Europace (1999) 1, 22–25
The North American experience with the Ablate and
Pace Trial (APT) for medically refractory atrial
fibrillation
M. A. Wood, G. N. Kay* and K. A. Ellenbogen for the APT Investigators†
Medical College of Virginia, Richmond; Virginia; *University of Alabama at Birmingham, Birmingham,
Alabama, U.S.A.
The Ablate and Pace Trial (APT) was a prospective registry
study of clinical outcomes and survival following ablation
and pacing therapy for medically refractory atrial fibrillation. One hundred and fifty-six patients were enrolled at
16 centres in North America. The mean patient age was
6611 years, with mean left ventricular ejection fraction
of 48%18%. Seventy-eight percent of the patients had
structural heart disease.
During one year of follow up, multiple measures of qualityof-life showed significant and sustained improvement following ablation and pacing therapy. Also, left ventricular
ejection increased significantly for patients with baseline
left ventricular ejection fraction <45%. Metabolic exercise
testing showed trends toward improved exercise tolerance;
Introduction
The creation of complete heart block for management of
refractory supraventricular arrhythmia was the first
clinical use of catheter ablation in man. While radiofrequency ablation techniques have evolved to cure most
common supraventricular tachycardias (SVTs), atrioventricular (AV) junctional ablation has remained a
common application in the United States for the palliative treatment of refractory symptomatic atrial fibrillation. In the United States, widespread acceptance of
the procedure, despite the lack of large controlled clinical
studies to document efficacy, has rapidly occurred[1–4].
The Ablate and Pace Trial (APT) was conceived in the
early 1990s as the first attempt to examine the clinical
outcomes of AV junctional ablation and pacing in a
large prospective multicentre trial. Specifically, the
purpose of the APT was prospectively to quantitate
†Funded by a grant from Medtronic Inc, Minneapolis, Minnesota,
U.S.A.
Correspondence: Mark A. Wood, MD, Box 980053, Medical
College of Virginia, Richmond, VA 23298, U.S.A.
1099–5129/99/010022+04 $18·00/0
however, these did not achieve statistical significance. The
one year overall survival was 85%, with 3% of patients
experiencing sudden death.
In summary, this large, non-randomized, trial showed
significant improvement in quality of life and left ventricular function following ablation and pacing therapy. Ablation and pacing therapy is a viable strategy for palliative
management of patients with medically refractory, highly
symptomatic atrial fibrillation.
(Europace 1999; 1: 22–25)
Key Words: Atrial fibrillation, radiofrequency ablation,
quality of life, left ventricular function.
the effects of AV junctional ablation and pacing on the
health related quality of life, exercise capacity, left
ventricular function and survival in a consecutive series
of highly symptomatic patients with medically refractory
atrial fibrillation. Since completing enrollment in 1995,
the trial results have been published in abstract form
while the full results undergo peer review[5–8].
Methods
Study population
The potential study population included all patients
referred to each of 16 study centres (appendix) for AV
junctional ablation and pacemaker implant for the
management of highly symptomatic medically refractory
atrial fibrillation. One hundred and fifty-six patients
were enrolled between April 1994 and February 1995.
The only exclusion criteria were failure to provide
informed consent or life expectancy <12 months due to
non-cardiac diseases.
1999 The European Society of Cardiology
North American experience with APT
23
Study design
Left ventricular function
The study design was a prospective registry with one
year follow-up beginning at the time of ablation procedure. Prior to ablation each patient underwent baseline
physical examination, transthoracic echocardiogram,
quality of life assessment and, if possible, maximal
symptom-limited metabolic treadmill exercise testing.
Each of these measures was repeated at 3 and 12 months
after ablation and pacing. Decisions regarding the ablation technique, mode of pacing, pacemaker programming and use of antiarrhythmic drug therapy were left to
the discretion of each investigator. All echocardiograms
were read in a blinded fashion by a core laboratory. The
exercise tolerance test followed the chronotropic assessment exercise protocol[9] with determination of maximal
oxygen uptake (VO2 max) and anaerobic threshold.
Health-related quality of life was assessed with three
instruments: the Health Status Questionnaire Short
Form —36 (Health Outcomes Institute, 1993) containing eight subscales to measure overall well-being[10]; the
Quality of Life Index (Version III) adjusting satisfaction
scores in each of four dimensions to weight the overall
quality of life by aspects most important to the individual patient[11], the Symptom Checklist — Frequency
and Severity, assessing common arrhythmia-related
symptoms[12].
For the study group as a whole, left ventricular function
was improved significantly at 3 and 12 months compared to baseline[6]. For patients with baseline ejection
fraction <45% mean value (baseline 31%), ejection fraction improved to 42% at 3 months and to 41% at 12
months (both P<0·001). Patients with baseline ejection
fractions >45% or who were in sinus rhythm at the time
of radiofrequency ablation (RFA) had no changes in
ventricular function at follow-up.
Results
Study group
Of 161 patients referred for AV junctional ablation, 156
were enrolled in the study[6]. The mean age was 6611
years with 58% men. The mean left ventricular ejection
fraction was 4818%. Seventy-eight percent of patients
had structural heart disease, most commonly hypertension (52%), coronary artery disease (31%) and valvular
disease (24%). Congestive heart failure was present in
37% of patients[5]. Atrial fibrillation was chronic (>1
month) in 45% of patients and paroxysmal in 55%.
Complete heart block was achieved in 155/156 patients
(99·4%) after radiofrequency ablation. Of 156 implanted
pacemakers, 69% were VVI(R) and 31% were dual
chamber devices.
Quality of life assessment
For the study group who were severely disabled by their
symptoms at baseline, significant and marked improvement was demonstrated at follow-up for all three instruments[6]. At 3 months there was marked improvement in
all eight subscales of the Short Form — 36 and in the
overall Quality of Life Index, and a marked reduction in
symptom frequency and severity of the Symptom checklist. For all three instruments the improvements were
sustained at 1 year of follow-up.
Exercise testing
Seventy nine patients (51%) underwent baseline and
follow-up treadmill testing[6]. While a trend toward
improved exercise duration, and VO2 max were noted,
these values did not achieve statistical significance
during follow-up.
Survival
Twenty three patients died during follow-up including
five sudden deaths[5]. The overall survival at 12 months
was 85%. For patients with baseline ejection fraction
<45%, 1 year survival was 75% compared to 93% for
patients with baseline ejection fraction >45%[5].
Discussion
The APT study in perspective
The APT study was an early attempt to quantify the
outcome of ablation and pacing in a large multicentre
experience. As such, the study was a non-randomized,
prospective registry of medically refractory, highly
symptomatic patients with atrial fibrillation for whom
no other therapies were available. In this setting, each
patient may, in effect, serve as his or her own control by
entering the study on maximally tolerated medical
therapy. Ablate and pace therapy has been rapidly
accepted in the United States, as evidenced by the rapid
enrollment in the APT, the numerous publications supporting its benefits and the difficulty in initiating a large
multicentre randomized ablate and pace trial in the
United States, primarily due to physician bias towards
the procedure[2–7]. The results of the APT provide strong
evidence for the clinical benefits of this procedure in
highly symptomatic patients and these results are very
consistent with other studies. By examining quality of
life measures, the APT documents the severe disability
that can accompany uncontrolled chronic and paroxysmal atrial fibrillation. Consistent with other studies,
ablation and pacing provides dramatic and sustained
symptomatic relief[2–4]. Fitzpatrick et al. examined quality of life, retrospectively, prior to ablation and during
Europace, Vol. 1, January 1999
24
M. A. Wood et al.
an average of 2·3 years of follow-up in 107 patients
treated at a single centre[2]. This study also documented
marked improvement in quality of life, symptom reduction and ease of activities of daily life. Also significant
were reductions in physician visits, hospitalizations and
drug burden. Left ventricular function was not followed
after ablation in this study[2]. Brignole et al. demonstrated improved quality of life after only 15 days in 12
patients randomized to ablation and pacing compared
with 11 patients receiving pacing alone for chronic atrial
fibrillation[1]. Jensen et al. showed improved quality of
life in 88% of 50 patients after ablation and pacing[3]. In
this study, 5/6 patients dying during follow-up showed
improved quality of life. Numerous reports have
documented an improvement in left ventricular function
after ablation and pacing[1,13]. The 35% improvement in
left ventricular function in the APT patients with low
baseline ejection fraction is similar to the 34–44%
improvement in other reports[1,13].
By examining the subset of patients with baseline
congestive heart failure, the APT extends the understanding of tachycardia-induced cardiomyopathy in this
patient cohort. Preliminary analysis suggests that
paroxysmal atrial fibrillation may be associated with a
lower incidence of tachycardia-induced cardiomyopathy
and that significant tachycardia-induced cardiomyopathy may be present in more than 25% of this patient
population[7]. Also, the APT documents that neither
improvement in ventricular function nor prolongation
of maximal treadmill exercise time are necessary for
dramatic improvements in quality of life[5,6]. The choice
of appropriate end-points must be considered in the
design of future studies.
Few studies have compared formal exercise
testing before and after ablation and pacing, as in the
APT. In contrast to the APT results, Brignole et al.
documented a 15% improvement in exercise time
after ablation and pacing[1]. Metabolic testing was not
performed. The trend towards improved exercise in the
APT failed to reach statistical significance. Factors
which can influence exercise testing after ablation and
pacing are many and may include exclusion of the most
ill patients at baseline from exercise testing, and suboptimal rate-response pacemaker programming. Such
factors should be considered in the design of future
studies as well as the relevance of treadmill times as a
clinical end-point.
The significant mortality in the APT is a
reminder of the degree of illness in the patient population and that this therapy, despite symptomatic
improvement, is only palliative. Other studies have
documented up to 18% mortality in 2 years after
ablation and pacing[2]. While much of the mortality
arises from non-cardiac causes in these studies, it
remains unclear whether the consistent component of
cardiac mortality results from a gravely ill patient
cohort or pro-arrhythmic responses to abrupt reduction in ventricular rate[2,5]. In a retrospective study
Windecker et al.[14] report similar 2 year survivals
(87%) among patients undergoing ablation and pacing
Europace, Vol. 1, January 1999
(n=132) or medical therapy (n=137) for atrial fibrillation. However, the true effect of ablation and pacing
on survival remains unknown.
Future directions
The APT strongly supports ablation and pacing for the
most symptomatic and medically refractory patients.
However, studies are needed to expand and define
the full patient population that can benefit from this
procedure. In particular, data supports that even patients with ‘controlled’ ventricular rates may develop
tachycardia-induced cardiomyopathy and could benefit
from ablation and pacing. In addition, regularization
of the ventricular rate can optimize hemodynamics in
patients with atrial fibrillation, even in patients with
preserved ventricular function[4,15]. The APT documents an appreciable mortality in the study cohort and
does not provide insight into mechanisms of death or
mortality rates compared with medical management.
For this latter question, randomized controlled studies
would seem necessary.
Appendix
The APT Investigators
G. Neal Kay, MD, University of Alabama at
Birmingham; Mark Josephson, MD, Beth Israel
Hospital; George Crossley, MD, Bowman Gray School
of Medicine; David Wilber, MD, University of Chicago;
Bruce Wilkoff, MD, The Cleveland Clinic Foundation;
Andrea Natale, Duke University Medical Center; Anne
Curtis, MD, University of Florida College of Medicine;
Michael C. Giudici, MD, Genesis Medical Center;
Steven Kutalek, MD, Hahnemann University Medical
Center; Peter J. Wells, MD, Heart Place; John R.
Onufer, MD, Sentara Norfolk General Hospital;
Michael Prior, MD, Tulane School of Medicine;
Kenneth A. Ellenbogen, MD, Medical College of
Virginia; Bruce S. Stambler, MD, Hunter Holmes
McGuire Veterans Administration Medical Center;
John P. DiMarco, MD, PhD, University of Virginia
Medical Center; Stephen C. Hammill, MD, Mayo
Clinic.
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North American experience with APT
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