Table 1 Inclusion and exclusion criteria

Patients affected by clinical diagnosis of reflex syncope who meet all the following criteria:

 1- Age ≥40 years

 2- Significant limitation of social and working life due to unpredictable frequent syncopal recurrences (≥2 within the last year)

 3- Type 2B cardio-inhibitory response to the TT (according to the VASIS classification)

 4- Alternative therapies have failed or were not feasible

 5- Exclusion of other possible competitive causes of syncope

1- Any other indication to pacemaker, implantable defibrillator or cardiac resynchronization therapy, according to current guidelines

2- Any cardiac dysfunctions possibly leading to loss of consciousness:

 Overt heart failure

 Left ventricular ejection fraction (LVEF) <40% (echo-assessed within 3 months prior to study participation)

 Myocardial infarction Diagnosis of hypertrophic or dilated cardiomyopathy

 Clinically significant valvular disease

 Sinus bradycardia <50 bpm or sinoatrial block

 Mobitz I second-degree atrioventricular block

 Mobitz II second or third-degree atrioventricular block

 Bundle-branch block

 Rapid paroxysmal supraventricular tachycardia or ventricular tachycardia

 Pre-excited QRS complexes

 Prolonged QT interval

 Brugada syndrome

 Arrhythmogenic right ventricular cardiomyopathy

3- Symptomatic orthostatic hypotension diagnosed by standing BP measurement

4- Non-syncopal loss of consciousness (e.g., epilepsy, psychiatric, metabolic, drop-attack, cerebral transient ischemic attack, intoxication, cataplexy)

5- Symptomatic cardio-inhibitory carotid sinus hypersensitivity