INTRODUCTION: Ventricular desynchronization imposed by right ventricular (RV) apical pacing is associated with an increased risk of heart failure hospitalization and atrial tachyarrhythmia (ATA).As an alternative procedure, the RV septal pacing from various sites has been attempted because this method would be more physiological.The purpose of the present study was to determine if pacemaker-dependent patients have an increased benefit from alternative RV mid-septal pacing compared with conventional RV apical pacing in a Japanese cohort study.METHODS: A total of 263 patients (74±11 years, 131 men) requiring a pacemaker for symptomatic bradycardia were enrolled in the study, and were randomly assigned to the following treatment arms; the septal pacing (SP) (n=108) or the apical pacing (AP) (n=155).For patients assigned to SP, an active lead was used and the tip was fixed in the middle of inter-ventricular septum, where the shortest QRS duration was yielded by pace mapping.For AP, the tip of a pacing lead was fixed in the apical area.They were periodically followed at our outpatient clinics for 24 months.RESULTS: No complications occurred during follow-up period in all patient groups.At 24 months after implantation, QRS duration on paced beats was still significantly shorter in the SP group compared to the AP group (144±17 vs.169±15 msec; P<0.001).Cumulative percentage of ventricular pacing and data from standard echocardiogram did not differ significantly between the SP group and the AP group.B-type natriuretic peptide level in the blood, however, was significantly higher in the SP group than that in the AP group (68±72 vs.138±161 pg/ml; P<0.01).In patients assigned to SP, the risk of development of ATA were significantly lower (hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.20 to 0.81 ; P<0.001), and cumulative ATA burden were significantly less (52.6±181.3 vs.756.0±2425.9 hours; P<0.05) as compared to AP group.There was a significantly lower rate of the cumulative risk of cardiovascular death, hospitalization for heart failure or stroke in the SP group (HR, 0.18; 95% CI, 0.05 to 0.63; P<0.001).The difference in the rate of hospitalization for heart failure was not significant in unadjusted analyses between SP and AP groups (P=0.10).CONCLUSION: In pacemaker-dependent patients, alternative site pacing from RV mid-septum provides benefit over conventional apical pacing for the prevention of death due to cardiovascular causes, heart failure hospitalization or stroke.RV mid-septal pacing reduces the risk of ATA.