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Cardiac resynchronization therapy (CRT) is a new ther- Heart Association class, Minnesota Quality of Life score,
apeutic option for patients who have drug-refractory and 6-minute walking distance were evaluated at base-
end-stage heart failure. Much information has been ob- line and after 6 months of CRT. Long-term follow-up was
tained from patients who have sinus rhythm, but the use <2 years. New York Heart Association class, Minnesota
of CRT in patients who have chronic atrial fibrillation (AF) Quality of Life score, and 6-minute walking distance
has not been studied extensively. Accordingly, we eval- improved significantly in the 2 groups after 6 months of
uated the clinical response and long-term survival rate CRT. The number of nonresponders was greater among
of CRT in patients who had heart failure and chronic AF, patients who had AF. Nevertheless, the long-term sur-
and the results were compared with those in patients vival rate was comparable between patients who had
who had sinus rhythm and who underwent CRT. Sixty sinus rhythm and those who had AF. Patients who had
patients who had end-stage heart failure (30 had sinus
AF demonstrated comparable benefit from CRT as those
rhythm and 30 had chronic AF), New York Heart Asso-
who had sinus rhythm. 2004 by Excerpta Medica
ciation classes III to IV, left ventricular ejection fraction
Inc.
<35%, QRS interval >120 ms, and a left bundle branch
(Am J Cardiol 2004;94:1506 1509)
block received a biventricular pacemaker. New York
1506 2004 by Excerpta Medica Inc. All rights reserved. 0002-9149/04/$see front matter
The American Journal of Cardiology Vol. 94 December 15, 2004 doi:10.1016/j.amjcard.2004.08.028
TABLE 1 Characteristics of Patients Who Had Sinus Rhythm (n 30) and Atrial Fibrillation (n 30) at Baseline and Six-Month
Follow-up
Sinus Rhythm AF
(n 30) (n 30)
in the DDDR mode; in patients who had AF, the rection. For all tests, a p value 0.05 was considered
pacemaker was switched to the VVI-R mode. statistically significant.
Clinical evaluation: At baseline and after 6 months
of CRT, patients were clinically evaluated. Heart fail- RESULTS
ure symptoms were classified with the NYHA score. Baseline characteristics: Thirty consecutive patients
Quality of life score was assessed with the Minnesota who had sinus rhythm and 30 consecutive patients
Living With Heart Failure questionnaire.9 This ques- who had AF underwent CRT and were included in the
tionnaire contains 21 questions concerning the pa- study. The study population comprised 51 men and 9
tients perception of the effects of heart failure on women (mean age 65 9 years). Underlying etiology
daily-life activities. Questions are scored from 0 to 5, was nonischemic in 31 patients (52%) and ischemic in
resulting in a total score from 0 to 105, with the 29 patients (48%). Mean NYHA class was 3.2 0.4,
highest score reflecting the worst quality of life. QRS with most patients (80%) in NYHA class III. Medi-
duration and morphology were measured from the cation included diuretics in all patients, angiotensin-
surface electrocardiogram by 2 independent observ- converting enzyme inhibitors in 90%, blockers in
ers. Exercise capacity was evaluated by assessing a 50%, spironolactone in 39%, and amiodarone in 27%;
6-minute walking distance.10 Two-dimensional echo- all patients also used anticoagulants. Of the 30 pa-
cardiography at rest was performed at baseline and tients who had AF, 17 (57%) required permanent
6-month follow-up to assess left ventricular ejection ventricular pacing due to previous atrioventricular
fraction. From the apical 2- and 4-chamber images, junction ablation (18 6 months before CRT). There
left ventricular ejection fraction was determined by were no significant differences in baseline character-
using the biplane Simpsons rule.11 Interrogation of istics between patients who had sinus rhythm and
the device showed the percentage of ventricular pac- those who had AF (Table 1).
ing in patients who had AF over 6 months of CRT. Six-month follow-up: clinical evaluation: In patients
Long-term follow-up: Long-term follow-up was per- who had sinus rhythm (n 30), mean QRS duration
formed by chart review, telephone contact, and out- on the electrocardiogram decreased from 180 33 ms
patient clinical visits. Follow-up data were acquired to 160 21 ms (p 0.05). Mean NYHA class de-
for 2 years. Events were classified as cardiac death creased from 3.2 0.4 to 2.2 0.8 (p 0.05) after 6
(defined by a hospital chart that documented arrhyth- months of CRT. The 6-minute walking distance im-
mic death, sudden cardiac death, or death attributable proved significantly by 76%, and the quality of life
to congestive heart failure or myocardial infarction), score decreased by 28%. Of note, 21 patients (70%)
nonfatal myocardial infarction, and congestive heart had a 25% improvement in walking distance at
failure that required hospitalization. Moreover, the 6-month follow-up and 17 patients (57%) had a de-
average length of hospital stay per patient (expressed crease of 25% in quality of life score. Left ventric-
as days per year) was compared before and after ular ejection fraction increased significantly after 6
pacemaker implantation. months of CRT (Table 1).
Statistical analysis: Data are expressed as mean In patients who had AF, mean QRS duration de-
SD. Comparison of data were performed with Stu- creased from 205 15 ms to 164 35 ms (p 0.05).
dents t test for paired and unpaired data when appro- Mean NYHA class decreased from 3.2 0.4 to 2.3
priate. In case of non-normal distribution of data, the 0.6 (p 0.05) after 6 months of CRT. In addition, the
Mann-Whitney U statistic test was used. Univariate 6-minute walking distance increased significantly by
analysis for categorical variables was performed by 66% (p 0.05), and the quality of life score decreased
using chi-square test with Yates correction. Simulta- by 19% (p 0.05). Of note, 18 patients (60%) showed
neous comparison of 2 mean values was performed an improvement of 25% in walking distance at
by 1-way analysis of variance with Bonferronis cor- 6-month follow-up and 14 patients (47%) had a de-
NYHA class 3.1 0.3 2.2 0.5 0.05 3.2 0.4 2.4 0.7 0.05
Quality of life score 42 19 28 21 0.05 44 13 37 22 NS
6-Minute walking test (m) 229 125 388 172 0.05 224 101 310 134 0.05
LV ejection fraction (%) 21 7 30 12 0.05 19 9 26 10 0.05
Abbreviation as in Table 1.
crease 25% in quality of life score. Left ventricular 33 24 (p 0.05). When survival rate was compared
ejection fraction increased from 20 11% to 27 between patients who had sinus rhythm and those who
8% (p 0.05) after 6 months of CRT (Table 1). When had AF, mortality rate was not statistically different
patients who had AF and atrioventricular node abla- between groups, although patients who had AF tended
tion were compared with those who had AF and no to have a higher mortality rate (10% vs 23%, p
ablation, clinical improvement was comparable be- 0.07). The actual survival curves of the 2 groups are
tween groups (Table 2). However, in patients who did shown in Figure 1.
not have atrioventricular node ablation, percent ven-
tricular pacing was 82% versus 100% in patients who DISCUSSION
had ablation (p 0.05). In the present study, the benefit of CRT in patients
Responders were defined as those patients who who had AF was compared with that in patients who
improved 1 class in NYHA score after 6 months of had sinus rhythm. The main findings are that (1)
CRT. At 6-month follow-up, 43 patients (72%) were benefit, as measured by clinical parameters (NYHA
accordingly classified as responders and 17 (28%) as class, exercise capacity, and quality of life score), was
nonresponders. There was a significant difference be- comparable between patients who had sinus rhythm
tween the percentage of responders in the sinus and those who had AF; (2) the number of nonre-
rhythm group (n 24, 80%) compared with the AF sponders was higher among patients who had AF; (3)
group (n 19, 64%; p 0.05). In the AF group, there the decrease in hospitalization rate was comparable
was a difference in percentage of clinical responders between patients who had AF and those who had sinus
that favored patients who had atrioventricular node rhythm; and (4) long-term survival rate on CRT was
ablation compared with patients who did not have comparable between patients who had sinus rhythm
ablation (71% vs 54%, p NS). and those who had AF. Different studies have dem-
Follow-up data: Patients who had sinus rhythm onstrated the benefit of CRT in patients who have
were hospitalized for congestive heart failure an av- heart failure.4 6 These studies showed improvements
erage of 3.9 4.8 days/year before pacemaker im- in symptoms, exercise capacity, and systolic left ven-
plantation compared with 0.5 1.5 days/year after tricular function.4 6 In addition, a decrease in hospi-
implantation (p 0.05). The number of annual hospi- talization for decompensated heart failure was found,
talizations per patient decreased from 0.8 0.9 before as was a favorable mid-term survival rate with CRT
implantation to 0.2 0.4 after implantation versus optimal medical therapy.4 6
(p 0.05). Mean follow-up of patients who had sinus Recent studies have focused on the benefit of CRT
rhythm was 25 9 months (range 8 to 37). During in patients who have AF and demonstrated that pa-
follow-up, 3 patients (10%) died due to end-stage tients who have AF may benefit from this thera-
heart failure (Figure 1). After 2 years of follow-up, py.5,12,13 Etienne et al 12 reported an acute improve-
mean NYHA class remained significantly decreased, ment in hemodynamics immediately after CRT in 11
from 3.2 0.4 to 2.3 1.0 (p 0.05), and quality of patients who had AF. In a substudy from the Multisite
life score remained decreased, from 43 13 to 30 Stimulation in Cardiomyopathies trial,13 37 patients
19 (p 0.05). Patients who had AF were hospitalized who had AF showed improved clinical parameters
for congestive heart failure on average 4.1 4.8 after a 3-month period of active CRT. In particular, a
days/year before CRT versus 0.7 1.8 days/year after 10% improvement in 6-minute walking distance and a
implantation (p 0.05). The number of annual hospi- 13% improvement in peak oxygen consumption were
talizations per patient decreased from 0.9 1.0 before shown. Mortality rate at 9-month follow-up was 11%.
implantation to 0.3 0.5 after implantation In the present study, similar results were obtained.
(p 0.05). Mean follow-up of patients who had AF Patients who had sinus rhythm and those who had AF
was 19 11 months (range 4 to 46). During follow- exhibited benefit from CRT, and these patients dem-
up, 7 patients (23%) died, 6 (20%) due to end-stage onstrated significant improvement in clinical parame-
heart failure and 1 to a noncardiac cause. After 2 years ters. The response to CRT in patients who have AF is
of follow-up, mean NYHA class remained decreased, currently unclear. Careful analysis of data from the
from 3.2 0.4 to 2.4 0.8 (p 0.05), and the quality Multicenter InSync Randomized Clinical Evaluation
of life score also remained decreased, from 43 17 to (MIRACLE) trial has shown that 20% to 30% of