Guideline-based Pacing Therapy for Reflex Syncope
Guideline-based Pacing Therapy for Reflex Syncope
Study hypothesis: Dual-chamber pacemaker therapy with rate-hysteresis features is effective
 in preventing syncopal recurrences in patients affected by cardioinhibitory (CI) forms of
 reflex syncope diagnosed by means of carotid sinus massage, tilt table testing or implantable
 loop recorder (ILR). The outcome is measured either by the time to first syncopal recurrence
 or the total syncope burden.
Background Divergence of opinion exists regarding the efficacy of cardiac pacing in patients
 affected by different forms of reflex syncope.

 Definitions.

 Severe syncope is defined when:

 -  it is perceived by patient that it alters his/her quality of life, and

 -  is unpredictable because occurs without, or with very short prodromes < 10 sec (thus
 exposing patients to risk of trauma) or, if preceded by prodromes, syncope recurs
 despite appropriate therapies (CPM or drugs).

 Recurrent syncopes: at least 2 episodes during the last year (including the index episode) or
 3 episodes during the last 2 years (including the index episode).

 Suspected (undetermined) reflex syncope: the suspicion of reflex syncope is based on a
 history of uncertain syncope in the absence of (i) severe structural heart disease,
 significant ECG abnormalities, or rhythm disturbances; (ii) orthostatic hypotension; and
 (iii) non-syncopal causes of transient loss of consciousness.

 Study protocol

 1. The eligible patients undergo firstly carotid sinus massage (according to the method of
 symptoms); if a diagnosis of cardioinhibitory carotid sinus syndrome (CI-CSS) is made, a
 pacemaker is implanted and follow-up immediately starts.

 2. If the carotid sinus massage is negative or vasodepressor, the patients undergo tilt
 table testing (with nitroglycerin or clomipramine drug challenge); if a diagnosis of
 VASIS 2B form is made, a pacemaker is implanted and follow-up immediately starts.

 3. If tilt table testing is negative or a form different from VASIS 2B is induced, the
 patients undergo ILR implantation. If a diagnosis of asystolic reflex syncope is made, a
 pacemaker is implanted and follow-up immediately starts.

 End-points End-point of the study is syncope recurrence after pacemaker (PM) implantation.
 Syncope is defined as complete transient loss of consciousness. Pre-syncope is counted but it
 is not an end-point.

 Primary end-points:

 1. Comparison of the time to first syncopal recurrence in CI-CSS and CI-TTT pts with PM and
 in control patients with ILR.

 2. Intra-patient comparison of the syncope burden in the year before and in the year
 following PM implant in all patients receiving a PM (CCS, TTT and ILR groups). Index
 syncope is not counted.

 Follow-up One year after PM implantation for all enrolled patients for burden of syncope
 end-points Until the study end for time to first syncope recurrence end-points. Thus, the
 study ends one year after the enrollment of the last patient.

 Study size Based on the sample size calculation the study will stop when 700 patients are
 enrolled.
Inclusion Criteria:

 -  Patients affected by severe, recurrent, certain or suspected (undetermined) reflex
 syncopes, aged ≥ 40 years.

 Exclusion Criteria:

 -  Reflex syncopes due to reversible causes, e.g., vasoactive drugs, concomitant
 diseases, etc

 -  Suspected of certain cardiac syncope

 -  Syncope caused by orthostatic hypotension

 -  Non-syncopal causes of transient loss of consciousness