title: Polymorphism modulates symptomatic response to antiarrhythmic drug therapy in patients with lone atrial fibrillation.
abstract: BACKGROUND
  The angiotensin-converting enzyme (ACE) deletion allele, ACE D, is associated with increased ACE activity and adverse outcomes in cardiovascular disease. Although activation of the renin-angiotensin-aldosterone system (RAAS) now appears to play a role in the pathophysiology of atrial fibrillation (AF), it remains to be determined if ACE genotype impacts response to conventional AAD therapy in patients with AF.
  
  
  OBJECTIVE
  The purpose of this study was to investigate whether response to antiarrhythmic drug (AAD) therapy in patients with AF is modulated by the ACE I/D polymorphism.
  
  
  METHODS
  We studied 213 patients (147 men, 66 women; ages 52 +/- 15 years) prospectively enrolled in the Vanderbilt AF Registry. AAD therapy outcome was defined prospectively as response if there was a >or=75% reduction in symptomatic AF burden or nonresponse if AF burden was unchanged, necessitating a change in drugs or therapy.
  
  
  RESULTS
  Lone AF (age <65 years, no identifiable cause) was present in 72 (34%) patients, whereas hypertension was the most common underlying disease in the remaining 141 (41%). AF was paroxysmal in 170 (80%) and persistent in 43 (20%). The frequencies of the DD, ID, and II genotypes were in Hardy-Weinberg equilibrium. Lone AF and DD/ID genotypes were highly significant predictors of failure of drug therapy (P <.005). In patients with lone AF, failure of drug response was 5%, 41%, and 47% in patients with II, ID, and DD genotypes, respectively, (P <.005, II vs. ID/DD).
  
  
  CONCLUSIONS
  These results provide further evidence for a role of RAAS activation in the pathophysiology of AF and point to a potential role for stratification of therapeutic approaches by ACE genotype.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37323-6602, USA. dawood.darbar@vanderbilt.edu
authors.forename: Dawood
authors.initials: D
authors.lastname: Darbar
authors.forename: Alison A
authors.initials: AA
authors.lastname: Motsinger
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.forename: James V
authors.initials: JV
authors.lastname: Gainer
authors.forename: Dan M
authors.initials: DM
authors.lastname: Roden
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism*; D000483:Alleles; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D000889:Anti-Arrhythmia Agents; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; D000111:Acetylcysteine