International study on syncope of uncertain aetiology 3 (ISSUE 3): pacemaker therapy for patients with asystolic neurally-mediated syncope: rationale and study design.
OBJECTIVE
To assess the effectiveness of pacing therapy for preventing syncope recurrence in patients with a high probability of cardio-inhibitory neurally-mediated syncope (NMS).


METHODS



METHODS
Multi-centre, prospective, double-blind, randomized placebo-controlled study.


METHODS
Eligible patients are at least 40 years of age and have suffered, in the prior 2 years, > or = 3 syncope episodes of suspected NMS (with the exception of carotid sinus syndrome), which is considered by the attending physician to have a severe clinical presentation requiring treatment initiation. Patients with positive and negative tilt testing are included.


METHODS
Patients with one or more of the following are excluded: carotid sinus syndrome; suspected or definite heart disease and high likelihood of cardiac syncope; symptomatic orthostatic hypotension diagnosed by standing blood pressure measurement; loss of consciousness different from syncope (e.g. epilepsy, psychiatric, metabolic, drop-attack, TIA, intoxication, cataplexy); subclavian steal syndrome.


METHODS
Eligible patients receive an Implantable Loop Recorder and are followed till the first documented syncopal recurrence or a significant asystolic event. Those patients who have an asystolic pause (sinus arrest or AV block) > 6 s or a syncopal asystolic pause > or = 3 s receive a dual-chamber pacemaker implantation and are randomized to active therapy (Pm ON) or to placebo therapy (Pm OFF). End-points: Primary end-point is the first syncope recurrence after pacemaker implant. Sample size and duration: A maximum of 710 patients are to be enrolled during an anticipated period of 2 years to allow randomization of 60 patients in the Pm ON arm and 60 in the Pm OFF arm (total 120).
Brignole
M
M
Department of Cardiology, Ospedali del Tigullio, Via don Bobbio, 16033 Lavagna, Italy. mbrignole@ASL4.liguria.it
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002170:Canada; D004311:Double-Blind Method; D005060:Europe; D006801:Humans; D008875:Middle Aged; D010138:Pacemaker, Artificial; D011446:Prospective Studies; D012107:Research Design; D055502:Secondary Prevention; D013575:Syncope / Q000209:etiology* / Q000628:therapy*; D014481:United States