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Lamas GA, et al.. "Ventricular pacing or dual-chamber pacing for sinus-node dysfunction". The New England Journal of Medicine. 2002. 346(24):1854-62.
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Clinical Question

In patients who require permanent pacing support for bradycardia in the setting of sinus node dysfunction, does dual-chamber pacing improve mortality or stroke incidence compared to single chamber ventricular pacing?

Bottom Line

In patients who require permanent pacing support for bradycardia in the setting of sinus node dysfunction, dual-chamber pacing does not improve mortality or stroke incidence compared to single chamber ventricular pacing. However, dual-chamber pacing was associated with a 20% lower incidence of atrial fibrillation and a 2% decrease in heart failure hospitalizations.

Major Points

In the early 2000s, the predominant forms of permanent pacemaker (PPM) programming for bradycardic patients were single chamber ventricular pacing (VVIR) and dual-chamber pacing (DDIR). Although the newer DDIR technology had been developed many years prior and was being using routinely in patients with clinically significant bradycardia requiring pacer support, there was no RCT evidence to guide the choice of an appropriate pacing mode. Furthermore, DDIR devices are slightly more complex as they require a lead in the atrium as well as the ventricle, with slightly higher procedural complication rates.[1] Theoretically, by stimulating the atrium first followed by the ventricle, dual-chamber devices allow for AV synchrony which may lead to decreased atrial wall stress and a lower incidence of pacemaker syndrome (hypotension or discomfort attributable to atrial contraction against a closed semilunar valve).

The 2002 MOde Selection Trial (MOST) randomized 2010 patients to DDDR or VVIR pacing and investigated whether DDDR pacing led to lower mortality or stroke risk. After nearly three years of follow up, there was no significant difference between the pacing modes for this primary outcome. However, DDDR pacing was associated with a 20% relative risk reduction in new atrial fibrillation, an absolute 2% reduction in hospitalization for heart failure, and a significant decrease in heart failure symptoms.

Overall, these findings are highly consistent with those of the previous smaller CTOPP study which also demonstrated a lower rate of atrial fibrillation with DDDR pacing but failed to show a significant difference in terms of mortality or stroke. Importantly, over 30% of patients assigned to VVIR pacing had crossed over to DDDR pacing by the end of the study primarily due to pacemaker syndrome, potentially resulting in underestimation of the benefits of DDDR pacing. As a result, despite no difference in the primary endpoint, given the significant morbidity associated with AF and worsening heart failure, as well as increased experience and advances in DDDR technology allowing for lower procedural complication rates, data from these studies have made DDDR pacing the standard of care in patients undergoing PPM implantation for symptomatic bradycardia.


No guidelines have been published reflecting the results of this study.


  • Multicenter, double-blind, randomized, controlled trial
  • N=2,010
    • Dual-chamber pacing (n=1,014)
    • Single-chamber ventricular pacing (n=996)
  • Setting: 91 sites in the US
  • Period: Sept 25, 1995 - Oct 13, 1999
  • Median follow-up: 33.1 months
  • Analysis: Intention-to-treat
  • Primary outcome: Death or nonfatal stroke


Inclusion Criteria

  • 21 years old
  • Initial implantation of dual-chamber, rate modulated pacing system for sinus node dysfunction
  • In sinus rhythm at randomization
  • Mini Mental State Examination score > 16

Exclusion Criteria

  • Serious concurrent illness

Baseline Characteristics

From the ventricular pacing group.

  • Demographics: Median age 74, female 48%, white 86%
  • Co-morbidities: HTN 61%, HLD 34%, smoker 9%, prior MI 24%, heart failure 18%, prior stroke 11%, DM 20%, cardiomyopathy 11%, COPD 11%
  • Arrhythmia: SVT 52%, AF 44%, AV block 21%, CHB 5%, VT/VF 2%


  • All patients received dual-chamber capable devices
    • Patients then randomized 1:1 to DDDR or VVIR pacing mode
    • For both arms, lower heart rate set at 60bpm and upper heart rate set at 110bpm
  • Baseline measures at randomization
    • Comorbidities as assessed with Charlson Comorbidity Index
    • Quality of life as assessed with SF-36 questionnaire
    • Cardiovascular functional status as assessed with Specific Activity Scale
  • Follow-up evaluations occurred four times during the first year and twice yearly thereafter


Comparisons are DDDR vs. VVIR pacing. All p-values are adjusted.

Primary Outcome

Death or nonfatal stroke
21.5% vs. 23.0% (HR 0.91; 95% CI 0.78-1.13; P=0.48)

Secondary Outcomes

Death, stroke, or hospitalization for heart failure
27.6% vs. 29.9% (HR 0.85; 95% CI 0.72-1.00; P=0.05)
19.7% vs. 20.5% (HR 0.95; 95% CI 0.78-1.16; P=0.64)
4.0% vs. 4.9% (HR 0.81; 95% CI 0.54-1.23; P=0.33)
Hospitalization for heart failure
10.3% vs. 12.3% (HR 0.73; 95% CI 0.56-0.95; P=0.02)
Atrial fibrillation
21.4% vs. 27.1% (HR 0.77; 95% CI 0.64-0.92; P=0.004)
Heart failure score
1.49 vs. 1.75 (P<0.001)

Subgroup Analysis

There were no statistically significant differences in the risk of death, stroke, and hospitalization for heart failure between the two treatment groups among patients over 75 years of age, women, nonwhite patients, or patients with a history of supraventricular tachycardia.

Adverse Events

  • 30 day complication rate: 4.8%
    • Dislodgement or failure of atrial lead: 1.8%
    • Pneumothorax 1.5%
    • Dislodgement or failure of ventricular lead: 1.1%


  • Modest reduction in hospitalization for heart failure with DDDR pacing becomes statistically significant only after adjustment for baseline imbalances in comorbidities between the two therapy arms.
  • A significant proportion of patients assigned to the VVIR arm (31.4%) had crossed over to dual-chamber pacing by the end of follow up, primarily as a result of pacemaker syndrome. As a result, the benefits of DDDR pacing are likely underestimated.
  • Quality-of-life benefits of DDDR pacing were generally small, bringing into question their clinical relevance.


  • Some authors with ties to corporate sponsors providing financial support for the study

Further Reading

  1. Effects of Physiologic Pacing versus Ventricular Pacing on the Risk of Stroke and Death Due to Cardiovascular Causes 'N Engl J Med' 2000;342:1385-91