The vasovagal Syncope and pacing (Synpace) trial: rationale and study design

Area of Science:

• Cardiology
• Electrophysiology
• Neurology

Background:

• Recurrent vasovagal syncope (VVS) significantly impacts quality of life, though not directly fatal.
• Previous studies suggest dual-chamber pacemaker implantation may reduce VVS recurrences.
• The efficacy of VVS drug therapy remains controversial, and prior pacemaker studies lacked placebo control.

Purpose of the Study:

• To determine if dual-chamber pacemakers with the rate drop response algorithm ON reduce syncope relapses compared to OFF in VVS patients.
• To evaluate hemodynamic responses during tilt-induced syncope to identify patients who benefit most from pacemaker implantation.
• To conduct a multicenter, prospective, randomized, double-blind, placebo-controlled trial (Synpace trial).

Main Methods:

• Patients with at least six lifetime syncopal episodes and positive head-up tilt testing (asystolic or mixed response) with recurrence post-tilt were enrolled.
• Exclusion criteria included non-vasovagal syncope and other indications for pacing.
• The study protocol involved 20 minutes of head-up tilt at 60 degrees, followed by 15 minutes after sublingual nitroglycerin.

Main Results:

• The study hypothesizes a 70% annual syncope recurrence risk without intervention.
• A 20% risk reduction is attributed to placebo effect (pacemaker OFF), leading to a 50% recurrence risk.
• A 60% risk reduction is expected with the pacemaker ON, implying a 10% annual recurrence incidence versus 50% with the pacemaker OFF.

Conclusions:

• The Synpace trial aims to provide placebo-controlled evidence for dual-chamber pacemaker efficacy in managing recurrent vasovagal syncope.
• Identifying specific hemodynamic responses (asystolic vs. mixed) may refine patient selection for pacemaker therapy.
• The study will analyze results separately and globally for both patient groups.