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Atrial Fibrillation and Heart Failure


Atrial Fibrillation and Heart Failure
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Credits:William G. Stevenson, M.D., Usha B.Tedrow, M.D., and Jens Seiler, M.D.
From:The Cardiovascular Division,Department of Medicine,Brigham and Women’s Hospital,Harvard Medical School,Boston, Massachusetts

Address for Correspondence:William G. Stevenson, M.D.,Cardiovascular Division,Brigham and Women’s Hospital,75 Francis St, Boston, MA 02115


doi : 10.4022/jafib.v1i1.401

Abstract

Atrial fibrillation is common in heart failure patients and is associated with increased mortality.  Pharmacologic trials have not shown any survival benefit for a rhythm control over a rate control strategy.  It has been suggested that sinus rhythm is associated with a survival benefit, but that the risks of anti-arrhythmic drug treatment and poor efficacy offset the beneficial effect.  Catheter ablation for atrial fibrillation can establish sinus rhythm without the risks of anti-arrhythmic drug therapy.  Data from randomized trials demonstrating a survival benefit for patients undergoing an ablation procedure for atrial fibrillation are still lacking.  Ablation of the AV junction and permanent pacing remain a treatment alternative in otherwise refractory cases.  Placement of a biventricular system may prevent or reduce negative consequences of chronic right ventricular pacing.  Current objectives and options for treatment of atrial fibrillation in heart failure patients are reviewed.

Keywords: atrial fibrillation, heart failure, anticoagulation, antiarrhythmic drugs, ablation

Introduction

Atrial fibrillation and heart failure are epidemics of contemporary cardiovascular medicine.  In the US, more than 2 million people are suffering from atrial fibrillation and more than 5 million have heart failure.[1-3]  Atrial fibrillation and heart failure often coexist, and patients with one condition, who subsequently develop the other, have an increased mortality.[4]  Heart failure is associated with a 4.5 to 5.9-fold risk for atrial fibrillation.[5]  The prevalence of atrial fibrillation increases with the severity of heart failure from ≤ 5% in patients with functional class NYHA I to nearly 50% in patients with functional class NYHA IV.[6]  Approximately 40-50% of heart failure patients have preserved left ventricular function, which is often associated with older age, female gender and a history of hypertension.[7-9]  In these patients, atrial fibrillation is even more prevalent than in patents with reduced ejection fraction.[7,  9, 10] 

Atrial fibrillation may lead to further hemodynamic deterioration in heart failure patients.  An inappropriately fast or slow ventricular response, ventricular rhythm irregularity and loss of mechanical atrial function can have negative hemodynamic consequences and may elicit an increase in sympathetic tone.[6,  11,  12]  A chronic fast ventricular response may lead to tachycardia-induced cardiomyopathy causing exacerbation or aggravation of heart failure.[13] 

This article focuses on clinical management of atrial fibrillation in heart failure patients.  Treatment options to prevent thromboembolism, control heart rate and maintain sinus rhythm will be discussed.

Anticoagulation

Data from the National Registry for Atrial Fibrillation suggest an overall stroke risk of 4.4% per year in patients with non-rheumatic atrial fibrillation aged 65 to 95 years.  The annual stroke risk ranges from 1.9% in the absence of, to 18.2% per year in the presence of all of the following risk factors, recent congestive heart failure, history of hypertension, age ≥ 75 years, diabetes mellitus and prior stroke or history of prior thromboembolism.[14]  Data from the Framingham Heart Study suggest that the risk of stroke is increased by 4.8-fold in atrial fibrillation and by 4.3-fold in heart failure.  The presence of atrial fibrillation in patients with heart failure almost doubles the risk of stroke in men and triples the risk of stroke in women.[15]  Recent meta-analyses showed, that dose-adjusted warfarin reduces the risk of stroke by 64% to 67%, but antiplatelet agents (i.e. aspirin and dipyridamole) are less effective, reducing stroke by only by 22%. [16,  17]  Heart failure and left ventricular ejection fraction ≤ 35% are both considered moderate risk factors for thromboembolic events in patients with atrial fibrillation.  Anticoagulation with dose-adjusted warfarin should be maintained in all patients with heart failure and a history of atrial fibrillation unless contraindicated.[18,  19] 

Data from the AFFIRM trial shows that major bleeding during anticoagulation with warfarin in patients at risk of stroke occurs in approximately 2% of patients per year.  Congestive heart failure increases the risk of major bleeding by 43%.  However, the rate of major bleeding in patients with atrial fibrillation at risk of stroke is usually lower than the expected rate of a thromboembolic event.[20]  Thus, anticoagulation is still favored.

Pharmacologic approach to maintain sinus rhythm

In prior randomized trials (AFFIRM, RACE and STAF) comparing rhythm control and rate control with antiarrhythmic drugs, neither strategy demonstrated a survival benefit over the other.[21-23]  The recently completed AF-CHF study addressed this issue specifically in heart failure patients.  A total of 1,376 patients with heart failure symptoms, a left ventricular ejection fraction of ≤ 35% and at least one episode of atrial fibrillation within 6 months preceding enrollment were included.  Mean left-ventricular ejection fraction was 27%; 31% of patients were in functional class NYHA III to IV and atrial fibrillation was persistent in 69% of patients.  After a mean follow-up of 37 months, there was no difference between rate and rhythm control groups in the primary endpoint of cardiovascular mortality.  Secondary outcomes including total mortality, worsening heart failure and stroke were also not different between groups.[24,  25]  Patients included in these studies are likely different from those usually considered for catheter ablation of atrial fibrillation.  It is conceivable, that patients with severe symptomatic episodes of atrial fibrillation would not have been considered as optimal participants.  In the AFFIRM study, only patients of at least 65 years of age or with other risk factors for stroke or death could be enrolled.[21]  The mean age of the participants in the AFFIRM, RACE, STAF and AF-CHF studies was 66 to 70 years.[21-23,  25]  In contrast, the mean age of patients undergoing catheter ablation for atrial fibrillation was 60 years in a recent large multicenter registry.[26] 

The AFFIRM, RACE and other studies have shown that maintenance of sinus rhythm is associated with improved survival and less hospitalizations, but in AFFIRM, antiarrhythmic drug use was associated with a worse outcome.[27-30]  Thus, whether sinus rhythm is only a marker of less severe illness or causative for a better outcome remains controversial.[27] 

In the absence of data clearly favoring one strategy over the other, therapy has to be individualized.  Our practice is to consider rhythm control in patients with a first episode of persistent atrial fibrillation, for symptomatic paroxysms of atrial fibrillation, and when adequate rate control is difficult to achieve.[31] 

Amiodarone or dofetilide, both class III antiarrhythmic drugs, are the major pharmacologic considerations for attempted maintenance of sinus rhythm in patients with heart failure.[18]  Amiodarone was shown to be safe in heart failure patients in the CHF-STAT trial with a trend to a better survival in patients with non-ischemic cardiomyopathy.[32]  In the SCD-HeFT trial, amiodarone did not significantly influence overall mortality, but subgroup analysis showed an increased mortality in patients with NYHA III heart failure.  Whether this result is biologically plausible was questioned by the authors of the study, but the findings do raise concern as to drug toxicity.[33]  Amiodarone has a high efficacy in maintaining sinus rhythm, and it can safely be initiated in an outpatient setting.[29,  34]  Major concerns early during therapy include drug-induced bradycardia necessitating adjustment of concomitant drug therapy or pacemaker implantation in up to one third of the patients.[34]  Noncardiac lung, liver, neurologic and thyroid toxicities are major concerns during long-term treatment.  Amiodarone has to be discontinued in approximately 8% of patients per year due to extracardiac side effects.[35] 

Dofetilide was shown to be relatively safe in heart failure patients, provided that several precautions are taken in its use.[36]  In this patient group, it has efficacy in converting atrial fibrillation to sinus rhythm and maintaining sinus rhythm.[30,  36]  As an IKr blocker, dofetilide prolongs the QT interval.  It caused torsade de pointes in approximately 3% of patients in the DIAMOND trial, even after dose-adjustment according to renal function and attention to following the QT interval.  The peak increase in the QT interval was seen within the first 2 days, and 76% of cases of torsades de pointes occurred within the first 3 days of dofetilide therapy.  In-hospital monitored initiation of dofetilide for 3 days is warranted.[36]  ICDs may provide protection from death due to this arrhythmia.  There is no head-to-head comparison of amiodarone and dofetilide in heart failure patients.

Sotalol is another class III antiarrhythmic drug that is an IKr blocker and also a non-selective beta-blocker.  It may be considered as a therapeutic alternative.  Data from the CTAF and SAFE-T trials show, that amiodarone is superior to sotalol in maintenance of sinus rhythm, but sotalol is still superior to placebo.[37,  38]  In patients with coronary artery disease, sotalol and amiodarone are similarly efficacious.[38]  Of note, the minority of patients in both trials had abnormal left ventricular function.[37,  38]  Sotalol has a proarrhythmic potential similar to that of dofetilide.  This effect may have been the cause of excess mortality that led to premature termination of the SWORD trial in which the d-isomer of sotalol was administered to patients with a history of prior myocardial infarction and an ejection fraction ≤ 40%.  Excess in total mortality was driven by arrhythmic cardiac deaths.  However, torsade de pointes were reported in only 0.2% of patients receiving sotalol.[39]  The proarrhythmic effect of sotalol warrants in-hospital initiation of the drug.

The CAST trial showed an excess of mortality with use of class I antiarrhythmic drugs (sodium channel blockers, including flecainide) in patients with structural heart disease.[40]  Heart failure patients may be prone to suffer from arrhythmogenic and cardiodepressant side effects of class I antiarrhythmic drugs.  Accordingly, these drugs should be avoided in heart failure patients.[19] 

Non-pharmacologic approach to maintain sinus rhythm

Over the last 20 years, surgical and catheter ablation techniques for treatment of atrial fibrillation have been developed and improved, with most of the trials in populations with no or little heart failure.  The Cox maze III procedure, which was introduced into surgical treatment in 1988, is regarded as the gold standard for surgical treatment of atrial fibrillation.  Long-term success in over 90% of patients, most of them off drugs, has been reported.[41,  42]  A review of recent publications on radiofrequency catheter ablation for atrial fibrillation shows consistently success rates in approximately 80% of patients, most of them off drugs, although more than one procedure is required in a significant number.[43]  It is difficult to extrapolate these results for heart failure patients, since patients in these trials are selected to be reasonable ablation candidates, often with no or minimal structural heart disease.  As for most therapies, lower success rates would be anticipated in patients with heart failure.  Left atrial scarring, decreased left ventricular function, persistent atrial fibrillation and age were identified as predictors of procedural failure in catheter ablation for atrial fibrillation.[44,  45] 

Surgical and catheter ablation procedures in patients with depressed left ventricular function were investigated in several recent studies.  In a retrospective study of 37 patients with a left ventricular ejection fraction < 55% (mean, 44%), who underwent a Cox maze procedure for paroxysmal and chronic atrial fibrillation and flutter, there was no perioperative mortality, and 3 patients required placement of a permanent pacemaker.  During a median follow-up of 48 months, atrial arrhythmias recurred in 4 patients.  Mean left ventricular ejection fraction improved significantly to 54%.  Improvement in functional capacity was noted in 56% of patients, deterioration of functional capacity was not observed.[46]  Surgical risks are an important consideration.  A recent review of 48 studies on surgical treatment of atrial fibrillation including the classical Cox maze III procedure, most performed with concomitant valve or bypass procedures, reported a 30-day mortality of 2 to 4%, major complications in 8% and the need for pacemaker implantation in 5 to 6% of cases.[47] 

Hsu and coworkers studied 58 patients with congestive heart failure and a left ventricular ejection fraction < 45% (mean, 35%), who underwent radiofrequency catheter ablation for atrial fibrillation.  One patient died 3 months after the procedure of heart failure.  After a follow-up period of 12 months, 78% of patients remained in sinus rhythm, 69% off antiarrhythmic drugs.  To achieve this result, a second procedure was required in 50% of patients.  Success rates in a control group were 84% and 71%, respectively.  Mean left ventricular ejection fraction improved to 56%, and left ventricular dimensions decreased.  This translated into better functional capacity and quality of life.[48]  Similar results were seen in another study on catheter ablation for atrial fibrillation, which included 90 patients with a reduced left ventricular ejection fraction of < 40% (mean, 36%).  After a follow-up of 14 months, 73% of patients were free of atrial fibrillation, compared to 87% of patients in a control group.  The increase in left ventricular ejection fraction to 41% was not significant, but quality of life improved significantly.  In 22% of patients a second procedure was successful.[45]  Major complications of catheter ablation for atrial fibrillation occur in 4 to 6% of patients, and it can be anticipated that heart failure patients will generally be at greater risk.[26,  49] 

These reports from highly experienced centers with selected patients are promising, but controlled data confirming a prognostic benefit for patients undergoing these procedures are still lacking.  The ongoing CABANA trial, which compares catheter ablation for atrial fibrillation with current state-of-the-art medical therapy, addresses this issue with a primary outcome measure of total mortality, but does not focus solely on a heart failure population.[50]  At present, catheter ablation for atrial fibrillation in heart failure is warranted in selected symptomatic patients with atrial fibrillation refractory to at least one antiarrhythmic drug.  Surgical ablation for atrial fibrillation is usually considered for symptomatic patients undergoing other cardiac surgery, such as mitral valve repair.  Patients may also be considered for surgical ablation, when they prefer a surgical approach, have failed one or more catheter ablation procedures or are not candidates for catheter ablation.[18,  42] 

Pharmacologic control of heart rate

Atrial fibrillation with a fast ventricular response may have immediate adverse hemodynamic effects and places the patient at risk for tachycardia-mediated cardiomyopathy, particularly if the chronic heart rate exceeds 100 beats per minute.[6,  13]  Digoxin is recommended for rate control in patients with heart failure, but it slows atrioventricular conduction more effective at rest than during exercise.  Beta-blockers are usually indicated in all symptomatic patients with systolic heart failure, but in heart failure initiation should be at a low dose followed by a gradual increase, because negative inotropic effects may cause fluid retention and worsening of heart failure.  Combination of beta-blockers and digoxin may be more effective than beta-blockers alone.  Amiodarone is an alternative for pharmacologic rate control in patients, where the abovementioned medications are contraindicated or fail, but it has a considerable potential of adverse drug effects and is usually avoided for rate control alone.  Non-dihydropyridine calcium channel blockers verapamil and diltiazem slow heart rate during exercise, but should be avoided due to their negative inotropic effect, which increases the risk of exacerbation of heart failure.[18,  19] 

Pharmacologic rate control with atrioventricular nodal blocking agents is chosen either as first line strategy or when attempts to establish and maintain sinus rhythm fail.  Heart rate goals are 60 to 80 beats per minute at rest and 90 to 115 beats per minute during moderate exercise, but may vary according to patient age.[18] 

Non-pharmacologic control of heart rate

Radiofrequency catheter ablation of the atrioventricular junction and pacemaker placement may be warranted in medically refractory atrial fibrillation where sinus rhythm cannot be maintained and adequate rate control is not possible.  Limitations of this approach include the persistent need for anticoagulation, loss of atrioventricular synchrony and pacemaker dependency.[18] 

A meta-analysis of 21 studies showed, that ablation and pacing reduces symptoms and healthcare use and improves left ventricular function, exercise duration and quality of life, with a one year total and sudden death mortality of 6.3% and 2.0%, respectively.[51] 

However, right ventricular apical pacing may be detrimental by worsening heart failure and increasing mortality.[52]  Right ventricular pacing induces electrical and mechanical dyssynchrony, which can adversely influence contraction and relaxation, ultimately causing unfavorable ventricular remodeling.  It may be less well tolerated in patients with pre-existing systolic heart failure and mitral regurgitation.[53,  54]  Consistent with this consideration is the observation that atrioventricular node ablation and permanent pacing for refractory atrial fibrillation leads to hemodynamic deterioration in certain patients.  Ozcan and coworkers studied this approach in patients with left ventricular dysfunction with a mean left ventricular ejection fraction of 26% before the procedure.[55]  Mean ejection fraction increased to 34% after ablation.  The twenty-nine percent of patients with near normalization of the left ventricular ejection fraction to ≥ 45% had a survival comparable to that of normal subjects.  However, the majority of patients had a persistent low ejection fraction and a poor prognosis with a mortality of 48% during a mean follow-up of 40 months.[55]  In some patients with heart failure, ablation and pacing is followed by aggravation of mitral regurgitation.[56]  Vanderheyden and coworkers found hemodynamic deterioration in 7% of patients undergoing ablation and pacing therapy, which was related to worsening mitral regurgitation.  Of note, baseline echocardiograms in patients with hemodynamic deterioration showed left ventricular dilation and subnormal fractional shortening.[57] 

The PAVE study compared conventional right ventricular with biventricular pacing in patients undergoing atrioventricular node ablation for the management of atrial fibrillation.[58]  Biventricular pacing was associated with improvement in functional capacity at 6 months.  Left ventricular ejection fraction remained unchanged after implantation of a biventricular system in contrast to right ventricular pacing, where a slight but significant decline in ejection fraction was observed.  Patients with a baseline ejection fraction of ≤ 45% or NYHA functional class II / III symptoms had a greater improvement in functional capacity than patients with normal left ventricular function or class I symptoms.[58]  In another study of patients with severe heart failure after atrioventricular node ablation and right ventricular pacing for management of chronic atrial fibrillation, upgrade to a biventricular system was followed by improvement in left ventricular dimensions and function, and quality of life and a decrease in hospitalizations.[59]  The HOBIPACE study compared bi-ventricular to right ventricular pacing for 3 months in a randomized cross-over design trial in 30 patients.  Biventricular pacing was superior to conventional right ventricular pacing with regard to left ventricular function, exercise capacity and quality of life in patients with left ventricular dysfunction and standard indication for pacemaker implantation.[60] 

Accordingly, implantation of a biventricular pacemaker is a reasonable consideration for patients who are undergoing atrioventricular node ablation for drug-refractory atrial fibrillation with heart failure or depressed left ventricular function.  An upgrade to a biventricular system should be contemplated in patients with persistent heart failure, who have undergone atrioventricular junctional ablation and have only right ventricular pacing.[18] 

Polymorphic ventricular tachycardia, ventricular fibrillation and sudden death were not uncommonly observed early after ablation of the atrioventricular junction and pacemaker implantation.  These complications occurred in 6% of cases in a larger study of Geelen and coworkers.  Ventricular arrhythmias mostly occurred during slow ventricular escape rhythms or slow pacing rates of ≤ 60 beats per minute.  Bradycardia and pacing-related prolongation of repolarization, change in ventricular activation, increased dispersion of repolarization, increased sympathetic tone and individual factors like heart failure, hypokalemia and female gender may increase the vulnerability to these arrhythmias.  Pacing at 90 beats per minute for 1 to 3 months after the procedure appears to prevent this complication.[61,  62] 

The recently completed PABA CHF trial compared catheter ablation for atrial fibrillation with atrioventricular node ablation and biventricular pacing.  Preliminary results showed a significantly greater ejection fraction in the catheter ablation group at 6 months post procedure.[63] 

Prevention of atrial fibrillation in heart failure

Perhaps the best way to deal with atrial fibrillation and its negative consequences is through prevention.  Angiotensin converting enzyme inhibitors, angiotensin receptor blockers and beta-blockers belong to the standard pharmacologic armamentarium for treatment of heart failure.[19]  There is strong evidence of participation of the renin-angiotensin system in electrical and structural atrial remodeling, involved in the pathogenesis of atrial fibrillation.[64]  Both angiotensin converting enzyme inhibitors and angiotensin receptor blockers reduce atrial fibrillation in patients with heart failure or hypertension, as supported by meta-analysis.[65]  The benefit was similar between these two classes of drugs and greatest in patients with heart failure with a 44% relative risk reduction.[65]  A recent meta-analysis on the efficacy of beta-blockers in heart failure trials showed a significant prevention of atrial fibrillation by use of beta-blockers with a 27% relative risk reduction.[66] 

The protective effect of cardiac resynchronization therapy is still unclear.  Although a small study showed a significantly lower incidence of atrial fibrillation in patients with cardiac resynchronization therapy, data from the CARE-HF study did not support this hypothesis.[67,  68] 

Conclusions

Atrial fibrillation is common in heart failure.  Patients with one condition who subsequent develop the other have an increased mortality.  Treatment has to be individualized in these complex patients and the risks and benefits of the different therapeutic options carefully considered.  Anticoagulation and rate control are crucial in all patients with atrial fibrillation and heart failure.  Pharmacologic rhythm control offers no survival benefit over rate control, and may be used in selected symptomatic patients.  Catheter ablation of atrial fibrillation in selected patients can be successful, but also has risks.  Atrioventricular node ablation and placement of a biventricular pacemaker for drug-refractory atrial fibrillation is an option when rate control and sinus rhythm can not be maintained.  The important question, of whether catheter ablation for atrial fibrillation has the potential to prolong life, is still unresolved.  The answer may have substantial impact on our approach to treat atrial fibrillation in the future.

References


1. Braunwald E. Shattuck lecture--cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N Engl J Med 1997; 337: 1360-1369.

2. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001; 285: 2370-2375.

3. Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, Hailpern SM, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell C, Roger V, Sorlie P, Steinberger J, Thom T, Wilson M, Hong Y, American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2008; 117: e25-146.

4. Wang TJ, Larson MG, Levy D, Vasan RS, Leip EP, Wolf PA, D'Agostino RB, Murabito JM, Kannel WB, Benjamin EJ. Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study. Circulation 2003; 107: 2920-2925.

5. Benjamin EJ, Levy D, Vaziri SM, D'Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. JAMA 1994; 271: 840-844.

6. Maisel WH, Stevenson LW. Atrial fibrillation in heart failure: epidemiology, pathophysiology, and rationale for therapy. Am J Cardiol 2003; 91: 2D-8D.

7. Bhatia RS, Tu JV, Lee DS, Austin PC, Fang J, Haouzi A, Gong Y, Liu PP. Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med 2006; 355: 260-269.

8. Parkash R, Maisel WH, Toca FM, Stevenson WG. Atrial fibrillation in heart failure: high mortality risk even if ventricular function is preserved. Am Heart J 2005; 150: 701-706.

9. Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 2006; 355: 251-259.

10. Olsson LG, Swedberg K, Ducharme A, Granger CB, Michelson EL, McMurray JJ, Puu M, Yusuf S, Pfeffer MA, CHARM Investigators. Atrial fibrillation and risk of clinical events in chronic heart failure with and without left ventricular systolic dysfunction: results from the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) program. J Am Coll Cardiol 2006; 47: 1997-2004.

11. Verma A, Newman D, Geist M, Greenhut S, Laslop J, DeBellis L, Freeman MR, Dorian P. Effects of rhythm regularization and rate control in improving left ventricular function in atrial fibrillation patients undergoing atrioventricular nodal ablation. Can J Cardiol 2001; 17: 437-445.

12. Wasmund SL, Li JM, Page RL, Joglar JA, Kowal RC, Smith ML, Hamdan MH. Effect of atrial fibrillation and an irregular ventricular response on sympathetic nerve activity in human subjects. Circulation 2003; 107: 2011-2015.

13. Fenelon G, Wijns W, Andries E, Brugada P. Tachycardiomyopathy: mechanisms and clinical implications. Pacing Clin Electrophysiol 1996; 19: 95-106.

14. Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001; 285: 2864-2870.

15. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22: 983-988.

16. Lip GY, Edwards SJ. Stroke prevention with aspirin, warfarin and ximelagatran in patients with non-valvular atrial fibrillation: a systematic review and meta-analysis. Thromb Res 2006; 118: 321-333.

17. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007; 146: 857-867.

18. Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le Heuzey JY, Kay GN, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann S, Smith SC,Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Halperin JL, Hunt SA, Nishimura R, Ornato JP, Page RL, Riegel B, Priori SG, Blanc JJ, Budaj A, Camm AJ, Dean V, Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo JL, Zamorano JL, American College of Cardiology/American Heart Association Task Force on Practice Guidelines, European Society of Cardiology Committee for Practice Guidelines, European Heart Rhythm Association, Heart Rhythm Society. 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.

19. Hunt SA, American College of Cardiology, American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol 2005; 46: e1-82.

20. DiMarco JP, Flaker G, Waldo AL, Corley SD, Greene HL, Safford RE, Rosenfeld LE, Mitrani G, Nemeth M, AFFIRM Investigators. Factors affecting bleeding risk during anticoagulant therapy in patients with atrial fibrillation: observations from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. Am Heart J 2005; 149: 650-656.

21. Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL, Mickel MC, Dalquist JE, Corley SD, Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002; 347: 1825-1833.

22. Van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, Said SA, Darmanata JI, Timmermans AJ, Tijssen JG, Crijns HJ, Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation Study Group. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002; 347: 1834-1840.

23. Carlsson J, Miketic S, Windeler J, Cuneo A, Haun S, Micus S, Walter S, Tebbe U, STAF Investigators. Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the Strategies of Treatment of Atrial Fibrillation (STAF) study. J Am Coll Cardiol 2003; 41: 1690-1696.

24. Roy D. AF-CHF abstract. 13th Annual Boston Atrial Fibrillation Symposium, January 17th-19th, 2008.

25. Roy D, Talajic M, Nattel S, Wyse DG, Dorian P, Lee KL, Bourassa MG, Arnold JM, Buxton AE, Camm AJ, Connolly SJ, Dubuc M, Ducharme A, Guerra PG, Hohnloser SH, Lambert J, Le Heuzey JY, O'Hara G, Pedersen OD, Rouleau JL, Singh BN, Stevenson LW, Stevenson WG, Thibault B, Waldo AL, Atrial Fibrillation and Congestive Heart Failure Investigators. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med 2008; 358: 2667-2677.

26. Bertaglia E, Zoppo F, Tondo C, Colella A, Mantovan R, Senatore G, Bottoni N, Carreras G, Coro L, Turco P, Mantica M, Stabile G. Early complications of pulmonary vein catheter ablation for atrial fibrillation: a multicenter prospective registry on procedural safety. Heart Rhythm 2007; 4: 1265-1271.

27. Corley SD, Epstein AE, DiMarco JP, Domanski MJ, Geller N, Greene HL, Josephson RA, Kellen JC, Klein RC, Krahn AD, Mickel M, Mitchell LB, Nelson JD, Rosenberg Y, Schron E, Shemanski L, Waldo AL, Wyse DG, AFFIRM Investigators. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study. Circulation 2004; 109: 1509-1513.

28. Hagens VE, Crijns HJ, Van Veldhuisen DJ, Van Den Berg MP, Rienstra M, Ranchor AV, Bosker HA, Kamp O, Tijssen JG, Veeger NJ, Van Gelder IC, RAte Control versus Electrical cardioversion for persistent atrial fibrillation study group. Rate control versus rhythm control for patients with persistent atrial fibrillation with mild to moderate heart failure: results from the RAte Control versus Electrical cardioversion (RACE) study. Am Heart J 2005; 149: 1106-1111.

29. Deedwania PC, Singh BN, Ellenbogen K, Fisher S, Fletcher R, Singh SN. Spontaneous conversion and maintenance of sinus rhythm by amiodarone in patients with heart failure and atrial fibrillation: observations from the veterans affairs congestive heart failure survival trial of antiarrhythmic therapy (CHF-STAT). The Department of Veterans Affairs CHF-STAT Investigators. Circulation 1998; 98: 2574-2579.

30. Pedersen OD, Bagger H, Keller N, Marchant B, Kober L, Torp-Pedersen C. Efficacy of dofetilide in the treatment of atrial fibrillation-flutter in patients with reduced left ventricular function: a Danish investigations of arrhythmia and mortality on dofetilide (diamond) substudy. Circulation 2001; 104: 292-296.

31. Stevenson WG, Tedrow U. Management of atrial fibrillation in patients with heart failure. Heart Rhythm 2007; 4: S28-30.

32. Singh SN, Fletcher RD, Fisher SG, Singh BN, Lewis HD, Deedwania PC, Massie BM, Colling C, Lazzeri D. Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure. N Engl J Med 1995; 333: 77-82.

33. Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, Domanski M, Troutman C, Anderson J, Johnson G, McNulty SE, Clapp-Channing N, Davidson-Ray LD, Fraulo ES, Fishbein DP, Luceri RM, Ip JH, Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005; 352: 225-237.

34. Weinfeld MS, Drazner MH, Stevenson WG, Stevenson LW. Early outcome of initiating amiodarone for atrial fibrillation in advanced heart failure. J Heart Lung Transplant 2000; 19: 638-643.

35. Chun SH, Sager PT, Stevenson WG, Nademanee K, Middlekauff HR, Singh BN. Long-term efficacy of amiodarone for the maintenance of normal sinus rhythm in patients with refractory atrial fibrillation or flutter. Am J Cardiol 1995; 76: 47-50.

36. Torp-Pedersen C, Moller M, Bloch-Thomsen PE, Kober L, Sandoe E, Egstrup K, Agner E, Carlsen J, Videbaek J, Marchant B, Camm AJ. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. N Engl J Med 1999; 341: 857-865.

37. Roy D, Talajic M, Dorian P, Connolly S, Eisenberg MJ, Green M, Kus T, Lambert J, Dubuc M, Gagne P, Nattel S, Thibault B. Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators. N Engl J Med 2000; 342: 913-920.

38. Singh BN, Singh SN, Reda DJ, Tang XC, Lopez B, Harris CL, Fletcher RD, Sharma SC, Atwood JE, Jacobson AK, Lewis HD,Jr, Raisch DW, Ezekowitz MD, Sotalol Amiodarone Atrial Fibrillation Efficacy Trial (SAFE-T) Investigators. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med 2005; 352: 1861-1872.

39. Waldo AL, Camm AJ, deRuyter H, Friedman PL, MacNeil DJ, Pauls JF, Pitt B, Pratt CM, Schwartz PJ, Veltri EP. Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d-Sotalol. Lancet 1996; 348: 7-12.

40. Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991; 324: 781-788.

41. Prasad SM, Maniar HS, Camillo CJ, Schuessler RB, Boineau JP, Sundt TM,3rd, Cox JL, Damiano RJ,Jr. The Cox maze III procedure for atrial fibrillation: long-term efficacy in patients undergoing lone versus concomitant procedures. J Thorac Cardiovasc Surg 2003; 126: 1822-1828.

42. European Heart Rhythm Association (EHRA), European Cardiac Arrhythmia Society (ECAS), American College of Cardiology (ACC), American Heart Association (AHA), Society of Thoracic Surgeons (STS), Calkins H, Brugada J, Packer DL, Cappato R, Chen SA, Crijns HJ, Damiano RJ,Jr, Davies DW, Haines DE, Haissaguerre M, Iesaka Y, Jackman W, Jais P, Kottkamp H, Kuck KH, Lindsay BD, Marchlinski FE, McCarthy PM, Mont JL, Morady F, Nademanee K, Natale A, Pappone C, Prystowsky E, Raviele A, Ruskin JN, Shemin RJ. 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: 816-861.

43. Verma A, Natale A. Should atrial fibrillation ablation be considered first-line therapy for some patients? Why atrial fibrillation ablation should be considered first-line therapy for some patients. Circulation 2005; 112: 1214-1222; discussion 1231.

44. Verma A, Wazni OM, Marrouche NF, Martin DO, Kilicaslan F, Minor S, Schweikert RA, Saliba W, Cummings J, Burkhardt JD, Bhargava M, Belden WA, Abdul-Karim A, Natale A. Pre-existent left atrial scarring in patients undergoing pulmonary vein antrum isolation: an independent predictor of procedural failure. J Am Coll Cardiol 2005; 45: 285-292.

45. Chen MS, Marrouche NF, Khaykin Y, Gillinov AM, Wazni O, Martin DO, Rossillo A, Verma A, Cummings J, Erciyes D, Saad E, Bhargava M, Bash D, Schweikert R, Burkhardt D, Williams-Andrews M, Perez-Lugones A, Abdul-Karim A, Saliba W, Natale A. Pulmonary vein isolation for the treatment of atrial fibrillation in patients with impaired systolic function. J Am Coll Cardiol 2004; 43: 1004-1009.

46. Stulak JM, Dearani JA, Daly RC, Zehr KJ, Sundt TM,3rd, Schaff HV. 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 500-501.

47. Khargi K, Hutten BA, Lemke B, Deneke T. Surgical treatment of atrial fibrillation; a systematic review. Eur J Cardiothorac Surg 2005; 27: 258-265.

48. Hsu LF, Jais P, Sanders P, Garrigue S, Hocini M, Sacher F, Takahashi Y, Rotter M, Pasquie JL, Scavee C, Bordachar P, Clementy J, Haissaguerre M. Catheter ablation for atrial fibrillation in congestive heart failure. N Engl J Med 2004; 351: 2373-2383.

49. Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J, Kim YH, Klein G, Packer D, Skanes A. Worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circulation 2005; 111: 1100-1105.

50. U.S. National Institutes of Health. Ablation vs drug therapy for atrial fibrillation - pilot trial (CABANA). http://clinicaltrials.gov/show/NCT00578617.htm (accessed March 13th, 2008).

51. Wood MA, Brown-Mahoney C, Kay GN, Ellenbogen KA. Clinical outcomes after ablation and pacing therapy for atrial fibrillation : a meta-analysis. Circulation 2000; 101: 1138-1144.

52. Wilkoff BL, Cook JR, Epstein AE, Greene HL, Hallstrom AP, Hsia H, Kutalek SP, Sharma A, Dual Chamber and VVI Implantable Defibrillator Trial Investigators. Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA 2002; 288: 3115-3123.

53. Sweeney MO, Prinzen FW. A new paradigm for physiologic ventricular pacing. J Am Coll Cardiol 2006; 47: 282-288.

54. Tops LF, Schalij MJ, Holman ER, van Erven L, van der Wall EE, Bax JJ. Right ventricular pacing can induce ventricular dyssynchrony in patients with atrial fibrillation after atrioventricular node ablation. J Am Coll Cardiol 2006; 48: 1642-1648.

55. Ozcan C, Jahangir A, Friedman PA, Munger TM, Packer DL, Hodge DO, Hayes DL, Gersh BJ, Hammill SC, Shen WK. 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: 33-37.

56. Twidale N, Manda V, Holliday R, Boler S, Sparks L, Crain J, Carrier S. Mitral regurgitation after atrioventricular node catheter ablation for atrial fibrillation and heart failure: acute hemodynamic features. Am Heart J 1999; 138: 1166-1175.

57. Vanderheyden M, Goethals M, Anguera I, Nellens P, Andries E, Brugada J, Brugada P. Hemodynamic deterioration following radiofrequency ablation of the atrioventricular conduction system. Pacing Clin Electrophysiol 1997; 20: 2422-2428.

58. Doshi RN, Daoud EG, Fellows C, Turk K, Duran A, Hamdan MH, Pires LA, PAVE Study Group. Left ventricular-based cardiac stimulation post AV nodal ablation evaluation (the PAVE study). J Cardiovasc Electrophysiol 2005; 16: 1160-1165.

59. Leon AR, Greenberg JM, Kanuru N, Baker CM, Mera FV, Smith AL, Langberg JJ, DeLurgio DB. Cardiac resynchronization in patients with congestive heart failure and chronic atrial fibrillation: effect of upgrading to biventricular pacing after chronic right ventricular pacing. J Am Coll Cardiol 2002; 39: 1258-1263.

60. Kindermann M, Hennen B, Jung J, Geisel J, Bohm M, Frohlig G. Biventricular versus conventional right ventricular stimulation for patients with standard pacing indication and left ventricular dysfunction: the Homburg Biventricular Pacing Evaluation (HOBIPACE). J Am Coll Cardiol 2006; 47: 1927-1937.

61. Geelen P, Brugada J, Andries E, Brugada P. Ventricular fibrillation and sudden death after radiofrequency catheter ablation of the atrioventricular junction. Pacing Clin Electrophysiol 1997; 20: 343-348.

62. Nowinski K, Gadler F, Jensen-Urstad M, Bergfeldt L. Transient proarrhythmic state following atrioventricular junction radiofrequency ablation: pathophysiologic mechanisms and recommendations for management. Am J Med 2002; 113: 596-602.

63. Khan M, Jais P, Cummings JE, Sanders P, Kautzner J, Hao S, Themistoclakis S, Fanelli R, Potenza D, Belden W, Wazni O, Wang P, Al-Ahmad A, Beheiry S, Pisano E, Santarelli P, Starling R, Dello Russo A, Pelargonio G, Brachmann J, Gunther J, Bonso A, Raviele A, Haissaguerre M, Natale A. Randomized controlled trial of pulmonary vein antrum isolation vs. AV node ablation with bi-ventricular pacing for treatment of atrial fibrillation in patients with congestive heart failure (PABA CHF). Circulation 2005; 112 [Suppl. II]: II-394.

64. Patlolla V, Alsheikh-Ali AA, Al-Ahmad AM. The renin-angiotensin system: a therapeutic target in atrial fibrillation. Pacing Clin Electrophysiol 2006; 29: 1006-1012.

65. Healey JS, Baranchuk A, Crystal E, Morillo CA, Garfinkle M, Yusuf S, Connolly SJ. Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis. J Am Coll Cardiol 2005; 45: 1832-1839.

66. Nasr IA, Bouzamondo A, Hulot JS, Dubourg O, Le Heuzey JY, Lechat P. Prevention of atrial fibrillation onset by beta-blocker treatment in heart failure: a meta-analysis. Eur Heart J 2007; 28: 457-462.

67. Fung JW, Yu CM, Chan JY, Chan HC, Yip GW, Zhang Q, Sanderson JE. Effects of cardiac resynchronization therapy on incidence of atrial fibrillation in patients with poor left ventricular systolic function. Am J Cardiol 2005; 96: 728-731.

68. Hoppe UC, Casares JM, Eiskjaer H, Hagemann A, Cleland JG, Freemantle N, Erdmann E. Effect of cardiac resynchronization on the incidence of atrial fibrillation in patients with severe heart failure. Circulation 2006; 114: 18-25.



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