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  • Generally patients with VVS do not need continuous


    Generally, patients with VVS do not need continuous cardiac pacing, but require physiological pacing only at the moment of the vasovagal response. Petersen et al. [7] reported the efficacy of permanent DDI pacing with rate hysteresis in selected patients who presented with cardioinhibitory VVS. Previous studies [8,24] have shown that DDD with the RDR algorithm reduced syncopal episodes in patients with severe forms of the cardioinhibitory type of VVS. In the RDR algorithm, the pacemaker senses small decreases in I-BET-762 rate of around 10–20 beats per minute (bpm), then paces at a high rate of 110–120bpm for 1–2min. Ammirati et al. [25] showed that DDD-RDR pacing was preferable to DDD pacing with rate hysteresis. The ideal device for VVS should sense the initial heart rate drop and pace early in the episode at a relatively high rate [25]. The closed-loop stimulation (CLS) pacemaker algorithm is a system that permanently monitors the contractile state of the myocardium and converts the intrinsic information into rate regulation [26]. The concept of the CLS algorithm for preventing VVS is as follows: the CLS system detects a change in the contraction dynamics in the early generation phase of syncope, and counteracts the drop in blood pressure with an acceleration of the heart rate, preventing the syncope [26]. In 1998, Deharo et al. [27] reported the efficacy of a rate-responsive pacemaker driven by heart contractility for preventing the vasodepressive response. Deharo et al. [28] reported a multicenter, randomized study using a crossover design for comparison between DDDR pacing (a basic rate of 60bpm) driven by contractility and DDI pacing (a basic rate of 70bpm) with a rate hysteresis of 20bpm. Inclusion criteria were (1) >6 cumulative syncopal episodes or ≥1 syncope within 6 months of a positive HUT test, and (2) a positive HUT test with bradycardia. After implantation, the pacemakers were randomly programmed for 2 successive periods of 6 months to DDDR or DDI mode. Although the quality-of-life scores were not different, the numbers of episodes of syncope and presyncope were significantly less frequent during pacing in the DDDR mode (0.09±0.29 episodes per person) than in the DDI mode (0.48±0.73 episodes per person) (P<0.05). The efficacy of the CLS algorithm has been evaluated in several clinical studies [29–32]. The INotropy controlled pacing in VAsovagal SYncope (INVASY) study [29] demonstrated that CLS pacing was more effective than DDI pacing at preventing VVS recurrence in patients with a cardioinhibitory response to HUT. However, this study had several limitations: the low number of controls (n=9), relatively short-term follow-up (mean, 19 months), and use of DDI mode programmed at 40ppm. Kanjwal et al. [30] showed the role of DDD-CLS pacing in the reduction of the syncope burden for 32 highly symptomatic patients with asystole (>10s) or severe bradycardia (<30bpm) documented by IRL or during HUT in their short-term follow-up study (9±3 months). Bortnik et al. [31] reported the long-term (mean, 5.1±2.9 years) efficacy of DDDR-CLS pacing in prevention of recurrent VVS. Palmisano et al. [32] showed the superiority in prevention of the recurrence of syncope of CLS pacing compared with the RDR algorithm during the long-term follow-up (mean, 4.4±3.0 years) in a retrospective analysis. In 2013, Russo et al. [26] reported the effect of DDD-CLS pacing on syncope recurrence in VVS patients with a tilt-induced cardioinhibitory response in a prospective, randomized, single-blind, crossover study. The study consisted of 50 patients (mean age, 53±5 years) with indication for permanent DDD pacing for tilt-induced cardioinhibitory VVS. The patients were randomized after a 1-month period of stabilization to have CLS algorithm features programmed OFF or ON for 18 months each, using a crossover design. The numbers of syncopal and presyncopal episodes during active treatment were lower compared to those registered during no treatment (syncope: 2 vs. 15; P=0.007 and presyncope: 5 vs. 30; P=0.004). The pacing intervention in the early phase of VVS using the DDD-CLS algorithm seems to have a potential for preventing not only asystole or bradycardia, but also hypotension. However, we were unable to draw conclusions as to the best pacing algorithm for VVS due to the lack of a direct comparison study between the DDD-CLS algorithm and DDD-RDR pacing in the prevention of syncope recurrence in VVS.