Pacemaker Therapy in Patients With Neurally Mediated Syncope and Documented Asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE-3): A Randomized Trial

Study Questions:

Are pacemakers helpful in patients with asystole during episodes of neurally mediated syncope (NMS)?


Seventy-seven patients ≥40 years in age (mean age 63 years) with recurrent NMS and documented asystole for ≥3 seconds (mean 11 seconds) underwent implantation of a dual-chamber pacemaker with rate drop pacing capability. In double-blind fashion, the patients were randomly assigned to pacemaker-on (n = 38) or pacemaker-off (n = 39), and followed for 2 years. The primary outcome was recurrence of syncope.


The incidence of recurrent syncope was significantly higher in the pacemaker-off group than in the pacemaker-on group at 1 year (37% vs. 25%) and at 2 years (57% vs. 25%) of follow-up. Pacemaker therapy was associated with a 57% lower risk of recurrent syncope at 2 years.


The authors concluded that dual-chamber pacemakers significantly reduce the risk of recurrent syncope in patients with NMS and documented asystole.


Studies that have used implantable loop recorders have demonstrated that approximately 50% of episodes of NMS are associated with asystole. Although this high-quality study provides convincing evidence that pacemakers reduce the syncope burden in patients with NMS and asystole, only a small percentage of such patients have syncope that is frequent enough or disabling enough to justify any measures other than counseling, with or without therapy with fludrocortisone for volume expansion. Because a mixed cardioinhibitory-vasodepressor response is common during NMS, patients who are treated with a pacemaker should be informed that complete elimination of syncope is not guaranteed.

Clinical Topics: Arrhythmias and Clinical EP, Invasive Cardiovascular Angiography and Intervention, Implantable Devices, SCD/Ventricular Arrhythmias

Keywords: Cerebral Angiography, Fludrocortisone, Syncope, Pacemaker, Artificial, Heart Arrest, Cost of Illness

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