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The Role of Pacemakers

in the Management
of Patients with Atrial
Fibrillation
Gautham Kalahasty, MDa,*, Kenneth Ellenbogen, MDa,b

KEYWORDS
 Pacemaker  Implantable cardioverter defibrillator
 Atrial fibrillation  Sinus node dysfunction
 Atrioventricular junction ablation

This article reviews the wide range of implantable effect, understanding the role of pacemakers in
device–based therapies (mainly pacemakers) that the management of AF requires an understanding
are being used in the management of atrial fibrilla- of the role of pacemakers in SND. Pacemaker im-
tion (AF), atrial flutter, and atrial tachycardia (AT). plantation practice patterns in the United States
Pacemakers have an important and evolving role vary from those in Europe. Dual-chamber (rather
in the management of some patients with AF. than single-chamber) pacemakers are usually im-
The frequency of their use relative to other non- planted in the United States for patients who
pharmacologic strategies has increased over have sick sinus syndrome and paroxysmal AF
time as the incidence and prevalence of AF in- even if there is no AV conduction abnormality at
crease, especially in the elderly. In fact, almost the time of implantation. In one study, the inci-
all the increase in pacemaker implantation rates dence of developing AV block was 8.4% over a pe-
has been for the indication of sinus node dysfunc- riod of 34 months.2 In a European study of patients
tion (SND). The clinical burden of AF in the elderly who received a single-chamber (AAI) pacemaker
population is staggering. In the groups aged 70 to for sick sinus syndrome, there was a 1.7% annual
79 years and 80 to 89 years, the prevalence of AF incidence of AV block.3 Because the incidence of
is at least 4.8% and 8.8%, respectively. By 2050, it AV block is not insignificant, in the United States,
is estimated that 50% of the patients with AF are patients who have paroxysmal AF and sick sinus
going to be more that 80 years old.1 Box 1 sum- syndrome almost universally receive dual-cham-
marizes the most common strategies that have ber pacemakers. With careful patient selection,
been used for device-based management of pa- however, the incidence of development of AV
tients with AF. The goals of this article are first to block can be as low as 0.6%.4 Thoughtful pace-
review the evolution of the important current para- maker programming and careful pacemaker
digms of pacing as they relate to AF and then to mode selection with the goal of maintaining ‘‘phys-
discuss how pacemakers are used in the specific iologic pacing’’ are critical.
subpopulations of patients with AF. In the current American College of Cardiology
The most common indication for pacemaker (ACC)/American Heart Association (AHA)/Heart
implantation in the United States is for SND. AF Rhythm Society (HRS) guidelines, AF is described
is a primary feature of SND in many patients. In as permanent or chronic if it is long standing (eg,
cardiology.theclinics.com

A version of this article originally appeared in Medical Clinics of North America, volume 92, issue 1.
a
Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, PO Box
980053, Richmond, VA 23298–0053, USA
b
Cardiac Electrophysiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond,
VA, USA
* Corresponding author.
E-mail address: gkalahasty@mcvh-vcu.edu (G. Kalahasty).

Cardiol Clin 27 (2009) 137–150


doi:10.1016/j.ccl.2008.09.009
0733-8651/08/$ – see front matter ª 2009 Elsevier Inc. All rights reserved.
138 Kalahasty & Ellenbogen

Box 1 Box 2
Device-related applications for the management Potential adverse effects of ventricular pacing right
of atrial fibrillation ventricle in sinus node dysfunction

Rate control Ventricular dyssynchrony


Pacing to facilitate the use of rate-lowering Altered cardiac hemodynamics attributable to
agents loss of ‘‘atrial kick’’
Pacing in chronic AF Atrial proarrhythmia
Pacing for rate regularization Ventricular proarrhythmia
Pacing in conjunction with AV node ablation or Increased valvular regurgitation
modification Adverse electrical remodeling of the atria
Rhythm control or maintenance of sinus rhythm promoting AF
Pacing to facilitate the use of antiarrhythmic Pacemaker syndrome
medication
Pacing to maintain or promote sinus rhythm
Algorithms to promote sinus rhythm these effects are not unique to dyssynchronous
Multisite pacing (dual site, biatrial) pacing but may occur with dual-chamber pacing
Novel site pacing and are discussed elsewhere in this article. Even
ventricular proarrhythmia (ventricular tachycardia
Pacing or defibrillation to terminate AF
and ventricular fibrillation) has been described
with single-chamber ventricular and dual-chamber
pacing.6 Ventricular remodeling, hemodynamic
longer than 1 year) and if cardioversion has failed or parameters, quality-of-life (QOL) measures, and
has been foregone. AF is called persistent if it lasts clinical end points (eg, incidence of AF, stroke
more than 7 days regardless of whether cardiover- risk, congestive heart failure [CHF], mortality)
sion is needed to restore sinus rhythm; it is consid- have all been investigated. In terms of the inci-
ered paroxysmal if episodes of AF terminate dence of AF, the data from the large clinical trials
spontaneously.5 Pacemakers have applications in supporting physiologic pacing are fairly compel-
each of these clinical types of AF. ling. In terms of the other clinical end points,
such as QOL, stroke risk, and mortality, however,
PHYSIOLOGIC PACING the data are not entirely consistent and continue
to evolve. Hemodynamic studies have demon-
An appreciation of the role of pacemakers in the strated that AV synchrony improves stroke volume
management of AF (especially in the context of and cardiac output and reduces right atrial pres-
SND) requires an understanding of the evolution sure and pulmonary-capillary wedge pressures.
of the meaning of ‘‘physiologic pacing’’ and opti- A significant number of patients who receive a
mal pacing modalities. The function of a pace- single-chamber ventricular (VVI) pacemaker for
maker is to approximate normal cardiac function sick sinus syndrome develop pacemaker syn-
as much as possible. Therefore, careful mode se- drome, consisting of such symptoms as fatigue,
lection (eg, AAI, VVI, DDI, DDD) and proper pro- palpitations, and chest pain. These symptoms re-
gramming (eg, AV delay, hysteresis, mode switch solve after patients receive atrioventricular (AV)
rates) are needed to optimize the beneficial effects synchronous pacing.7,8 When comparisons are
and minimize the potentially detrimental effects of made within an individual patient testing different
pacing. Although ‘‘demand’’ ventricular pace- pacing modes rather than between patients,
makers have been in clinical use since the 1960s, dual-chamber synchronous pacing is strongly pre-
and although it seems intuitive that dual-chamber ferred to single-chamber ventricular pacing.9
pacing would be superior to ventricular demand Table 1 summarizes the key clinical findings in
pacing, the body of clinical data needed to support the eight major randomized studies that have dem-
this conclusion took almost 20 years to accumu- onstrated the benefits of AV synchronous pacing
late. The benefits of dual-chamber AV syn- or atrial-based pacing. These trials have collec-
chronous pacing in patients with SND and tively enrolled nearly 9000 patients. Although it
paroxysmal AF are now widely accepted. More re- was a small study with limited power, the Danish
cently, the potentially adverse effects of ventricular study was the first randomized prospective study
pacing (synchronous or asynchronous) have been to support the concept that selection-specific pac-
recognized and are summarized in Box 2. Some of ing modalities could improve outcomes in patients
Table 1
Clinical Trials in Pacing

Average
Follow-Up
Trial Year (years) Design Key Findings
Danish (Andersen and 1994 5.5 AAI versus VVI in 225 At long-term follow-up (mean of 5.5 years), the incidence of
colleagues)4 patients paroxysmal AF and chronic AF was reduced in the AAI
with SSS group. Overall survival, heart failure, and thromboembolic
events were reduced with atrial-based pacing.
PASE7 1998 2.5 Single-blind assignment of VVIR Patients with SSS showed a trend toward a lower incidence of
or DDDR mode in 407 patients AF and all-cause mortality (AF: 19% versus 28%, P 5 .06;
with SSS, AV block, and other mortality: 12% versus 20%, P 5 .09). QOL was not different
indications between the two pacing modes. Twenty-six percent of
patients developed pacemaker syndrome when paced in the
VVIR mode
Mattioli and colleagues54 1998 2.0 VVI/VVIR versus AAI/DDD/DDDR/VDD Incidence of AF was 10% at 1 year, 23% at 2 years, and 31% at
pacing in patients with AV block 5 years. An increase in the incidence of chronic AF was
(n 5 100) and SSS (n 5 110) observed in patients with SSS in the VVI/VVIR arm.
Canadian Trial of Physiologic 2000 6.0 2568 patients randomized to The annual rate of AF was less with physiologic pacing. No
Pacing (CTOPP)10 ventricular pacing (VVIR) versus difference was observed in stroke or cardiovascular death
physiologic pacing (DDDR or AAIR) between the two groups. There was a 27% reduction in the
for any appropriate indication annual rate of progression to chronic AF.
Mode Selection in Sinus-Node 2002 4.5 2010 patients with sinus node AF was reduced in patients randomized to physiologic pacing.
Dysfunction Trial (MOST)11 dysfunction (only) randomized No difference in mortality and stroke rates was observed

Pacemakers and Atrial Fibrillation


to VVIR versus DDDR programming; between pacing modes. Thirty-one percent of patients
more than 50% had prior AF crossed over from the VVIR to the DDDR mode, 49% of
which was attributable to pacemaker syndrome.
Pacemaker Atrial Tachycardia 2001 2.0 198 patients with sinus node dysfunction and Abstract only; full report remains to be published. Mortality
(PAC-ATACH)13 a history of atrial arrhythmias randomized was lower in the dual-chamber group. (3.2% versus 6.8%;
to DDDR pacing or VVIR pacing P 5 .007) There was no difference in the AF recurrence rate.
United Kingdom Pacing and 2002 4.6 2021 patients, aged >70 years There was no difference in all-cause mortality, rate of stroke,
Cardiovascular Events randomly assigned to three arms: or incidence of AF between the dual-chamber group and
(UKPACE)12 DDD (50%), VVIR (25%), and VVI ventricular pacing group.
25%)
Search Atrioventricular 2007 1.7 530 patients in DDD mode and 535 Persistent AF occurred in 12.7% of patients in the
Extension and Managed patients in AAI)/DDD mode for conventional pacing group and 7.9% of
Ventricular Pacing symptomatic sinus node dysfunction; patients in the minimal ventricular pacing group.
for Promoting Atrioventricular nearly an equal number of patients in
Conduction (SAVEPACe)17 both groups (38%) had paroxysmal AF

139
140 Kalahasty & Ellenbogen

with sick sinus syndrome (SSS).4 Another study, were associated with a greater risk for hospitaliza-
the Pacemaker Selection in the Elderly (PASE) trial, tion for heart failure.11 If ventricular pacing oc-
did not show a difference in the QOL scores be- curred more than 40% of the time, there was
tween those patients programmed to the VVIR ver- a twofold increase in the risk for developing CHF.
sus DDDR mode; however, up to 45% of patients This study suggests that the relative benefits of
with SSS who were in VVIR mode developed pace- AV synchronous pacing compared with ventricular
maker syndrome.7 The Canadian Trial of Physio- only pacing are attributable to the deleterious ef-
logic Pacing (CTOPP) showed a clear benefit for fects of right ventricular (RV) pacing rather than
physiologic pacing in terms of reducing the inci- to the presumed advantages of AV synchronous
dence of AF, but it did not demonstrate a preferen- pacing. The CTOPP and MOST studies had rela-
tial advantage in patients with SSS. In addition, the tively few patients with true atrial only–based pac-
CTOPP study demonstrated a higher rate of perio- ing (AAI) without the confounding effect of
perative complications in those patients who re- ventricular pacing. In the MADIT II study, patients
ceived a dual-chamber pacemaker compared who received an implantable cardioverter defibril-
with those who received a single-chamber device lator (ICD) had higher survival rates but also dem-
(9.0% versus 3.5%, respectively). The risk for AF onstrated a trend toward increased rates of CHF;
was lower for physiologic pacing (21.5%) than for 73 patients (14.9%) in the conventional therapy
ventricular pacing (27.1%).10 The power of the group and 148 in the defibrillator group (19.9%)
Mode Selection in Sinus-Node Dysfunction Trial were hospitalized with heart failure (P 5 .09).15 In
(MOST) may have been compromised because the Dual Chamber and VVI Implantable Defibrilla-
of the high rate of crossover from VVI mode to tor (DAVID) trial, a composite end point of time to
DDD mode. Nevertheless, this trial, contrary to death and first hospitalization for CHF was com-
the CTOPP study, showed improvements in QOL pared in patients who had ICDs programmed to
scores after reprogramming to a dual-chamber receive dual-chamber pacing (DDDR-70) or ven-
mode.11 The United Kingdom Pacing and Cardio- tricular backup pacing (VVI-40).16 At 1 year,
vascular Events (UKPACE) trial is remarkable for 83.9% of the patients in the VVI-40 group were
its negative results. Patients received single- free from the composite end point compared
chamber (VVI or VVIR) pacemakers or dual-cham- with 73.3% of patients in the DDDR-70 group.
ber pacemakers for AV block. Patients with Hospitalization for CHF occurred in 13.3% of
permanent AF or paroxysmal AF that was present VVI-40 patients compared with 22.6% of DDD-70
for more than 3 months were excluded from the patients, trending in favor of the VVI-40 group. Al-
trial. There was no benefit from dual-chamber pac- though the DAVID study looked only at an ICD
ing modes over single-chamber modes in terms of population, it has had a major impact on the pro-
stroke rate or AF.12 The Pacemaker Atrial Tachy- gramming of dual-chamber pacemakers. By high-
cardia (PAC-ATACH) trial is the only trial to demon- lighting the deleterious effects of RV pacing, it
strate a mortality benefit for dual-chamber pacing underscores the importance of mode selection in
compared with ventricular pacing; however, the patients with SND and paroxysmal AF. The pro-
results of that trial have been presented only in ab- grammed parameters of a pacemaker or ICD
stract form.13 A recent meta-analysis by Healey should promote minimal ventricular pacing.
and colleagues14 pooled data from five of these tri- All major pacemakers have features that allow for
als (Danish, PASE, CTOPP, MOST, and UKPACE) maximization of the AV delay to promote intrinsic
to detect clinically significant outcomes that the in- ventricular depolarization. Algorithms even exist
dividual trials were not powered to detect. The that allow the dual-chamber pacemaker to change
combined data from these trials represent 35,000 from single-chamber atrial-based pacing (AAIR) to
patient-years of follow-up and demonstrated that dual-chamber AV sequential pacing (DDDR) auto-
although the incidence of AF was less with atrial- matically. When selected, the device operates in
based pacing compared with ventricular-only an AAIR mode until AV block occurs and then in-
pacing, there was no significant benefit in terms stantly changes to a DDDR mode (Fig. 1). In a study
of all-cause mortality. Despite the reduced inci- by Sweeney and colleagues (Search Atrioventricu-
dence of AF, there was no significant reduction in lar Extension and Managed Ventricular Pacing for
the risk for stroke. Promoting Atrioventricular Conduction [SAVE
In a secondary analysis of the MOST data, two PACe]),17 there was a 40% relative risk reduction
additional important findings were reported. In- in the development of persistent AF as compared
creasing proportions of ventricular pacing were with conventional dual-chamber pacing for pa-
found to be associated with an increasing inci- tients with SND and normal left ventricular (LV)
dence of AF during VVIR and DDDR pacing. function. There was no difference in mortality be-
Also, greater percentages of ventricular pacing tween the two groups.
Pacemakers and Atrial Fibrillation 141

Fig. 1. Managed ventricular pacing (MVP; Medtronic, Inc., Minneapolis, Minnesota) is an atrial-based pacing
mode that significantly reduces unnecessary right ventricular pacing by primarily operating in an AAIR pacing
mode while providing the safety of a dual-chamber backup mode if necessary. As shown in the figure, the algo-
rithm allows for a single blocked beat before a back-up ventricular paced beat is delivered. Mode switch occurs
only if two blocked beats occur. Two sequential blocked beats cannot occur because of back-up ventricular
pacing.

Data from the MADIT II and DAVID studies [CRT] indications) is the mode of choice. AV
only involved patients with severe LV dysfunc- synchrony alone is not adequate.
tion. This raises the question as to whether or
not the detrimental effects of RV pacing (in
PACEMAKER DIAGNOSTICS
terms of heart failure and mortality) are seen in
patients with lesser degrees of LV dysfunction Pacemaker diagnostics not only can provide in-
or normal LV function. There are limited data sight into the burden of AF but can reveal the pres-
with which to answer this question. If physio- ence of asymptomatic AF that was not previously
logic pacing can be thought of as the pacing suspected.18 Routine interrogation of a pacemaker
mode that most closely mimics normal cardiac implanted for SND may reveal episodes of AF that
physiology while yielding the best outcomes have been stored in the memory as mode switch
with the least detrimental effects, it seems that episodes or atrial high-rate episodes. ‘‘Mode
atrial-based pacing that promotes intrinsic con- switch’’ refers to a programmable function allow-
duction and minimizes RV apical pacing (in pa- ing the pacemaker to change from a dual-chamber
tients with no cardiac resynchronization therapy pacing mode (DDD) to a nontracking mode (DDI or
142 Kalahasty & Ellenbogen

VVI). This feature is available in all current pace- oversensing of atrial or far field ventricular events
makers and ICDs. Once selected, it is an auto- can result in inappropriate mode switch episodes.
matic function and does not require office-based Stored data should be reviewed and interpreted by
reprogramming. An atrial arrhythmia that meets someone who is knowledgeable in the interpreta-
a programmed duration (a few seconds) and rate tion of intracardiac electrograms. Capucci and
(usually 160 beats per minute [bpm]) results in colleagues21 demonstrated that patients with
a mode switch event and an entry into the log. device-monitored AF for longer than 24 hours
When the atrial arrhythmia terminates, dual-cham- had an increased risk for embolic events. Identifi-
ber pacing is resumed. Mode switching prevents cation of appropriate mode switches can have
rapid ventricular pacing in response to the tracking a significant impact on the management of pa-
of rapid atrial rhythms. The frequency and duration tients in terms of initiation of anticoagulation, per-
of atrial arrhythmias, including AF and atrial flutter, haps reducing the risk for future thromboembolic
can be recorded and stored. Most current pace- events. All major manufacturers of pacemakers
makers are capable of storing intracardiac and ICDs have the capability of some form remote
electrograms, sometimes allowing the clinician to monitoring. Remote monitoring frequency and
distinguish between AF, AT, and atrial flutter. alerts can be individualized to meet the needs of
Some older devices are only capable of reporting the each patient and each physician.
the number and duration of mode switch episodes Fig. 2 shows the interrogation report from a dual-
without storing any associated electrograms. In chamber pacemaker. It was implanted for symp-
these cases, an event monitor may be needed to tomatic sinus bradycardia in a 73-year-old patient
document the atrial arrhythmias. Overall, the not previously known to have AF. During the 1
false-positive detection of AF is reported at ap- month after implantation, the patient had 186 epi-
proximately 2.9%.19 In contrast, the results of the sodes of atrial high rates, 4 of which were longer
Balanced Evaluations of Atrial Tachyarrhythmia in than 1 minute in duration. The longest mode switch
Stimulated Patients (BEATS) study showed that episode lasted almost 6 hours. These episodes
ATs could occur in 54% of patients with stored were asymptomatic. Based on these findings, the
electrograms compared with only 15% of patients initiation of warfarin sodium was discussed with
screened by surface electrocardiograms and the patient and the dose of the beta-blocker was
24-hour Holter monitors.20 Artifact and increased. Fig. 3 shows an example of a stored

Fig. 2. Arrhythmia summary report from a dual-chamber pacemaker (Adapta Dual Chamber Pacemaker;
Medtronic, Inc., Minneapolis, Minnesota).
Pacemakers and Atrial Fibrillation 143

Fig. 3. Example of stored electrograms (EMGs) from an appropriate mode switch episode. The atrial channel
shows a rapid irregular atrial rate with a maximum atrial rate of 253 bpm.

electrogram of an atrial tachyarrhythmia resulting incompetence. Physicians and patients frequently


in an appropriate mode switch. dismiss these nonspecific symptoms as a natural
In addition to mode switch events, pacemaker consequence of aging. In addition, comorbid con-
diagnostics can provide other important informa- ditions may be present, which can result in similar
tion. Rate histograms can provide insight into the symptoms confounding the diagnosis of SSS.
adequacy of the rate response and suggest the Therefore, a Holter monitor or event monitor may
need for more a sensitive sensor setting to provide be needed to obtain true symptom-rhythm
appropriate chronotropic support in a patient with correlation. A single-chamber rate-responsive
AF and a slow ventricular rate. Rate histograms pacemaker (VVIR) can provide symptom relief
can help to assess the adequacy of rate control and improve functional capacity.
in patients with AF. It is also important to know Bradycardia may also be an unavoidable conse-
the percentage of ventricular pacing in patients quence of the medications used to prevent a rapid
with intact AV conduction. The practice of maxi- ventricular response associated with AF. Beta-
mizing the AV delay to promote intrinsic AV con- blockers, calcium channel blockers, and digoxin
duction is supported by data from the DAVID, are used to control rapid ventricular rates during
MADIT II, and MOST studies. AF but can result in intermittent symptomatic bra-
dycardia or long pauses that can lead to syncope
or presyncope. Of note, pauses up to 2 to 3 sec-
Chronic or Permanent Atrial Fibrillation
onds during sleep are not unusual and are not
It is not uncommon for patients with chronic AF to solely an indication for pacing. Instead, this brady-
require a permanent pacemaker. Over time, these cardia is just a function of the relatively high vagal
patients may develop a slow ventricular response tone that is present during sleep. Dosage adjust-
resulting in symptomatic bradycardia. Progres- ment of medications or the use of beta-blockers
sively slower conduction is often the result of with intrinsic sympathomimetic activity (ISA) can
age-related degeneration of the conduction sometimes mitigate the bradycardia or pauses
system. Because this process is gradual, some but can also result in suboptimal rate control
elderly patients do not readily recognize or com- when a patient is active and awake. A pacemaker
plain of the symptoms of exercise intolerance, is indicated to facilitate the use of medications that
dyspnea on exertion, and easy fatigability that are considered essential and for which there
can accompany bradycardia and chronotropic are no other suitable alternatives. Typically,
144 Kalahasty & Ellenbogen

pacemakers in these patients are programmed to therapy cannot reach the desired rate targets and
VVI or VVIR mode with a lower rate of 60 bpm. for whom there are no other alternatives, ablation
Pharmacologic therapy prevents extreme of the AVJ and pacemaker implantation is the pre-
tachycardia. ferred strategy. Although more commonly used in
Whatever the indication, a rate-responsive patients with chronic AF, it is also performed in se-
pacemaker can also provide an appropriate chro- lect patients with paroxysmal AF and in whom anti-
notropic response to the patient’s physiologic arrhythmic drugs (AADs) do not provide adequate
needs. Current pacemakers use a variety of rhythm control or in whom AF ablation is not the
sensor-driven algorithms to increase the heart preferred option. These patients should receive
rate according to the patient’s needs. The two a dual-chamber pacemaker with mode switch ca-
most common sensors are accelerometers (based pability to maintain AV synchrony when the patient
on movement) and minute ventilation monitors is in sinus rhythm. Otherwise, a standard single-
(based on thoracic impedance). Some devices chamber ventricular rate-responsive pacemaker
can use both in combination. Optimal use of these is all that is need in patients with preserved LV func-
devices requires routine office-based follow-up tion and chronic AF.
and reprogramming. The benefits of AVJ ablation and pacemaker im-
plantation are significant and were summarized in
Regulation of Atrioventricular Nodal a meta-analysis covering 21 studies that included
Conduction by Pacing 1181 patients.24 Echocardiographic parameters,
such as ejection fraction (EF), have been shown
During AF, the rapid ventricular rate and irregular
to improve, as have the number of office visits,
ventricular response contribute to deleterious he-
hospital admissions, and the New York Heart As-
modynamic effects. Irregular ventricular response
sociation (NYHA) functional capacity. QOL mea-
can result in decreased cardiac output and in-
sures, such as QOL scores, activity level,
creased wedge pressure independent of mean
exercise intolerance, symptom frequency and se-
rate.22 It has also been shown that cycle length var-
verity, were also improved.24
iability has more influence on ventricular perfor-
Despite the expected advantages, there are
mance at faster heart rates. Ventricular pacing
some serious disadvantages that should be con-
can result in concealed conduction into the AV
sidered and explained to patients. The most obvi-
node and His-Purkinje system, resulting in slowing
ous is that the procedure, unlike medications, is
of AV conduction. Algorithms have been developed
generally irreversible and renders the patient
that result in pacing slightly faster than the mean
pacemaker dependent for life. The procedure itself
ventricular rate but with more regular ventricular re-
is generally of low risk, nearly 100% successful,
sponse. Despite the expected benefits, the clinical
and usually not technically difficult. Patients are
trials that studied regularization algorithms yielded
exposed to a small risk for thromboembolic events
mixed and somewhat disappointing results. In the
if their anticoagulation is stopped for the ablation
AF Symptoms Study, the effect of ventricular rate
procedure. There is a small risk for vascular
regularization on the end points of QOL, AF symp-
complications, such as hematoma and pseudoa-
toms, and exercise capacity was evaluated. The in-
neurysm formation. A recurrence rate of 5% ne-
vestigators reported that ventricular rate regulation
cessitating repeat ablation has been reported.
had a positive impact on reported symptoms, par-
Although practice patterns vary widely, there is
ticularly palpitations, but did not have a significant
growing evidence that pacemaker implantation
impact on overall QOL or functional capacity.23
and pacemaker generator replacements can be
Based on these studies, ventricular pacing during
performed safely while patients are on therapeutic
chronic rapid AF using regularization algorithms
doses of coumadin.25,26 Most importantly, AVJ ab-
cannot be considered an alternative to atrioventric-
lation does not obviate the need for long-term anti-
ular junction (AVJ) ablation.
coagulation. AV synchrony is not preserved, and in
those patients with significant diastolic dysfunc-
Atrioventricular Junction Ablation
tion, the expected symptomatic improvement
It is not possible to achieve typical heart rate targets may be lessened by the loss of the ‘‘atrial kick.’’
in many patients with chronic or paroxysmal AF There was a concern that patients are at risk for
with medical therapy alone. A resting heart rate of sudden death after AVJ ablation and pacemaker
80 bpm or less, 24-hour Holter average of 100 implantation. Based on reported survival data, the
bpm or less, and heart rate of 120 bpm or less risks for sudden death and total mortality are 2%
with modest activity are reasonable empiric goals to 6% at 1 year, respectively. Long-term (6 years)
for rate control but should be individualized based mortality is similar in patients undergoing pacing
on symptoms. For patients in whom pharmacologic and ablation compared with continued medical
Pacemakers and Atrial Fibrillation 145

therapy, however.27 The increased risk is thought The Atrial Pacing Periablation for the Prevention
to be attributable to bradycardia-dependent ar- of AF (PA3) trial was the first to examine the effect
rhythmias (torsades de pointes). Programming the of pacing on the frequency and duration of AF in
lower rate of the pacemaker at 80 to 90 bpm for patients with medically refractory AF who were
the first month has been shown to minimize this also being considered for AVJ ablation and pace-
risk.28 Another concern is the risks associated maker implantation.30 These patients did not
with lead dislodgement in these patients, who are otherwise have a bradycardia indication for pace-
usually pacemaker dependent. Because of these maker implantation. This study showed that atrial
concerns, many physicians implant the pacemaker rate-adaptive pacing does not prevent paroxysmal
several weeks in advance of the ablation proce- AF recurrence or reduce the frequency or duration
dure. The use of a CRT device or standard RV of AF. The duration of this study was short term
pacing device in patients with significant LV dys- (3 months), and no specific overdrive pacing algo-
function is discussed elsewhere in this review. rithms were used.
Overdrive pacing algorithms seek to reduce
APCs and prevent pauses and bradycardia.
Paroxysmal or Persistent Atrial Fibrillation
Fixed-rate atrial pacing alone (lower rate of 70
The results of the Atrial Fibrillation Follow-up In- bpm) has been shown to have no effect on AF bur-
vestigation of Rhythm Management (AFFIRM) trial den. The major device manufacturers have algo-
do not apply to every subset of patients with AF; rithms that attempt to reduce AF recurrence and
therefore, rhythm control remains an appropriate overall AF burden. The dynamic atrial overdrive
strategy in many patients with paroxysmal AF.29 algorithm (DAO; St. Jude Medical, Sylmar, Califor-
Such factors as symptoms, QOL, and the interplay nia) is one example that has been shown to
between AF and comorbidities are important con- achieve a modest reduction in symptomatic AF
siderations when selecting a rhythm control strat- burden31 and has been given US Food and Drug
egy over a rate control strategy. For example, Administration (FDA) labeling for this indication.
patients with diastolic dysfunction or valvular heart The effect of this algorithm on total AF burden is
disease, such as aortic or mitral stenosis, do not unknown. Overall, several other pacing algorithms
tolerate AF and require aggressive rhythm control. have been studied in a relatively small number of
Some patients are also at risk for developing CHF patients yielding, at best, inconsistent results on
or tachycardia-induced cardiomyopathy. Despite the effect on AF burden. Therefore, the clinical util-
their limited efficacy and potential for side effects, ity of these algorithms is limited.
including proarrhythmia, AADs play an important Multisite atrial pacing involves placement of one
role in the treatment of AF. Symptomatic bradycar- lead in the high right atrium and another lead near
dia and bradycardia-dependent polymorphic ven- the coronary sinus ostium (dual site) or into the
tricular tachycardia (VT) have been reported with coronary sinus to pace the left atrium (biatrial).
sotalol, propafenone, and, rarely, with amiodar- Small nonrandomized studies show conflicting
one. These medications can also exacerbate AV results in terms of reducing AF burden.32,33 A pro-
conduction disease, which is sometimes seen in longed P wave duration (>120 milliseconds) may
patients with SND. Pauses seen immediately after be a necessary condition for multisite pacing to
termination of AF may also be prolonged by these be beneficial compared with single-site pacing.34
drugs. Pacemakers can be used to facilitate the Larger clinical trials have not demonstrated a sig-
use of these medications. nificant AF burden reduction. In one study, dual-
There has been a great deal of interest in pre- site right atrial pacing reduced the recurrence
venting AF in patients with paroxysmal AF by the risk for AF compared with standard pacing only
use of device-based algorithms designed to ad- in those patients treated with AADs.35 Biatrial pac-
dress two aspects of the pathophysiology of AF: ing seems to have a limited routine clinical applica-
triggers and substrate. Clinical and experimental tion when used acutely in postoperative patients.
data suggest that AF may be triggered by atrial A meta-analysis involving eight studies enrolling
premature complexes (APCs). The atria of some 776 patients reported a significant reduction in
patients may be more susceptible to AF because the risk for developing AF in patients after heart
of inhomogeneous atrial refractoriness. These pa- surgery who received temporary biatrial pacing
tients sometimes have atrial myopathy and often using two epicardial wires.36
have atrial remodeling and enlargement. Overdrive The premise of alternate-site atrial pacing is that
pacing, multisite pacing (dual and biatrial), and al- more uniform interatrial conduction can be
ternate site pacing are device-based strategies achieved by pacing at the interatrial septum. The re-
designed to reduce AF burden by addressing sultant decrease in heterogeneity of atrial refractori-
these pathophysiologic mechanisms. ness is expected to reduce AF burden. Pacing can
146 Kalahasty & Ellenbogen

be done from the high atrial septum (Bachmann’s parallel those that are seen in patients who have
bundle) or the low atrial septum (near the coronary heart failure but do not have a CRT device. The
sinus os). The Atrial Septal Pacing Efficacy Clinical most immediate effect on AF of biventricular pac-
Trial (ASPECT) is a small study that demonstrated ing is the loss of AV synchrony, possibly leading to
no reduction in AF burden with septal or Bach- decompensated heart failure. In one small study of
mann’s bundle pacing sites compared with tradi- acute hemodynamics, systolic function as mea-
tional right atrial appendage pacing sites, even sured by dP/dT was worse in patients who had
when combined with atrial pacing algorithms.37 heart failure with RR-irregularity and rapid ventric-
Other studies have yielded conflicting results in a ular rates (120 bpm) but was better when ventric-
relatively small number of patients. The variability ular rates were regular at approximately 120 bpm
in results may be attributable to the difficulty in con- or when ventricular rates were in the normal range
firming the location or positioning the lead near (80 bpm).40 The timing of ventricular pacing is
Bachmann’s bundle. based on sensed or paced atrial events. AV syn-
In summary, there are not enough long-term chrony can be maintained only during sinus
clinical data to support the recommendation of rhythm. Most CRT devices have algorithms that
overdrive pacing algorithms, multisite pacing, or promote biventricular pacing even during AF, de-
alternate-site pacing as a primary indication for spite the loss of AV synchrony. These algorithms
pacemaker implantation in the management of are imperfect, and despite device-reported biven-
AF. The results of some of the available studies tricular pacing of greater than 90%, clinical bene-
have likely been confounded by the presence of fits are less certain. This is attributable to
ventricular pacing. In fact, data from the MOST variable degrees of fusion between the intrinsic
suggest that for every 1% increase in ventricular conduction and the paced ventricular complex.
pacing, there is a 1% decline in the benefit of Furthermore, these algorithms tend to result in
dual-chamber atrial-based pacing in terms of AF. pacing rates that are, on average, faster than dur-
ing intrinsic conduction (up to the programmed up-
per pacing rate), raising the concern of
Cardiac Resynchronization Therapy
tachycardia-induced cardiomyopathies.
and Atrial Fibrillation
Does CRT reduce the likelihood of developing
CRT, also known as biventricular pacing, is an im- AF? As in patients with normal LV function, the
portant treatment modality in patients who have benefits of biventricular pacing in patients with
moderate and advanced CHF. The current ACC/ a CRT device in terms of the reduction of AF bur-
AHA/HRS guidelines indicate that patients with den are mixed and uncertain. In a small cohort
a left ventricular ejection fraction (LVEF) less than study, the annual incidence of AF was 2.8%
or equal to 35%, sinus rhythm, and NYHA class in the CRT group and 10.2% in the control group
III or ambulatory class IV symptoms despite rec- (P 5 .025).41 Analysis of data from the Cardiac
ommended optimal medical therapy and who Resynchronization in Heart Failure Trial did not
have cardiac dyssynchrony (currently defined as show that the incidence of AF was affected by
a QRS duration greater than 120 milliseconds) CRT, however.42 Most studies do not show any
should receive CRT. Many patients who are candi- benefit of CRT pacing on the incidence of AF.
dates for CRT also have a history of paroxysmal or What is the effect of chronic AF on CRT benefit?
chronic AF. In patients who were candidates for Large-scale clinical trial data elucidating the bene-
CRT defibrillators (CRT-Ds), a history of paroxys- fits of CRT in patients with AF are limited. The Mul-
mal AF is associated with as much as a 25% inci- tisite Stimulation in Cardiomyopathies (MUSTIC)
dence of AF within the first 6 months from the time study reported on a small number of patients
of implantation. Patients with a CRT indication are with chronic AF who received a CRT device. Pa-
also at high risk for developing AF. The prevalence tients in the sinus rhythm group and the AF group
and incidence of AF increases with increasing showed improvements in heart failure class, in the
severity of heart failure.38 The risk for AF may be 6-minute walk test results, and in the need for hos-
as high as 50% in patients who have class IV pitalization.43 The improvement was greater in the
CHF.39 In fact, either condition is known to predis- sinus rhythm group. In a recent prospective obser-
pose to the other condition. There are several vational study, the benefit of CRT in patients who
issues to examine when considering the benefits had heart failure with AF was similar to that seen
of CRT in patients who have chronic and paroxys- in patients who had heart failure without AF, even
mal AF. at 3 years of follow-up.44 In a study by Molkoek
First, in those patients with existing CRT and colleagues,45 patients with normal sinus
devices, what are the hemodynamic and clinical rhythm and with chronic AF derived benefit from
impacts of the development of AF? The effects CRT. Heart failure class, QOL score, and exercise
Pacemakers and Atrial Fibrillation 147

capacity were improved in both groups. In the Pacing therapies are more suitable for relatively
group with AF, those who had a previous AVJ ab- slow AT with a regular cycle length. They are not
lation derived the most benefit. Those patients well suited for AF. AF has been known to organize
who had not previously had an AVJ ablation did into atrial flutter or AT that may be more suscepti-
not show an improvement in QOL scores at 6 ble to pace termination, however. There is no evi-
months. There were more nonresponders in the dence that 50-Hz burst pacing has any significant
AF group than in the sinus group (36% versus efficacy in terminating AF or in reducing the overall
20%; P<.05). The Atrioventricular Junction burden of AF in humans. There are conflicting data
Ablation Followed by Resynchronization Therapy with respect to the effect that these therapies have
in Patients with CHF and AF (AVERT-AF) study is on the overall burden of AF. In the ATTEST trial,
a prospective, randomized, double-blind, multi- prevention and termination algorithms were tested
center trial that is going to test the hypothesis prospectively and failed to show a reduction in AF
that AVJ ablation followed by biventricular pacing burden.49 In another prospective trial, atrial thera-
significantly improves exercise capacity and func- pies resulted in a reduction of AT burden from
tional status as compared with pharmacologic rate a mean of 58.5 to 7.8 hours per month. This study
control in patients with chronic AF and depressed enrolled patients with a standard ICD indication
EF, regardless of rate or QRS duration. Enrollment and atrial tachyarrhythmias.50
is scheduled to be completed in 2008.46 Stand-alone implantable atrial defibrillators are
Another unresolved issue is the timing of im- not used clinically and are not currently marketed
plantation of a CRT-D device versus a standard in the United States. ICDs with atrial defibrillation
pacemaker relative to AVJ ablation. Given that capability have been developed, but their use is
there can be an improvement of the LVEF in limited by the painful nature of the shock. The
some patients after AVJ ablation, some pain threshold for an atrial defibrillation shock is
practitioners implant a standard dual-chamber far less than the threshold for successful AF. The
pacemaker in patients with borderline LVEF ADSAS 2 study demonstrated that premedication
(30%–35%). The EF is then re-evaluated after with oral midazolam has been effective in mitigat-
a specific period of time (ie, 6 months), and the ing some of the perceptions of pain.51 This option
need for a CRT device is determined.47 Others can only be used in select highly motivated
elect to implant a CRT-D or CRT pacemaker patients.
without defibrillation capability (CRT-P) at initial Currently, there are no guidelines that advocate
implantation to avoid the need for another proce- using devices with these features as a primary
dure within a relatively short period. means to manage ATs. Most physicians use these
A CRT-P is a consideration in patients with features as adjunctive therapy in patients with
a more preserved EF. The Post Atrioventricular other standard indications for pacemakers or
Nodal Ablation Evaluation (PAVE) trial has pro- ICDs. Overall, they have limited utility.
vided some important insights into the type of pac-
ing that is best in this group of patients. This trial
compared chronic biventricular pacing with RV- SUMMARY
only pacing in patients undergoing AVJ ablation The role of pacemakers in the management of
for the management of AF with rapid ventricular patients with AF and in the prevention of AF has
rates. The mean LVEF was 46%  16% in the been extensively studied. Based on well-designed
two groups. The mean LVEF in the RV pacing prospective clinical trials, only a few of these strat-
group was 45% at the onset of the study and egies can be recommended for routine clinical
41% at 6 months (P<.05).48 There are no guide- use in related subpopulations. From the available
lines for the use of a CRT-P in patients with mod- studies, several key considerations are apparent:
erate LV dysfunction who are undergoing AVJ
ablation. 1. The definition of physiologic pacing has
evolved. It is no longer enough to maintain AV
synchrony with a dual-chamber atrial-based
Atrial Therapies
pacemaker. A single-chamber ventricular-
Some implantable devices are capable of deliver- based pacemaker should be avoided in
ing electrical therapy to manage AF and atrial patients with paroxysmal AF and SND. When
flutter. These therapies include antitachycardia possible, intrinsic AV conduction should be
pacing with burst and ramp pacing in the atrium, promoted to minimize the deleterious effects
high-frequency (50 Hz) burst pacing, and atrial de- of RV pacing. Therefore, mode selection is im-
fibrillation. All three have been successfully used in portant (AAI)/DDD, DDI, or DDD with long
terminating ATs and atrial flutter. AV delays). Unresolved questions include the
148 Kalahasty & Ellenbogen

maximum hemodynamically acceptable AV de- 5. Fuster V, Ryden LE, Asinger RW, et al. ACC/AHA/
lay and the optimal site for RV pacing.52 ESC 2006 a report of the American College of Cardi-
2. In appropriate patients, pacemaker implantation ology/American Heart Association Task Force on
and AVJ ablation provide clinical and mortality Practice Guidelines and the European Society of
benefits. The procedure should be considered Cardiology Committee for Practice Guidelines (Writ-
in any patient with suboptimal rate control and ing Committee to Revise the 2001 Guidelines for the
in any patient who is at risk for developing or Management of Patients with Atrial Fibrillation). J Am
has developed tachycardia-mediated cardiomy- Coll Cardiol 2006;48:854–906.
opathy. Although this procedure is most often 6. Sweeney MO, Ruetz LL, Belk P, et al. Bradycardia
done in patients with chronic AF, it is also appro- pacing-induced short-long-short sequences at the
priate for some patients with paroxysmal AF. onset of ventricular tachyarrhythmias: a possible
3. The benefits of pacing in patients with a CRT mechanism of proarrhythmia? J Am Coll Cardiol.
device may be maximized in those patients 2007;50(7):614–22.
with AF who have undergone AVJ ablation. In 7. Lamas GA, Orav J, Stambler BS, et al. for the Pace-
patients with chronic AF who are receiving maker Selection in the Elderly Investigators. Quality
a CRT device, AVJ ablation can be recommen- of life and clinical outcomes in elderly patients
ded if adequate rate control to allow LV pacing treated with ventricular pacing as compared with
cannot be achieved by medical therapy. This is- dual chamber pacing. N Engl J Med 1998;338:
sue is unresolved in patients with paroxysmal 1097–104.
AF who receive a CRT device. 8. Lamas GA, Lee KL, Sweeney MO, et al. Ventricular
4. Pacing in chronic AF to promote ventricular rate pacing or dual-chamber pacing for sinus-node dys-
regularization has limited clinical value, and function. N Engl J Med 2002;346:1854–62.
careful attention should be paid to overall ade- 9. Sulke N, Chamber J, Dritsas A, et al. A randomized
quacy of rate control. An average ventricular double blind crossover comparison of four rate-re-
rate greater than the upper pacing limit may sponsive pacing modes. J Am Coll Cardiol 1991;
lead to tachycardia-mediated cardiomyopathy 17:696–706.
and signals the need for more aggressive rate 10. Connolly SJ, Kerr CR, Gent M, et al. Effects of phys-
control or AVJ ablation. iologic pacing versus ventricular pacing on the risk
5. Pacing algorithms that attempt to prevent AF of stroke and death due to cardiovascular causes.
have limited value. As a sole indication, they N Engl J Med 2000;342:1385–91.
are not widely accepted or recommended as 11. Sweeney MO, Hellkamp AS, Ellenbogen KA, et al.
a primary indication for pacemaker implanta- Adverse effect of ventricular pacing on heart failure
tion in patients with paroxysmal or persistent and atrial fibrillation among patients with normal
AF.53 baseline QRS duration in a clinical trial of pace-
6. Multisite and novel site pacing strategies do not maker therapy for sinus node dysfunction. Circula-
have broad clinical applications at this time. An tion 2003;107:2932–7.
exception is the use of short-term multisite pac- 12. Toff WD, Skehan JD, deBono DP, et al. The United
ing at the time of cardiac surgery. Kingdom Pacing and Cardiovascular Events Trial.
[UK Pacing Clinical Electrophysiology]. Heart
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