Effectiveness of Closed Loop Stimulation pacing in patients with cardio-inhibitory vasovagal reflex syncope is questionable

This commentary refers to ‘Cardiac pacing in severe recurrent reflex syncope and tilt induced asystole’, by M. Brignole et al., doi:10.1093/eurheartj/ehaa936 and the discussion piece ‘Are convictions more dangerous enemies of truth than lies?’ by M. Brignole et al., doi:10.1093/eurheartj/ehab164. The results of the study by Brignole et al.1 of cardiac pacing in patients with severe reflex syncope and tilt-induced asystole (BioSync trial) are impressive. The estimated syncope recurrence rate at 2 years was 22% in paced patients vs. 68% in controls. Nevertheless, numerous questions about the role of cardiac pacing in patients with cardio-inhibitory vasovagal reflex syncope (ciVVS) remain.2,3 To be plausible, results of Closed Loop Stimulation (CLS) pacing need to be backed up by physiological theory.3 With regard to the CLS device, the authors suggest that early, rapid pacing of the right ventricle prevents the progressive fall in cardiac output during early presyncope before ‘full-blown’ ciVVS develops.1,3 Rapid pacing is triggered by a change in right ventricular impedance, which indicates an increase in right ventricular contractility, a suggested marker of impending ciVVS.1,4 We emphasize that all of these assumptions are hypothetical. At present, there is no physiological evidence to support the new CLS pacing algorithm as a plausible intervention. A cardio-inhibitory tilt test was used as a main inclusion criterion for patient selection in the BioSync study. Although not stated in the study protocol, a ‘reinterpretation’ of type 2B of the VASIS classification of tilt test results was used to define cardio-inhibition. Type 2B of the VASIS classification was defined as asystole >3 s after a fall in heart rate, which preceded or coincided with the onset of hypotension.5 The BioSync study ‘reinterpreted’ VASIS type 2B as asystole of >3 s regardless of when heart rate fell with blood pressure. This ‘reinterpretation’ of VASIS type 2B is relevant because it meant that patients with asystoles occurring after syncope were included in the BioSync study.3 A placebo or ‘expectation’ effect has been a major problem in previous studies of pacing in patients with ciVVS and needs to be considered as an explanation of the positive results of DDD-CLS pacing in the BioSync study.3 Rapid right ventricular pacing (up to 120 ppm) used in the BioSync study could cause palpitations, thereby unblinding the patients. This would have a reassuring effect in some, perhaps making them less likely to report hypotensive symptoms. It could also function as an early warning system for patients without prodromal symptoms giving them sufficient time to sit/lie down or use physical countermanoeuvres.3 The BioSync study does not address the important issue whether patients managed to unblind themselves or not.2 As far as blinding of physicians, an optional additional repeat tilt table test 1 month after implantation was part of the study protocol.4 No data are available about the blinding procedure during this additional tilt test. We conclude that the effectiveness of CLS pacing in patients with ciVVS remains highly questionable. Conflict of interest: none declared.