Management of atrial fibrillation in patients with heart failure

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, Departmen...

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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.


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.


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.


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


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




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