More Bad News for Chronic RV Pacing: MOST Substudy Finds Less Is More

June 30, 2003

June 30, 2003 - Recent data add weight to the argument that chronic right ventricular pacing in the dual chamber rate modulated (DDDR) mode produces poor outcomes. The latest findings from a substudy of the MOdeSelection Trial (MOST) indicate that ventricular desynchronization caused by chronic right ventricular pacing in patients with symptomatic sinus node dysfunction (SND) and normal QRS duration increases the risk of heart failure hospitalizations (HFHs) and atrial fibrillation (AF), even when atrioventricular synchrony is preserved. [1] The study was the first to report a strong association between ventricular pacing in the DDDR mode and heart failure in a clinical trial of pacemaker therapy for symptomatic SND. Investigators suggest that preservation of normal ventricular activation through minimal pacing strategies may reduce the risk of HFH and AF, however, they emphasize that further research is warranted.

Data for the current analysis was extracted from stored pacemaker diagnostic data acquired at each follow-up visit during the course of the MOST trial, a 6-year prospective, randomized comparison of single-chamber ventricular rate modulated (VVIR) pacing and DDDR in patients with SND. Percent ventricular paced was determined from stored pacemaker diagnostic data obtained at each follow-up visit (median follow-up of 33.1 months), and cumulative percent ventricular paced (Cum%VP) was calculated for each patient. Baseline QRS duration < 120 ms was observed in 1339 patients; of these, 707 patients (52.8%) were assigned randomly to DDDR and 632 patients (47.2%) were assigned to VVIR. Most patients had normal left ventricular function (median ejection fraction, 55%) and mild or no symptoms of congestive heart failure at baseline.

Cum%VP was a strong predictor of HFH

Investigators found that Cum%VP was significantly higher in the DDDR group than in the VVIR group (median, 90% vs 58%, respectively; P < .001), and 50% of the DDDR group was ventricular paced continuously or nearly continuously, compared with only 20% in the VVIR group.

In total, 128 of the 1339 patients (9.6%) had >= 1 HFH during the study period. The authors noted that ventricular pacing > 40% of the time in DDDR mode was associated with a 2.6-fold increased risk of HFH, compared with pacing < 40% of the time ( P = .040) (Table). This risk increased to 3-fold when multiple HFHs were considered, suggesting not only that highly paced patients are at greater risk of HFH, but that they are also hospitalized for heart failure more often. According to the authors, the risk of HFH in DDDR mode might be reduced to ~ 2% if ventricular pacing is minimized to < 40%.

In VVIR mode, HFH risk did not increase until patients were paced > 80% of the time. In this group, ventricular pacing > 80% of the time was associated with a 2.5-fold increased risk of HFH, compared with pacing < 80% of the time (Table). Kaplan-Meier plots relating time to first HFH also showed early, sustained, and increasing incidence of HFH in DDDR patients with Cum%VP > 40% and in VVIR patients with Cum%VP > 80%.

Table. Effect of Cumulative Percent Ventricular Paced on HFH
Pacing Mode Hazard Radio (95% CI) P value
Cum%VP > 40 vs <= 40
First HFH

Unadjusted model* 3.01 .018
Adjusted model** 2.60 .040
Unadjusted model* 3.66 .0064
Adjusted model** 2.99 .024
Cum%VP > 80 vs <= 80
Unadjusted model* 3.13 .0001
Adjusted model** 2.50 .0012
Unadjusted model* 3.60 .0001
Adjusted model** 2.56 .0007

*Cum%VP as the only predictor
**Adjusted for other known predictors of HFH
CI indicates confidence interval; Cum%VP, cumulative percent ventricular paced; DDDR, dual chamber rate modulated; HFH, heart failure hospitalization; VVIR, single-chamber ventricular rate modulated

Risk of AF increased in both pacing modes as Cum%VP increased up to 80% to 85%

In addition to increasing HFH, ventricular pacing in both modes was associated with an increased rate of AF when Cum%VP increased up to about 80% to 85%. Kaplan-Meier plots showed early, sustained, and increasing incidence of AF among both DDDR and VVIR patients as Cum%VR increased. The magnitude of the increased risk was about 1% for each 1% increase in Cum%VP (up to 85%) in the DDDR group ( P = .0001) and it increased by 0.7% for each 1% increase in Cum%VP (up to 80%) in VVIR patients ( P = .014). This increased AF risk persisted when the models were adjusted for all other known baseline predictors of AF.

Increased HFH and AF rates in frequently paced patients is possibly related to ventricular desynchronization

The authors concluded that although DDDR pacing maintains AV synchrony, compared with ventricular pacing, it might come at the cost of a normal ventricular activation sequence. "The results of the present study strongly suggest that the discrepancy between the relative benefits of atrial compared with dual-chamber pacing in SND is due to adverse effects of asynchronous electrical activation of the left ventricle imposed by right ventricular apical pacing," the authors said. They added that the association between increased ventricular pacing and increased risk of HFH and AF might possibly relate to ventricular desynchronization and could be more "dramatic" in patients with reduced ventricular function and heart failure. Prospective, randomized trials comparing DDDR pacing with new dual-chamber minimal ventricular pacing techniques, and perhaps cardiac resynchronization therapy, are necessary to confirm these findings.

  1. Sweeney MO, Hellkamp AS, Ellenbogen KA, et al. Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction. Circulation. 2003;107:2932-2937.

By Staff Writer, Medscape CRM
Reviewer: Albert A. Del Negro, MD