Title of Trial
Danish Mode Selection Trial

Date and citation of primary publication(s) or References
Andersen HR, Theusen L, Bagger JP, et al. Prospective randomized trial of atrial versus ventricular pacing in sick sinus syndrome. Lancet 1994; 344: 1523-8.

Andersen HR, Nielsen JC, Thomsen PE, Thuesen L, Mortensen PT, Vesterlund T, Pedersen AK. Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet 1997;350:1210-1216.

Nielsen JC, Andersen HR, Thomsen PEB, et al. Heart failure and echocardiographic changes during long-term follow-up of patients with sick sinus syndrome randomized to single chamber atrial or ventricular pacing. Circulation 1998; 97: 987-95.

Purpose of the Trial
Evaluate the effects of pacing mode choice in patients with symptomatic sinus node dysfunction.

Study Category
Pacing

Patient Population
Inclusion Criteria
Sinus node dysfunction (heart rate < 50 beats per minute, symptomatic pauses > 2 seconds) requiring implantation of a pacing system. 1:1 atrioventricular relationship with atrial pacing at 100 bpm.

Exclusion Criteria
Atrial fibrillation, < 50 years old, blood pressure > 250/120 mm Hg, cerebral disease or stroke within the last 3 months.

Study Design
Unblinded randomized trial. Patients randomized to atrial pacing or ventricular pacing from 1988 to 1991. Initial evaluation in 1993; several subsequent analysis of the same patient cohort.

Primary Endpoint
Frequency of atrial fibrillation, thromboembolic events

Secondary Endpoints

• Mortality
• cardiovascular death
• congestive heart failure
• echocardiographic changes

Baseline Characteristics
Patient number: 225 patients
Mean Age: 75 ± 8 years
Gender: % female; 70% female
Other characteristics: PR interval: 190 ± 30 ms. Symptoms: syncope in 50%, dizziness in 50%, NYHA heart failure class II or higher: 24%.

Years to Follow-up
Original study: 3.3 years. Subsequent analysis: 5.5 years

Results
As summarized in the tables below, atrial pacing was associated with a non- significant reduction in the frequency of atrial fibrillation (atrial: 14% vs. ventricular: 23%) and a significant reduction in thromboembolic events (atrial: 5.5% vs. ventricular: 17%; p = 0.0083). Long-term follow-up demonstrated persistent reduction in the incidence of the primary endpoints of atrial fibrillation (p = 0.012) and thromboembolic events (p = 0.023) as well as the secondary endpoints of development of chronic atrial fibrillation (p = 0.004) and all-cause mortality (p = 0,045). In addition, at the longer follow-up point, ventricular pacing was associated with an increased incidence of heart failure (atrial: 4% vs. ventricular: 16%,; p < 0.05) and higher rate of all-cause mortality. Four patients in the atrial pacing group developed atrioventricular block (annual risk 0.6%). Two of the patients had right bundle branch block on the initial ECG. Finally, ventricular pacing was associated with worsening echocardiographic measurements of left ventricular function.

 Lancet 1994

Endpoint	AAI (n=110)	VVI (n =115)	P
Thromboembolic events	5.5%	17%	0.0083
Atrial fibrillation	14%	23%	0.12
Chronic atrial fibrillation	7%	13%	0.24
All-cause mortality	19%	22%	0.74

Lancet 1997

Endpoint	AAI (n=110)	VVI (n =115)	P
Thromboembolic events	12%	23%	0.023
Atrial fibrillation	24%	35%	0.012
Chronic atrial fibrillation	8%	19%	0.004
All-cause mortality	35%	50%	0.045

Circulation 1998

Endpoint	AAI (n=110)	VVI (n =115)	P
Heart failure (NYHA Class I/II/III/IV)	84/22/2/1	65/44/4/0	0.01
Increase in NYHA class	9%	31%	<0.0005
Change in left ventricular fractional shortening	0.35 ± 0.13 to 0.33 ± 0.09	0.36 ± 0.12 to 0.31 ± 0.09	0.087
Heart failure mortality	3%	6%	0.18

Sponsors
Danish Heart Foundation, Sygekassernes Helsefond

Trial Status: Completed