Head-up Tilt Test in Patients With Reflex Syncope and Asystolic Response Who Received a Dual-chamber Pacemaker With the Closed Loop Stimulation (CLS) and Participated in the BIOSync Trial

The 2021 European Society of Cardiology guidelines recommend cardiac pacing in patients aged \>40 years with tilt-induced asystolic reflex syncope (class I, level of evidence A). The recommendation relies on recent results from the multicentre, randomised, double-blinded, parallel-design BIOSync trial (NCT02324920). The BIOSync study provided evidence of benefit of dual chamber pacing in patients with tilt-induced reflex syncope and confirmed the role of Head-up Tilt Table (HUTT) test as a diagnostic method for cardiac pacing in reflex syncope. The Closed Loop Stimulation (CLS) is able to measure changes in intracardiac impedance during the systolic phase of each cardiac cycle which are strictly correlated to the increased heart rate and right ventricular contraction speed which are usually present during the pre-syncope phase of the reflex. It was hypothesized that an early onset of CLS pacing may be triggered by the compensatory increase in heart rate to counteract vasodilation and pressure drop during the pre-syncope phase of the reflex. The BIOSync study showed a 77% reduced risk of syncope in the DDD-CLS group as compared to pacing off. The design of the BIOSync study did not allow to assess the specific effect that CLS adds to dual-chamber pacing. Despite DDD-CLS pacing, 22% of patients had syncopal recurrence in 2 years. Further investigations are therefore needed in order to reduce this failure rate. Indeed, it is still unclear whether syncopal recurrences should be ascribed to dominant vasodilation or if the CLS programming/functioning needs optimization to more adequately sustain cardiac output during reflex in these specific cases.