Recent clinical trials have shown that selected patients with recurrent vasovagal syncope (VVS) may benefit from permanent cardiac pacing. In a previous study using head-up tilt testing (HUT) the authors demonstrated that the increase in sympathetic activity preceding syncope could be sensed by a microaccelerometer located in the tip of a ventricular pacing lead and used to drive a rate adaptive pacer. They compared in a single blind randomized crossover study, DDDR pacing driven by this system, with conventional DDI pacing in patients with recurrent VVS. Twenty-three patients (age 61.8 +/- 15.2 years, 19 men) with recurrent VVS were enrolled at seven European centers and underwent implantation of a "MiniLivingD/Best" pacing system. Inclusion criteria were (1) > 6 cumulative syncopal episodes or > or = 1 syncope within 6 months of a positive HUT, and (2) a positive HUT with bradycardia. Using a crossover study design, the pacemakers were randomly programmed for two successive periods of 6 months to DDDR or DDI mode. The numbers of episodes of syncope and presyncope, and quality-of-life (QOL), were assessed at the end of each period. During the 6 months before implant, the mean number of syncopal episodes per patient was 3.2 +/- 9. During pacing in the DDDR mode, 0.09 +/- 0.29 syncope/presyncope per patient was observed, while during the DDI period 0.48 +/- 0.73 episodes per patient were reported (P < 0.05). QOL scores were 77.40 +/- 11.32 in the DDDR mode versus 74.45 +/- 14.59 in the DDI mode (NS). In patients with recurrent VVS, symptomatic recurrences were less frequent during contractility-driven DDDR pacing, than during DDI pacing. QOL was similar in the two pacing modes.