Pacemaker Therapy in Patients with Neurally-Mediated Syncope and Documented Asystole. Third International Study on Syncope of Uncertain Etiology (ISSUE-3): A Randomized Trial
Background—The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally-mediated syncope (NMS) is controversial. We wanted to determine if pacing therapy reduces syncopal recurrences in patients with severe asystolic NMS.
Methods and 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 suffered ≥3 syncopal episodes in the prior 2 years. Initially, 511 patients, received a ILR; 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 (Pm) OFF and 8 to PmON. The 2-year estimated syncope recurrence rate was 57% (95% CI: 40-74) with Pm OFF and 25% (95% CI: 13-45) with Pm 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 NMS. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign NMS.
Clinical Trial Registration Information—ClinicalTrials.gov; Identifier: NCT00359203.
- Received November 26, 2011.
- Accepted April 2, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited