DANPACE II: Minimizing atrial pacing in sinus node dysfunction leads to increased syncope with no difference in development of AF

By Lucas Marinacci on

Key Points

  • This trial randomizing patients with an indication for initial dual chamber (DDD) permanent pacemaker implantation (PPI) for sinus node dysfunction (SND) to a base rate of 60 beats per minute (BPM) with rate adaptive pacing (DDDR-60) or base rate of 40 BPM with non-rate adaptive pacing (DDD-40) found that there was no difference in the primary endpoint of atrial fibrillation (AF) lasting more than 6 minutes during 2 years of follow up.
  • There was also no difference in the secondary endpoints of AF lasting more than 6 or 24 hours, progression to permanent or persistent AF, cardioversions for AF, all cause mortality, quality of life, or 6 minute walk test.
  • However, rates of syncope were significantly higher in the DDD-40 group, as were the rates of crossover from the DDD-40 to the DDDR-60 group.
  • These results indicate that minimizing atrial pacing in patients SND did non prevent AF but did lead to an increased risk of pre-syncope or syncope.

The first DANPACE trial randomized patients with SND to single lead atrial pacing (AAIR) or dual chamber pacing (DDDR) and found that AAIR was associated with higher incidence of paroxysmal AF.1  A subsequent pot-hoc analysis among those in the DDDR arm found no association between percentage of atrial pacing and development of AF.2  However, meta-analyses have since demonstrated a dose-response relationship between atrial pacing burden and incident AF.3  Whether strategies to reduce atrial pacing for patients requiring PPI for SND would lead to a reduction in subsequent AF is unknown.

On August 28th, 2023 the results of the Minimized Atrial Pacing and Risk of Atrial Fibrillation in Sinus Node Dysfunction: DANPACE II trial were presented in a Hot Line Session at ESC Congress 2023.

In this open label clinical trial, patients across 11 centers in Denmark who underwent first-time dual chamber PPI for SND were randomized in a 1:1 fashion to DDDR-60 or DDD-40 and followed for two years.  Patients with permanent or persistent AF or persistent bradycardia or chronotropic incompetence that would preclude the lower base rate were excluded. The primary endpoint was AF lasting at least 6 minutes.

Overall, 539 patients were analyzed.  The median age was 73 years; 48% were female.  The median atrial pacing burden was 1% in the DDD-40 group and 49% in the DDDR-60 group (p<0.001).  There was no difference in the primary endpoint; 46% of both the DDDR-60 and DDD-40 groups AF lasting at least 6 minutes (HR 0.97, 95% CI 0.76-1.25; p = 0.83).  There was also no difference in the secondary endpoints of AF lasting at least 6 or 24 hours, progression to permanent or persistent AF, cardioversions for AF, all-cause mortality, or quality of life or 6-minute walk test assessed at 12 months.

However, the rate of syncope or presyncope was significantly higher in the DDD-40 group (22% vs. 13%, HR 1.71, 95% CI 1.13-2.59; p=0.01).   Similarly, the rate of crossover from DDD-40 to DDDR-60 was higher than the rate of crossover from DDDR-60 to DDD-40 (23% vs. 3%, respectively).  Among those who crossed over from DDD-40 to DDDR-60 , the most common indications were chronotropic incompetence (61%) and syncope or presyncope (29%).

According to study author Dr. Mads Brix Kronborg of Aarhus University Hospital, Denmark: “Atrial pacing minimization in patients with sinus node disease does not reduce the incidence of atrial fibrillation.  Programming a base rate of 40 BPM without rate-adaptive pacing was associated with an increased risk of syncope or presyncope.”


  1. Nielsen JC, Thomsen PEB, Højberg S, et al. A comparison of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome. Eur Heart J. 2011;32:686–96.
  2. Hjortshøj S, Riahi S, Nielsen JC, Skjøth F, Lundbye-Christensen S, Andersen HR. Does atrial pacing lead to atrial fibrillation in patients with sick sinus syndrome? Insights from the DANPACE trial. Europace. 2014;16:241–245.
  3. Elkayam LU, Koehler JL, Sheldon TJ, Glotzer T V, Rosenthal LS, Lamas GA. The influence of atrial and ventricular pacing on the incidence of atrial fibrillation: a meta-analysis. Pacing Clin Electrophysiol. 2011;34:1593–9.