The latest results from the PACE study show that biventricular pacing continues to prevent deterioration of systolic function


Two-year results from the PACE study show that right ventricular apical pacing continues to be associated with left ventricular adverse remodelling and this deterioration is prevented biventricular pacing.

The two-year results of the PACE (Pacing to avoid cardiac enlargement) study were simultaneously published at the European Society of Cardiology (ESC) Congress and published online in the European Heart Journal. They are consistent with the results of the original PACE study: that biventricular pacing provides protection against the adverse effects of right ventricular apical pacing on systolic function and remodelling.

In the original PACE study (Yu et al, N Eng J Med 2009; 36: 2123–34), 177 patients with bradycardia and preserved left ventricular ejection fraction were randomised to receive right ventricular apical pacing or biventricular pacing. It showed that, at one year, biventricular pacing was superior to right ventricular apical pacing at preventing left ventricular adverse remodelling and preventing the deterioration of systolic dysfunction. In this two-year follow up study, 92% (88) of the patients in the right ventricular apical pacing group and 92% (82) of the biventricular pacing group were available for assessment. As in the original study, the co-primary endpoints were left ventricular ejection fraction and left ventricular end-systolic volume.

After two years, there were no significant differences in the rate of ventricular pacing between the groups (97.9±11.8% for right ventricular apical pacing vs. 92.9±22.6% for the biventricular pacing). However while left ventricular ejection fraction continued to decrease in patients with right ventricular pacing, there was no change in left ventricular ejection fraction in patients with biventricular pacing. Therefore, there was a significant 9.9% difference (p<0.001) in left ventricular ejection fraction between the two groups at two years.

Also, left ventricular end-systolic volume continued to increase in patients with right ventricular apical pacing but again, no increase was observed in patients with biventricular pacing. This resulted in a significant 13.0ml in left ventricular end-systolic volume (p<0.001) between the two groups at two years.

Investigators Chan et al reported in their discussion: “The PACE study was the first randomised study to show that biventricular pacing protects against the adverse effects of right ventricular apical pacing on left ventricular structure and function, and the current extended follow-up demonstrates that the protective effect persists for two years, even with high pacing burden.”

In accompanying editorial in the European Heart Journal, Kenneth Dickstein from the University of Bergen, Stavanger University Hospital in Norway, said that although the PACE trial provided evidence that physicians who are managing patients with a conventional pacing indication should take into account, several important questions remain. “As pointed out in the editorial accompanying the publication of the one-year results of PACE, right ventricular pacing in patients with sinus mode dysfunction without atrioventricular block is not required and may have resulted in avoidable reverse remodelling in these patients. This is perhaps the most important methodological and ethical criticism of this trial.” He added that another issue, which (as Dickstein reports) the PACE authors also acknowledge, is that the trial was underpowered for analysis of clinical events. “The sample size was small and the follow-up short, especially for asymptomatic patients with preserved ejection fraction.”

Dickenstein concludes his editorial by saying there is now a need to identify the target population who are at greatest risk for adverse remodelling following right ventricular pacing and, therefore, who are likely to receive the most benefit from receiving biventricular pacing instead. Although, he says using cardiac resynchronisation therapy (biventricular pacing) instead of right ventricular pacing will have a “considerable” impact on health resources, he explains it would be a good investment if the use of cardiac resynchronisation therapy in patients with bradycardia and preserved systolic function (ie, the patient population in the PACE study) is found to prevent meaningful adverse endpoints (such as hospitalisation for heart failure). “Benjamin Franklin put it well: ‘An ounce of prevention is worth a pound of cure.’ In this case, it is about two ounces.”