© 2001 by European Society of Cardiology
PACING
The Vasovagal Syncope and Pacing (Synpace) trial: rationale and study design
1Division of Cardiology, Ospedale Umberto I Mestre (VE), Italy; 2Royal Brompton Hospital London, UK; 3Division of Cardiology, Ospedale Civile Cento (FE), Italy; 4Section of Arrhythmology, Ospedale Riuniti Lavagna (GE), Italy; 5Division of Cardiology, Ospedale Civile Fucecchio (FI), Italy; 6Division of Cardiology, Ospedale S.S. Annunziata Chieti, Italy; 7Division of Cardiology, Ospedale Civile Pescara, Italy; 8Section of Arrhythmology, Ospedale S. Maria Nuova Reggio Emilia, Italy
Abstract
BACKGROUND: Though vasovagal syncope probably does not directly cause death, it is often associated with severe trauma and, when recurrent, significantly impairs the patient's quality of life. While drug therapy for vasovagal syncope is still controversial, recently two randomized studies revealed the 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 effect of the pacemaker.
AIM OF THE STUDY: The aim of the vasovagal Syncope and pacing (Synpace) trial, a multicentre, prospective, randomized, double-blind, placebo-controlled trial, is to ascertain whether, in patients suffering from recurrent vasovagal syncope, the implantation of a dual-chamber pacemaker with rate drop response algorithm programmed to ON, will reduce syncope relapses compared with the implantation of a pacemaker programmed to OFF. Moreover, in order to evaluate the role of the haemodynamic response during tilt-induced syncope in identifying those patients who will benefit most from pacemaker implantation, enrolled patients will be divided into two groups on the basis of their haemodynamic behaviour during tilt-induced syncope: group 1, asystolic response (development of asystole >3 s), and group 2, mixed response (development of bradycardia <60 bpm, without asystole >3 s). The head-up tilt testing protocol will consist of 20 min at 60 degrees without drug potentiation, followed by 15 min at the same inclination after 400 µg of sublingual nitroglycerin. Results from the two groups will be analysed both separately and globally. The primary clinical endpoint of the study will be syncope.
INCLUSION AND EXCLUSION CRITERIA: To be enrolled, patients will have to meet the following criteria: at least six syncopal episodes in the patient's lifetime; positive head-up tilt testing with asystolic or mixed response; at least one syncope recurrence following a positive head-up tilt test. The following constitute exclusion criteria: non-vasovagal syncope; other indications for pacing.
SAMPLE SIZE: We hypothesize a risk of syncope recurrence of 70% after one year, and we estimate that — owing to the placebo effect alone — pacemaker will produce a 20% decrease in risk, which corresponds to a 50% risk of recurrence after one year, in those patients randomized to ‘pacemaker OFF’. We calculate 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 enrolled in the study: 25 patients for each group.
Key Words: Vasovagal syncope, dual-chamber pacemaker
Correspondence: Antonio Raviele, MD, Ospedale Umberto I, Via Circonvallazione, 50, 30174 Mestre-Venezia, Italy.
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  A. Raviele, F. Giada, C. Menozzi, G. Speca, S. Orazi, G. Gasparini, R. Sutton, M. Brignole, and for the Vasovagal Syncope and Pacing Trial Investi A randomized, double-blind, placebo-controlled study of permanent cardiac pacing for the treatment of recurrent tilt-induced vasovagal syncope. The vasovagal syncope and pacing trial (SYNPACE) Eur. Heart J., October 1, 2004; 25(19): 1741 - 1748. [Abstract] [Full Text] [PDF]
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