate logistic regression analysis demonstrated that independent of age less than 1 month, use of cardiopulmonary bypass, duration of cardiopulmonary bypass, RACHS-1 score greater than 3, and the use of epinephrine or dopamine, milrinone use on admission to the cardiac intensive care unit remained independently associated with an increase in the odds of postoperative tachyarrhythmia resulting in an intervention (OR 2.8 [95%CI 1.3–6.0], p=0.007). In conclusion, milrinone use is an independent risk factor for clinically significant tachyarrhythmias in the early postoperative period following congenital heart surgery.

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 (TOF), balanced atrioventricular septal defect (AVSD), and ventricular septal defect (VSD) at a single center. The incidence of postoperative JET was associated with previously identified clinical risk factors and ACE I/D genotype. Results Of 174 children who underwent the above surgeries, 21% developed JET. Post-operative JET developed in 31% of children with the D/D genotype and only 16% of those with I/I or I/D genotype (p=0.02). Clinical predictors of JET were selected a priori and included age, inotrope score, cardiopulmonary bypass and cross clamp times. Multivariable logistic regression identified a significant correlation between the D/D genotype and postoperative JET independent of these predictors (OR=2.4; 95% CI, 1.04-5.34; p=0.04). A gene-dose effect was apparent in the homogenous subset of AVSD subjects (58% JET in D/D subjects, 12% JET in I/D, and 0% JET in I/I; p<0.01). Conclusion The common ACE deletion polymorphism is associated with a greater than two-fold increase in the odds of developing JET in children undergoing surgical repair of AVSD, TOF, VSD, or Norwood or arterial switch procedures. These findings may support the potential role of the renin-angiotensin-aldosterone system in the etiology of JET.

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 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 through 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<0.001) and ICU length of stay (p<0.001). 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 (OR 1.6, 95%CI 1.1–2.3, p=0.02). 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=0.01), driven by a five-fold reduction in tachyarrhythmias among I/I genotype patients (OR 0.19, 95% CI 0.04–0.88, p=0.02). Conclusions 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.