The Vasovagal Syncope and Pacing (Synpace) trial: rationale and study design

Background Though vasovagal syncope probably does not directly cause death, it is often associated with severe trauma and, when recurrent, significant ly impairs the patient's quality of life. While drug therapy for vasovagal syncope is still controversial, recently two randomized studies revealed th e efficacy of dual-chamber pacemaker implantation in decreasing recurrences in very symptomatic patients. However, since both studies were not placebo -controlled, the benefits observed might have been due to the placebo effec t of the pacemaker. Aim of the study The aim of the vasovagal Syncope and pacing (Synpace) tria l, a multicentre, prospective, randomized, double-blind, placebo-controlled trial, is to ascertain whether, in patients suffering from recurrent vasov agal syncope, the implantation of a dual-chamber pacemaker with rate drop r esponse algorithm programmed to ON, will reduce syncope relapses compared w ith the implantation of a pacemaker programmed to OFF. Moreover, in order t o evaluate the role of the haemodynamic response during tilt-induced syncop e in identifying those patients who will benefit most from pacemaker implan tation. enrolled patients will be divided into two groups on the basis of t heir haemodynamic behaviour during tilt-induced syncope: group 1, asystolic response (development of asystole > 3 s), and group 2, mixed response (dev elopment of bradycardia < 60 bpm, without asystole > 3 s). The head-up tilt testing protocol will consist of 20 min at 60 degrees without drug potenti ation, followed by 15 min at the same inclination after 400 mug of sublingu al nitroglycerin. Results from the two groups will be analysed both separat ely and globally. The primary clinical endpoint of the study will be syncop e. Inclusion and exclusion criteria To be enrolled, patients will have to meet the following criteria: at least six syncopal episodes in the patient's li fetime, positive head-up tilt testing with asystolic or mixed response; at least one syncope recurrence following a positive head-up tilt test. The fo llowing constitute exclusion criteria: non-vasovagal syncope, other indicat ions for pacing. Sample size We hypothesize a risk of syncope recurrence of 70% after one ye ar, and we estimate that - owing to the placebo effect alone - pacemaker wi ll produce a 20% decrease in risk, which corresponds to a 50% risk of recur rence after one year, in those patients randomized to 'pacemaker OFF'. We c alculate conservatively a risk decrease of 60% in patients with 'pacemaker ON'. This implies a 10% incidence of syncope recurrence after one year, vs 50%. in patients with 'pacemaker OFF'. Fifty patients will need to be enrol led in the study: 25 patients for each group. (C) 2001 The European Society of Cardiology.