The role of pacemakers in the prevention of atrial fibrillation

INTRODUCTION — The principal reason to place a pacemaker in a patient with atrial fibrillation (AF) is to treat symptomatic bradycardia. Pacing has not been shown to prevent the development of AF.

This topic will review the role of pacemakers in the prevention of AF. Brief mention will be given to implantable cardioverter defibrillators. The utility of other nonpharmacologic strategies for preventing AF is discussed separately. (See "Atrial fibrillation: Catheter ablation" and "Atrial fibrillation: Surgical ablation".)

PATIENTS WITHOUT AN INDICATION FOR A PACEMAKER — In patients with a history of atrial fibrillation (AF), pacing from one or both atria has been suggested as a means to reduce AF recurrences. There is no conclusive evidence to support the implantation of an atrial pacemaker to prevent AF in patients with a history of AF but no indication for pacing [1]. Similar to societal guidelines, we do not recommend the insertion of an atrial pacemaker for this purpose [2]. (See 'Overdrive (antitachycardia) atrial pacing' below.)

PATIENTS WITH SYMPTOMATIC BRADYCARDIA — Many patients with atrial fibrillation (AF) have sinus node dysfunction with symptomatic bradycardia requiring pacemaker placement. Moreover, antiarrhythmic drug treatment may lead to sinus or atrioventricular nodal dysfunction that may require pacing in order to permit up-titration of drug dose. The appropriate pacing modes for patients with sinus node dysfunction are discussed separately. (See "Sinus node dysfunction: Treatment", section on 'Treatment'.)

In patients who require permanent pacing, only physiologic pacing from the right atrium has been shown to prevent episodes of AF.

Physiologic pacing

Background — The term "physiologic pacing" has historically been used to describe the maintenance of atrioventricular (AV) synchrony.

For patients with non-permanent AF who require permanent pacing, we place a dual chamber pacemaker and program it to physiologic pacing, which is discussed below. Physiologic pacing results in a significantly lower rate of AF.

Sinus rhythm leads to a predictable myocardial activation sequence of different regions of the heart. This sequence optimizes cardiac output. Several mechanisms may contribute to the benefit of physiologic pacing in preventing AF in patients who are treated with standard dual-chamber pacing. (See "The electrocardiogram in atrial fibrillation".)

Types of physiologic pacing and their benefits are summarized as follows:

●Maintenance of AV synchrony – This lowers the potential for AF by preventing the development of right atrial electrical and left atrial mechanical remodeling [3-5].

●His bundle pacing – Compared with right ventricular (RV) pacing, His bundle pacing may reduce left atrial dysfunction by preventing left ventricular (LV) dyssynchrony and reducing LV compliance [6].

●Reductions in the dispersion of refractoriness – These reductions may be in part due to lowering average atrial pressure and therefore stretch-related changes [7]. Another factor may be suppression of ectopic atrial premature beats that can initiate AF [8,9].

There are several adverse physiologic effects of pacing the RV. Isolated RV pacing disrupts the normal sequence of activation of the atria and ventricles in patients in normal sinus rhythm. This can cause both AV and RV dyssynchrony, which are both described below:

●AV dyssynchrony – The failure to activate the atria before the ventricles with RV pacing is termed AV dyssynchrony. AV dyssynchrony may promote AF. Preventing AV dyssynchrony is part of the rationale for atrial pacing in patients with paroxysmal AF.

●Ventricular dyssynchrony – RV pacing causes the RV to contract before the LV and causes the septum to contract before the lateral wall of the LV; this sequence for activation is similar to that of a native left bundle branch block. The phenomenon is referred to as ventricular dyssynchrony or asynchrony and can also lead to AF. Therefore, the risk of AF with pacing can be reduced by maintaining AV synchrony (physiologic pacing) and by minimizing the amount of ventricular pacing [10].

Evidence for efficacy of physiologic pacing

His bundle versus RV pacing — There may be a beneficial role of His bundle pacing in the prevention of AF or for reduction of AF burden in those with pacing indications; however, this has not been definitively established [11,12]. A retrospective study of 410 patients without AF who were referred for permanent pacemaker and followed for an average of 1.6 years showed that those with left bundle branch area pacing had less new-onset AF compared with those with RV pacing (5.2 versus 18 percent; hazard ratio [HR] 0.33, 95% CI 0.16-0.67) [6]. (See "Modes of cardiac pacing: Nomenclature and selection", section on 'Modes to minimize ventricular pacing' and "Modes of cardiac pacing: Nomenclature and selection", section on 'Dual-chamber pacing'.)

Atrial versus ventricular pacing — The potential benefit of physiologic pacing on the development of AF has been evaluated in a number of clinical trials [13-23]. Physiologic pacing may be accomplished with atrial or AV pacing, which is also referred to as dual-chamber pacing.

A 2006 meta-analysis of randomized trials of physiologic versus ventricular pacing included 7231 patients and over 35,000 patient-years of follow-up [13]. Most patients assigned to physiologic pacing received a dual-chamber (DDD) pacemaker, and some received AAI pacing. Physiologic pacing resulted in a significantly lower rate of AF (HR 0.80, 95% CI 0.72-0.89). However, there was no significant reduction in mortality or heart failure. Another trial not included in the meta-analysis has come to similar conclusions [18].

Site of atrial pacing — The impact of the site of atrial pacing was evaluated in the SAFE study of 385 patients with paroxysmal AF and sinus node dysfunction with an indication for long-term pacing [24]. Individuals were randomly assigned to pacing at the right atrial appendage or the right septum. After a mean follow-up of 3.1 years, there was no difference in the rate of occurrence of persistent AF between the two sites.

Alternate strategies — As discussed above, we place a dual chamber pacemaker in patients with non-permanent AF who have symptomatic bradycardia and no indication for biventricular pacing. When possible, we pace from the right atrium only. While attempting physiologic pacing has been standard of care for decades, data suggests a physiologic benefit of His bundle pacing when feasible [11]. (See "Sinus node dysfunction: Treatment", section on 'Long-term management'.)

The ability of other atrial pacing systems to suppress AF recurrences has been evaluated in several studies and has not been found to prevent the development of AF.

Alternative-site, dual-site right atrial, and biatrial pacing — Based on the available evidence, we do not perform alternative site, dual-site right atrial, or biatrial pacing to prevent episodes of AF.

The atria can be paced at sites other than the right atrial appendage, such as at the high interatrial septum near Bachman’s bundle, or at two sites simultaneously to provide greater synchronization of atrial tissue, which might protect against AF. Biatrial pacing usually involves pacing simultaneously from a lead in the right atrial appendage to stimulate the right atrium and a lead in the coronary sinus to stimulate the left atrium [25]. Alternatively, two sites in the right atrium can be paced simultaneously (eg, the high right atrium and low on the interatrial septum near the coronary sinus ostium) [26].

The following summarizes the lack of robust evidence for efficacy of alternative pacing strategies:

●Dual versus single site atrial pacing – Possible mechanisms by which arrhythmia recurrence rates are lowered with dual-site pacing include a reduction in atrial conduction delay and a smaller increase in the width of the atrial electrogram caused by an early premature beat, measured at the right posterior interatrial septum.

Whereas smaller observational studies suggested a benefit of dual-site versus single-site pacing [27-31], in the larger DAPPAF trial [26], no benefit was observed. In the DAPPAF trial, 118 patients with paroxysmal symptomatic AF and a bradyarrhythmic indication for pacing were randomly assigned to each of three pacing modes: right atrial, dual-site right atrial, and support (DDI or VDI) pacing [26]. Although there were no overall differences in incident AF among patients assigned to these pacing groups, subgroup analysis suggested that dual-site pacing was more effective than single-site or support pacing in patients receiving a class I or III antiarrhythmic drug and in those with ≤1 symptomatic AF episode per week.

●Pacing from specific sites in right atrium and coronary sinus – In the PASTA trial 142 patients with pacing indications were randomly assigned to pacing from either the free right atrial wall, right atrial appendage, coronary sinus ostium, or dual site right atrial pacing from the coronary sinus ostium and the right atrial appendage [31]. There was no statistically significant difference with respect to the occurrence of AF between the four groups after 24 months.

●Intraatrial septal versus right atrial pacing – A meta-analysis of 12 randomized controlled trials enrolling 1146 patients compared right atrial appendage pacing with interatrial septum pacing. Compared with right atrial appendage pacing, interatrial septum pacing was associated with a reduction in the number of AF episodes and burden. However, the development of permanent AF and the prevalence of recurrent AF were similar between the two pacing modes [32].

Overdrive (antitachycardia) atrial pacing — We consider using overdrive atrial pacing in patients with frequent, symptomatic episodes of AF whose episodes have been difficult to manage with rate or rhythm control. (See 'Patients without an indication for a pacemaker' above.)

The rationale for overdrive or antitachycardia pacing that predominates over intrinsic atrial activity is that triggering of AF might be reduced by affecting the pattern of atrial depolarization and suppressing atrial premature beats. Initial studies produced variable results [25]. This was followed by the development of complex algorithms that keep the pacing rate slightly faster than the intrinsic atrial rate in an attempt to minimize the sudden rate change that occurs after premature beats.

●Proprietary pacing algorithms – Some combinations of proprietary pacing algorithms designed to both prevent AF by overdrive pacing and to pace-terminate AF at its onset have been shown to have a statistically significant positive impact on AF burden. However, their impact is clinically small, often leads to symptoms such as palpitations related to overdrive pacing, and should not be considered as a treatment option in patients who do not have a bradycardia indication for pacing. In addition, overdrive atrial pacing is not as efficacious as antiarrhythmic drug therapy or catheter ablation for preventing AF. Some [33-36], but not all [24], of these algorithms appear to more effectively reduce the total number of episodes of AF or the burden of symptomatic AF compared to DDDR alone [33-36]. We do not routinely use any of these algorithms for overdrive atrial pacing.

The following studies are representative:

•POT trial – The Prevention Or Termination trial studied the effect of antitachycardia pacing on AF burden when added to preventive pacing algorithms (PPA) [37]. The study consisted of 85 patients who received a DDDR (rate-adaptive dual-chamber pacemaker) with antitachycardia pacing (ATP) algorithms who had greater than 30 minutes per week of AF. They were randomly assigned either to PPA or to PPA with ATP for three months, and then they were crossed to the alternative therapy for the same amount of time with a one-month washout period. Both groups showed a significant decrease in AF burden at the end of the first period (64 versus 81 percent), but there was no further decrease in AF burden of the number of episodes when adding ATP to PPA.

•SAFARI trial – The Study of Atrial Fibrillation Reduction (SAFARI) was designed to determine the impact of preventive pacing algorithms on patients with pacing indications and a history of paroxysmal AF. The study randomized 240 patients to receive either continuous overdrive and triggered overdrive pacing therapies (PPTs) or standard pacing. The primary efficacy end point was post-randomization AF burden, defined as the average number of hours per day spent in atrial tachyarrhythmia during the longest period of at least 90 days between the 4- and 10-month visits. There was no difference in the development of permanent AF between the PPTs ON group (0 percent) compared with the OFF group (2.5 percent). Patients randomized to the PPTs ON group had a median reduction in AF burden to 0.08 hours/day compared with no change in the OFF group [38].

•ADOPT-A trial – The randomized Atrial Dynamic Overdrive Pacing Trial (ADOPT-A) trial assessed the efficacy of a pacemaker algorithm designed to pace the atrium at rates slightly faster than intrinsic in patients with a history of symptomatic paroxysmal or persistent AF and an indication for dual chamber pacing. The primary end points of the study were symptomatic AF burden and adverse events. A total of 319 patients were randomized. The burden of symptomatic atrial arrhythmias (defined as AF, atrial flutter, and atrial tachyarrhythmias) was reduced by 26.5 percent, from 2.6 percent in the control group to 1.9 percent in the treatment group. The mean number of AF episodes (4.3 ± 11.5 control versus 3.2 ± 8.6 treatment) and adverse event rates were not statistically different between groups.

•ASSERT trial – The main objective of the Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial (ASSERT) was to evaluate the risk of stroke in patients with dual chamber pacemakers and ICDs and subclinical AF episodes lasting >six minutes. Patients with pacemakers were also randomly assigned to receive or not to receive continuous atrial overdrive pacing to evaluate long-term atrial arrhythmia risk. Of the 2451 pacemaker patients randomized, there was no difference in the annual rate of atrial tachyarrhythmia development (1.96 percent per year in patients randomized to receive atrial overdrive pacing versus 1.44 percent per year in control patients) and no difference in the combined end point of stroke, systemic embolism, myocardial infarction, death from vascular causes, or hospitalization for heart failure [39].

•MINERVA trial – This trial evaluated a novel atrial antitachycardia pacing feature (DDDRP). In the study, DDDRP alone was compared with DDDRP with managed ventricular pacing (MVP) or with MVP alone in patients with bradycardia and previous atrial arrhythmias [40]. The reactive antitachycardia pacing algorithm used in the study continually monitors the atrial rhythm and delivers tiered pacing therapies based on atrial rate. The primary AF objective was to assess rates of permanent AF in the 1166 enrolled patients. At two years, permanent or persistent AF occurred in 19 percent of patients in the control DDDRP arm, 25 percent in the MVP arm, and 15.1 percent in the DDDRP + MVP arm [2].

PATIENTS WHO REQUIRE ICD OR RESYNCHRONIZATION THERAPY — The number of patients with atrial fibrillation (AF) who are receiving an implantable cardioverter defibrillator (ICD) or who require cardiac resynchronization therapy is increasing.

Many patients who have ICD indications (eg, low left ventricular ejection fraction) may have a history of AF or may have subclinical AF detected on routine follow-up. In patients with a history of non-permanent AF and both pacing and ICD indications, we place a dual-chamber ICD. In patients with no known AF history in whom an ICD is indicated, we place a single-chamber device. An atrial sensing only (VDD) ICD lead is also available and may be useful in the diagnosis of AF in a patient with a single lead ICD. A stand-alone atrial defibrillator was previously evaluated but is no longer available due to the high risk of recurrent AF and the pain associated with shocks. These devices are capable of sensing within and defibrillating the right atrium. However, we do not recommend their placement to terminate AF nor do we use them for AF outside the hospital setting.

The use of cardiac resynchronization in patients with AF is discussed separately. (See "Cardiac resynchronization therapy in atrial fibrillation", section on 'Our approach'.)

RECOMMENDATIONS OF OTHERS — We agree with recommendations made by the American College of Cardiology Foundation/American Heart Association/Heart Rhythm Society guidelines and their focused updates [2,41,42].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topic (see "Patient education: Pacemakers (The Basics)")

●Beyond the Basics topic (see "Patient education: Pacemakers (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Patients without an indication for a pacemaker – Patients with atrial fibrillation (AF) should not receive a permanent pacemaker to prevent or reduce the frequency of AF in the absence of another indication for pacing. (See 'Alternate strategies' above.)

●Avoiding right ventricular (RV) apical pacing – In patients without chronic AF who require a pacemaker for bradycardia, we recommend dual-chamber or atrial pacing, rather than ventricular pacing (Grade 1A). RV pacing can increase the risk of AF. Conduction system pacing, particularly left bundle area pacing, may be superior to RV apical pacing in those expected to require a high degree of ventricular pacing. (See 'Patients with symptomatic bradycardia' above.)

Similarly, in patients with intact atrioventricular (AV) conduction who receive a dual-chamber device, we recommend the use of pacing modes/parameters that minimize RV pacing (Grade 1B). (See 'Patients with symptomatic bradycardia' above.)

●Ineffective strategies – We do not use alternative-site, dual-right atrial, or biatrial pacing to prevent AF, as available evidence does not support the efficacy of these approaches. (See 'Alternate strategies' above.)

●No role for overdrive pacing to prevent AF – We do not use overdrive pacing (antitachycardia pacing) to prevent AF in patients who do not have a bradycardia indication for pacing, as available evidence does not support the efficacy of this approach in all patients.

We consider using overdrive atrial pacing in patients with frequent, symptomatic episodes of AF whose episodes have been difficult to manage with rate or rhythm control. (See 'Overdrive (antitachycardia) atrial pacing' above.)

●Patients with implantable cardioverter-defibrillator (ICD) indications who also have AF – In patients with a history of non-permanent AF and both pacing and ICD indications, we place a dual-chamber ICD. An atrial sensing only (VDD) ICD lead is also available and may be useful in the diagnosis of AF in a patient with a single-lead ICD. (See 'Patients who require ICD or resynchronization therapy' above.)