title: Pacemaker therapy in patients with neurally mediated syncope and documented asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE-3): a randomized trial.
abstract: BACKGROUND
  The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope.
  
  
  RESULTS
  Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of syncope with ≥3 s asystole or ≥6 s asystole without syncope within 12 ± 10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned to pacemaker OFF and 8 to pacemaker ON. The 2-year estimated syncope recurrence rate was 57% (95% CI, 40-74) with pacemaker OFF and 25% (95% CI, 13-45) with pacemaker ON (log rank: P=0.039 at the threshold of statistical significance of 0.04). The risk of recurrence was reduced by 57% (95% CI, 4-81). Five patients had procedural complications: lead dislodgment in 4 requiring correction and subclavian vein thrombosis in 1 patient.
  
  
  CONCLUSIONS
  Dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ≥40 years with severe asystolic neurally mediated syncope. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign neurally mediated syncope.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359203.
authors.affiliation: Department of Cardiology, Ospedali del Tigullio, Lavagna, Italy. mbrignole@ASL4.liguria.it
authors.forename: Michele
authors.initials: M
authors.lastname: Brignole
authors.forename: Carlo
authors.initials: C
authors.lastname: Menozzi
authors.forename: Angel
authors.initials: A
authors.lastname: Moya
authors.forename: Dietrich
authors.initials: D
authors.lastname: Andresen
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Blanc
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Krahn
authors.forename: Wouter
authors.initials: W
authors.lastname: Wieling
authors.forename: Xulio
authors.initials: X
authors.lastname: Beiras
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Deharo
authors.forename: Vitantonio
authors.initials: V
authors.lastname: Russo
authors.forename: Marco
authors.initials: M
authors.lastname: Tomaino
authors.forename: Richard
authors.initials: R
authors.lastname: Sutton
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006323:Heart Arrest / Q000150:complications*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010138:Pacemaker, Artificial; D055502:Secondary Prevention; D012720:Severity of Illness Index; D013575:Syncope / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome