Downloaded from http://heart.bmj.com/ on July 16, 2015 - Published by group.bmj.
com
1
Department of Cardiology,
Royal Melbourne Hospital,
Melbourne, Australia;
2 which will be examined later in the review. An
Department of Medicine,
University of Melbourne,
Parkville, Victoria, Australia;
3
The Baker Heart Research
Institute, Melbourne, Australia;
4
The Heart Centre, The Alfred
Hospital, Melbourne, Australia
Correspondence to:
Dr P M Kistler, The Heart Centre,
The Alfred Hospital, Commercial
Road, Melbourne, Australia
3004; peter.kistler@
baker.edu.au
Accepted 10 June 2008
Published Online First
16 July 2008
Heart 2009;95:535–539. doi:10.1136/hrt.2007.140640
Atrial fibrillation in heart failure: the chicken or the
egg?
R Balasubramaniam,1 P M Kistler1,2,3,4
ABSTRACT
Atrial fibrillation (AF) and heart failure (HF) are the
emerging epidemics of cardiovascular disease in the new
millennium. Both are responsible for considerable
morbidity and mortality and health budget expenditure.
The advent of catheter ablation for patients with AF has
provided important new insights into the relative
contribution of AF to left ventricular dysfunction. The aim
of this review is to discuss the complex interplay in the
pathophysiology of AF and HF to improve our under-
standing of the basis for current treatment strategies and
guide future research direction.
SEARCH STRATEGY
A comprehensive literature search was performed
of electronic bibliographic databases (eg, PubMed,
Cochrane) using the following keywords: atrial
fibrillation, heart failure, pathophysiology, epide-
miology, catheter ablation, management, anti-
coagulation, etc. Reference lists from selected
articles and reviews were also examined for further
relevant articles, and abstracts from international
meetings were searched.
EPIDEMIOLOGY
Atrial fibrillation (AF) is the most common
sustained cardiac arrhythmia with an incidence of
0.84% increasing to 7% in those aged .85.1 It
accounts for nearly 1% of the total National
Health Service expenditure.2 Conversely, heart
failure (HF) is estimated to affect 3.1% of patients
aged >45 in the UK.3 The prevalence of AF in HF
increases according to New York Heart Association
(NYHA) class, ranging from 4% in NYHA class I to
50% in patients who are NYHA class IV.4
PATHOPHYSIOLOGY OF AF IN HF
Whether AF is a cause or consequence of HF is an
area of much contention, although both are likely.
The relative contribution of AF to left ventricular
(LV) dysfunction is often difficult to evaluate in an
individual patient, particularly when both coexist
in the initial presentation.
The pathophysiology of AF remains incomple-
tely understood. The multiple wavelet hypothesis
proposed by Moe and Abildskov in 19595 describes
the interaction of multiple re-entrant wavelets
occurring simultaneously within the atria, with
perpetuation favoured by slow conduction, short-
ened refractory periods and increased atrial mass. A
heterogeneous distribution of refractory periods
promotes re-entry by creating regions of functional
conduction delay and block.5 6 A critical number of
wavelets are required to maintain AF with a
Review
constant supply of triggers necessary. The triggers
largely originate from the pulmonary veins (PVs),
alternative theory describes mother ‘‘rotors’’ or
counter-rotating vortices anchored at the PV
antrum with the surrounding atria unable to
conduct in a 1:1 fashion, resulting in fibrillatory
conduction.7
AF in HF: ‘‘the egg’’
Distinct differences in the electrical, ionic and
structural remodelling are seen with AF in the
presence of abnormal LV function. Rapid atrial
pacing animal models demonstrate shortening of
refractoriness with loss of rate adaptation, in
contrast to rapid atrial pacing superimposed on
the ventricular tachypacing HF model where
refractoriness is relatively preserved but atrial
fibrosis is prominent with associated changes in
conduction.8 In animals with HF treated with ACE
inhibitors (ACEIs), the effects of HF on conduction
slowing, atrial fibrosis and AF duration were
attenuated.9 This was more than a haemodynamic
effect, as vasodilator therapy did not affect
ventricular tachypacing-induced atrial fibrosis or
AF promotion. Retrospective studies in patients
with LV dysfunction have shown a significant
reduction in the occurrence of AF in the group
treated with ACEIs.10 Following acute myocardial
infarction complicated by LV dysfunction,
Pedersen et al showed a 55% reduction in the
development of AF in patients treated with
ACEIs.11 The renin–angiotensin system plays an
important role in structural remodelling and the
development of myocardial fibrosis in congestive
heart failure (CHF).12 Angiotensin II has also been
shown to have several proinflammatory proper-
ties,13 which is important given an emerging role
for inflammation in the pathogenesis of AF,14 with
raised circulating inflammatory markers such as C-
reactive protein (CRP) increased in patients with
AF.13
3-Hydroxy-3-methylglutaryl coenzyme A
(HMG-CoA) reductase inhibitors demonstrate
pleiotropic properties including anti-inflammatory
effects and improved endothelial function.15 In a
canine model, simvastatin attenuated AF promo-
tion and CHF-induced atrial structural remodelling
in dogs.16 A recent meta-analysis has demonstrated
a reduction in recurrent AF in patients treated with
statins.17
Animal models of HF have also demonstrated a
role for triggered activity and calcium-sensitive
delayed afterdepolarisations, and drugs that reduce
intracellular calcium have been shown to terminate
AF.18 Conversely, alcohol, which has been
535
 Downloaded from http://heart.bmj.com/ on July 16, 2015 - Published by group.bmj.com
Review
associated with a reduction in intracellular calcium transients in
addition to HF, is associated with an increase in AF incidence,
though the underlying mechanisms linking alcohol to HF and
AF are complex and not fully understood and may involve the
direct toxic effects of acetaldehyde and a decreased sensitivity of
myofilaments to calcium.19
In humans, Kalman and coworkers elegantly demonstrated
the atrial structural and electrical remodelling that occurs in
patients with HF. Patients with a mean EF of 26% and no prior
atrial arrhythmias demonstrated areas of frank scar with
associated conduction slowing and block. AF was inducible
during effective refractory period testing in 40%.20 Similar atrial
remodelling, although to a lesser degree, has been demonstrated
with ageing.21 The presence of fibrosis provides the substrate for
re-entry by conduction slowing and block. Although the
responsible mechanisms behind atrial fibrosis in HF have been
incompletely determined, the renin–angiotensin system and
transforming growth factor b1 (TGFb1) appear to be important.
In transgenic mice overexpression of TGFb1 has resulted in
atrial fibrosis with ventricular sparing with an increase in atrial
conduction heterogeneity and AF.22
AF in HF: ‘‘the chicken’’
AF may contribute to LV dysfunction as a consequence of rapid
ventricular rates, irregularity in ventricular rhythm or owing to
loss of atrial systole. Tachycardia-mediated cardiomyopathy
secondary to uncontrolled AF has been well described as a
reversible cause of LV dysfunction.23 The loss of atrial transport
that results in AF is also thought to cause a reduction in
diastolic filling, stroke volume and cardiac output and an
increase in right atrial and pulmonary capillary wedge pres-
sures,24 with detrimental effects on ventricular function.
Additionally, an irregular ventricular response is associated
with a reduction in cardiac output when compared with regular
ventricular pacing.25
MANAGEMENT OF AF IN HF
The preferred treatment strategy of rate versus rhythm control
in AF is limited by a lack of effective tools for maintaining sinus
rhythm. This has been demonstrated in clinical trials, such as
the AFFIRM study, which did not show a significant difference
in mortality between rate versus rhythm control arms.26
However, subgroup analysis of the study demonstrated a
significant reduction in mortality in the rhythm control group
who maintained sinus rhythm.27 Only a small number of
patients with LV dysfunction were included in the study. The
preliminary results from the AF-CHF trial, rate versus rhythm
control in HF, have shown no difference in the primary end
point of cardiovascular death and the composite end point of
cardiovascular death, worsening HF and stroke (presented at
late-breaking trials session, American Heart Association 200728).
The trial compared rate versus rhythm control strategies for AF
with 82% of patients in the rhythm control arm receiving
amiodarone. As with the AFFIRM study it is important not to
extrapolate these findings to the patient group with symptoms
or a clear deterioration in LV function in concert with the
advent of AF. Similar randomised control studies with non-
pharmacological approaches to rhythm control such as catheter
ablation are in progress.
The pharmacological approach to rate control for AF in HF
has involved the use of b blockers and/or digoxin aiming for a
resting heart rate of between 60–80 and 90–115 during
moderate exertion.29 The goals for rate control are based on
536
short-term haemodynamic studies. An inability to achieve
pharmacological rate control should prompt consideration of a
‘‘pace and ablate’’ strategy with insertion of a permanent
pacemaker and catheter ablation of the atrioventricular (AV)
node. This strategy is generally associated with symptomatic
improvement and an improvement in LV function.30 In a
minority of patients right ventricular apical pacing with the
creation of interventricular dyssynchrony may result in a
decline in LV function. Whether patients with significant LV
dysfunction who require bradycardia support should have a
resynchronisation device first line is yet to be determined. The
PAVE study demonstrated a significant improvement in the
6 min walk test and ejection fraction with biventricular pacing
compared with right ventricular apical pacing and AV nodal
ablation for patients with uncontrolled AF. The beneficial
effects of cardiac resynchronisation were more pronounced in
patients with impaired systolic function or symptomatic HF.31
However, these findings were based on small patient numbers
with LV dysfunction. In addition, the group with right
ventricular apical pacing demonstrated a significant decline in
LV function at short-term follow-up. In contrast, Chen et al
demonstrated preservation of LV function during a mean
follow-up of 20 months in 286 patients who underwent an
ablate and pace strategy with right ventricular apical pacing.32
RHYTHM CONTROL: PHARMACOLOGICAL
A strategy of rhythm control may be preferred in symptomatic
patients with paroxysmal AF compared with patients with
persistent AF where currently available antiarrhythmic drugs
have limited efficacy compounded by longer-duration AF and
HF, in which there is an increased risk of proarrhythmia
secondary to torsade de pointes.33 In this patient population rate
control may be preferred until improvements in pharmacologi-
cal and ablation techniques improve.
Nevertheless, subgroup analysis from AFFIRM demonstrated
a significant survival advantage in the rhythm control group
who maintained sinus rhythm.27 Amiodarone is the preferred
Figure 1 Catheter ablation for atrial fibrillation. The left atrium is seen
as represented by an MRI image incorporated into the NAVX non-contact
mapping system. The signals shown from pulmonary veins (PVs) 1, 2 to
19, 20 are from the bipoles on the circular mapping catheter (CMC)
recording electrograms from the right inferior pulmonary vein (RIPV). The
double arrow highlights the loss of PV electrograms in the RIPV during
ablation, resulting in PV electrical isolation. Abl, ablation; LAA, left atrial
appendage; MA, mitral annulus; RSPV, right superior pulmonary vein.
Heart 2009;95:535–539. doi:10.1136/hrt.2007.140640
 Downloaded from http://heart.bmj.com/ on July 16, 2015 - Published by group.bmj.com
drug for patients with paroxysmal AF and HF with better
efficacy than sotalol but is limited by potential toxicities. The
new antiarrhythmic drug, dronedarone, pharmacologically
similar to amiodarone but with structural differences intended
to eliminate the detrimental effects of amiodarone on thyroid
and pulmonary function, is promising.34 However, the
ANDROMEDA study, investigating the use of dronedarone in
moderate to severe LV dysfunction, was discontinued owing to
a potential increase in mortality.35 By contrast, the selective
class III investigational agent, azimilide has been shown to be
safe and effective in postinfarct patients with LV dysfunction,
but severe neutropenia (1%) and torsade de pointes (1.5%) have
been reported.35 Future pharmacological treatments may be
based on atrial-selective antiarrhythmic drugs35 and antifibrotic
drugs such as pirfenidone which is thought to reduce the
expression of TGFb1,36 in addition to the use of ACEIs and
statins for the treatment of AF as discussed earlier. ACEIs or
angiotensin receptor blockers are the preferred first-line agent in
patients with hypertension and AF due to antifibrotic effects in
addition to afterload reduction with consequent effects on left
atrial pressure and stretch.37
CATHETER ABLATION FOR AF
Catheter ablation of AF provides exciting opportunities to
isolate the triggers for AF largely anchored in the PVs and
modify the substrate or changes within the atria induced by AF
or LV dysfunction, or both (fig 1). In the seminal studies from
Haissaguerre et al, ectopy arising from the PVs was identified as
the trigger largely responsible for the initiation of AF.38 Catheter
ablation targeting these triggers evolved and remains the
cornerstone for most AF ablation procedures (fig 2).6 It is
becoming increasingly clear, however, that the mechanisms
underlying the initiation and maintenance of AF are complex
and multifactorial and ablation techniques continue to evolve in
concert with this. The current approach to catheter ablation
extends beyond PV isolation to involve circumferential ablation
around the right and left PV ostia which encompass more
proximal triggers, ganglionic plexi and dominant rotors thought
to anchor at the PV–LA junction.6 Other approaches include
Figure 2 Catheter ablation for atrial fibrillation using the CARTO
contact mapping system. The left atrium is seen with ablation (Abl)
points encircling the pulmonary veins (PVs) in pairs with an external view
on the left side of the figure and internal view of the left PVs on the right
side. LAA, left atrial appendage; LIPV, left inferior pulmonary vein; LSPV,
left superior pulmonary vein; RIPV, right inferior pulmonary vein; RSPV,
right superior pulmonary vein.
Heart 2009;95:535–539. doi:10.1136/hrt.2007.140640
Review
specifically targeting ganglionic plexi identified by high-
frequency endocardial stimulation and ablation of complex
fractionated potentials.39 These sites have been postulated to
represent conduction slowing or pivot points where wavelets
turn around at sites of functional block.40
The role and appropriate lesion set for catheter ablation in
patients with AF and LV dysfunction is the focus of continuing
research. Nonetheless, several studies have demonstrated
marked improvements in LV function in patients undergoing
successful catheter ablation.41–44 Haissaguerre and coworkers
performed catheter ablation in 58 patients with predominantly
chronic AF and impaired ventricular function.42 At 12-month
follow up, 78% of patients remained in sinus rhythm with a
second procedure was required in 50%. LV ejection fraction
normalised or improved by an absolute 20% or greater in 72% of
patients. The improvement in ejection fraction was seen in all
subgroups including patients with ‘‘adequate’’ rate control and
ischaemic or valvular heart disease. Significant improvements
were also demonstrated in LV dimensions, quality of life and
exercise capacity.42 Tondo et al completed circumferential PV
ablation with a mitral isthmus line in 40 patients with LV
dysfunction. Sinus rhythm was achieved in 87% at a mean
follow-up of 14 months and resulted in equivalent improve-
ments in LV function, symptoms and quality of life.43
Marchlinski and coworkers performed catheter ablation in 67
patients with predominantly paroxysmal AF with successful
restoration of sinus rhythm in 86%. A significant improvement
in LV function was seen with only 22% of patients classified as
inadequate rate control at baseline.44 The study by Chen et al
showed a non-significant improvement in ejection fraction but
a significant improvement in quality of life for 73% of the 94
patients with impaired LV function, free of AF recurrence at
14 months after the procedure.41
These studies suggest that catheter ablation for AF is
successful in the majority of patients and associated with
substantial improvements in LV function, notwithstanding the
difficulties that exist when assessing LV function in patients
with AF. The recovery of LV function is apparent in the setting
of ‘‘adequate’’ rate control, strengthening the argument for
detrimental effects on ventricular function beyond a tachy-
cardia-mediated mechanism.
The PABA-CHF trial randomised 77 patients with HF and
drug-refractory paroxysmal (54%) or persistent AF (46%) to AV
node ablation and biventricular pacing or pulmonary vein
isolation (PVI).45 Freedom from AF was demonstrated in 72% of
patients in the PVI group (and not surprisingly 0% in the
AV node ablation group) at 6 months. The mean ejection
fraction was significantly higher in the PVI group (35% vs
28%) and an improvement was seen in 74% of patients in the
PVI group compared with 24% in the AV node ablation
cohort. The 6 min walk and quality-of-life measures were also
better in the PVI group. Results were similar in patients with
paroxysmal or permanent AF. The findings indicate the super-
iority of successful rhythm control with PVI versus AV node
ablation and biventricular pacing. However, the results are as
yet unpublished. The trial was small with a relatively short
follow-up, included few patients with an atrial diameter .5 cm
and was completed in a highly experienced AF ablation centre
with some patients in the PVI cohort undergoing multiple
procedures. Catheter ablation is associated with potentially
serious complications, including cardiac tamponade, PV steno-
sis, phrenic nerve injury, stroke and, rarely, atrio-oesophageal
fistula and death.6 Coronary artery occlusion, mitral valve
trauma and relatively common vascular complications can also
537
 Downloaded from http://heart.bmj.com/ on July 16, 2015 - Published by group.bmj.com
Review
occur and operator and patient both receive significant radiation
doses. Nonetheless, despite the initial conclusions from
AFFIRM, if sinus rhythm can be successfully and safely restored
there are likely to be substantial improvements in quality of life
and LV function. Whether this translates to improved survival
advantage is the core of continuing multicentre trials.6
SURGICAL ABLATION OF AF
In the 1980s, James Cox pioneered the classic cut-and-sew
surgical Maze procedure which formed the benchmark for the
surgical treatment of AF.46 Today the classic cut-and-sew
approach has been largely abandoned owing to the length of
the procedure and associated morbidity and replaced with
varying strategies using differing energy sources, including
unipolar and bipolar radiofrequency, cryoablation and ultra-
sound. Concerns remain about the achievement of transmural
ablation lines and the lack of verification of electrical PV
isolation, the hallmarks of the endocardial approach.
Nonetheless, refining the surgical approach is important given
the significant population of patients who require coronary
bypass and valvular surgery and who also have AF. One small
surgical series reported on 37 patients with impaired LV
function who underwent the surgical ablation for AF alone.
All but one patient remained in sinus rhythm at 63 months’
follow-up with significant improvements in LV function seen in
those patients with prior chronic AF (n = 23), though not in the
paroxysmal group (n = 14).47 Thus surgical treatment of AF is
essentially reserved for patients with AF undergoing cardiac
surgery for other reasons. Surgery for AF alone has only been
recommended for ‘‘symptomatic patients with AF who prefer a
surgical approach, for patients for whom one or more attempts
at catheter ablation have failed, or who are not candidates for
catheter ablation’’,6 when medical treatment has failed.
ANTICOAGULATION
Patients with AF and HF are at significant risk of stroke with
the evidence strongly in favour of anticoagulation with warfarin
despite a possible increase in major bleeding risk in the HF
population. The annual risk of embolic stroke in AF is 6%,
which is increased by 40% in patients with HF.29 The
importance of anticoagulation in the AF population with risk
factors for stroke was evident from the AFFIRM study. A
reduction in mortality was associated with warfarin use in the
rhythm and rate control arms of the study.27 It is thus currently
recommended that patients with a CHADS2 score of >2
(table 1) should continue to receive long-term warfarin after
successful catheter ablation,6 and this should apply to successful
Table 1 CHAD2 score, expected stroke rate/100
patient-years of aspirin[49] and recommended long-term
treatment for stroke prevention
CHAD2 score Stroke rate Recommended treatment
0 1.9 Aspirin or nothing
1 2.8 Aspirin or warfarin
2 4.0 Warfarin
3 5.9 Warfarin
4 8.5 Warfarin
5 12.5 Warfarin
6 18.2 Warfarin
The CHAD2 score is devised by calculating the cumulative score for
each patient using the following scheme: one point each for
congestive heart failure, hypertension, age .75, diabetes mellitus,
two points for prior stoke or transient ischaemic attack.
538
pharmacological restoration of sinus rhythm. It has been shown
that in patients with a stroke risk exceeding 4 per 100 patient-
years of aspirin, warfarin treatment consistently improves
quality-adjusted survival.48 The cessation of anticoagulation
should be approached with caution given the risk of asympto-
matic recurrent AF and the lack of long-term outcome data after
catheter ablation. Both HF and AF are associated with an
increase in markers of platelet activation and clotting.
Inflammation has also been linked to enhanced platelet
activation and thrombus formation, and inflammatory markers
such as CRP and interleukin 6 were found to be raised in both
conditions. CRP and interleukin 6 have in turn been shown to
be independent predictors of thromboembolism in patients with
AF.13 The importance of anticoagulation therefore cannot be
emphasised sufficiently in that cohort of patients identified
above.
CONCLUSION
HF and AF frequently coexist, with each having deleterious
effects on the other. Successful restoration of sinus rhythm may
be achieved pharmacologically; however, long-term efficacy and
safety are limited. Restoration of sinus rhythm is likely to be
preferable where the onset of AF is associated with increasing
symptoms or deterioration in LV function. Irrespective of a
strategy of rhythm or rate control, anticoagulation is para-
mount. Catheter ablation can successfully restore sinus rhythm
with improvements in quality of life and LV function. However,
catheter ablation needs to be repeated in a significant number of
patients, is associated with potentially serious complications
and long-term outcomes are yet to be determined. Further
insights into the complex interplay between the emerging
epidemics of HF and AF are critical to the progress of new
therapeutic modalities.
Competing interests: Declared. PMK is the recipient of the Neil Hamilton Fairley
Fellowship from the National Health and Medical Research Council and National Heart
Foundation of Australia.
REFERENCES
1. Murphy NF, Simpson CR, Jhund PS, et al. A national survey of the prevalence,
incidence, primary care burden and treatment of atrial fibrillation in Scotland. Heart
2007;93:606–12.
2. Stewart S, Murphy NF, Walker A, et al. Cost of an emerging epidemic: an economic
analysis of atrial fibrillation in the UK. Heart 2004;90:286–92.
3. Davies M, Hobbs F, Davis R, et al. Prevalence of left-ventricular systolic dysfunction
and heart failure in the Echocardiographic Heart of England Screening study: a
population based study. Lancet 2001;358:439–44.
4. Maisel WH, Stevenson LW. Atrial fibrillation in heart failure: epidemiology,
pathophysiology, and rationale for therapy. Am J Cardiol 2003;91:2D–8D.
5. Moe GK, Abildskov JA. Atrial fibrillation as a self-sustaining arrhythmia independent
of focal discharge. Am Heart J 1959;58:59–70.
6. Calkins H, Brugada J, Packer DL, et al. HRS/EHRA/ECAS expert Consensus
Statement on catheter and surgical ablation of atrial fibrillation: recommendations for
personnel, policy, procedures and follow-up. A report of the Heart Rhythm Society
(HRS) Task Force on catheter and surgical ablation of atrial fibrillation. Heart Rhythm
2007;4:816–61.
7. Jalife J, Berenfeld O, Mansour M. Mother rotors and fibrillatory conduction: a
mechanism of atrial fibrillation. Cardiovasc Res 2002;54:204–16.
8. Shinagawa K, Shi YF, Tardif JC, et al. Dynamic nature of atrial fibrillation substrate
during development and reversal of heart failure in dogs. Circulation 2002;105:2672–
8.
9. Boldt A, Scholl A, Garbade J, et al. ACE-inhibitor treatment attenuates atrial
structural remodeling in patients with lone chronic atrial fibrillation. Basic Res Cardiol
2006;101:261–7.
10. Vermes E, Tardif JC, Bourassa MG, et al. Enalapril decreases the incidence of atrial
fibrillation in patients with left ventricular dysfunction: insight from the Studies Of Left
Ventricular Dysfunction (SOLVD) trials. Circulation 2003;107:2926–31.
11. Pedersen OD, Bagger H, Kober L, et al. Trandolapril reduces the incidence of atrial
fibrillation after acute myocardial infarction in patients with left ventricular
dysfunction. Circulation 1999;100:376–80.
12. Everett TH, Olgin JE. Atrial fibrosis and the mechanisms of atrial fibrillation. Heart
Rhythm 2007;4(Suppl):S24–7.
Heart 2009;95:535–539. doi:10.1136/hrt.2007.140640
 Downloaded from http://heart.bmj.com/ on July 16, 2015 - Published by group.bmj.com
13. Boos CJ, Anderson RA, Lip GY. Is atrial fibrillation an inflammatory disorder? Eur
Heart J 2006;27:136–49.
14. Boos CJ, Lip GY. Inflammation and atrial fibrillation: cause or effect? Heart
2008;94:133–4.
15. Fischer D, Rossa S, Landmesser U, et al. Endothelial dysfunction in patients with
chronic heart failure is independently associated with increased incidence of
hospitalization, cardiac transplantation, or death. Eur Heart J 2005;26:65–9.
16. Shiroshita-Takeshita A, Schram G, Lavoie J, et al. Effect of simvastatin and
antioxidant vitamins on atrial fibrillation promotion by atrial-tachycardia remodeling in
dogs. Circulation 2004;110:2313–9.
17. Fauchier L, Pierre B, de Labriolle A, et al. Antiarrhythmic effect of statin therapy and
atrial fibrillation a meta-analysis of randomized controlled trials. J Am Coll Cardiol
2008;51:828–35.
18. Stambler BS, Fenelon G, Shepard RK, et al. Characterization of sustained atrial
tachycardia in dogs with rapid ventricular pacing-induced heart failure. J Cardiovasc
Electrophysiol 2003;14:499–507.
19. Ren J, Brown RA. Influence of chronic alcohol ingestion on acetaldehyde-induced
depression of rat cardiac contractile function. Alcohol Alcohol 2000;35:554–60.
20. Sanders P, Morton JB, Davidson NC, et al. Electrical remodeling of the atria in
congestive heart failure: electrophysiological and electroanatomic mapping in
humans. Circulation 2003;108:1461–8.
21. Kistler PM, Sanders P, Fynn SP, et al. Electrophysiologic and electroanatomic
changes in the human atrium associated with age. J Am Coll Cardiol 2004;44:109–
16.
22. Verheule S, Sato T, Everett T 4th, et al. Increased vulnerability to atrial fibrillation in
transgenic mice with selective atrial fibrosis caused by overexpression of TGF-beta1.
Circ Res 2004;94:1458–65.
23. Peters KG, Kienzle MG. Severe cardiomyopathy due to chronic rapidly conducted
atrial fibrillation: complete recovery after restoration of sinus rhythm. Am J Med
1988;85:242–4.
24. Naito M, David D, Michelson EL, et al. The hemodynamic consequences of cardiac
arrhythmias: evaluation of the relative roles of abnormal atrioventricular sequencing,
irregularity of ventricular rhythm and atrial fibrillation in a canine model. Am Heart J
1983;106:284–91.
25. Clark DM, Plumb VJ, Epstein AE, et al. Hemodynamic effects of an irregular
sequence of ventricular cycle lengths during atrial fibrillation. J Am Coll Cardiol
1997;30:1039–45.
26. Wyse DG, Waldo AL, DiMarco JP, et al. A comparison of rate control and rhythm
control in patients with atrial fibrillation. N Engl J Med 2002;347:1825–33.
27. Corley SD, Epstein AE, DiMarco JP, et al. Relationships between sinus rhythm,
treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm
Management (AFFIRM) study. Circulation 2004;109:1509–13.
28. Roy D. Rationale for the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial.
Card Electrophysiol Rev 2003;7:208–10.
29. Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the
Management of Patients with Atrial Fibrillation: a report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines and the
European Society of Cardiology Committee for Practice Guidelines (Writing Committee
to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation):
developed in collaboration with the European Heart Rhythm Association and the Heart
Rhythm Society. Circulation 2006;114:e257–354.
Heart 2009;95:535–539. doi:10.1136/hrt.2007.140640
Review
30. Ozcan C, Jahangir A, Friedman PA, et al. Significant effects of atrioventricular node
ablation and pacemaker implantation on left ventricular function and long-term
survival in patients with atrial fibrillation and left ventricular dysfunction. Am J Cardiol
2003;92:33–7.
31. Doshi RN, Daoud EG, Fellows C, et al. Left ventricular-based cardiac stimulation post
AV nodal ablation evaluation (the PAVE study). J Cardiovasc Electrophysiol
2005;16:1160–5.
32. Chen L, Hodge D, Jahangir A, et al. Preserved left ventricular ejection fraction
following atrioventricular junction ablation and pacing for atrial fibrillation. J Cardiovasc
Electrophysiol 2008;19:19–27.
33. Stevenson WG, Tedrow U. Management of atrial fibrillation in patients with heart
failure. Heart Rhythm 2007;4(Suppl):S28–30.
34. Singh BN, Connolly SJ, Crijns HJ, et al. Dronedarone for maintenance of sinus
rhythm in atrial fibrillation or flutter. N Engl J Med 2007;357:987–99.
35. Goldstein RN, Stambler BS. New antiarrhythmic drugs for prevention of atrial
fibrillation. Prog Cardiovasc Dis 2005;48:193–208.
36. Lee KW, Everett TH 4th, Rahmutula D, et al. Pirfenidone prevents the development of
a vulnerable substrate for atrial fibrillation in a canine model of heart failure.
Circulation 2006;114:1703–12.
37. Healey JS, Connolly SJ. Atrial fibrillation: hypertension as a causative agent, risk
factor for complications, and potential therapeutic target. Am J Cardiol 2003;91:9G–
14G.
38. Haissaguerre M, Jais P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by
ectopic beats originating in the pulmonary veins. N Engl J Med 1998;339:659–66.
39. Nademanee K, McKenzie J, Kosar E, et al. A new approach for catheter ablation of
atrial fibrillation: mapping of the electrophysiologic substrate. J Am Coll Cardiol
2004;43:2044–53.
40. Konings KT, Smeets JL, Penn OC, et al. Configuration of unipolar atrial electrograms
during electrically induced atrial fibrillation in humans. Circulation 1997;95:1231–41.
41. Chen MS, Marrouche NF, Khaykin Y, et al. Pulmonary vein isolation for the treatment
of atrial fibrillation in patients with impaired systolic function. J Am Coll Cardiol
2004;43:1004–9.
42. Hsu LF, Jais P, Sanders P, et al. Catheter ablation for atrial fibrillation in congestive
heart failure. N Engl J Med 2004;351:2373–83.
43. Tondo C, Mantica M, Russo G, et al. Pulmonary vein vestibule ablation for the control
of atrial fibrillation in patients with impaired left ventricular function. Pacing Clin
Electrophysiol 2006;29:962–70.
44. Gentlesk PJ, Sauer WH, Gerstenfeld EP, et al. Reversal of left ventricular
dysfunction following ablation of atrial fibrillation. J Cardiovasc Electrophysiol
2007;18:9–14.
45. Adams GL, Mills JS, Melloni C, et al. Highlights from the 56th annual scientific
sessions of the American College of Cardiology: March 25 to 27, 2007, Atlanta,
Georgia. Am Heart J 2007;154:247–59.
46. Prasad SM, Maniar HS, Camillo CJ, et al. The Cox maze III procedure for atrial
fibrillation: long-term efficacy in patients undergoing lone versus concomitant
procedures. J Thorac Cardiovasc Surg 2003;126:1822–8.
47. Stulak JM, Dearani JA, Daly RC, et al. Left ventricular dysfunction in atrial fibrillation:
restoration of sinus rhythm by the Cox-maze procedure significantly improves systolic
function and functional status. Ann Thorac Surg 2006;82:494–500; discussion 500–1.
48. Gage BF, van Walraven C, Pearce L, et al. Selecting patients with atrial fibrillation for
anticoagulation: stroke risk stratification in patients taking aspirin. Circulation
2004;110:2287–92.
539
 Downloaded from http://heart.bmj.com/ on July 16, 2015 - Published by group.bmj.com

Atrial fibrillation in heart failure: the chicken

or the egg?
R Balasubramaniam and P M Kistler

Heart 2009 95: 535-539 originally published online July 16, 2008
doi: 10.1136/hrt.2007.140640

Updated information and services can be found at:

http://heart.bmj.com/content/95/7/535

These include:

References This article cites 48 articles, 18 of which you can access for free at:
http://heart.bmj.com/content/95/7/535#BIBL

Email alerting Receive free email alerts when new articles cite this article. Sign up in the
service box at the top right corner of the online article.

Notes

To request permissions go to:

http://group.bmj.com/group/rights-licensing/permissions

To order reprints go to:

http://journals.bmj.com/cgi/reprintform

To subscribe to BMJ go to:

http://group.bmj.com/subscribe/