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Circulation Journal
Official Journal of the Japanese Circulation Society
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CONTROVERSIES IN CARDIOVASCULAR MEDICINE
Rhythm Control Should Be Better for the Management
of Patients With Atrial Fibrillation and Heart Failure
– Rhythm Control vs. Rate Control: Which Is Better
in the Management of Atrial Fibrillation? (Rhythm-Side) –
Takashi Kurita, MD, PhD; Koichiro Motoki, MD, PhD; Ryobun Yasuoka, MD, PhD;
Takayoshi Hirota, MD, PhD; Yuzuru Akaiwa, MD;
Yasuhito Kotake, MD; Shunichi Miyazaki, MD, PhD
The incidence of atrial fibrillation (AF) increases with advancing NHYA cardiac functional class, and it significantly
affects the cardiac function of a failing heart. In such situations, clinicians should aim to maintain sinus rhythm in
these patients with heart failure (HF) in order to improve their prognosis. However, according to various randomized clinical studies demonstrating the non-superiority of rhythm control over rate control, many clinicians seem to
prefer to take the line of least resistance (ie, rate control). Curative catheter ablation mainly based on isolation
procedure of the pulmonary veins in patients with AF and HF has demonstrated a significant improvement in left
ventricular function, even in the presence of adequate ventricular rate control before the ablation. On the other
hand, ablation and biventricular pacing therapy, which is an extreme rate control strategy, has not shown any
beneficial effects for these patients. Therefore, a regular RR interval with an appropriate cycle length only is not
sufficient to improve cardiac performance, and maintenance of sinus rhythm, which restores atrial contraction and
the atrioventricular synchrony, is thought to be essential for an improvement in HF. Thoughtful clinicians should
do their best to find a way to keep HF patients in sinus rhythm. (Circ J 2011; 75: 979 – 985)
Key Words: Antiarrhythmic drug; Atrial fibrillation; Catheter ablation; Heart failure
T
he incidence of atrial fibrillation (AF) increases with
advancing NHYA cardiac functional class.1,2 The
contribution of the atrial contraction to the cardiac
performance in a normal heart is considered to be small, but
the development of AF in a failing heart significantly affects
cardiac function by diminishing the atrial kick (atrioventricular (AV) synchrony) and inducing an inappropriately rapid
ventricular rate with an irregular RR interval.3–5 Furthermore,
the presence of AF in heart failure (HF) patients sometimes
results in severe systemic embolization. In such a clinical situation, clinicians should aim to maintain sinus rhythm in
these HF patients in order to improve their prognosis. However, it is regrettable that many clinicians seem to prefer to
take the line of least resistance (ie, rate control) based on various randomized clinical studies that have demonstrated the
non-superiority of rhythm control over rate control.6–10 We
should be so careful when interpreting the results of the large
randomized studies because those studies may have various
tricks in order to provide an over- or underestimation of 1 arm
of a selected treatment, and are not always compatible with
the actual clinical situation.
Because a pharmacological or non-pharmacological therapy
for AF patients can be used in either strategy (rhythm or rate
control), we will discuss the advantages of rhythm control
with regard to each issue.
Pharmacological Rhythm Control
Several recent randomized studies that compared pharmacological rhythm control to rate control in patients with AF and
HF could not demonstrate any significant superiority over
rhythm control.6–10 However, detailed interpretation of the
studies reveals different aspects of the 2 different treatments.
The AFFIRM study6 was a large randomized study that
compared 2 different approaches to the treatment of AF
(rhythm control: cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm; rate control: usage
of rate-controlling drugs). A total of 4,060 patients who
ere over 65 years old were enrolled in the study, and they
were equally divided into rate- and rhythm-control groups.
The opinions expressed in this article are not necessarily those of the editors or of the Japanese Circulation Society.
Received January 14, 2011; accepted February 3, 2011; released online March 11, 2011
Division of Cardiology, Faculty of Medicine, Kinki University, Osaka-Sayama, Japan
Mailing address: Takashi Kurita, MD, PhD, Division of Cardiology, Faculty of Medicine, Kinki University, 377-2 Ohono-Higashi,
Osaka-Sayama 589-8511, Japan. E-mail: [email protected]
ISSN-1346-9843 doi: 10.1253/circj.CJ-11-0075
All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: [email protected]
Circulation Journal Vol.75, April 2011
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KURITA T et al.
Figure 1. Cumulative mortality in the rhythm- and rate-control groups in AFFIRM study. More deaths occurred in the rhythmcontrol group than in the rate-control group, but the difference in mortality between the 2 groups was not statistically significant
(P=0.08).6 (Copyright © 2011 Massachusetts Medical Society. All rights reserved.)
Figure 2. Cumulative mortality in the rhythm- and rate-control groups in the AF-CHF study. The survival curves of the 2 groups
unexpectedly completely overlapped throughout the study.10 (Copyright © 2011 Massachusetts Medical Society. All rights reserved.)
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(Rhythm) Rhythm Control for AF Associated With CHF
981
Figure 3. Cumulative percentage of non-targeted results in the AF-CHF study. The percent of atrial fibrillation (%) in the
rhythm- and rate-control groups (AF-CHF study). Approximately 30% of patients in the rhythm-control group (gray bars) had AF
recurrence.10 (Copyright © 2011 Massachusetts Medical Society. All rights reserved.)
Table. Maintenance of Sinus Rhythm Significantly Associated With Survival Results in the AFFIRM Study11
Covariate
P value
HR
Age at enrollment
<0.0001
Coronary artery disease
HR: 99%CI
Lower
Upper
1.06
1.05
1.08
<0.0001
1.56
1.20
2.04
Congestive heart failure
<0.0001
1.57
1.18
2.09
Diabetes
<0.0001
1.56
1.17
2.07
Stroke or transient ischemic attack
<0.0001
1.70
1.24
2.33
Smoking
<0.0001
1.78
1.25
2.53
Left ventricular dysfunction
0.0065
1.36
1.02
1.81
Mitral regurgitation
0.0043
1.36
1.03
1.80
Sinus rhythm
<0.0001
0.53
0.39
0.72
Warfarin use
<0.0001
0.50
0.37
0.69
Digoxin use
0.0007
1.42
1.09
1.86
Rhythm-control drug use
0.0005
1.49
1.11
2.01
*Per year of age.
HR, hazard ratio; CI, confidence interval.
Although a history of HF was not required for enrollment
into this study, 26.0% had a depressed left ventricular (LV)
function (<50%). Figure 1 demonstrates the cumulative mortality in both groups. More deaths occurred in the rhythmcontrol group than in the rate-control group, but the difference in mortality between the 2 groups was not statistically
significant (P=0.08).
Because the adverse effects of developing AF could be more
significant in a failing heart, rhythm control in patients with
HF and AF may provide a better prognosis. The AF-HF trial
(Atrial Fibrillation and Congestive Heart Failure Trial)10 was
designed to determine whether the prevention of AF would
improve the survival in patients with HF. A total of 1,376 AF
patients with HF (LV ejection fraction (LVEF) <35%) were
enrolled and were randomly assigned equally to 2 groups. As
shown in Figure 2, the survival curves of the 2 groups unexpectedly completely overlapped throughout the study.
Based on these results,6,10 it is possible to conclude that
rate control alone, a simpler strategy, is adequate to treat the
AF in patients with HF. We are afraid that these results may
encourage a trend toward not maintaining sinus rhythm in
the majority of AF patients.
Figure 3 demonstrates the cumulating percentage of nontargeted results in both groups in the AFFIRM study6 and
Circulation Journal Vol.75, April 2011
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KURITA T et al.
Figure 4. Beneficial effect of sinus rhythm in patients with heart failure. The CHF-STAT study demonstrated that spontaneous
conversion of atrial fibrillation to sinus rhythm using amiodarone improved the survival rate in patients with heart failure.12
Figure 5. Improvement in left ventricular (LV) function and dimensions after ablation in patients with congestive heart failure.
Maintenance of sinus rhythm after curative catheter ablation demonstrates significant improvement of several parameters of
cardiac function.19 (Copyright © 2011 Massachusetts Medical Society. All rights reserved.)
AF-HF trial110 (eg, AF in the rhythm-control and sinus
rhythm in the rate-control group). From 30% to 35% of the
patients in the AFFIRM study, and approximately 30% of
those in the AF-HF study had either AF in the rhythm-control group or sinus rhythm in the rate-control group. The
results from a subanalysis of the AFFIRM study showed
favorable effects of sinus rhythm on survival (Table).11 Furthermore, the CHF-STAT study demonstrated that the spontaneous conversion of AF to sinus rhythm using amiodarone
improved the survival rate in patients with HF (Figure 4).12
Therefore, in the real world, we should at least once challenge the rhythm control strategy using appropriate antiarrhythmic agents, such as amiodarone, especially in patients
with HF. If AF recurs after antiarrhythmic drug therapy without any significant symptoms, rate control may be selected as
the second best approach.
Non-Pharmacological Rhythm Control
Trials of curative catheter ablation (CA) of AF, which pri-
Circulation Journal Vol.75, April 2011
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Figure 6. Efficacy of maintenance of sinus rhythm with previous rate-control conditions. The ejection fraction improved significantly not only in patients with inadequate but also in those with adequate rate-control before the ablation.19 LV, left ventricular.
(Copyright © 2011 Massachusetts Medical Society. All rights reserved.)
Figure 7. Effect of pulmonary vein isolation (PVI) as compared to atrioventricular (AV) node ablation with biventricular pacing.
There were significant improvements in each component of the primary endpoint in the group of patients who underwent PVI,
as compared with those who underwent AV node ablation with biventricular pacing (BiV).25 (Copyright © 2011 Massachusetts
Medical Society. All rights reserved.)
marily used pulmonary vein (PV) isolation, have shown the
procedure to be efficacious in reducing morbidity, and thus
improving quality of life and functional capacity.13–16 As
mentioned previously, several randomized studies did not
support a routine strategy of rhythm control in patients with
AF and HF. This disappointing result can be explained by the
fact that HF patients are more prone to have adverse effects
from antiarrhythmic agents.17,18 We can expect that the prevention of AF using an appropriate and advanced ablation
procedure without the use of any antiarrhythmic drugs would
improve survival in patients with HF.
Hsu et al19 studied 58 consecutive patients with HF and
LVEF <45% who were undergoing CA for AF. As matched
controls they selected 58 patients without HF who were also
undergoing ablation for AF. After a 12-month follow-up,
78% of the patients with HF and 84% of the controls remained
in sinus rhythm. The patients with HF had a significant
improvement in LV function, exercise capacity and symptoms (Figure 5). Interestingly, the EF improved significantly
in the patients with adequate rate control before the ablation
(Figure 6), which suggests that the HF could not be attributed to tachycardia-mediated cardiomyopathy alone, and this
is also supported by the following clinical study.
AV nodal ablation and ventricular pacing (ablate and pace)
therapy for permanent symptomatic AF is an extreme but
perfect form of rate control.20 However, right ventricular
(RV) pacing provides a left bundle branch block pattern and
results in dyssynchronized LV contraction.21 In such a clinical situation, biventricular pacing is expected to resolve the
harmful effects of RV pacing.22–24 The PABA-CHF study
Circulation Journal Vol.75, April 2011
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KURITA T et al.
(Pulmonary Vein Antrum Isolation versus AV Node Ablation
with Bi-Ventricular Pacing for Treatment of Atrial Fibrillation in Patients with Congestive Heart Failure)25 was undertaken to compare PV isolation to AV-node ablation and CRT
with an implantable cardioverter–defibrillator function in
patients with a low EF and symptomatic AF. This study was
a prospective, multicenter clinical trial in patients with symptomatic, drug-resistant AF, an EF ≤40%, and HF of NYHA
class II or III who underwent either PV isolation (n=41) or
AV node ablation with biventricular pacing (n=40). After 6
months of follow-up, sinus rhythm was maintained in 88% of
the patients in the PV isolation group with or without the use
of antiarrhythmic drugs. As shown in Figure 7, for PV isolation compared to AV node ablation with biventricular pacing,
at 6 months the EF was significantly higher (35±9% vs.
28±6%, P<0.001), 6-min walking distance significantly longer (340±49 m vs. 297±36 m, P<0.001), and MLWHF (the
Minnesota Living with Heart Failure) scores significantly
better (60±8 vs. 82±14, P<0.001) in the PV isolation group.
This study provides strong evidence that atrial contraction
and AV synchrony significantly contribute to improving cardiac function, especially in HF patients.
Conclusion
Theoretically, it is obvious that the maintenance of sinus
rhythm provides beneficial effects for cardiac function in HF
patients. If a physician could eliminate the AF in HF patients
without any significant adverse effects of antiarrhythmic
drugs or CA, a rhythm-control strategy may improve the
patient prognosis.11,12,19,20,26
Several large randomized studies could not demonstrate
any significant improvement in mortality with a rhythm control approach.6–10 This disappointing result can be partly
explained by the unexpected response in an assigned strategy (eg, AF recurrence in the rhythm-control group). Because
AF was documented in more than 30% of the patients in the
rhythm-control arm, it might have had an effect on the deterioration of their outcome.9,10 When we analyzed the data
from another aspect (ie, the restoration of sinus rhythm), the
patients apparently had a better outcome. The adverse sideeffects of antiarrhythmic drugs, which are more likely in a
failing heart, are thought to be one of the reasons why rhythm
control did not improve the patients’ outcomes.17,18
Curative CA mainly based on the PV isolation procedure
in patients with AF and HF has demonstrated a significant
improvement in LV function and exercise capacity, even in
the presence of concurrent structural heart disease and adequate ventricular rate control before ablation.19 On the other
hand, ablation and biventricular pacing therapy, which is the
ultimate rate-control strategy, has not shown any beneficial
effects for patients with AF and HF.20 These facts mean that
a regular RR interval with an appropriate cycle length only is
not sufficient to improve cardiac performance. Consequently,
the maintenance of sinus rhythm, which restores atrial contraction and AV synchrony, is thought to be essential for an
improvement in HF.
AF deteriorates patients’ quality of life (QOL) by producing uncomfortable symptoms, such as palpitations or dyspnea.
According to the J-Rhythm study, the maintenance of sinus
rhythm contributed to an improved QOL, even in AF patients
without organic heart disease.27,28 Much less for HF patients,
in whom AF caused more severe symptoms. We do know
now whether or not a successful rhythm-control treatment (in
particular, CA) eliminates patients’ symptoms and results in a
dramatic improvement in QOL.13–16
In the real clinical world, it is not acceptable for a physician to easily give up a strategy to maintain sinus rhythm in
patients with AF and HF. It is a fact that restoration and maintenance of sinus rhythm provide a better prognosis in these
patients. Therefore, thoughtful clinicians should do their best
to find a way to keep HF patients in sinus rhythm.
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Chinushi M, Iijima K. Rate control is a better initial treatment for
patients with atrial fibrillation and heart failure: Rhythm control vs.
rate control: Which is better in the management of atrial fibrillation?
(Rate-Side) Circ J 2011; 75: 970 – 978.
Authors’ Comments on the Rate-Side Authors
Dr Chinushi et al have written a very thoughtful and detailed review concerning the management of atrial fibrillation (AF) and
heart failure (HF). We really respect their great effort to lead many readers to support the viewpoint of rate control.29
We agree with their comment that the efficacy of rhythm control for AF patients with HF has considerable limitations. In particular, the negative results obtained from several randomized studies such as the AFFIRM or AF-HF trial (Atrial Fibrillation
and Congestive Heart Failure Trial) have had a significant impact in facilitating a simpler strategy for AF (ie, rate control). Based
on those studies, Dr Chinushi et al seem to have come to the conclusion that physicians should give up the possibility of providing
rhythm control, even in cases of first AF attack. It is obvious that the occurrence of AF sometimes results in both a poor prognosis
and poor QOL for HF patients. In such a clinical situation, we should consider at least once an approach to restore and maintain
sinus rhythm. Non-self-terminating or frequent recurrences of AF occasionally result in a deterioration of the substrate of AF
(the AF begets AF theory). If a physician sits idly without preventing worsening of the electrical remodeling, the atrium rapidly
falls into a malignant spiral. As Dr Chinushi et al clearly state, enlarged atria and damaged atrial myocardium, as well as the
pulmonary veins, can participate as the arrhythmogenic substrate of AF. Therefore, once the first physician coming in contact
with the patient leaves the newly developed AF as it is, any pharmacological or non-pharmacological treatment will never be
completely successful in restoring sinus rhythm thereafter. The strategy of rhythm control can later always be switched to that of
rate control. However, the opposite (ie, rate control to rhythm control) is almost impossible. It would be too late.
Circulation Journal Vol.75, April 2011

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