title: A common angiotensin-converting enzyme polymorphism and preoperative angiotensin-converting enzyme inhibition modify risk of tachyarrhythmias after congenital heart surgery.
abstract: 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).
  
  
  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.
authors.affiliation: Thomas P. Graham Jr. Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee; Division of Pediatric Critical Care Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee. Electronic address: andrew.h.smith.1@vanderbilt.edu.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Smith
authors.affiliation: Thomas P. Graham Jr. Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: English C
authors.initials: EC
authors.lastname: Flack
authors.affiliation: Thomas P. Graham Jr. Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Kristie Y
authors.initials: KY
authors.lastname: Borgman
authors.affiliation: Thomas P. Graham Jr. Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee; Division of Pediatric Critical Care Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Jill P
authors.initials: JP
authors.lastname: Owen
authors.affiliation: Thomas P. Graham Jr. Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Fish
authors.affiliation: Department of Pediatric Cardiac Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: David P
authors.initials: DP
authors.lastname: Bichell
authors.affiliation: Thomas P. Graham Jr. Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Prince J
authors.initials: PJ
authors.lastname: Kannankeril
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006330:Heart Defects, Congenital / Q000601:surgery*; D006801:Humans; D054643:INDEL Mutation; D007223:Infant; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000517:prevention & control; D011300:Preoperative Care; D012307:Risk Factors; D013610:Tachycardia / Q000517:prevention & control*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A
keywords: Arrhythmias; Cardiac surgery; Congenital heart disease; Genomics; Pharmacogenetics