title: Cardiac pacing in patients with neurally mediated syncope and documented asystole: effectiveness analysis from the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) Registry.
abstract: OBJECTIVE
  The randomized, double-blind Third International Study on Syncope of Uncertain Etiology (ISSUE-3) showed that dual-chamber permanent pacing was effective in reducing the recurrence of syncope in patients ≥ 40 years with severe asystolic, probably neurally mediated syncope (NMS), documented by implantable loop recorder (ILR). Analysis in ISSUE-3 was performed according to the intention-to-treat principle. In the present study, we performed an on-treatment analysis, which included additionally those non-randomized patients followed up in the ISSUE registry to evaluate in a better manner the effectiveness of cardiac pacing therapy.
  
  
  RESULTS
  Initially, 504 patients received an ILR, 162 (32%) patients had a diagnosis consistent with NMS within a mean observation period of 15 ± 11 months: 99 (19%) patients had documentation of syncope with ≥ 3 s asystole or ≥ 6 s asystole without syncope. Sixty patients affected by asystolic NMS received cardiac pacing therapy and 86 (33 asystolic and 53 non-asystolic NMS) were untreated; 16 patients were lost to follow-up. Paced and unpaced groups had similar clinical characteristics. During subsequent follow-up, syncope recurred in 10 paced (17%) and in 40 non-paced (46%) patients. At 21 months, the estimated product-limit syncope recurrence rates were 27% [95% confidence interval (CI) 15-47] and 54% (95% CI 43-67), respectively (P = 0.01). With cardiac pacing, the risk of recurrence was reduced by 57% (hazard ratio = 0.43, 95% CI = 0.2-0.8). Complications of pacemaker therapy were haemothorax at implantation in one patient and lead dislodgement that required correction in two patients.
  
  
  CONCLUSIONS
  Permanent cardiac pacing is effective in reducing recurrence of syncope in patients ≥ 40 years with severe asystolic possible NMS with a few complications. The study shows that 61% of patients with a diagnosis of NMS made by ILR received a pacemaker but 5.1 ILRs had to be implanted to find one patient who finally had a pacemaker implanted.
authors.affiliation: Department of Cardiology, St. Mary's Hospital, Imperial College Healthcare NHS Trust, W2 1NY London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Sutton
authors.forename: Andrea
authors.initials: A
authors.lastname: Ungar
authors.forename: Paolo
authors.initials: P
authors.lastname: Sgobino
authors.forename: Vitantonio
authors.initials: V
authors.lastname: Russo
authors.forename: Riccardo
authors.initials: R
authors.lastname: Massa
authors.forename: Donato
authors.initials: D
authors.lastname: Melissano
authors.forename: Xulio
authors.initials: X
authors.lastname: Beiras
authors.forename: Nicola
authors.initials: N
authors.lastname: Bottoni
authors.forename: Hans H
authors.initials: HH
authors.lastname: Ebert
authors.forename: Maura
authors.initials: M
authors.lastname: Francese
authors.forename: Marcella
authors.initials: M
authors.lastname: Jorfida
authors.forename: Silvia
authors.initials: S
authors.lastname: Giuli
authors.forename: Angel
authors.initials: A
authors.lastname: Moya
authors.forename: Dietrich
authors.initials: D
authors.lastname: Andresen
authors.forename: Michele
authors.initials: M
authors.lastname: Brignole
mesh_terms: D000368:Aged; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects; D004311:Double-Blind Method; D004867:Equipment Design; D006323:Heart Arrest / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D010138:Pacemaker, Artificial; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012008:Recurrence; D012042:Registries; D013575:Syncope / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
keywords: Cardiac pacing; Loop recorder; Neurally- mediated syncope; Pacemaker; Syncope