The Danish Multicenter Randomised Study on AAI Versus DDD Pacing in Sick Sinus Syndrome
The Danish Multicenter Randomised Study on AAI Versus DDD Pacing in Sick Sinus Syndrome
Hypothesis Treatment with rate adaptive single chamber atrial pacing (AAIR) reduces the risk
 of death compared with rate adaptive dual chamber pacing (DDDR) in patients with sick sinus
 syndrome (SSS).

 Primary purpose The primary purpose of this randomised trial is to compare AAIR and DDDR
 pacing in patients with SSS and normal atrioventricular (AV) conduction with respect to the
 primary end point overall mortality.
Background In patients with isolated SSS, who need pacemaker treatment, any pacemaker can be
 used to treat the symptomatic bradycardia: a single chamber atrial (AAI) pacemaker, a single
 chamber ventricular (VVI) pacemaker, or a dual chamber (DDD) pacemaker. In the USA and in
 most European countries, DDD pacing is used in most cases. It is now known from the Danish
 AAI/VVI trial, that AAI pacing is superior to VVI pacing, since VVI pacing is associated with
 a higher mortality and a higher incidence of atrial fibrillation, thromboembolic
 complications and heart failure. This confirms previous findings in observational studies.
 Therefore, VVI pacing should no longer be used in patients with SSS.

 The main argument for using DDD pacing is the concern, that the patients will develop
 symptomatic atrioventricular (AV) block. In the Danish AAI/VVI trial, the risk of AV block
 was approximately 0.6% per year, which is equivalent to the risk found in a larger meta
 analysis. This is only a little higher that the risk of atrioventricular block in the
 age-matched non-paced population. Implantation of a DDD pacemaker in all patients will
 effectively prevent development of symptomatic bradycardia in the minority of patients who
 develops AV block. However, the most important disadvantage during DDD pacing is the
 stimulation (pacing) of the ventricles by the pacemaker a large part of the time, also in
 patients without AV block. Pacing the right ventricle causes an asynchronous electrical
 activation and mechanical contraction of the ventricles as compared with the normal
 physiological contraction.

 At present time, a randomised comparison of AAI and DDD pacing in patients with SSS has never
 been conducted, and to our knowledge, such a trial is not planned anywhere else.

 Since several of the patients with SSS suffer from chronotropic incompetence, pacemakers with
 rate adaptive function are chosen for all patients included in the present trial.

 All patients, that fulfils the inclusion criteria and none of the exclusion criteria and who
 give written informed consent, are included into the study. For all other patients undergoing
 primary pacemaker implantation in the study period, an exclusion data sheet is filled in
 stating the reason for exclusion. A total of 1,900 patients are included into the study.

 Prior to the pacemaker implantation patients are randomised by lot (envelope) to either AAIR
 or DDDR pacing. The randomisation is performed after written informed consent has been
 obtained from the patient. Randomisation will ensure that all centres will randomise an equal
 number of patients into each treatment group.

 Patients randomised to AAIR pacing will have a bipolar lead implanted in their right atrium
 connected to a single chamber pacemaker with rate adaptive function. Patients randomised to
 DDDR pacing will have two leads (one bipolar lead in their right atrium and a uni- or bipolar
 lead in their right ventricle) connected to a DDDR pacemaker.

 Out of hospital follow-up The patients must attend for out of hospital follow-up after 3
 months and 12 months and then once every year.

 Criteria for closing the study

 The DANPACE study is stopped and results are analysed when all of the following three
 criteria are fulfilled:

 1. 1,900 patients have been randomised.

 2. The last randomised patient has been followed for at least 1 year.

 3. The mean follow-up for the whole study population is at least 5.5 years.
Inclusion Criteria:

 General:

 A. Undergoing primary pacemaker implantation B. Able to appear for outpatient follow-up C.
 Age > 18 years

 Symptoms:

 D. Syncope or E. Dizzy spells or F. Congestive heart failure

 Electrocardiographic:

 G. Sinus bradycardia <40/minute for at least 1 minute in a conscious awake state or H.
 Sinus arrest/sinoatrial block >2 seconds or I. Bradycardia/tachycardia with sinus-pauses >2
 seconds

 Exclusion Criteria:

 Clinical:

 A. Malignant disease. B. Severe psychogenic disease including severe decrepitude and
 dementia. C. Impending larger operation expected to influence the major end point. D.
 Cardiac disorder expected to need cardiac surgery during the follow-up period.

 E. Need for other device implantation: ICD (implantable cardioverter defibrillator) or
 implantable DC converter (for atrial fibrillation).

 F. Carotid sinus syndrome (positive carotid sinus massage with pauses >3 seconds).

 Electrocardiographic:

 G. Atrioventricular block. H. Bundle-branch block (complete RBBB, LBBB, bifascicular
 bundle-branch block or non-specific intraventricular block with QRS >0.12 seconds).

 I. Chronic atrial fibrillation. J. Atrial fibrillation/atrial flutter with QRS pauses >3
 seconds during atrial fibrillation.

 K. Atrial fibrillation/atrial flutter with QRS frequency <40/minute for 1 minute.