Assessment of Atrioventricular Junction Ablation and VVIR

Pacemaker Versus Pharmacological Treatment in Patients

With Heart Failure and Chronic Atrial Fibrillation
A Randomized, Controlled Study
Michele Brignole, MD; Carlo Menozzi, MD; Lorella Gianfranchi, MD; Giacomo Musso, MD;
Roberto Mureddu, MD; Nicola Bottoni, MD; Gino Lolli, MD

Background—Uncontrolled studies have suggested that atrioventricular junction ablation and pacemaker implantation
have beneficial effects on quality of life in patients with chronic atrial fibrillation (AF).
Methods and Results—We performed a multicenter, controlled, randomized, 12-month evaluation of the clinical effects of
atrioventricular junction ablation and VVIR pacemaker (Abl1Pm) versus pharmacological (drug) treatment in 66 patients
with chronic (lasting .6 months) AF who had clinically manifest heart failure and heart rate .90 bpm on 3 standard ECGs
recorded at rest during stable clinical conditions on different days. Before completion of the study, withdrawals occurred in
8 patients of the drug group and in 4 patients of the Abl1Pm group. At the end of the 12 months, the 28 Abl1Pm patients
who completed the study showed lower scores in palpitations (278%; P50.000) and effort dyspnea (222%; P50.05) than
the 26 of the drug group. Lower scores, although not significant, were also observed for exercise intolerance (220%), easy
fatigue (217%), chest discomfort (250%), Living with Heart Failure Questionnaire (214%), New York Heart Association
functional classification (24%), and Activity scale (212%). The intrapatient comparison between enrollment and month 12
showed that in the Abl1Pm group, all variables except easy fatigue improved significantly from 14% to 82%. However,
because an improvement was also observed in the drug group, the difference between the 2 groups was significant only for
palpitations (P50.000), effort dyspnea (P50.01), exercise intolerance (P50.005), easy fatigue (P50.02), and chest
discomfort (P50.02). Cardiac performance, evaluated by means of standard echocardiogram and exercise test, did not differ
significantly between the 2 groups and remained stable over time.
Downloaded from http://ahajournals.org by on May 9, 2020

Conclusions—In patients with heart failure and chronic AF, Abl1Pm treatment is effective and superior to drug therapy
in controlling symptoms, although its efficacy appears to be less than that observed in uncontrolled studies because some
improvement can also be expected in medically treated patients. Cardiac performance is not modified by the treatment.
(Circulation. 1998;98:953-960.)
Key Words: catheter ablation n atrioventricular node n fibrillation n pacemakers

lthough a few uncontrolled studies1–4 have suggested the

A beneficial effect of atrioventricular (AV) junction ablation
during long-term follow-up in patients with chronic AF, these
did not include a control group of patients with similar arrhyth-
mias treated without catheter ablation. A single controlled trial
showed that ablation was superior to medical therapy in improv-
ing specific symptoms 15 days after ablation.5 Rigorous quanti-
fication of the impact of ablation therapy on specific symptoms
and on the total well-being of the person, including physical and
psychological aspects, has been performed only recently by
Bubien et al6 in a wide variety of tachyarrhythmias. After
ablation, the patients with AF exhibited persistently lower
quality-of-life scores than those with the other types of arrhyth-
mia. However, baseline values were also significantly worse in
AF patients; moreover, chronic and paroxysmal AF were con-
sidered together. The main aim of this study was to test the
hypothesis that AV junction ablation and VVIR pacemaker
(Abl1Pm) treatment is superior to pharmacological therapy in
improving quality of life and controlling specific symptoms
during a long-term follow-up period in patients affected by
manifest heart failure and chronic AF. Secondary aims were to
evaluate the effect of ablation and pacemaker implantation on
cardiac performance and to assess the clinical complications of
such treatment.
See p 941
Methods
Protocol
This prospective, randomized, multicenter trial was designed to
compare the clinical efficacy of Abl1Pm treatment and conventional

Received January 12, 1998; revision received April 13, 1998; accepted April 27, 1998.
From the Department of Cardiology and Arrhythmologic Center, Ospedali Riuniti, Lavagna (M.B., L.G.); the Department of Cardiology and Arrhythmologic
Center, Ospedale S Maria Nuova, Reggio Emilia (C.M., N.B., G.L.); and the Section of Arrhythmology, Ospedale Civile, Imperia (G.M., R.M.).
Correspondence to Michele Brignole, MD, Via A Grilli 164, 16041 Borzonasca (GE), Italy. E-mail brignole@omninet.it
© 1998 American Heart Association, Inc.

953
 954 Ablation and Pacing for Chronic AF
drug therapy. Each patient was followed up for 12 months. Compar-
ison was performed at the end of this study period. The study
protocol had been approved by the Ethics Committee of the Hospital
of Reggio Emilia and by the institutional review committees of the
hospitals participating in the study. The enrolled subjects gave
informed consent.
Assignment and Blinding
Randomization was effected centrally, blocking on study centers to
minimize possible biases caused by differences in patient character-
istics between centers. The allocation of sequences was computer-
generated and the intervention assignments were hidden from par-
ticipants in the trial until the time of allocation.
Patients were recruited from September 1993 to June 1996 among
subjects referred to our institutions from the emergency room,
inpatient service, and outpatient arrhythmia clinic. The study was
terminated in July 1997.
Inclusion Criteria
Consecutive patients affected by chronic AF (lasting .6 months)
who met all the following criteria were considered eligible for
inclusion: (1) clinically manifest heart failure responsible for epi-
sodes of congestive heart failure or pulmonary edema or persistent
severe symptoms including palpitations, dyspnea, easy fatigue, and
chest discomfort that limited daily life and were intolerable for the
patient; (2) evidence of structural heart disease; and (3) heart rate
.90 bpm on 3 standard ECGs recorded at rest during stable clinical
conditions on different days.
Exclusion Criteria
The following were criteria for exclusion from the study: end-stage
heart failure; patients in class IV of the functional classification of
the New York Heart Association; acute cardiovascular diseases
during the previous 6 months, for example, myocardial infarction,
Downloaded from http://ahajournals.org by on May 9, 2020
unstable angina, or stroke; associated severe general medical ill-
nesses; significant renal or hepatic disease; history of sustained
ventricular tachyarrhythmias; follow-up not possible.
End Points
The primary end point was the evaluation of quality of life and
specific symptoms during the 12th month after randomization.
Secondary end points were intrapatient comparison of quality of
life and specific symptoms between enrollment and month 12;
recording of major clinical events occurring during the 12-month
study period, for example, death and major morbidities, complica-
tions of the treatment, and number of hospitalizations; and objective
assessment of cardiac performance at the beginning and end of the
study.
Outcome Measurements
These were made at the time of enrollment and at the end of the
12-month study period.
Quality-of-Life Questionnaire
A comprehensive evaluation of the patient’s quality of life was made
with the Minnesota LHFQ.7 This 21-item, self-administered ques-
tionnaire comprehensively covers physical, socioeconomic, and
psychological impairments occurring during the previous month that
patients often relate to their heart disease. A score based on how each
person ranks each item on a common scale is used to quantify the
extent of impairment and how it is affected by therapeutic interven-
tion. The maximum possible score is 105. In patients with heart
failure refractory to conventional therapy, the median score proved
to be 52; this decreased to 10 in asymptomatic patients with heart
disease.7 In patients with severely symptomatic paroxysmal AF
uncontrolled by conventional drugs, the mean score was 50 and
decreased to 20 after AV junction ablation and DDDR mode-
switching pacemaker treatment.8 The reliability and validity of this
questionnaire in detecting therapeutic benefits has been previously
demonstrated.8 –11
Specific Symptoms Scale
The Specific Symptoms Scale was developed as a disease-specific
instrument to measure the patient’s perception of the frequency and
severity of arrhythmia-related symptoms. This instrument has been
demonstrated to discern changes in the symptoms of patients with
atrial fibrillation both in sequential and in case-control studies.5 It
consists of a self-administered semiquantitative questionnaire. Each
patient is asked to quantify by means of a score scale (05absence,
105maximum score) each of the following symptoms occurring
during the previous month: palpitations, effort dyspnea (shortness of
breath during physical activity), rest dyspnea (shortness of breath at
rest), exercise intolerance (fatigue during mild physical activity),
easy fatigue at rest, and chest discomfort.
New York Heart Association Classification
Functional capacity was also assessed objectively by the investiga-
tors on enrollment and at the end of the study period, using the
4-class functional classification of the NYHA.
Specific Activity Scale
The Specific Activity Scale assigns 1 to 4 functional classes on the
basis of the single most difficult activity the patient can perform from
a list of specific activities. It has been shown in particular to be better
than the NYHA classification for the evaluation of true class II
patients and less likely to underestimate treadmill performance.12
Ablation Procedure and Pacemaker Implantation
The ablation end point was the production of complete, persistent
AV block. The ablation procedure was followed, after 1 hour, by
pacemaker implantation during the same session. All patients re-
ceived a single-chamber rate-responsive pacemaker. Unless other-
wise indicated, devices were programmed to the VVIR mode, a
lower rate of 80 bpm, an upper rate limit of 120 bpm. The other
programmable parameters were set as appropriate for each individual
patient.
Follow-up
Patients from both groups underwent the commonly accepted con-
ventional treatments for heart failure, including digitalis, diuretics,
angiotensin-converting enzyme inhibitors and nitrates. The patients
assigned to the drug arm were also treated with calcium-antagonists,
sotalol, and amiodarone when necessary to control rapid ventricular
heart rates. During the 12-month study period, changes in drug
therapy were permitted to minimize the patient’s discomfort and to
further improve the treatment. b-Blockers, amiodarone, and calcium-
antagonists were also used in the Abl1Pm group when clinically
indicated for other reasons. Antithrombotic therapy was used in
accordance with the published guidelines.13 Anticoagulants were
prescribed whenever possible at a therapeutic value of INR of 2.5
(tolerance limits 2 to 3). Antiplatelet therapy or no therapy was
prescribed when anticoagulants were contraindicated. In patients
older than 75 years, the decision to adopt anticoagulant therapy was
taken on the basis of careful risk/benefit evaluation.
Patients were seen at the outpatient clinic every 3 months for 12
months. The follow-up visit included the gathering of data on clinical
status, symptoms, drug treatments, and side effects. Moreover, on
enrollment and at the 12-month visit, the patients underwent 24-hour
Holter recording, echocardiography, and exercise stress testing.
Statistics
This study was performed on '30 patients per group. On the basis
of a previous study,5 we assumed that the Abl1Pm group had a 60%
reduction in palpitations and a 50% reduction in effort dyspnea
scores compared with the drug group. This sample size provided
80% power to show difference between groups with a probability
of 95%.
Comparison between continuous variables was obtained by paired
and unpaired Student’s t test, as appropriate; comparison between
proportions was obtained by Fisher’s exact test.

Progress through various stages of the trial, including flow of
participants, withdrawals, and timing of primary and secondary
outcome measurements.
Results
Participant Flow and Follow-up
Progress through the various stages of the trial, including
flow of participants, withdrawals, and timing of primary and
secondary outcome measures, are shown in the Figure.
Sixty-six patients were enrolled. Screening logs were not
Downloaded from http://ahajournals.org by on May 9, 2020
maintained throughout the trial, but we used data from
intermittent surveys to calculate that '250 patients affected
by heart failure and high rate chronic AF were initially
screened. The most frequent reason for noneligibilty was a
decrease of heart rate from an initial value .90 bpm to a
value ,90 bpm during the run-in phase. Baseline character-
istics of the study population are shown in Table 1.
In all 32 patients assigned to the Abl1Pm arm, the ablation
end point (production of complete, persistent AV block) was
reached without complications, with a median of 2 burns
(range 1 to 31) at 30 to 40 W. Right-sided ablation was
successful in 27 patients and a sequential approach (right- and
left-sided ablation) in the other 5. In 3 patients, AV conduc-
tion resumed after a few days, and a second procedure was
rapidly performed that achieved persistent AV block. Four
patients assigned to the drug arm did not complete the study
period because of the occurrence of severe symptoms and
received ablation and pacemaker treatment after 1, 1, 4, and
6 months.
Analysis
Primary End Point
At the end of the 12-month study period, the Abl1Pm group
patients showed significantly lower scores in palpitations
(278%) and effort dyspnea (222%) in comparison with
those of the drug group (Table 2). When adjusted for baseline
values, exercise intolerance, easy fatigue, and chest discom-
fort also showed significantly lower scores in the Abl1Pm
group. Lower scores, although not significant, were also
Brignole et al September 8, 1998 955
observed for LHFQ, NYHA functional classification, and
activity scale.
Secondary End Points
The intrapatient comparisons between enrollment and month
12 are shown in Table 2. There was some improvement in
both groups. In the Abl1Pm group all variables improved
significantly, except for easy fatigue, from 14% to 82%. In
the drug group the scores for LHFQ, palpitation, rest dyspnea,
and easy fatigue improved significantly. NYHA class im-
proved in 46% and 37% of the patients and worsened in 7%
and 19%, respectively. Activity scale improved in 36% and
33% of the patients and worsened in 7% and 12%, respec-
tively (not significant).
Clinical events occurring during the study period are
reported in Table 3. Complications related to ablation oc-
curred in 2 patients: In a patient with severe heart failure an
episode of ventricular fibrillation occurred 12 hours after
ablation; this was possibly related to inappropriate program-
ming of his permanent pacemaker (inadvertent night-rate
drop to a rate of 50 bpm); in the other patient, pulmonary
embolism occurred 2 days after ablation, with subsequent full
recovery. No complications related to pacemakers were
observed during the follow-up.
Cardiac performance, evaluated by means of standard
echocardiography and exercise testing, did not differ signif-
icantly between the 2 groups and remained stable over time
(Table 4). In the subgroups of patients with ejection fraction
#40% on enrollment, the ejection fraction value was seen, at
the month-12 visit, to have increased by 4610 points in the
Abl1Pm group and by 4616 in the drug group (not statisti-
cally different).
As a consequence of the pacemaker, on the month-12
Holter recording, minimum and mean heart rate were higher
and maximum heart rate was lower in the Abl1Pm group
(Table 4). Antiarrhythmic and cardiovascular drugs adminis-
tered throughout the study are shown in Table 5. Therapy
remained stable during the study period, with a predominance
of calcium-antagonist therapy in the drug group and of nitrate
therapy in the Abl1Pm group.
Secondary Ablation and Pacemaker Treatment
In the drug group, a total of 10 patients received ablation and
pacemaker treatment because of worsening of their symp-
toms, 4 before the completion of the study and 6 immediately
after the month-12 visit, and continued to be followed-up. In
7 of these, outcome measurements were obtained at the time
of ablation and 1 year later (Table 6). Ablation and pace-
maker treatment caused not only an improvement compared
with the time of ablation but also a significant improvement
over the initial evaluation on enrollment, being of similar
magnitude to that observed in the Abl1Pm group.
Discussion
To date, ablation and pacemaker treatment of chronic AF
have not been evaluated against a control group of medically
treated patients during a long follow-up period. We enrolled
a heterogeneous population affected by heart failure and AF
with a relatively high ventricular rate that caused severe
symptoms of heart failure. The characteristics of the popula-
 956 Ablation and Pacing for Chronic AF

TABLE 1. Baseline Characteristics of Study Population

Abl1PM
(n532) Drug (n534)
Age, y 7269 7269
Male sex 18 (56) 13 (38)
Structural heart disease
Coronary artery disease 11 14
Previous myocardial infarction 3 4
Dilated cardiomyopathy 9 5
Valvular cardiopathy 4 6
Chronic obstructive pulmonary disease 1 3
Hypertensive or undefined 4 5
History of tachyarrhythmias
Atrial fibrillation only 29 29
Atrial fibrillation and atypical atrial flutter 3 7
Duration of arrhythmia, y 5.766.9 4.165
No. of hospitalizations caused by arrhythmia or heart failure 2.862.9 (2) 1.861.4 (2)
(median)
Heart rate during AF (standard ECG), bpm 101612 104613
Episodes of congestive heart failure 27 (84) 26 (76)
Episodes of acute pulmonary edema 11 (34) 8 (25)
NYHA class 2.860.7 2.760.6
Activity Scale class 2.760.9 2.860.7
LHFQ score 44618 45615
Specific Symptoms Scale score
Palpitations 5.762.6 5.762.7
Downloaded from http://ahajournals.org by on May 9, 2020

Effort dyspnea 7.162.6 6.362.3

Rest dyspnea 3.662.7 2.963.1
Exercise intolerance 6.862.6 6.062.2
Easy fatigue 4.162.9 3.363.0
Chest discomfort 0.962.2 0.561.4
Holter recording
Mean heart rate, bpm 89619 82619
Minimum heart rate, bpm 63619 62618
Maximum heart rate, bpm 151625 147630
$1 episode of nonsustained ventricular tachycardia (.3 beats) 9 (28) 9 (26)
$10 ventricular premature beats per hour 19 (59) 15 (49)
Echocardiographic data
Left ventricular end-diastolic diameter .32 mm/m2 22 (73) 24 (71)
Left atrial diameter .45 mm 25 (78) 26 (76)
Ejection fraction ,50% 26 (87)* 25 (74)*
Left ventricular hypertrophy 12 (37) 13 (38)
Systolic pulmonary pressure .30 mm Hg 11 (44)† 8 (38)†
Numbers indicated in parentheses are percentages. Values are mean6SD or number of patients.
*Ejection fraction was calculated in 30 and 30 patients, respectively, in the 2 groups.
†Systolic pulmonary pressure was calculated in 25 and 21 patients, respectively, in the 2 groups.

tion were similar to those of other studies. For example, the
mean LHFQ score before ablation was as high as that of 38
to 48 registered by patients with heart failure refractory to
conventional therapy who were undergoing studies on the
effects of new pharmacological agents.9 –11 The 1-year mor-
tality rate of our population was 11%, which is very similar to
that of the large series of patients affected by AF and
mild-to-moderate heart failure enrolled in the V-HeFT II
study.14
The main result of this study is that Abl1Pm treatment was
effective and superior to drug therapy in controlling specific
symptoms, although its efficacy was lower than that observed
in the intrapatient comparison, as some improvement was
also observed in the medically treated patients. Improvement
 Brignole et al September 8, 1998 957

TABLE 2. Results of Quality-of-Life Measurements in 28 Patients of Abl1Pm Arm and 26 Patients of Drug Arm Who Completed
12-Month Study Period
Difference, From Enrollment to Month 12

Enrollment Month 12 Abl1Pm Drugs Abl1Pm

vs Drugs,
Abl1Pm Drugs P ABL1Pm Drugs P % Reduction % P % P P
LHFQ questionnaire 43619 44615 0.83 32620 37618 0.34 214 226 0.02 216 0.01 0.57
Specific Symptoms Scale
Palpitations 5.562.7 5.762.6 0.78 1.061.4 4.562.9 0.000 278 282 0.000 221 0.05 0.000
Effort dyspnea 6.862.7 6.362.3 0.47 4.562.4 5.862.2 0.04 222 234 0.000 28 0.38 0.01
Rest dyspnea 3.562.7 3.063.0 0.52 1.662.8 1.562.3 0.89 111 254 0.003 250 0.05 0.66
Exercise intolerance 6.562.6 5.862.0 0.27 4.462.7 5.562.0 0.10 220 232 0.000 25 0.55 0.005
Easy fatigue 4.162.9 2.862.8 0.10 3.463.2 4.162.8 0.40 217 217 0.20 146 0.05 0.02
Chest discomfort 0.962.1 0.661.6 0.56 0.461.9 0.862.2 0.48 250 256 0.04 133 0.28 0.02
NYHA class 2.860.7 2.760.6 0.58 2.460.5 2.560.8 0.58 24 214 0.006 27 0.17 0.30
Activity Scale 2.760.8 2.860.7 0.63 2.360.8 2.660.9 0.20 212 215 0.02 27 0.10 0.35
Values are mean6SD.

was greater for the specific symptoms of the disease than for
the indexes of health-related quality of life, namely LHFQ,
NYHA, and activity scale, which failed to prove a statistically
significant benefit. Whether this finding was due to a low
sensitivity of these outcome measurements is open to ques-
tion. However, the absolute decrease of 11 points in LHFQ
score observed in the present study in the Abl1Pm group was
slightly superior to the 5- to 8-point decrease observed with
new inotropic agents in patients with severe heart failure10,11
Downloaded from http://ahajournals.org by on May 9, 2020
impairment of cardiac performance, serious adverse effects,
or increased risk of death in the 12 months after ablation.
Comparison With Previous Uncontrolled Studies
All previous studies showed that after ablation and pace-
maker implantation, patients did better and had improved
indexes of quality of life of a similar magnitude to that
observed by us in the Abl1Pm group. For example, Natale et
al4 ranked palpitations, effort dyspnea, rest dyspnea, exercise

but inferior to the 30-point decrease observed in patients with intolerance, and easy fatigue, and, after 12 months, found an
paroxysmal AF treated with ablation and pacemaker treat- improvement ranging from 46% to 88%. In our previous
ment.8 Given the lack of correlation between change in study,5 the items of the Specific Symptom Scale had im-
functional status and improvement in cardiac performance proved by 48% to 96% (3 months from ablation). Geelen et
(evaluated by means of echocardiographic and exercise in- al16 evaluated LHFQ at the baseline and after 6 months and
dexes), which remained stable during follow-up, one could found a 39% decrease (from 36 to 22) in this index.
suppose that the treatment had a greater effect on those Ellenbogen et al17 found an improvement of 37% in their
symptoms more directly linked to rapid and irregular rhythm Physical Function score, of 135% in Physical Limits, and of
than on the outcome of the underlying heart disease.15 This is 46% in Functional Quality of Life, 12 months after ablation.
Fitzpatrick et al2 observed a 94% increase in their Quality of
supported by the slight (not significant) reduction in adverse
Life index; moreover, the pooled score of All Activities
clinical events observed in the Abl1Pm group during the
increased by 26%. A significant decrease in NYHA class has
study period.
also been observed.4,5,17 Because of its controlled design, our
Ablation and pacing treatment is relatively simple to
study demonstrates that not all the benefits were due to
perform, elicits no complications, is safe, and does not cause
ablation and pacemaker treatment per se, as some improve-
ment occurred also in the conventional treatment group.
TABLE 3. Clinical Events in Randomized Population During
12-Month Study Period Several factors other than ablation and pacemaker therapy
may have contributed to determining the final results on
Abl1Pm Drugs outcome, including more thorough examinations during the
Event (n532) (n534) P study than before, higher motivation of the patients to treat
Death their disease, and an unrecognized clinical instability at the
Total 3 (9) 4 (12) 0.53 time of enrollment. However, it is well known that many
Cardiac, sudden 1 (3) 4 (12) 0.20 patients, even those affected by end-stage heart failure, may
Cardiac, nonsudden 1 (3) 0 (0) 0.48 experience an unexpected reversal of their heart failure.18
Several previous studies have suggested that ablation and
Hospitalization 9 (28) 13 (38) 0.27
pacemaker treatment may cause an improvement in cardiac
Episodes of acute pulmonary edema 0 (0) 3 (9) 0.13
performance as a consequence of rhythm regularization and
Episodes of congestive heart failure 13 (41) 15 (44) 0.48 better rate control. A prospective hemodynamic study16
Stroke 0 (0) 1 (3) 0.13 showed a significant increase in cardiac output from 1.9 to
Numbers in parentheses are percentages. 2.3 L/m2 (6 months after ablation). In a controlled study
 958 Ablation and Pacing for Chronic AF

TABLE 4. Echocardiographic, Exercise Stress Test, and Holter Recording Results in 28 Patients of Abl1Pm
Arm and 26 Patients of Drug Arm Who Completed 12-Month Study Period
Enrollment Month 12

Abl1Pm Drugs Abl1Pm Drugs

Echocardiographic data
Left ventricular end-diastolic diameter, mm 59611 58610 59610 59610
Left ventricular end-systolic diameter, mm 43613 42612 42613 42612
Fractional shortening, % 2769 29611 29611 30611
Ejection fraction, % 43612 (26) 44615 (24) 44611 (26) 41612 (24)
Left atrial diameter, mm 52610 4966 55611 4868
Exercise stress test (24) (21) (24) (21)
Exercise time, min 6.263.2 6.162.9 6.663.6 6.963.8
Maximum heart rate, bpm 161619 158626 106622* 156630*
METs 4.362.1 4.262.2 4.762.3 4.762.8
Holter recording (24) (26) (24) (26)
Mean heart rate, bpm 85618 78614 8666† 78612†
Minimum heart rate, bpm 64621 59616 7962* 58614*
Maximum heart rate, bpm 149627 149631 116622* 144630*
$1 episode of nonsustained ventricular 4 5 5 6
tachycardia (.3 beats)
$10 ventricular premature beats per hour 13 9 9 10
Values are mean6SD.
When data were not available for all patients, numbers of patients with data are indicated in parentheses.
*P50.000; †P50.003.

involving patients in whom the ventricular rate was believed shown to decrease, especially in patients with baseline
Downloaded from http://ahajournals.org by on May 9, 2020

to be well controlled (but irregular), Daoud et al19 found that depressed function, thus leading to improvements in the
an increase in cardiac output could be achieved by regular- indexes of systolic function, namely ejection fraction and
ization of the rhythm. The negative hemodynamic conse- fractional shortening.3–5,17,25–27 Exercise capacity has also been
quences of irregular sequences of R-R intervals during AF seen to improve after ablation.5,27,28 Contrary to these studies,
has been found to be independent of heart rate.20 In case we were unable to show significant modifications of echo-
report studies, the reversal of tachyarrhythmia-induced car- cardiographic parameters and exercise stress testing either in
diomyopathy has been observed after ablation21 as well as intergroup or intrapatient comparisons. Even though in pa-
after control of heart rate by means of medical therapy.22–24 tients with depressed left ventricular function we observed a
Echocardiographic left ventricular diameters have been slight increase in the value of the ejection fraction after 12
months, this increase was also observed in the control group,
TABLE 5. Antiarrhythmic and Cardiovascular Drugs
thus making it unlikely that it was due to a beneficial effect
Administered Throughout Study in 28 Patients of Abl1Pm Arm of ablation, as supposed in many uncontrolled studies.3,5,17,25,26
and 26 Patients of Drug Arm Who Completed 12-Month The lack of improvement in exercise capacity was also
Study Period observed in the Ellenbogen study.17 The reason for these
differences is unclear. Admittedly, our study did not have the
Beginning (Month 0) End (Month 12) power to show slight differences, if any, in cardiac perfor-
Abl1Pm Drugs Abl1Pm Drugs mance, and we recognize the limitations inherent in the
method of assessment of cardiac performance. Indeed, com-
Amiodarone 1 2 2 1
paring echocardiographic data from several different investi-
Sotalol 6 3 3 2 gators and between different underlying rhythms and the
b-Blockers 2 2 1 2 heterogeneous pathogenesis of the population might have
Verapamil/diltiazem 2* 12* 2* 12* generated confounding results. Furthermore, the low maximal
Digitalis 18 19 16 18 heart rate achieved during stress testing in the Abl1Pm group
Diuretics 21 16 25 19 may have contributed to lower stress tolerance in that
population. Moreover, the mean heart rate of our population,
Nitrates 9† 2† 9‡ 1‡
evaluated by means of Holter monitoring, was not particu-
ACE-inhibitors 19 16 19 15
larly high and might have been lower than that observed in
Warfarin 14 16 14 16 other studies. On the other hand, the beneficial hemodynamic
Aspirin 9 6 9 6 effect of regularization and rhythm control might have been
Values are numbers of patients. counteracted by the deleterious effect of asynergic ventricular
*P50.001; †P50.03; ‡P50.01. contraction caused by right apical ventricular pacing.29,30
 Brignole et al September 8, 1998 959

TABLE 6. Intrapatient Comparison of Quality-of-Life Measurements in 7 Patients

of Drug Arm Who Underwent Secondary Ablation and Pacemaker Implantation
Month 12 After Ablation

At Time of Difference From

Enrollment Ablation Enrollment, % P
LHFQ questionnaire 52611 6365 3269 238 0.007
Specific Symptoms Scale
Palpitations 7.361.5 7.262.0 1.362.6 281 0.001
Effort dyspnea 6.761.8 8.661.1 4.761.6 229 0.03
Rest dyspnea 2.162.3 3.863.1 2.062.0 25 0.93
Exercise intolerance 6.662.6 7.861.9 4.661.8 230 0.02
Easy fatigue 3.662.9 6.261.9 2.662.7 228 0.02
Chest discomfort 1.462.0 2.662.5 0.360.5 280 0.02
NYHA class 2.960.4 3.260.8 2.760.5 27 0.42
Activity Scale 3.160.7 3.460.9 2.760.5 213 0.16
Values are mean6SD.

No case of overt reversal of cardiac dysfunction was
observed, suggesting that tachycardia-induced cardiomyopa-
thy is rare in an unselected population of elderly patients with
a ventricular rate not particularly elevated and known cause
of heart disease. Indeed, tachycardia-induced cardiomyopa-
thy seems to be more likely in patients without evidence of
known heart disease and with a very high ventricular rate.21–24
On the other hand, fortunately, we did not observe any case
of severe hemodynamic deterioration caused by severe mitral
Downloaded from http://ahajournals.org by on May 9, 2020
needs further evidence because our study did not have the
power to show any slight differences in mortality rates. To
summarize, the different results of this study compared with
the previous uncontrolled studies give further demonstration
of the need to perform clinical trials including a control group
before considering a new treatment as established.
Conclusions
In patients with heart failure and chronic AF, the control of

regurgitation, as occurred after ablation in the population of
Vanderheyden et al.31 One explanation could be that we
excluded from enrollment the patients with end-stage heart
failure and those in NYHA functional class IV, who were
probably those at highest risk of adverse outcome. Moreover,
the patients who had recurrent episodes of heart failure,
worsening of symptoms, or cardiac death were balanced in
the Abl1Pm and drug groups, thus suggesting that the natural
course of the underlying disease, and not an adverse effect of
ablation, was the cause of the unfavorable outcome.
Finally, the results of the study did not evidence an
increased risk of death, especially sudden death, either early
or late after ablation. Early studies described sudden death in
patients after DC ablation of the AV junction.32,33 Life-
threatening ventricular arrhythmias and procedure-related
death have been observed in the immediate time period after
radiofrequency ablation.33–36 Concern has also been expressed
over the high mortality rate late after ablation, along with the
uncertainty whether this should be attributed to the natural
course of the underlying disease or to an adverse effect of the
ablation and pacemaker treatment.13,34,37 However, several
authors33,36 –39 have identified DC ablation, postablation bra-
dycardia, failure of temporary pacing, very severe heart
failure, and hypokalemia as factors able to predict these
complications. Our results suggest that when the above-
mentioned factors are under control, life-threatening ventric-
ular tachyarrhythmias are unlikely to occur, that long-term
survival is similar to that observed in patients treated with
conventional therapy, and that the sudden death rate is
slightly lower in ablated patients. However, this conclusion
rapid and irregular heart rate achieved by ablation and
pacemaker treatment can be proposed, in addition to conven-
tional pharmacological therapy, as an efficacious means of
improving quality of life without exposing patients to serious
adverse effects, complications, or death. However, this study
was unable to show a benefit of the treatment on cardiac
performance or on the progression of the disease.
References
1. Jensen SM, Bergfeldt L, Rosenquist M. Long-term follow-up of patients
treated by radiofrequency ablation of the atrioventricular junction. PACE.
1995;18(part I):1609 –1614.
2. Fitzpatrick AD, Kourouyan HD, Siu A, Lee R, Lesh MD, Epstein LM,
Griffin JC, Scheinman MM. Quality of life and outcomes after radiofre-
quency His-bundle catheter ablation and permanent pacemaker implan-
tation: impact of treatment in paroxysmal and established atrial fibril-
lation. Am Heart J. 1996;131:499 –507.
3. Rosenquist M, Lee M, Mouliner L, Springer M, Abbott J, Wu J, Langberg
J, Griffin J, Scheinman M. Long-term follow-up of patients after trans-
catheter direct current ablation of the atrioventricular junction. J Am Coll
Cardiol. 1990;16:1467–1474.
4. Natale A, Zimerman L, Tomassoni G, Kearney M, Kent V, Brandon MJ,
Newby K. Impact on ventricular function and quality of life of transcath-
eter ablation of the atrioventricular junction in chronic atrial fibrillation
with a normal ventricular response. Am J Cardiol. 1996;78:1431–1433.
5. Brignole M, Gianfranchi L, Menozzi C, Bottoni N, Bollini R, Lolli G,
Oddone D, Gaggioli G. Influence of atrioventricular junction radiofre-
quency ablation in patients with chronic atrial fibrillation and flutter on
quality of life and cardiac performance. Am J Cardiol. 1994;74:242–246.
6. Bubien RS, Knotts-Dolson SM, Plumb VJ, Kay GN. Effect of radiofre-
quency catheter ablation on health-related quality of life and activities of
daily living in patients with recurrent arrhythmias. Circulation. 1996;94:
1585–1591.
7. Rector TS, Kubo SH, Cohn JN. Patients’ self-assessment of their con-
gestive heart failure, II: content, reliability and validity of a new measure,
 960 Ablation and Pacing for Chronic AF
the Minnesota Living with Heart Failure Questionnaire. Heart Failure.
1987;3:198 –209.
8. Brignole M, Gianfranchi L, Menozzi C, Alboni P, Musso G, Bongiorni
MG, Gasparini M, Raviele A, Lolli G, Paparella N, Acquarone S. An
assessment of atrioventricular junction ablation and DDDR mode-
switching pacemaker versus pharmacological treatment in patients with
severely symptomatic paroxysmal atrial fibrillation: a randomized con-
trolled study. Circulation. 1997;96:2617–2624.
9. Rector TS, Cohn J. Assessment of patient outcome with the Minnesota
Living with Heart Failure Questionnaire: reliability and validity during a
randomized, double-blind, placebo-controlled trial of pimobendan. Am
Heart J. 1992;124:1017–1024.
10. Massie B, Berk M, Brozena S, Elkayam U, Plehn J, Kukin M, Packer M,
Murphy B, Neuberg G, Steingart R, Levine B, DeHaan H. Can further
benefit be achieved by adding flosequinan to patients with congestive
heart failure who remain symptomatic on diuretic, digoxin, and an an-
giotensin converting enzyme inhibitors? Circulation. 1993;88:492–501.
11. Bristow M, Gilbert E, Abraham W, Adams K, Fowler M, Hershberger R,
Kubo S, Narahara K, Ingersoll H, Krueger S, Young S, Shusterman N.
Carvedilol produces dose-related improvements in left ventricular
function and survival in subjects with chronic heart failure. Circulation.
1996;94:2807–2816.
12. Goldman L, Hashimoto B, Cook F, Loscalzo A. Comparative reproduc-
ibility and validity of systems for assessing cardiovascular functional
class: advantages of a new specific activity scale. Circulation. 1981;64:
1227–1234.
13. Prystowsky E, Benson DW, Fuster V, Hart RG, Kay GN, Myerburg RJ,
Naccarelli GV, Wyse G. Management of patients with atrial fibrillation:
a statement for healthcare professionals from the Subcommittee on Elec-
trocardiography and Electrophysiology, American Heart Association.
Circulation. 1996;93:1262–1277.
14. Carson P, Johnson G, Dunkman B, Fletcher R, Farrel L, Cohn J. The
influence of atrial fibrillation on prognosis in mild to moderate heart
failure: the V-HeFT studies. Circulation. 1993;87(suppl VI):IV-102-
IV-110.
15. Brown C, Mills R, Conti JB, Curtis A. Clinical improvement after
atrioventricular nodal ablation for atrial fibrillation does not correlate
Downloaded from http://ahajournals.org by on May 9, 2020
with improved ejection fraction. Am J Cardiol. 1997;80:1090 –1091.
16. Geelen P, Goethals M, de Bruyere B, Brugada P. A prospective hemo-
dynamic evaluation of patients with chronic atrial fibrillation undergoing
radiofrequency catheter ablation of the atrioventricular junction. Am J
Cardiol. 1997;80:1606 –1609.
17. Ellenbogen K, Kay N, Giudici M, Redfield M, Jenkins L, Takle-
Newhouse T, Jensen N, Martin R. Radiofrequency ablation of the AV
junction improves functional status in patients with congestive heart
failure: results from the ATP trial. Circulation. 1996;94(suppl I):I-682.
Abstract.
18. Levine TB, Levine AB, Goldberg D, Narins B, Goldstein S, Lesch M.
Reversal of end-stage heart failure is predicted by long-term therapeutic
response rather than initial hemodynamic and neurohormonal profile.
J Heart Lung Transplant. 1996;15:297–303.
19. Daoud E, Weiss R, Bahu M, Knight B, Bogun F, Goyal R, Harvey M,
Strickberger A, Man KC, Morady F. Effect of irregular ventricular
rhythm on cardiac output. Am J Cardiol. 1996;78:1433–1436.
20. Clark D, Plumb V, Epstein A, Kay GN. Hemodynamic effects of irregular
sequence of ventricular cycle lengths during atrial fibrillation. J Am Coll
Cardiol. 1997;30:1039 –1045.
21. Lemery R, Brugada P, Cheriex E, Wellens JJ. Reversibility of
tachycardia-induced left ventricular dysfunction after closed-chest
catheter ablation of the atrioventricular junction for intractable atrial
fibrillation. Am J Cardiol. 1987;60:1406 –1408.
22. Grogan M, Smith HC, Gersh B, Wood D. Left ventricular dysfunction
due to atrial fibrillation in patients initially believed to have idiopathic
dilated cardiomyopathy. Am J Cardiol. 1992;69:1570 –1573.
23. Phillips E, Levine SA. Auricular fibrillation without other evidence of
heart disease: a cause of reversible heart failure. Am J Med. 1949;7:
479 – 489.
24. Peters KG, Kienzle MG. Severe cardiomyopathy due to chronic rapidly
conducted atrial fibrillation: complete recovery after restoration of sinus
rhythm. Am J Med. 1988;85:242–244.
25. Heinz G, Siostrozonek P, Kreiner G, Gossinger H. Improvement in left
ventricular systolic function after successful radiofrequency His bundle
ablation for drug refractory, chronic atrial fibrillation and recurrent atrial
flutter. Am J Cardiol. 1992;69:489 – 492.
26. Rodriguez LM, Smeets J, Xie B, de Chillou C, Cheriex E, Pieters F,
Metzger J, den Dulk K, Wellens JJ. Improvement in left ventricular
function by ablation of atrioventricular nodal conduction in selected
patients with lone atrial fibrillation. Am J Cardiol. 1993;72:1137–1141.
27. Twidale N, Sutton K, Bartlett L, Dooley A, Winstanley S, Heddle W,
Hassam R, Koutsounis H. Effects on cardiac performance of atrioven-
tricular node catheter ablation using radiofrequency current for drug-
refractory atrial arrhythmias. PACE. 1993;16:1275–1284.
28. Kay GN, Bubien RS, Epstein AE, Plumb VJ. Effect of catheter ablation
of the atrioventricular junction on quality of life and exercise tolerance in
paroxysmal atrial fibrillation. Am J Cardiol. 1988;62:741–744.
29. Zile M, Blaustein A, Shimizu G, Gaasch W. Right ventricular pacing
reduces the rate of left ventricular relaxation and filling. J Am Coll
Cardiol. 1987;10:702–709.
30. Ausubel K, Furman S. The pacemaker syndrome. Ann Intern Med. 1985;
103:420 – 429.
31. Vanderheiden M, Goethals M, Anguera I, Nellens P, Andreis E, Brugada
J, Brugada P. Hemodynamic deterioration following radiofrequency
ablation of the atrioventricular conduction system. PACE. 1997;20:
2422–2438.
32. Barathi S, Scheinman M, Morady F, Hess DS, Levy M. Sudden death
after catheter/induced atrioventricular junctional ablation. Chest. 1985;
88:883– 889.
33. Brignole M, Menozzi C. Control of rapid heart rate in patients with atrial
fibrillation: drugs or ablation? PACE. 1996;19:348 –356.
34. Jordaens L, Rubbens L, Vertongen P. Sudden death and long-term
survival after ablation of the atrioventricular junction. Eur J Cardiac
Pacing Electrophysiol. 1993;3:232–237.
35. Peters R, Wever E, Hauer R, Wittkampf F, Robles de Medina E.
Bradycardia-dependent QT prolongation and ventricular fibrillation fol-
lowing catheter ablation of the atrioventricular junction with radiofre-
quency energy. J Am Coll Cardiol. 1993;21:102–109.
36. Geelen P, Brugada J, Andries E, Brugada P. Ventricular fibrillation and
sudden death after radiofrequency catheter ablation of the atrioventricular
junction. PACE. 1997;20:343–348.
37. Olgin J, Scheinman M. Comparison of high energy direct current and
radiofrequency catheter ablation of the atrioventricular junction. J Am
Coll Cardiol. 1993;21:557–564.
38. Darpo B, Walfridsson H, Aunes M, Bergfeldt L, Edvardsson N, Linde C,
Lurje L, van der Linden M, Rosenquist M. Incidence of sudden death
after radiofrequency ablation of the atrioventricular junction for atrial
fibrillation. Am J Cardiol. 1997;80:1174 –1177.
39. Evans T. Predictors of in-hospital mortality after DC catheter ablation of
atrioventricular junction: results of a prospective, international, multi-
center study. Circulation. 1991;84:1924 –1937