1160

Left Ventricular-Based Cardiac Stimulation Post AV Nodal

Ablation Evaluation (The PAVE Study)
RAHUL N. DOSHI, M.D., EMILE G. DAOUD, M.D.,∗ CHRISTOPHER FELLOWS, M.D.,†
KYONG TURK, M.D.,‡ AURELIO DURAN, M.D.,§ MOHAMED H. HAMDAN, M.D.,¶
and LUIS A. PIRES, M.D.†† for the PAVE Study Group
From the Cardiovascular Consultants of Nevada, Las Vegas, Nevada, ∗ Riverside Methodist Hospital, Columbus, Ohio, †Virginia Mason
Medical Center, Seattle, WA, ‡Nebraska Heart Institute, Lincoln, Nebraska, §Orlando Heart Center, Orlando, Florida, ¶University of Utah
Health Sciences Center, Salt Lake City, Utah, and ††St. John Hospital and Medical Center, Detroit, Michigan

PAVE Study. Background: Chronic right ventricular pacing has been reported to promote cardiac dyssyn-
chrony. The PAVE trial prospectively compared chronic biventricular pacing to right ventricular pacing in
patients undergoing ablation of the AV node for management of atrial fibrillation with rapid ventricular
rates.
Methods and Results: One hundred and eighty-four patients requiring AV node ablation were randomized
to receive a biventricular pacing system (n = 103) or a right ventricular pacing system (n = 81). The study
endpoints were change in the 6-minute hallway walk test, quality of life, and left ventricular ejection fraction.
Patient characteristics were similar (64% male; age: 69 ± 10 years, ejection fraction: 0.46 ± 0.16; 83%,
NYHA Class II or III). At 6 months postablation, patients treated with cardiac resynchronization had a
significant improvement in 6-minute walk distance, (31%) above baseline (82.9 ± 94.7 m), compared to
patients receiving right ventricular pacing, (24%) above baseline (61.2 ± 90.0 m) (P = 0.04). There were
no significant differences in the quality-of-life parameters. At 6 months postablation, the ejection fraction
in the biventricular group (0.46 ± 0.13) was significantly greater in comparison to patients receiving right
ventricular pacing (0.41 ± 0.13, P = 0.03). Patients with an ejection fraction ≤45% or with NYHA Class
II/III symptoms receiving a biventricular pacemaker appear to have a greater improvement in 6-minute
walk distance compared to patients with normal systolic function or Class I symptoms.
Conclusion: For patients undergoing AV node ablation for atrial fibrillation, biventricular pacing pro-
vides a significant improvement in the 6-minute hallway walk test and ejection fraction compared to right
ventricular pacing. These beneficial effects of cardiac resynchronization appear to be greater in patients
with impaired systolic function or with symptomatic heart failure. (J Cardiovasc Electrophysiol, Vol. 16,
pp. 1160-1165, November 2005)

biventricular pacing, atrial fibrillation, atrioventricular node, ablation, 6-minute walk

Introduction efit from cardiac resynchronization therapy, even if prior to

AV node ablation the patient does not have a reduced ejection
Biventricular pacing has been demonstrated to reduce fraction, a prolonged QRS duration, or congestive symptoms.
mortality and hospitalizations as well as to improve left ven- The purpose of the PAVE study was to prospectively com-
tricular ejection fraction, exercise tolerance, and quality of pare chronic biventricular to right ventricular pacing in pa-
life.1-7 The majority of these trials have enrolled patients with tients who require ablation of the AV node for management of
a prolonged QRS duration and congestive symptoms despite atrial fibrillation associated with excessive ventricular rates.
optimal medical therapy. In an analogous fashion, patients
with congestive symptoms and a prolonged QRS duration
generated by chronic right ventricular pacing also benefit Methods
from cardiac resynchronization therapy.8 Furthermore, even Inclusion and Exclusion Criteria
in the absence of structural heart disease, chronic right ven-
tricular pacing may result in regional wall motion abnormal- The PAVE study was a prospective, patient-blinded, ran-
ities and adverse hemodynamics.9-11 These findings imply domized, multicenter clinical trial comparing chronic biven-
that patients who undergo ablation of the atrioventricular tricular to right ventricular pacing in patients with chronic
(AV) node and chronic right ventricular pacing may ben- atrial fibrillation undergoing AV node ablation. Study enroll-
ment criteria consisted of (1) chronic atrial fibrillation for
This study was supported by St. Jude Medical, Inc., Sylmar, California. >30 days; (2) requirement for AV node ablation and pac-
ing therapy to manage medically refractory rapid ventricular
Address for correspondence: Rahul Doshi, M.D., Cardiovascular Consul- rates; (3) symptoms limiting ambulation to <450 m with
tants of Nevada, 2300 Corporate Circle, Suite 100, Henderson, NV 89074. a 6-minute hallway walk test; and (4) stable medical ther-
Fax: (702) 939-1812; E-mail: [email protected]
apy. Exclusion criteria were (1) New York Heart Association
Manuscript received 31 January 2005; De Novo manuscript received 26
(NYHA) Class IV; (2) requirement for defibrillator therapy
April 2005; Accepted for publication 1 June 2005. or cardiac surgery; and (3) presence of a prosthetic valve
because of the potential for confounding echocardiographic
doi: 10.1111/j.1540-8167.2005.50062.x measurements. The protocol was performed in the United
 Doshi et al. PAVE Study 1161

was not successfully implanted compared to those receiving

TABLE 1
a biventricular pacemaker. Medical therapy was similar at the
Baseline Clinical Characteristics time of randomization (Table 1) and at 6 months postimplan-
Demographic Variable RV (n = 81) BV (n = 103) P Value tation. Also, there was no significant difference between the
two groups with regard to the duration of follow-up (mean:
Age (year) 67 ± 10 70 ± 10 0.10 RV 24 ± 8 months, BV: 21 ± 8 months) and the percentage
Gender (% male) 64 63 1.00
Preablation ejection fraction 0.45 ± 0.15 0.47 ± 0.16 0.51
of cumulative paced complexes (mean: 98 ± 3%).
NYHA (%)
Class I 25 13 Study Protocol
Class II 46 54 0.10
Class III 29 33 Prior to device implantation, patients completed a 6-
Structural heart disease (%) minute hallway walk test and a quality-of-life survey (SF-
Hypertension 56 63 0.36 36 Health Survey). Patients randomized to right ventricular
Coronary artery disease 30 38 0.28
Nonischemic cardiomyopathy 16 14 0.68 pacing received market-released single-chamber pacemak-
Valvular heart disease 19 16 0.69 ers (Model 5172, 5142, or 5130, St. Jude Medical, Sylmar,
Hypertrophic cardiomyopathy 2 2 1.00 CA, USA) with a bipolar right ventricular lead positioned in
Other medical conditions (%) the apex. Patients randomized to biventricular pacing under-
Diabetes 20 19 1.00
COPD 23 19 0.59
went implantation with a biventricular pacing device (Model
Stroke 4 11 0.10 5508, St. Jude Medical), a bipolar right ventricular lead,
Systemic emboli 2 5 0.47 and a unipolar coronary sinus lead (Model 1055K, St. Jude
Cardiovascular medication (%) Medical).
ACE inhibitors 43 48 0.65 Ablation of the AV node was permitted up to 4 weeks
Anticoagulants 64 68 0.64
Antiplatelets 17 21 0.58 postimplantation. If ablation was postponed, the device was
Beta blockers 54 54 1.00 programmed to VVI with a lower rate of 40 pulses per minute
Calcium channel blockers 38 44 0.55 (ppm). After successful ablation, the pacemaker was repro-
Cardiac glycosides 57 51 0.55 grammed to a VVIR mode with a lower rate of 80 ppm for the
Diuretics 65 62 0.76
next 4 weeks so to mitigate the risk of polymorphic ventricu-
ACE = angiotensin converting enzyme; BV = patients randomized to lar tachycardia. All patients received rate-responsive pacing,
biventricular pacing; COPD = chronic obstructive pulmonary disease; RV = with the sensor optimized 4 weeks after implantation.
patients randomized to right ventricular pacing.

Study Endpoints and Follow-Up

States and Canada from August 2000 to August 2003. The
institutional review board of each center approved the study The primary study endpoint was the degree of change in
protocol and all patients gave written informed consent. the distance walked during the 6-minute hallway walk test
performed just prior to AV node ablation (baseline) com-
Patient Population pared to 6 months postablation in patients randomized to
right ventricular and biventricular pacing. To assess the pat-
The PAVE study enrolled 305 patients. The initial study tern of change in the 6-minute hallway walk test, the test was
design included patients randomized to left ventricular only performed at baseline, and then at 6 weeks, 3 months and
pacing (n = 53); however, in order to focus on the effects 6 months postablation.
of biventricular pacing and to accelerate enrollment, in con- The secondary study endpoints include the change in the
currence with the Food and Drug Administration (FDA), SF-36 Health Status Scale quality-of-life survey measured
randomization was subsequently performed in a 2:1 manner just before AV node ablation (baseline), then at 6 weeks,
of biventricular pacing:right ventricular pacing. The patients 3 months, and 6 months postablation; and, left ventricular
randomized to left-ventricular-only pacing are not included ejection fraction measured at baseline and at 6 weeks and
in this analysis. 6 months postablation. The postablation ejection fraction was
Of 146 patients randomized to receive a biventricular pac- calculated by an independent echocardiography core labora-
ing system, 103 completed the protocol. Of the remaining tory. The preimplant left ventricular ejection fraction data
43 patients, 22 did not have paired data due to lack of follow- were obtained from clinical studies from the medical record
up or death; and, in 21 patients, placement of the left ventricu- within the last year prior to device implantation.
lar lead was unsuccessful. As predefined in the protocol, these
21 patients were followed for 30 days and were then with- Statistical Analysis
drawn from the study and precluded from data analysis.
Of the 106 patients randomized to right ventricular pac- The study analysis represents paired data from 81 patients
ing, 81 patients are included in this study’s analysis. Paired randomized to right ventricular pacing and 103 patients who
data were not available for 25 patients due to lack of follow- underwent successful implantation of a biventricular pac-
up or death. The right ventricular system was successfully ing system. Continuous variables were compared based on
implanted in the each patient. analysis of variance, and comparisons between categorical
The final efficacy analysis, therefore, compares 103 pa- variables were performed using a chi-square test, Fisher’s
tients randomized to biventricular pacing and 81 patients ran- exact test, or Wilcoxon-Mann-Whitney test. Analysis of the
domized to right ventricular pacing (Table 1). There were no 6-minute hallway walk test and quality-of-life scores were
statistical differences in demographic data between the two performed based on the analysis of covariance. Adverse
study populations. Additionally, there were no differences be- events and total mortality were reviewed by a Data Safety
tween the 21 patients in whom a biventricular pacing system Monitoring Board.
1162 Journal of Cardiovascular Electrophysiology Vol. 16, No. 11, November 2005

Figure 2. Temporal changes in the left ventricular ejection fraction. Key is

same as for Figure 1.
Figure 1. Temporal changes in the 6-minute hallway walk test. The solid
diamonds and the solid squares represent the mean distance walked in meters
for patients randomized to biventricular pacing and right ventricular pacing, Left Ventricular Ejection Fraction (Fig. 2)
respectively. Baseline represents the 6-minute walk distance just prior to AV
junction ablation. There is a significant improvement in the distance walked There was no significant difference in the left ventricular
in both groups at 6 weeks postablation versus baseline, which remains at ejection fraction between the two groups at the time of study
3 months postablation. However, at 6 months postablation, the distance enrollment (0.46 ± 0.16).
walked by patients randomized to right ventricular pacing decreases while
Postablation, the ejection fraction for patients in the biven-
that of the biventricular group remains stable.
tricular pacing group remained stable; however, the ejection
fraction in the right ventricular group showed a deterioration
of 3.1% at 6 weeks (P = 0.04) and 3.7% at 6 months (P =
0.03). The ejection fraction at 6 months in the biventricular
A post hoc analysis of the 6-minute hallway walk test and group (0.46 ± 0.13) was significantly greater in comparison
quality-of-life scores was performed based on stratification to patients receiving only right ventricular pacing (0.41 ±
of the patients by the presence or absence of structural heart 0.13, P = 0.03).
disease (ejection fraction ≤0.45 vs >0.45) and the presence
or absence of heart failure (NYHA Class I vs NYHA Class Data Analysis Stratified by Ejection Fraction: 6-Minute
II/III) at the time of implantation of the device. A P value Hallway Walk Test and Quality of Life
<0.05 was considered significant.
Results of the 6-minute hallway walk test stratified by
left ventricular ejection fraction (>45% vs ≤45%) measured
Results at the time of study enrollment are outlined in Figure 3 and
Table 2. For patients with an ejection fraction ≤45%, the hall-
Six-Minute Hallway Walk (Table 1; Fig. 1) way walk distance improvement at 6 months was 73% greater
The distance walked at the baseline 6-minute hallway walk for patients randomized to biventricular pacing in compari-
test completed just prior to AV node ablation was similar son to patients receiving right ventricular pacing (96.9 ± 97.7
for each group, (right ventricular pacing, 260.3 ± 110.9 m, m vs 55.9 ± 96.1 m, P = 0.04).
biventricular pacing 265.9 ± 111.3 m, P = 0.73).
At 6 weeks postablation, the 6-minute hallway walk dis-
tance improved for patients randomized to either group. The
cardiac resynchronization group had a 26% increase above
baseline (69.8 ± 102.5 m), and the right ventricular pacing
group had a 22% increase above baseline (58.1 ± 95.6 m,
P = 0.16).
At 3 months postablation, there was no difference in the
distance walked between the two study groups.
At 6 months postablation, patients with cardiac resynchro-
nization had a significant degree of improvement, 31% above
baseline (82.9 ± 94.7 m), compared to patients receiving
right ventricular pacing, 24% above baseline (61.2 ± 90.0 m)
(P = 0.04) (Fig. 1).

Quality-of-Life Survey
Although there were improvements in some of the cate- Figure 3. Temporal changes in the 6-minute hallway walk test stratified
gories of the SF-36 Health Status Scale, there was no signif- by left ventricular ejection fraction (>45% vs ≤45%) for patients random-
icant difference in quality of life between the treatment and ized to biventricular versus right ventricular pacing. Key is same as for
control groups. Figure 1.
 Doshi et al. PAVE Study 1163

TABLE 2
Six-Minute Walk Distance (Meters) for Patients Randomized to Biventricular (BV) and Right Ventricular (RV) Pacing
RV BV
n Mean ± SD n Mean ± SD P Value
All patients
Preimplant 81 260.3 ± 110.9 103 265.9 ± 111.3 0.73
6 weeks 81 318.4 ± 108.4 103 335.7 ± 124.3 0.32
3 months 80 338.3 ± 144.4 97 353.1 ± 108.6 0.38
6 months 81 321.5 ± 107.4 103 348.8 ± 122.4 0.11
Improvement between preimplant and 6 months 61.2 ± 90.0 82.9 ± 94.7 0.04∗
LVEF >45%
Preimplant 35 242.7 ± 87.8 54 287.3 ± 108.9 0.45
6 weeks 35 309.6 ± 110.3 54 353.8 ± 106.7 0.23
3 months 35 337.2 ± 112.6 50 353.8 ± 106.7 0.49
6 months 35 304.4 ± 105.1 54 354.8 ± 127.7 0.05
Improvement between preimplant and 6 months 61.7 ± 86.0 67.5 ± 81.9 0.25∗
LVEF ≤45%
Preimplant 39 268.5 ± 127.4 37 252.5 ± 112.5 0.56
6 weeks 39 315.3 ± 112.7 37 334.3 ± 126.2 0.69
3 months 39 327.9 ± 117.9 37 353.5 ± 113.5 0.34
6 months 39 324.4 ± 104.2 37 349.4 ± 113.2 0.32
Improvement between preimplant and 6 months 55.9 ± 96.1 96.9 ± 97.7 0.04∗
NYHA Class I
Preimplant 20 299.4 ± 120.8 13 299.3 ± 115.1 1.00
6 weeks 20 389.8 ± 116.2 13 392 ± 120.8 0.96
3 months 20 414.4 ± 115.7 12 395.5 ± 117.9 0.66
6 months 20 389.9 ± 109.8 13 410.0 ± 160.7 0.67
Improvement between preimplant and 6 months 90.5 ± 97.0 110.7 ± 111.1 0.29∗
NYHA Class II and III
Preimplant 61 247.4 ± 105.3 90 261.1 ± 110.6 0.45
6 weeks 61 295 ± 95.6 90 327.6 ± 123.3 0.07
3 months 60 313 ± 102.9 85 347.1 ± 106.6 0.06
6 months 61 299.0 ± 97.5 90 340.0 ± 114.4 0.02
Improvement between preimplant and 6 months 51.6 ± 86.3 78.9 ± 92.2 0.01∗
Key is same as in Table 1.
∗ Improvement between preimplant and 6 months using analysis of covariance, P < 0.05.

There was no difference in the improvement of distance Morbidity and Mortality (Table III)
walked at 6 months between the study groups for patients
with an ejection fraction >45% (67.5 ± 81.9 m vs 61.7 ± During the 3-year study period, there were 27 complica-
86.0 m, P = 0.25). tions. Six complications occurred among the 106 (6%) pa-
There were no significant results in any of the quality-of- tients randomized to right ventricular pacing and the remain-
life subscales when stratified by ejection fraction. ing 21 complications occurred in 20 patients among the 146
(15%) patients assigned to biventricular pacing (P = 0.06).
There were 13 deaths (8%) in the biventricular pacing group
and 19 deaths (18%) in the right ventricular pacing patients
Data Analysis Stratified by NYHA: 6-Minute Hallway (P = 0.16).
Walk Test and Quality of Life
Results of the 6-minute hallway walk test stratified by
NYHA functional class (Class I vs Class II / III) measured
at the time of study enrollment are outlined in Figure 4 and
Table 2 The high and low ejection fraction groups (>45%
and ≤45%) were equally distributed within the patients with
NYHA Class II/III (51% and 49%, respectively). For pa-
tients with NYHA Class I, there is no difference between the
groups in distance walked at 6 months (110.7 ± 111.1 m vs
90.5 ± 97.0 m, P = 0.29). For patients with symptomatic
heart failure (NYHA Class II or III), the hallway walk dis-
tance measured at 6 months was 53% greater for patients
randomized to biventricular pacing in comparison to patients
receiving right ventricular pacing (78.9 ± 92.2 m vs 51.6 ±
86.2 m, P = 0.01). Figure 4. Temporal changes in the 6-minute hallway walk test stratified
There were no consistent significant findings in any of the by New York Heart Association (NYHA Class I vs Class II/III) for patients
quality-of-life subscales when stratified by NYHA functional randomized to biventricular versus right ventricular pacing. Key is same as
class. for Figure 1.
1164 Journal of Cardiovascular Electrophysiology Vol. 16, No. 11, November 2005

majority of subsets showed no difference with biventricular

TABLE 3
pacing compared to right ventricular pacing. Perhaps the rea-
Morbidity and Mortality son why there was clinical benefit with biventricular pacing
Morbidity RV (n = 106) BV (n = 146) but few differences in the quality-of-life scores is that AV
node ablation provided important therapy for patients in both
Diaphragmatic stimulation 0 4 study groups.
High implant thresholds 0 4
LV lead dislodgment/loss of capture 0 5 Previous Studies
RV lead dislodgment/malfunction 3 2
CS perforation 0 2 Previous studies have also reported clinical benefit with
RV perforation 1 1
Oversensing 0 1
biventricular pacing in comparison to right ventricular pac-
Pneumothorax 0 1 ing in the setting of atrial fibrillation and AV node ablation.
Tamponade 0 1 Hay et al. demonstrated through pressure-volume analysis
Hematoma 1 0 that biventricular pacing acutely enhances both systolic and
Infection 1 0 diastolic function over single-site right ventricular pacing in
Total 6 21
patients with a depressed ejection fraction and heart failure.12
Mortality RV (n = 106) BV (n = 146) Leon et al. assessed the effects of adding a left ventricular
Cardiac lead for chronic biventricular pacing to patients with a de-
Arrhythmic 1 1 pressed ejection fraction, severe heart failure, and prior AV
Other cardiac 7 3
Cardiac unknown 0 1
node ablation and chronic right ventricular pacing.8 Etienne
Noncardiac 5 2 et al. have evaluated the effects of left ventricular pacing in
Unknown 6 6 patients with atrial fibrillation and heart failure.13 Cardiac
Total 19 13 resynchronization therapy resulted in a significant improve-
ment in heart failure symptoms as well as systolic function.
The current study extends these prior reports by completing a
Discussion large randomized trial that enrolled all patients with chronic
Main Findings atrial fibrillation requiring AV node ablation, regardless of
ejection fraction or heart failure symptoms.
The main finding of this study is that among patients un- Prior studies have been inconsistent with respect to
dergoing AV node ablation for management of atrial fibril- changes in left ventricular ejection fraction. Kay et al. demon-
lation with rapid ventricular rates, there is a significant in- strated an overall improvement in ejection fraction.14 How-
crease in the 6-minute hallway walk distance at 6 months ever, others have reported an overall decrease in systolic
postablation for patients assigned to biventricular pacing in function.15,16 We hypothesize that these differences reflect
comparison to conventional single-site right ventricular pac- differences in the prevalence of tachycardia-induced car-
ing. Furthermore, the subgroup analysis suggests this benefit diomyopathy in the study population. The current article sup-
is seen predominantly among those patients who have a de- ports these latter studies and further demonstrates that biven-
pressed ejection fraction (≤45%) or have NYHA Class II or tricular pacing can mitigate the risks of potential deterioration
III symptoms. It is important to note, however, that the dif- in ejection fraction.
ference between the two pacing groups was due to a decline
in the hallway distance in the right ventricular pacing group, Study Limitations
rather than an increase in the distance in the biventricular One limitation is that data analysis was not based on an
pacing group. A similar phenomenon was also noted with intention to treat since patients in whom a left ventricular lead
temporal changes in ejection fraction. The ejection fraction was not successfully placed were excluded from analysis.
decreased in patients assigned to right ventricular pacing, but When considering how to manage this patient group, it did not
it remained stable in patients with a biventricular pacing sys- seem to be of scientific benefit to include these patients’ data
tem. These findings imply that the clinical benefit of biven- in the biventricular pacing group when pacing was performed
tricular pacing is attributable to the absence of the deleterious only from the right ventricle Also, it is important to note
effects of chronic right ventricular pacing. that there were no clinical differences between patients with
and without successful placement of the left ventricular lead.
Another major limitation of the study is the lack of consistent
Study Design
baseline or method in determining preimplant left ventricular
Unlike previous trials assessing the effects of chronic car- ejection fraction. Both groups were found to have similar
diac resynchronization therapy, the PAVE trial enrolled pa- baseline values.
tients regardless of their ejection fraction, NYHA class, or
duration of their baseline QRS. Therefore, the results of this
study may apply to all patients undergoing AV node abla- Clinical Implications
tion and highlight the adverse effects of a pacing-induced The findings of the PAVE study suggest that, in order to
left bundle branch block pattern when stimulating only from avoid the adverse effects of cardiac dyssynchrony generated
the right ventricle. by pacing only from the right ventricle, a biventricular pacing
Quality of Life device should be considered for patients who require AV node
ablation for management of atrial fibrillation and who have a
Although some quality-of-life subsets improved with left ventricular ejection fraction ≤45% or who have NYHA
biventricular pacing, when considering all 10 subsets, the Class II or III symptoms. Because the pathophysiology is
 Doshi et al. PAVE Study 1165

similar, cardiac resynchronization therapy may also be con- 5. Higgins SL, Hummel JD, Niazi IK, Giudici MC, Worley SJ, Saxon
sidered for patients who require pacing therapy because of LA, Boehmer JP, Higginbotham MB, DeMarco T, Foster E, Yong PG:
Cardiac resynchronization therapy for the treatment of heart failure in
severe AV node/infranodal conduction disease, as well as patients with intraventricular conduction delay and malignant ventric-
for patients who require defibrillator therapy in addition to ular tachyarrhythmias. J Am Coll Cardiol 2003;42:1454-1459.
chronic ventricular pacing therapy, regardless of the duration 6. Linde C, Leclercq C, Rex S, Garrigue S, Lavergne T, Cazeau S,
of the native QRS. McKenna W, Fitzgerald M, Deharo JC, Alonso C, Walker S, Braun-
schweig F, Bailleul C, Daubert JC: Long-term benefits of biventric-
ular pacing in congestive heart failure: Results from the MUltisite
Acknowledgments: The authors wish to gracefully acknowledge the follow- STimulation In Cardiomyopathy (MUSTIC) study. J Am Coll Cardiol
ing investigators and their staff who participated in the PAVE clinical trial: 2002;40:111-118.
David Delurgio, M.D., Ray Kawasaki, M.D., Jay Franklin, M.D., Stuart 7. Young JB, Abraham WT, Smith AL, Leon AR, Lieberman R, Wilkoff
Winston, M.D., Jonathan Steinberg, M.D., Ann Curtis, M.D., Jay Patterson, B, Canby RC, Schroeder JS, Liem LB, Hall S, Wheelan K: Com-
M.D., Charles Haffejee, M.D., W. Ben Johnson, M.D., Steven Zukerman, bined cardiac resynchronization and implantable cardioversion defib-
M.D., Stephen Keim, M.D., Bernard Thibault, M.D., Wesley Haisty, M.D., rillation in advanced heart failure: The MIRACLE ICD Trial. JAMA
Andrew Kaplan, M.D., Larry Chinitz, M.D., David Broudy, M.D., Jeffrey 2003;289:2685-2694.
Rottman, M.D., J. Rod Gimbel, M.D., Anthony Tang, M.D., David Newman, 8. Leon AR, Greenberg JM, Kanuru N, Baker CM, Mera FV, Smith AL,
M.D., Allan Greenspan, M.D., Robert Rea, M.D., Judith Mackall, M.D., G. Langberg JJ, Delurgio DB: Cardiac resynchronization in patients with
Stephen Greer, M.D., Timothy Malinowski, M.D., Gery Tomassoni, M.D., congestive heart failure and chronic atrial fibrillation: Effect of upgrad-
Raymond Miller, M.D., Donald Chilson, M.D., Seth Worley, M.D., Samir ing to biventricular pacing after chronic right ventricular pacing. J Am
Saba, M.D., Sajad Gulamhusein, M.D., Mark Myers, M.D., Bruce Lerman, Coll Cardiol 2002;39:1258-1263.
M.D., Larry Price, M.D., Erick Burton, M.D., Kriegh Moulton, M.D., Leslie 9. Bedotto JB, Grayburn PA, Black WH, Grayburn PA, Black WH, Raya
Saxon, M.D., Westby Fisher, M.D., Mark Kremers, M.D., and Bendt Her- TE, McBride W, Hsia HH, Eichorn EJ: Alterations in left ventricular
weg, M.D. The authors wish to acknowledge the laboratory of Dr. Karen relaxation during atrioventricular pacing in humans. J Am Coll Cardiol
Hamilton at the University of Florida, Shands for their contribution of Echo 1990;15:658-664.
data analysis, and to Jack McAnulty, M.D., Al Hallstrom, Ph.D., Peter Pak, 10. Karpawich PP, Rabah R, Haas JE: Altered cardiac histology following
M.D., Ray Schaerf, M.D., and Rene’e Wright Gallagher, R.N.P., for their apical right ventricular pacing in patients with congenital atrioventric-
participation on the Data Safety Monitoring Board. Also, the authors wish ular block. Pacing Clin Electrophysiol 1999;22:1372-1377.
to thank Andrew Epstein, M.D., Mark Carlson, M.D., and Mark Roelke, 11. Tse HF, Lau CP: Long-term effect of right ventricular pacing on
M.D., for their participation as the mortality review board. The authors wish myocardial perfusion and function. J Am Coll Cardiol 1997;29:744-
to further acknowledge Xin Ding, Nicole Harbert, Michael Delahunty, Eric 749.
Fain, M.D., and Chunlei Ke from St. Jude Medical for their help in preparing 12. Hay I, Melenovsky V, Fetics BJ, Judge DP, Kramer A, Spinelli J,
this manuscript. Reisten C, Kass DA, Berger RD: Short-term effects of right-left heart
sequential cardiac resynchronization in patients with heart failure,
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