heart failure", section on 'Antiarrhythmic agents' and "Clinical uses of sotalol", section on 'Heart failure'.) Sotalol can be used if the QT is not prolonged, if there is no renal dysfunction, if there are normal electrolytes (specifically normal potassium), if there is no acute decompensation, and if the LVEF is no more than modestly impaired (ie, if LVEF is >30 percent). However, sotalol can cause marked bradycardia and worsen HF in HFrEF in some instances. https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 12/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate Beta blockers Chronic beta blocker therapy may reduce the likelihood of development of AF in patients with HF due to systolic dysfunction. Likewise, in people with paroxysmal AF, beta blockers may help maintain sinus rhythm. Using beta blockers as antiarrhythmic therapy can serve a dual purpose because these medications are also an important component of optimal medical therapy for HF. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials", section on 'Beta blockers'.) Medications we do not suggest using in AF and HF patients include: Dronedarone In general, dronedarone has no role in the management of AF in a HF patient. In particular, dronedarone should not be used in patients with New York Heart Association class III to IV HF or LV systolic dysfunction (LVEF <0.40), as efficacy is low, and safety is a concern. It should also not be used in patients with longstanding persistent AF. This recommendation is consistent with that made by the European Medicines Agency in September of 2011 and the U S Food and Drug Administration in December of 2011. Strong evidence for an adverse effect of dronedarone use in patients with HFrEF comes from the ANDROMEDA trial (patients in this study had an LVEF 35 percent) [46] . The trial was discontinued early due to a significant increase in the incidence of death in the patients assigned to dronedarone versus placebo (8.1 versus 3.8 percent; HR 2.13, 95% CI 1.07-4.25). The primary cause of death among patients receiving dronedarone was worsening HF [46]. Dronedarone is likely less efficacious than amiodarone at AF rhythm control [47]. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials", section on 'Dronedarone'.) Class IC drugs Class IC drugs (flecainide, propafenone) are associated with an increased risk for proarrhythmia and sudden cardiac death and should not be used in patients with AF and HF ( table 1). Ibutilide We do not use this medication in decompensated HF due to the substantial risks of torsades de pointes. (See "Therapeutic use of ibutilide", section on 'Proarrhythmia'.) Catheter ablation For patients with symptomatic AF who have HFrEF that is not decompensated and recurrent AF despite electrical cardioversion and antiarrhythmic drug therapy (or side effect or intolerance to antiarrhythmic therapy), we perform CA of AF rather than continued attempts at cardioversion with or without antiarrhythmic drug therapy. In some patients, repeat CA is pursued if the first CA is unsuccessful. (See "Maintenance of sinus rhythm in atrial fibrillation: Catheter ablation versus antiarrhythmic drug therapy".) https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 13/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate Rarely, if a patient has a contraindication to all antiarrhythmic medications and there is new AF and/or paroxysmal AF, we will pursue CA as the initial therapy. An example is a patient with HF and AF who has a contraindication to dofetilide and/or sotalol (eg, kidney disease, a long QT interval) and propensity to develop amiodarone toxicity (eg, underlying thyroid, lung, or liver disease). Patients HFrEF and AF who are unlikely to benefit from CA If the patient has one or more of the following factors, they may be unsuitable for CA: Some patients with advanced HF (including those with LV assist device destination therapy or on ionotropic support). Severe comorbidities or medical instability. Patients asymptomatic on optimal HF therapy. Longstanding AF that is unrelated to progressive symptoms or concerns. Older-aged persons including those with frailty. We do not generally perform CA in persons >age 80 years of age. Markedly enlarged left atrial size and longstanding persistent and drug-resistant AF. There is no evidence that suggests a specific left atrial dimension cut point beyond which CA may not be useful. Patients with complete heart block (either spontaneous or related to an atrioventricular node ablation) and permanent ventricular pacing. If the patient is deemed unsuitable for CA for one or more of these reasons and has failed other attempts at rhythm control, we pursue a rate control strategy. (See 'Rate control in heart failure with reduced ejection fraction' below.) Efficacy of CA versus medical therapy The CASTLE-AF trial randomly assigned 363 patients with implantable cardioverter-defibrillators, symptomatic paroxysmal or persistent AF, New York Heart Association class II or higher, and an LVEF 35 percent to CA or medical therapy [48]. Death from any cause or hospitalization for HF occurred in fewer patients in the CA compared with medical therapy group (29 versus 45 percent; HR 0.62; 95% CI 0.43- 0.87). The time in AF was also lower with CA versus medical therapy (25 versus 60 percent). Several important limitations of the CASTLE-AF trial include patients lost to follow-up (particularly in the group assigned implantable cardioverter-defibrillator), lack of blinding, small sample size, and limited generalizability given that 85 percent of participants were https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 14/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate male (females have less successful CAs) and that all patients had defibrillators and/or cardiac resynchronization therapy. A greater number of patients in the ablation group than in the medical therapy group crossed over to the other treatment group (15.6 versus 9.8). Finally, although medical therapy (for both AF and HF) was managed per study protocol, it is possible that a nontraditional or more aggressive approach to medical management might have influenced the trial results. In a 2019 meta-analysis of six trials (775 patients), of which CASTLE-AF was the largest [49], CA reduced all-cause mortality compared with drug therapy (9 versus 18 percent). Studies have also shown that CA can increase exercise ability, LVEF, quality of life, and is associated with a decrease in pro-brain natriuretic peptide levels [34,36,37,50]. Efficacy of CA versus atrioventricular node ablation with biventricular pacing In a randomized trial of 81 patients with HF and symptomatic, drug-refractory AF, CA was associated with modest improvements in LVEF (35 versus 28 percent), six-minute walk distance (340 versus 297 meters), and score on the Minnesota Living With Heart Failure questionnaire [35]. The role of atrioventricular ablation and biventricular pacing in patients with AF is discussed in detail elsewhere. (See 'Atrioventricular node ablation with pacing' below and "Cardiac resynchronization therapy in atrial fibrillation", section on 'Cardiac resynchronization therapy outcomes in patients with atrial fibrillation'.) Rate control in heart failure with reduced ejection fraction Indications We pursue a rate control strategy for patients in whom rhythm control is not tolerated or has been unsuccessful. A rate control strategy is sometimes the preferred initial strategy in a subset of patients as outlined above. (See 'Exceptions' above.) Among patients with HF, rate control to prevent rapid AF usually leads to an improvement in symptoms. Slowing of the ventricular rate often leads to a moderate or even marked improvement in LV function [9,25,26]. (See 'mechanisms of cardiac dysfunction' above.) Rate control goal The broad goal of rate control is to minimize symptoms with exercise and rest. Thus, the adequacy of rate control should be assessed in both circumstances [21]. (See "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy".) The optimal heart rate in patients with AF and HF has not been well studied and is not certain. Our authors generally start with a heart rate goal of <85 beats per minute at rest and <110 beats per minute during moderate exercise (the strict approach). If this is not possible, the goal becomes <110 beats per minute at rest (the lenient approach). https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 15/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate In a symptomatic patient in whom the ventricular rate varies markedly with minimal changes in activity, a rhythm control strategy may be necessary. Medications Although we prefer to use just one rate-slowing medication, sometimes more than one medication is required to achieve adequate heart rate control. When titrating therapy, we measure the patient's ventricular rates at rest and with moderate exertion. (See 'Rate control goal' above.) Beta blocker We usually select a beta blocker as first therapy due to their superior safety profile in both AF and HF. We would avoid starting a beta blocker if the patient had decompensated HF. Most patients with preexisting HFrEF are already on a beta blocker for treatment of HF, and if possible, we increase the dosage of their medication. The alternatives of digoxin (lesser efficacy) and amiodarone (more side effects) have significant limitations. We start with carvedilol, extended-release metoprolol succinate, or bisoprolol. The doses should be optimized before considering a second agent. These drugs are discussed in detail separately. (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Evidence' and "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy", section on 'Elective and long-term management' and "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy".) Carvedilol is started at an oral dose of 3.125 mg twice daily. The usual dosage range is 3.125 to 25 mg twice daily but may be titrated higher for the purpose of treating HFrEF (up to 25 to 50 mg, depending on the patient's weight). A possible adverse effect of carvedilol is hypotension since this beta blocker also has alpha-adrenergic-receptor- blocking action [51]. Metoprolol succinate is started at an oral dose of 25 mg daily. This can be titrated up to a target dose of 200 mg daily in patients with HFrEF. Even if AF rate control is achieved at lower doses, the target for metoprolol succinate is higher for HFrEF. Bisoprolol is started at an oral dose of 2.5 mg once daily; the dose is increased gradually as tolerated to achieve ventricular rate control, and in patients with HFrEF, the target dose is 10 mg daily. Beta blockers have been shown to improve symptoms but not survival in AF and HF. In a meta-analysis of AF patients in 11 randomized trials of over 3000 patients, beta blockers reduced the ventricular rate (by 12 beats per minute) but did not decrease mortality when https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 16/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate compared with placebo (overall death rate 20 percent; HR 0.96, 95% CI 0.81-1.12) [52]. This finding was consistent with a prior study [53]. Digoxin In patients who cannot receive a beta blocker or are not adequately rate controlled despite their maximal-tolerated dose, and in whom rhythm control will not be attempted, digoxin may be considered. This may be relevant for patients with decompensated HF, in whom initiation or increase of beta blockers is contraindicated. If such a patient also has rapid AF requiring rate control, use of digoxin is suggested. However, digoxin is often ineffective when used alone. If two drugs are needed to control for long-term rate, we suggest adding digoxin to a beta blocker. Dosing and administration of digoxin are described separately. (See "Treatment with digoxin: Initial dosing, monitoring, and dose modification" and "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy".) Amiodarone In the event of inadequate rate control with beta blockers and/or digoxin, amiodarone can be used either alone or in combination with other rate control medications. We do not generally use amiodarone as a long-term rate control medication, but in the acute setting, it can assist with rate control as it is being loaded or can be used as a temporary rate control agent in patients who are unable to tolerate other therapies [43]. We exercise care when using amiodarone, especially in those without adequate anticoagulation since there is the possibility of pharmacologically restoring sinus rhythm. The usual maintenance dose of amiodarone from AF is 100 to 200 mg daily after a loading dose. Therapies that should be avoided for AF rate control and HFrEF include dronedarone, class IC drugs, and nondihydropyridine calcium channel blockers (verapamil and diltiazem). (See "Calcium channel blockers in heart failure with reduced ejection fraction" and "Drugs that should be avoided or used with caution in patients with heart failure".) Atrioventricular node ablation with pacing Rate control can also be achieved with radiofrequency ablation of the atrioventricular node and permanent pacemaker placement. This strategy may be useful in patients in whom rate control with antiarrhythmic drug or CA has failed or is contraindicated. Atrioventricular node ablation with pacing can be particularly helpful for patients with permanent AF. (See "Atrial fibrillation: Atrioventricular node ablation".) https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 17/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate If the LVEF is 45 percent or less and there is an expectation that ventricular pacing will occur more than 25 percent of the time, a biventricular, His bundle, or left bundle pacing system (also called cardiac resynchronization therapy) should be considered instead of a standard right ventricular pacing system. (See "Atrial fibrillation: Atrioventricular node ablation", section on 'Cardiac resynchronization therapy'.) In addition, atrioventricular node ablation may be necessary for some patients with HF and AF who are referred for cardiac resynchronization therapy for treatment of HF. This is because intact atrioventricular conduction may "override" pace and thus reduce efficacy of the cardiac resynchronization therapy device. In particular, atrioventricular node ablation may be beneficial for patients who are not pacing at least 90 percent with cardiac resynchronization therapy [54]. (See "Cardiac resynchronization therapy in atrial fibrillation", section on 'Role of atrioventricular node ablation in patients with heart failure and atrial fibrillation'.) Left bundle or His bundle pacing have also become options, although randomized controlled clinical trials have yet to definitively demonstrate an advantage of this approach versus a cardiac resynchronization therapy approach. Heart failure with preserved ejection fraction Our long-term management approach to patients with AF and HFpEF is similar to that of patients with AF and HFrEF. The main differences are with respect to the choice of specific rhythm and rate control medications. Rhythm control Rhythm control is the preferred long-term strategy for most patients. (See 'Evidence for cardiovascular benefit' above.) Antiarrhythmic therapy and CA approaches are similar in HFpEF and HFrEF. Some medication such as dofetilide and sotalol tend to have fewer complications in patients with preserved LVEF (See 'Rhythm control' above.) The efficacy and safety of CA have been evaluated in patients with diastolic HF. A meta-analysis of 12 retrospective cohort studies confirmed the safety of CA for patients with HFpEF; over a one- to three-year follow up, complications occurred in <1 percent of patients [55]. Fifty-eight percent of patients maintained sinus rhythm without using an antiarrhythmic medication. Admission for HF and all-cause mortality each occurred in 6 percent of patients. Rate control in heart failure with preserved ejection fraction For patients with AF and HFpEF, we attempt to maintain a resting heart rate of 80 bpm or less ("strict rate control"). Whereas some data indicate that faster rates may be acceptable (lenient rate control), this is not generally recommended. Exceptions include: https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 18/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate A patient with paroxysmal AF with frequent episodes of fast AF and slow, symptomatic rates when in sinus rhythm. A patient with permanent AF who is asymptomatic with resting rates as fast as 110 beats per minute. However, this group of patients has not been well studied. We typically start with a beta blocker. (See 'Medications' above.) In patients with HFpEF (but not HFrEF), we use a nondihydropyridine calcium channel blocker if a beta blocker is not tolerated. We use digoxin cautiously in HFpEF, but it can be helpful in combination with a beta blocker to control ventricular response rate, especially in older patients. Other strategies are similar to rate control strategies in patients with AF and HFrEF. (See 'Rate control in heart failure with reduced ejection fraction' above.) PROGNOSIS Observational studies present conflicting data as to whether AF is an independent predictor of mortality in patients with HF [6-8,56-59]. Most were performed several years ago and may not be as generalizable to current patients. However, two more recent studies suggest AF may be associated with increased mortality among patients with HF. A meta-analysis of 16 studies with nearly 54,000 patients showed that among patients with HF, AF was associated with modestly increased mortality (odds ratio of 1.4 among seven randomized trials of HF therapy; 1.15 among nine observational studies) [60]. A registry study of nearly one million patients with HF suggested that new-onset AF was associated with worse mortality than long-standing AF, over a follow-up period of over 13 years [61]. In this analysis, patients who developed new-onset AF had greater mortality than patients with long-standing AF (59 versus 49 percent). Among persons with HF and AF compared with persons with neither condition, the adjusted odds of death was 8.76 (95% CI 8.31 9.23). A post-hoc analysis of a beta blocker trial of nearly 2400 participants with HF showed that new- onset AF (in 190 patients) predicted worse HF-related outcomes [62]. In this study, participants with new-onset AF were at a higher risk of HF mortality (28 versus 23 percent, HR 2.0, 95% CI 1.50-2.67) and had more HF hospitalization days (average of 15 versus 7 days per patient) than those who did not develop AF. SOCIETY GUIDELINE LINKS https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 19/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults" and "Society guideline links: Heart failure in adults".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Basics topic (see "Patient education: Heart failure and atrial fibrillation (The Basics)") SUMMARY AND RECOMMENDATIONS Background and epidemiology Comorbid atrial fibrillation (AF) and heart failure (HF) is common. The prevalence of AF in patients with HF increases from 4 to 50 percent as HF functional class declines. (See 'Introduction' above and 'Epidemiology' above.) AF can impair myocardial atrial and ventricular function, which can both cause and worsen HF. (See 'mechanisms of cardiac dysfunction' above.) Acute management In all patients, we anticoagulate (irrespective of ejection fraction [EF] or whether a long-term rate or rhythm control management strategy is employed), treat acute HF decompensation with diuretics and vasodilators, and correct potential reversible causes of AF and HF. (See 'Acute decompensation' above.) In patients with AF and acute HF, we target rate control to <120 beats per minute; digoxin, amiodarone, and diltiazem are appropriate agents in this setting. (See 'Acute rate control' above.) https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 20/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate Cardioversion is rarely employed in the setting of AF with acute HF decompensation. (See 'Role of cardioversion' above.) Long-term management For most patients with AF and compensated HF, we suggest rhythm rather than rate control as an initial treatment strategy (Grade 2B). (See 'Long-term management' above.) A rate control strategy may be preferred in patients with long-standing AF or severe left atrial enlargement, as cardioversion is less likely to be successful or durable in these patients. A rate control strategy may also be reasonable for those unwilling to undergo the burdens of a rhythm control strategy, particularly if they tolerate AF well. (See 'Preference for rhythm over rate control' above and 'Rhythm control' above.) We employ a stepwise approach, including the following: Long-term anticoagulation Patients require anticoagulation prior to, during, and after electrical or pharmacologic cardioversion and catheter ablation (CA). (See "Atrial fibrillation in adults: Use of oral anticoagulants".) Cardioversion After acute stabilization, for nearly all patients with AF and HF, we suggest electrical cardioversion as initial treatment (Grade 2C). This can be done without an antiarrhythmic medication if this is the first episode of AF, AF is well tolerated, HF is not difficult to manage, and there is no hemodynamically significant mitral regurgitation or left atrial enlargement. (See 'Electrical cardioversion' above.) Antiarrhythmics For patients who return to persistent AF after electrical cardioversion or fail cardioversion, we suggest dofetilide (Grade 2C). Contraindications to dofetilide include QT prolongation, potassium fluctuations, and renal dysfunction. Amiodarone is a reasonable alternative for older individuals and sotalol for patients with mild renal dysfunction. (See 'Rhythm control' above.) Catheter ablation For patients with symptomatic AF who have HF without acute decompensation, and failure of antiarrhythmic drug therapy, we suggest CA of AF (Grade 2B). This recommendation assumes that the patient is a reasonable candidate. (See 'Catheter ablation' above.) Rate control If a rate control strategy is chosen in patients with HF with reduced EF (HFrEF), we recommend beta blockers rather than calcium channel blockers or digoxin as initial therapy (Grade 1B). (See 'Rate control in heart failure with reduced ejection fraction' above.) https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 21/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate We also suggest beta blocker therapy for rate control in patients with HF with preserved EF (HFpEF) (Grade 2C). Nondihydropyridine calcium channel blocker therapy is an alternative in patients with HFpEF who cannot tolerate or do not respond to beta blocker therapy. We use a heart rate goal of <85 beats per minute at rest and <110 beats per minute during moderate exercise (the strict approach). If this is not possible, the goal becomes <110 beats per minute at rest (the lenient approach). Lenient rate control goal is used more in patients with HFpEF. (See 'Rate control goal' above.) Atrioventricular node ablation with pacing For patients who fail a rate control strategy using medication and are either not candidates for or have failed a rhythm control strategy, atrioventricular node ablation with pacing is an effective therapeutic option. (See 'Atrioventricular node ablation with pacing' above and "Atrial fibrillation: Atrioventricular node ablation".) Prognosis AF is associated with an increased mortality and increased risk of HF progression. (See 'Prognosis' above.) ACKNOWLEDGMENT The UpToDate editorial staff thank Dr. Alan Cheng for his contributions as an author to prior versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Lip GY, Heinzel FR, Gaita F, et al. 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