- Email: [email protected]
Management of atrial fibrillation in patients with heart failure
Management of atrial fibrillation in patients with heart failure William G. Stevenson, MD, Usha Tedrow, MD From the Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. Atrial fibrillation is a marker for worse outcomes in patients with heart failure and requires careful, individualized management. Anticoagulation and rate control are important. Routine use of antiarrhythmic drug therapy for maintenance of sinus rhythm carries concerns of risk and limited efficacy. Catheter ablation for maintaining sinus rhythm is feasible for some patients, but further studies are needed to define the risks and benefits. A role remains for AV junction ablation and pacing, with consideration of biven-
tricular pacing to prevent dyssynchrony induced by chronic right ventricular pacing. Ongoing trials will continue to define the risks and benefits as these therapies evolve. KEYWORDS Atrial fibrillation; Antiarrhythmic drugs; Ablation; Heart failure (Heart Rhythm 2007;4:S28 –S30) © 2007 Heart Rhythm Society. All rights reserved.
Introduction
Rhythm control strategy to maintain SR
Approximately five million people in the United States have heart failure (HF). Half of these individuals have depressed left ventricular (LV) function, and 40% to 50% have HF with preserved LV function, often associated with hypertension and advancing age.1,2 The prevalence of atrial fibrillation (AF) increases with the severity of systolic HF, ranging from 6% of patients with mild HF to more than 40% of patients with advanced HF.3–5 AF may be even more common in HF with preserved systolic function, being found in 40% of patients in a large community study.4,5 Emergence of AF often is associated with deterioration of HF. Loss of atrial contribution to ventricular filling, inappropriately rapid or slow ventricular rate, and variability in time for cardiac filling can adversely impact hemodynamics and increase sympathetic tone.6,7 AF is associated with more frequent hospitalizations and greater mortality.5 The extent to which AF accelerates HF deterioration or is a marker of disease severity is unclear. Paramount management issues include anticoagulation, rate control, as well as consideration of therapy to restore and maintain sinus rhythm (SR).
Patients with HF and AF who maintain SR during antiarrhythmic drug therapy have better survival and fewer hospitalizations than do patients who continue in AF.10 –13 Whether successful maintenance of SR improves outcome or is a marker for disease severity remains uncertain. Selection of a rhythm control strategy requires careful consideration of the risks and benefits for each individual patient. Antiarrhythmic drug therapy for maintenance of SR often is favored for patients with a first episode of persistent AF, patients with symptomatic paroxysms of AF, and those in whom adequate rate control is difficult to achieve. Betaadrenergic blockers reduce mortality in HF and are helpful in controlling AF rate, but they often fail to prevent recurrences. Class I antiarrhythmic drugs (e.g., quinidine, flecainide, propafenone, procainamide, disopyramide) should be avoided because of their negative inotropic effects and potential proarrhythmic effects.8 Of the remaining antiarrhythmic drug options of amiodarone, dofetilide, and sotalol, amiodarone is most likely to be effective.14,15 In a randomized trial of 665 patients with persistent AF, less than 25% of whom had HF, amiodarone prolonged the median time to AF recurrence to 487 days vs 74 days for sotalol and 6 days for placebo.14 Amiodarone can be safely initiated in the outpatient setting.10 Drug-induced bradycardia can require drug adjustment or pacing in up to one third of patients with advanced HF.15 During long-term therapy, extracardiac toxicities are a major concern in approximately 8% of patients per year of therapy.14 Elevation of defibrillation thresholds in patients with cardioverter-defibrillators can be a concern. In the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), amiodarone therapy was associated with increased mortality in patients with New York Heart Association class III HF, indicating that the risk benefit is not necessarily favorable.16
Anticoagulation The risk of thromboembolic stroke in patients with AF is approximately 6% per year and is further increased by approximately 40% in HF.8 Major bleeding risk during therapy with warfarin is 1% to 2% per year in patients with AF, with HF patients experiencing increased risk.9 However, riskto-benefit considerations strongly favor anticoagulation. Dr. Stevenson is a consultant to Biosense Webster and receives occasional speaking honoraria from Medtronic, St. Jude, and Boston Scientific. Dr. Tedrow has received research support from Medtronic. Address reprint requests and correspondence: Dr. William G. Stevenson, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115. E-mail address: [email protected].
1547-5271/$ -see front matter © 2007 Heart Rhythm Society. All rights reserved.
doi:10.1016/j.hrthm.2006.12.003
Stevenson and Tedrow
Atrial Fibrillation and Heart Failure
Dofetilide and sotalol are class III drugs that block the rapid component of the delayed rectifier potassium current IKr. Dofetilide reduces recurrent AF in HF but has not been directly compared with amiodarone.11 Sotalol is also a nonselective beta-adrenergic blocker. Both drugs prolong the QT interval, inducing torsades de pointes in approximately 3% of patients even when precautions are taken to avoid administration in high-risk individuals with renal insufficiency or baseline QT prolongation. Consequently, in-hospital initiation with 3 days of monitoring is mandated for use of both drugs. The electrophysiologic changes accompanying hypertrophy in HF have been suggested to increase the risk of torsades de pointes such that administration of any QT-prolonging drug, including ibutilide, requires careful monitoring.
Surgical and catheter ablation for maintaining SR Catheter and surgical ablation for maintaining SR have been studied largely in patients with mild heart disease. In these selected patients, efficacy ranges from 62% to 85%.17–20 Success is less in patients with persistent AF, marked left atrial enlargement, areas of low-voltage atrial scar, and ventricular dysfunction, all of which seem more likely to be present in HF.20,21 Risks and benefits are not well defined in HF patients, but initial reports are encouraging.18,20,22 Stulak et al23 reported 37 patients with AF and abnormal LV function undergoing surgical maze without adjuvant surgery. Sixty-five percent of these patients had symptomatic HF. There was no perioperative mortality, but three patients required permanent pacing for sinus node dysfunction. LV ejection fraction improved after surgery. At a median follow-up of 63 months, all but one patient was free of symptomatic AF. Hsu et al22 compared results of catheter ablation in 58 patients with HF and depressed systolic function to the results in a clinically matched AF control group. AF was persistent or chronic in 90% of patients. Amiodarone was administered prior to ablation and stopped at the time of ablation in the majority of patients. After a mean follow-up of 12 ⫾ 7 months, 69% of HF patients and 71% of controls were in SR without antiarrhythmic drug therapy. Interestingly, LV function improved in the HF group, even for patients whose rate control appeared adequate prior to ablation. Major procedural complications occurred in 4% of patients (one stroke and one cardiac tamponade), and two procedures were required in half of the patients. Chen et al19 reported ablation outcomes for 94 patients with depressed LV function (mean LV ejection fraction 36% ⫾ 8%). After a mean follow-up of 14 ⫾ 5 months, 73% of patients were free of AF. There was a nonsignificant trend toward improvement in LV ejection fraction. Procedural complications included two strokes (2%) and one acute pulmonary edema. These initial reports originate from highly experienced centers and likely have referral biases. Further study of the risk and benefits is needed, but it now seems reasonable to consider ablation for selected patients with HF.
S29
Rate control When SR is not maintained, adequate rate control during AF is extremely important. Rapid rates exacerbate HF, and persistent rapid rates can lead to tachycardia induced cardiomyopathy that is reversible if the rate is brought under control. Aiming for a resting rate of 60 to 80 bpm during rest and 90 to 115 bpm during moderate exercise is recommended.8 Beta-adrenergic blockers and digoxin are the firstline options.8 Although nondihydropyridine calcium channel blockers slow heart rate, negative inotropic effects are of great concern.
AV junction ablation with ventricular pacing When SR cannot be maintained and adequate rate control cannot be achieved with medications, catheter ablation of the AV junction and implantation of a permanent pacemaker should be considered to achieve rate control and regularize the heart rhythm.24 The atria continue to fibrillate, necessitating anticoagulation. Although symptoms improve, objective improvement in functional capacity is not consistent. In one study, LV ejection fraction improved from a mean of 26% to 34% and became normal in 29% of patients.25 Although AV junction ablation with RV pacing is superior to uncontrolled heart rates for most patients, hemodynamic deterioration occurred in 7% of patients in one series.26 Right ventricular (RV) pacing-induced ventricular dyssynchrony caused worsening of LV dysfunction and mitral regurgitation.27–29 A growing body of evidence supports consideration of cardiac resynchronization therapy rather than RV pacing alone in patients with abnormal ventricular function. Kindermann et al30 studied 30 patients with AV block and LV dysfunction receiving biventricular vs RV pacing in crossover for 3 months. Cardiac resynchronization was associated with better LV function, quality of life, and exercise capacity. Doshi et al31 randomized 184 patients undergoing AV junction ablation to either RV or biventricular pacing. Both groups improved, but biventricular pacing appeared to provide greater benefit for the subgroup of patients with LV ejection fraction ⱕ45% or Class II or III symptoms. A substantial number of withdrawals limited the strength of the findings. Polymorphic ventricular tachycardia and cardiac arrest can occur after AV junction ablation. Ventricular slowing and change in activation sequence from pacing have been suggested to increase dispersion of refractoriness predisposing to this arrhythmia.32 Pacing at ⬎90 beats/min for the initial 1 to 3 months after ablation appears to reduce this risk.33
Conclusion AF is associated with worse patient outcomes and requires careful individualized management. The risks of therapy are an important determinant of whether maintaining SR will improve outcomes. Better understanding of the risks and benefits of pharmacologic and ablation therapies is emerging and will be further clarified by ongoing trials. Recent
S30
Heart Rhythm, Vol 4, No 3, March Supplement 2007
studies showing that therapies that favorably modify the course of HF reduce AF suggest that prevention is likely to be the ultimate therapeutic strategy.34
17.
References
18.
1. 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. 2. 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. 3. van Veldhuisen DJ, Aass H, El Allaf D, Dunselman PH, Gullestad L, Halinen M, Kjekshus J, Ohlsson L, Wedel H, Wikstrand J. Presence and development of atrial fibrillation in chronic heart failure. Eur J Heart Fail 2006;8:539 –546. 4. 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. 5. Olsson LG, Swedberg K, Ducharme A, Granger CB, Michelson EL, McMurray JJ, Puu M, Yusuf S, Pfeffer MA. 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. 6. 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. 7. 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. 8. 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, 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, Zamorano JL. 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. Circulation 2006;114:e257– e354. 9. DiMarco JP, Flaker G, Waldo AL, Corley SD, Greene HL, Safford RE, Rosenfeld LE, Mitrani G, Nemeth M. 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. 10. 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 (CHFSTAT). Circulation 1998;98:2574 –2579. 11. 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. N Engl J Med 1999;341:857– 865. 12. 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 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. 13. 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. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study. Circulation 2004;109:1509 –1513. 14. 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. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med 2005;352: 1861–1872. 15. 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. 16. 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, David-
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son-Ray LD, Fraulo ES, Fishbein DP, Luceri RM, Ip JH. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225–237. Verma A, Natale A. Should atrial fibrillation ablation be considered first-line therapy for some patients? Circulation 2005;112:1214 –1222. Cheema A, Dong J, Dalal D, Vasamreddy CR, Marine JE, Henrikson CA, Spragg D, Cheng A, Nazarian S, Sinha S, Halperin H, Berger R, Calkins H. Long-term safety and efficacy of circumferential ablation with pulmonary vein isolation. J Cardiovasc Electrophysiol 2006;17:1080 –1085. 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, AbdulKarim 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. Pappone C, Rosanio S, Augello G, Gallus G, Vicedomini G, Mazzone P, Gulletta S, Gugliotta F, Pappone A, Santinelli V, Tortoriello V, Sala S, Zangrillo A, Crescenzi G, Benussi S, Alfieri O. Mortality, morbidity, and quality of life after circumferential pulmonary vein ablation for atrial fibrillation: outcomes from a controlled nonrandomized long-term study. J Am Coll Cardiol 2003;42: 185–197. 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. 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. 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. 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. 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. 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. Sweeney MO, Prinzen FW. A new paradigm for physiologic ventricular pacing. J Am Coll Cardiol 2006;47:282–288. 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. 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. 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. Doshi RN, Daoud EG, Fellows C, Turk K, Duran A, Hamdan MH, Pires LA. Left ventricular-based cardiac stimulation post AV nodal ablation evaluation (the PAVE study). J Cardiovasc Electrophysiol 2005;16:1160 –1165. Medina-Ravell VA, Lankipalli RS, Yan GX, Antzelevitch C, Medina-Malpica NA, Medina-Malpica OA, Droogan C, Kowey PR. Effect of epicardial or biventricular pacing to prolong QT interval and increase transmural dispersion of repolarization: does resynchronization therapy pose a risk for patients predisposed to long QT or torsade de pointes? Circulation 2003;107:740 –746. 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. 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.
tricular pacing to prevent dyssynchrony induced by chronic right ventricular pacing. Ongoing trials will continue to define the risks and benefits as these therapies evolve. KEYWORDS Atrial fibrillation; Antiarrhythmic drugs; Ablation; Heart failure (Heart Rhythm 2007;4:S28 –S30) © 2007 Heart Rhythm Society. All rights reserved.
Introduction
Rhythm control strategy to maintain SR
Approximately five million people in the United States have heart failure (HF). Half of these individuals have depressed left ventricular (LV) function, and 40% to 50% have HF with preserved LV function, often associated with hypertension and advancing age.1,2 The prevalence of atrial fibrillation (AF) increases with the severity of systolic HF, ranging from 6% of patients with mild HF to more than 40% of patients with advanced HF.3–5 AF may be even more common in HF with preserved systolic function, being found in 40% of patients in a large community study.4,5 Emergence of AF often is associated with deterioration of HF. Loss of atrial contribution to ventricular filling, inappropriately rapid or slow ventricular rate, and variability in time for cardiac filling can adversely impact hemodynamics and increase sympathetic tone.6,7 AF is associated with more frequent hospitalizations and greater mortality.5 The extent to which AF accelerates HF deterioration or is a marker of disease severity is unclear. Paramount management issues include anticoagulation, rate control, as well as consideration of therapy to restore and maintain sinus rhythm (SR).
Patients with HF and AF who maintain SR during antiarrhythmic drug therapy have better survival and fewer hospitalizations than do patients who continue in AF.10 –13 Whether successful maintenance of SR improves outcome or is a marker for disease severity remains uncertain. Selection of a rhythm control strategy requires careful consideration of the risks and benefits for each individual patient. Antiarrhythmic drug therapy for maintenance of SR often is favored for patients with a first episode of persistent AF, patients with symptomatic paroxysms of AF, and those in whom adequate rate control is difficult to achieve. Betaadrenergic blockers reduce mortality in HF and are helpful in controlling AF rate, but they often fail to prevent recurrences. Class I antiarrhythmic drugs (e.g., quinidine, flecainide, propafenone, procainamide, disopyramide) should be avoided because of their negative inotropic effects and potential proarrhythmic effects.8 Of the remaining antiarrhythmic drug options of amiodarone, dofetilide, and sotalol, amiodarone is most likely to be effective.14,15 In a randomized trial of 665 patients with persistent AF, less than 25% of whom had HF, amiodarone prolonged the median time to AF recurrence to 487 days vs 74 days for sotalol and 6 days for placebo.14 Amiodarone can be safely initiated in the outpatient setting.10 Drug-induced bradycardia can require drug adjustment or pacing in up to one third of patients with advanced HF.15 During long-term therapy, extracardiac toxicities are a major concern in approximately 8% of patients per year of therapy.14 Elevation of defibrillation thresholds in patients with cardioverter-defibrillators can be a concern. In the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), amiodarone therapy was associated with increased mortality in patients with New York Heart Association class III HF, indicating that the risk benefit is not necessarily favorable.16
Anticoagulation The risk of thromboembolic stroke in patients with AF is approximately 6% per year and is further increased by approximately 40% in HF.8 Major bleeding risk during therapy with warfarin is 1% to 2% per year in patients with AF, with HF patients experiencing increased risk.9 However, riskto-benefit considerations strongly favor anticoagulation. Dr. Stevenson is a consultant to Biosense Webster and receives occasional speaking honoraria from Medtronic, St. Jude, and Boston Scientific. Dr. Tedrow has received research support from Medtronic. Address reprint requests and correspondence: Dr. William G. Stevenson, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115. E-mail address: [email protected].
1547-5271/$ -see front matter © 2007 Heart Rhythm Society. All rights reserved.
doi:10.1016/j.hrthm.2006.12.003
Stevenson and Tedrow
Atrial Fibrillation and Heart Failure
Dofetilide and sotalol are class III drugs that block the rapid component of the delayed rectifier potassium current IKr. Dofetilide reduces recurrent AF in HF but has not been directly compared with amiodarone.11 Sotalol is also a nonselective beta-adrenergic blocker. Both drugs prolong the QT interval, inducing torsades de pointes in approximately 3% of patients even when precautions are taken to avoid administration in high-risk individuals with renal insufficiency or baseline QT prolongation. Consequently, in-hospital initiation with 3 days of monitoring is mandated for use of both drugs. The electrophysiologic changes accompanying hypertrophy in HF have been suggested to increase the risk of torsades de pointes such that administration of any QT-prolonging drug, including ibutilide, requires careful monitoring.
Surgical and catheter ablation for maintaining SR Catheter and surgical ablation for maintaining SR have been studied largely in patients with mild heart disease. In these selected patients, efficacy ranges from 62% to 85%.17–20 Success is less in patients with persistent AF, marked left atrial enlargement, areas of low-voltage atrial scar, and ventricular dysfunction, all of which seem more likely to be present in HF.20,21 Risks and benefits are not well defined in HF patients, but initial reports are encouraging.18,20,22 Stulak et al23 reported 37 patients with AF and abnormal LV function undergoing surgical maze without adjuvant surgery. Sixty-five percent of these patients had symptomatic HF. There was no perioperative mortality, but three patients required permanent pacing for sinus node dysfunction. LV ejection fraction improved after surgery. At a median follow-up of 63 months, all but one patient was free of symptomatic AF. Hsu et al22 compared results of catheter ablation in 58 patients with HF and depressed systolic function to the results in a clinically matched AF control group. AF was persistent or chronic in 90% of patients. Amiodarone was administered prior to ablation and stopped at the time of ablation in the majority of patients. After a mean follow-up of 12 ⫾ 7 months, 69% of HF patients and 71% of controls were in SR without antiarrhythmic drug therapy. Interestingly, LV function improved in the HF group, even for patients whose rate control appeared adequate prior to ablation. Major procedural complications occurred in 4% of patients (one stroke and one cardiac tamponade), and two procedures were required in half of the patients. Chen et al19 reported ablation outcomes for 94 patients with depressed LV function (mean LV ejection fraction 36% ⫾ 8%). After a mean follow-up of 14 ⫾ 5 months, 73% of patients were free of AF. There was a nonsignificant trend toward improvement in LV ejection fraction. Procedural complications included two strokes (2%) and one acute pulmonary edema. These initial reports originate from highly experienced centers and likely have referral biases. Further study of the risk and benefits is needed, but it now seems reasonable to consider ablation for selected patients with HF.
S29
Rate control When SR is not maintained, adequate rate control during AF is extremely important. Rapid rates exacerbate HF, and persistent rapid rates can lead to tachycardia induced cardiomyopathy that is reversible if the rate is brought under control. Aiming for a resting rate of 60 to 80 bpm during rest and 90 to 115 bpm during moderate exercise is recommended.8 Beta-adrenergic blockers and digoxin are the firstline options.8 Although nondihydropyridine calcium channel blockers slow heart rate, negative inotropic effects are of great concern.
AV junction ablation with ventricular pacing When SR cannot be maintained and adequate rate control cannot be achieved with medications, catheter ablation of the AV junction and implantation of a permanent pacemaker should be considered to achieve rate control and regularize the heart rhythm.24 The atria continue to fibrillate, necessitating anticoagulation. Although symptoms improve, objective improvement in functional capacity is not consistent. In one study, LV ejection fraction improved from a mean of 26% to 34% and became normal in 29% of patients.25 Although AV junction ablation with RV pacing is superior to uncontrolled heart rates for most patients, hemodynamic deterioration occurred in 7% of patients in one series.26 Right ventricular (RV) pacing-induced ventricular dyssynchrony caused worsening of LV dysfunction and mitral regurgitation.27–29 A growing body of evidence supports consideration of cardiac resynchronization therapy rather than RV pacing alone in patients with abnormal ventricular function. Kindermann et al30 studied 30 patients with AV block and LV dysfunction receiving biventricular vs RV pacing in crossover for 3 months. Cardiac resynchronization was associated with better LV function, quality of life, and exercise capacity. Doshi et al31 randomized 184 patients undergoing AV junction ablation to either RV or biventricular pacing. Both groups improved, but biventricular pacing appeared to provide greater benefit for the subgroup of patients with LV ejection fraction ⱕ45% or Class II or III symptoms. A substantial number of withdrawals limited the strength of the findings. Polymorphic ventricular tachycardia and cardiac arrest can occur after AV junction ablation. Ventricular slowing and change in activation sequence from pacing have been suggested to increase dispersion of refractoriness predisposing to this arrhythmia.32 Pacing at ⬎90 beats/min for the initial 1 to 3 months after ablation appears to reduce this risk.33
Conclusion AF is associated with worse patient outcomes and requires careful individualized management. The risks of therapy are an important determinant of whether maintaining SR will improve outcomes. Better understanding of the risks and benefits of pharmacologic and ablation therapies is emerging and will be further clarified by ongoing trials. Recent
S30
Heart Rhythm, Vol 4, No 3, March Supplement 2007
studies showing that therapies that favorably modify the course of HF reduce AF suggest that prevention is likely to be the ultimate therapeutic strategy.34
17.
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