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][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00359203&atom=%2Fcirculationaha%2Fearly%2F2012%2F05%2F07%2FCIRCULATIONAHA.111.082313.atom