Canadian Trial of Physiologic Pacing - CTOPP


Physiologic vs. VVI pacing for prevention of cardiovascular death or stroke.


Physiologic pacing (AAI or DDD) would reduce the risk of cardiovascular death or stroke compared to ventricular pacing (VVI).

Study Design

Study Design:

Patients Screened: 7734
Patients Enrolled: 2568
Mean Follow Up: 36 months
Mean Patient Age: Mean 73

Patient Populations:

Sinus or AV node disease requiring pacing First pacemaker implant Age >18 years


Chronic atrial fibrillation Life expectancy <2 years

Secondary Endpoints:

Overall mortality Atrial fibrillation Hospitalization for CHF Systemic thromboembolism, Change of pacing mode Quality of life Cost

Drug/Procedures Used:

Ventricular vs. physiologic pacing

Principal Findings:

Among the 1474 patients randomized to VVI pacing, 25.2% received VVI devices, 73.3% received VVIR, 0.7% crossed over to a DDD, DDDR, or AAI device, and 0.2% did not receive a pacer. For the 1094 randomized to physiologic pacing, 52.8% received a DDD device, 35.2% received DDDR, 1.9% received AAI, 3.5% received AAIR, 5.7% crossed over to a VVI device, and 0.9% did not receive a pacer. The complication rate in the physiologic pacing group was 9.0% compared to 3.8% for the VVI arm, and was attributed to the additional lead needed for dual-chamber pacing. The two groups were equal with respect to pacer dependency, indication for implantation, and concomitant anti-ischemic, anti-platelet, and anti-arrhythmic therapy. The total study duration was 5 years, with a mean follow-up of 36 months. The event rate for the primary endpoint was 5.43 events per year for the VVI group and 4.78 events per year for the physiologic pacing group (p=.205). For all cause mortality, the event rate was 6.54 for the VVI group, and 6.25 events per year for the physiologic group. There were 1.09 strokes per year in the VVI group compared to 1.02 strokes per year in the physiologic pacing group. The incidence of CHF was 3.62 events per year in the VVI group compared to 3.02 per year in the physiologic group. None of these differences were statistically significant. Physiologic pacing was associated with a significant 18% relative reduction in the occurrence of atrial fibrillation (6.59 to 5.34 events per year, p = 0.0357), although this benefit did not become apparent until after 2 years. Seventy-five percent of patients were tested with a six-minute walk to assess their functional capacity. There was no significant difference in pre- or post- walk heart rates or in the total distance walked (VVI: 350+127 m, Phys: 356+127 m).


Ten nonrandomized studies have suggested a reduction in death and stroke from physiologic pacing. Previous suggestions for benefit have been prevention of atrial fibrillation and subsequent risk of stroke. Although there was a significant reduction in the occurrence of atrial fibrillation by physiologic pacing, the risk of death or stroke from atrial fibrillation is low. As a result, this large, randomized study provides little support for a reduction in cardiovascular death by physiologic pacing strategies. This study suggests that we rethink the role of physiologic pacing compared to ventricular pacing alone. Because the only differences are in the late development of AF between the two groups, there may be little evidence to support the use of physiologic pacing in many patients. The cost implications of this study are equally important. It is possible that a difference in incidence of atrial fibrillation between the two modalities would increase with time.


1. Connolly SJ, Kerr CR, Gent M, Roberts RS, Yusuf S, Gillis AM, Sami MH, Talajic M, Tang AS, Klein GJ, Lau C, Newman DM. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators.N Engl J Med 2000 May 11;342(19):1385-91.

Keywords: Stroke, Follow-Up Studies, Dichlorodiphenyldichloroethane, Blood Platelets, Heart Rate, Heart Ventricles, Atrioventricular Node

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