International Study on Syncope of Uncertain Etiology
International Study on Syncope of Uncertain Etiology
This is a multi-center, prospective, observational study enrolling 400 patients with
 suspected or certain neurally-mediated syncope, who undergo carotid sinus massage, tilt
 testing and Implantable Loop Recorder (ILR)implantation. In its second phase, which starts
 after the first ILR-documented syncope, the study will register the patient outcome after
 administration of ILR-guided therapy, which is left to the discretion of the physicians. The
 main objective is to verify the value of ILR in assessing the mechanism of syncope and the
 efficacy of the ILR-guided therapy after syncope recurrence.
Study purpose was to verify the value of an Implanted Loop Recorder (ILR) in assessing the
 mechanism of syncope and the efficacy of ILR-guided therapy after documentation of syncope
 recurrence in patients with suspected or certain neurally-mediated syncope at initial
 evaluation.

 Multi-center, prospective, observational study enrolling 400 patients with suspected or
 certain neurally-mediated syncope, who undergo carotid sinus massage, tilt testing and ILR
 implantation. In its second phase, which starts after the first ILR-documented syncope, the
 study will register the patient outcome after administration of ILR-guided therapy, which is
 left to the discretion of the physicians.

 Main objective: To verify the value of ILR in assessing the mechanism of syncope and the
 efficacy of the ILR-guided therapy after syncope recurrence.

 Secondary objectives:

 1. To define the exact mechanism of syncope in patients with suspected or certain
 neurally-mediated syncope based on the initial evaluation;

 2. To prospectively evaluate the correlation between tilt-induced syncope, ATP-induced
 asystolic response and/or carotid sinus hypersensitivity and ILR-documented spontaneous
 syncope associated with bradycardia and/or asystole;

 3. To assess the relationship between asymptomatic and symptomatic asystoles;

 4. To assess the effectiveness of pacing therapy for preventing syncope recurrence in
 patients implanted with a pacemaker after an ILR-documented syncope associated with
 asystole/bradycardia.

 Inclusion criteria:

 -  Suspected or certain neurally-mediated syncope, based on the Guidelines of the ESC TF on
 Syncope.

 -  3 syncope episodes in the last 2 years.

 -  Severe clinical presentation of syncope requiring treatment initiation in the judgement
 of the investigator.

 -  Age >30 years.

 -  Patients have undergone carotid sinus massage, and ILR implantation.

 Exclusion criteria:

 -  ILR not implanted for any reason; in this case, the patients are still followed in the
 ILR-not implanted group.

 -  Carotid sinus syndrome.

 -  Suspected or certain 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).

 -  Steal syndrome.

 -  Psychologically or physically (due to any other illness) unfit for participation in the
 study according to the opinion of the investigator.

 -  Patient compliance doubtful.

 -  Patients who are geographically or otherwise inaccessible for follow-up.

 -  Patient unwilling or unable to give informed consent;

 -  Pregnancy.

 -  Life expectancy < 1 year due to non-cardiac cause.

 Primary endpoints: Phase 1: first ECG-documented syncope Phase 2: first syncope recurrence
 after implementation of ILR-guided therapy

 Secondary endpoints: Phase 1:

 -  Asymptomatic ILR-documented arrhythmia

 -  ILR-documented pre-syncope/s

 Phase 2:

 -  Total number of syncopal recurrences

 -  Pre-syncope recurrence

 Study duration: ISSUE 2 will enroll a minimum of 400 patients during an anticipated period of
 3 years. As the study will continue for a period of 6 months after the enrollment of the last
 patient, total study duration will be approximately 4 years.
Inclusion Criteria:

 -  Suspected or certain neurally-mediated syncope, based on the Guidelines of the ESC TF
 on Syncope.

 -  3 syncope episodes in the last 2 years.

 -  Severe clinical presentation of syncope requiring treatment initiation in the
 judgement of the investigator.

 -  Age >30 years.

 -  Patients have undergone carotid sinus massage, and ILR implantation.

 Exclusion Criteria:

 -  ILR not implanted for any reason; in this case, the patients are still followed in the
 ILR-not implanted group.

 -  Carotid sinus syndrome.

 -  Suspected or certain 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).

 -  Steal syndrome.

 -  Psychologically or physically (due to any other illness) unfit for participation in
 the study according to the opinion of the investigator.

 -  Patient compliance doubtful.

 -  Patients who are geographically or otherwise inaccessible for follow-up.

 -  Patient unwilling or unable to give informed consent;

 -  Pregnancy.

 -  Life expectancy < 1 year due to non-cardiac cause