7/6/23, 3:10 PM The management of atrial fibrillation in patients with heart failure - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. The management of atrial fibrillation in patients with heart failure : Brian Olshansky, MD : Wilson S Colucci, MD, Bradley P Knight, MD, FACC : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Sep 30, 2022. INTRODUCTION Atrial fibrillation (AF) is common among patients with heart failure (HF). This topic will focus on the acute and long-term management and prognosis of AF in patients with HF, including those with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). Our recommendations are similar to those made in the 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society guideline, its 2019 focused update, the 2021 guideline for AF management in HFrEF, and the joint European Heart Rhythm Association/Heart Failure Association consensus document on AF [1-5]. The general management of patients with HFrEF and HFpEF is discussed separately: (See "Overview of the management of heart failure with reduced ejection fraction in adults".) (See "Treatment and prognosis of heart failure with preserved ejection fraction".) The management of AF in HF for patients with specific cardiomyopathies and valvular disease are discussed separately: Hypertrophic cardiomyopathy. (See "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation", section on 'Treatment'.) Amyloid cardiomyopathy. (See "Amyloid cardiomyopathy: Treatment and prognosis".) https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 1/30 7/6/23, 3:10 PM The management of atrial fibrillation in patients with heart failure - UpToDate Valvular heart disease. (See "Rheumatic mitral stenosis: Overview of management", section on 'Management of atrial fibrillation' and "Medical management of asymptomatic aortic stenosis in adults", section on 'Atrial fibrillation' and "Indications for intervention for chronic severe primary mitral regurgitation".) EPIDEMIOLOGY The prevalence of AF in patients with HF varies from less than 10 to 57 percent, depending in part upon the severity of HF [6-11]. For instance, the prevalence of AF increases from 4 to 50 percent as the New York Heart Association functional class increases from I to IV [12-19]. (See "Predictors of survival in heart failure with reduced ejection fraction", section on 'NYHA functional class'.) However, AF was recently associated with heart failure with reduced ejection fraction (HFrEF) and HF with preserved EF (HFpEF) events, with no significant difference in the strength of association among these subtypes, and many comorbidities (eg, anemia, renal failure, hypertension, valvular disease, coronary artery disease, etc) may also contribute to the development of AF in HF patients [20]. The presence of either HF or AF increases the likelihood that the other will develop over time [21]. The temporal associations of AF and HF were studied in over 10,000 individuals in the Framingham Heart Study [22]: Among 1737 persons with new AF, 37 percent had HF. Among 1166 persons with new HF, 57 percent had AF. Of these, 41 percent had HFpEF and 44 percent had HFrEF (15 percent could not be classified). The presence of both AF and HF predicted greater mortality risk compared with having neither condition, particularly among individuals with HFrEF. (See 'Prognosis' below.) In the investigation from the Framingham Heart Study, prevalent AF was more strongly associated with incident HFpEF than HFrEF (hazard ratios [HRs] 2.34 versus 1.48) [21]. However, a more recent study of over 25,000 participants in the REGARDS cohort did not show differential associations between AF and the development of HFpEF compared with HFrEF (HR 1.87 and 1.67 respectively, p interaction = 0.58) [20]. MECHANISMS OF CARDIAC DYSFUNCTION https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 2/30 7/6/23, 3:10 PM The management of atrial fibrillation in patients with heart failure - UpToDate AF can impair myocardial function by multiple mechanisms that cause or worsen HF [23]. (See "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm".) Specific mechanisms include: Tachycardia, bradycardia, abrupt heart rate change, and irregular rhythm may decrease cardiac output. Persistent tachycardia may lead to arrhythmia-induced cardiomyopathy or can worsen a preexisting cardiomyopathy [24-26]. (See "Arrhythmia-induced cardiomyopathy" and "Arrhythmia-induced cardiomyopathy", section on 'Atrial fibrillation and atrial flutter'.) Loss of atrial systole prevents optimal ventricular filling. Patients with diastolic HF are especially symptomatic in AF since left ventricular (LV) filling is more dependent on atrial contraction. (See "Pathophysiology of heart failure with preserved ejection fraction".) AF can lead to maladaptive vasoconstriction from angiotensin II, norepinephrine, and other procoagulant biochemicals. The left atrial remodeling that occurs in AF can lead to atrial fibrosis, dilation and dysfunction (this is sometimes referred to as an atriopathy ). This can cause mitral and/or tricuspid regurgitation, which exacerbate HF. HF is also a risk factor for AF, possibly mediated by left atrial stretch. (See "Mechanisms of atrial fibrillation", section on 'Triggers of AF'.) GOALS OF THERAPY For patients with AF and HF, we set the following goals of therapy: Manage acute HF exacerbation Control symptoms; prevent cardiac dysfunction and subsequent HF and/or hemodynamic compromise Prevent arterial thromboembolism, particularly stroke Reduce mortality and cardiac hospitalization ACUTE DECOMPENSATION The general approach to managing acute HF decompensation with AF involves anticoagulation, treating the acute HF exacerbation, rate control to <120 beats per minute, correction of https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 3/30 7/6/23, 3:10 PM The management of atrial fibrillation in patients with heart failure - UpToDate reversible causes, and (only in rare instances) cardioversion. To manage acute decompensated HF with uncontrolled rates in AF, hospitalization is generally required. AF can precede an acute HF exacerbation, and uncontrolled HF can accelerate the ventricular response of AF or precipitate AF in patients in sinus rhythm. Symptoms Patients can present with sudden pulmonary congestion and an increase in the ventricular rate of AF, causing palpitations and shortness of breath and hypotension leading to dizziness or even syncope. Anticoagulation Prior to or concurrent with treating the acute HF exacerbation, we anticoagulate patients with AF and HF; if the patient has acute HF symptoms, we prioritize HF treatment. Because of the high risk of thromboembolism in these patients, we anticoagulate irrespective of ejection fraction (EF), whether or not a long-term rate or rhythm control management strategy is employed, and even if patient has a CHA DS -VASc score of 1 [27]. 2 2 However, if a patient has contraindications to anticoagulation such as a high risk of bleeding, we do not anticoagulate them. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation".) In addition, effective anticoagulation is required prior to, during, and after cardioversion, whether it be pharmacological or electrical. Details regarding anticoagulation and the role of transesophageal echocardiography prior to cardioversion in patients with AF are discussed separately. (See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation".) Acute heart failure management We treat HF with diuretics, vasodilators, and other measures as appropriate. This is discussed separately. (See "Treatment of acute decompensated heart failure: Specific therapies", section on 'Initial therapy'.) As part of acute HF management in patients with AF, we also slow the ventricular response. Acute rate control We aim to reduce the ventricular rate to <120 beats per minute. We do not rate control to lower ventricular rates until the acute HF exacerbation is stabilized, as patients may need a higher heart rate to maintain their cardiac output. Our specific approach to acute rate control differs for patients with HFrEF and HFpEF. HF with reduced EF (HFrEF) For patients with HFrEF, we use intravenous (IV) amiodarone, IV digoxin, (and rarely IV diltiazem) to acutely control the heart rate. After starting the medication, we continually reassess the heart rate and titrate the medication https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 4/30 7/6/23, 3:10 PM The management of atrial fibrillation in patients with heart failure - UpToDate to achieve the goal heart rate of <120 beats per minute. Usually, we try the medication for one to two days, and if the heart rate remains elevated, we attempt another agent. The choice of medications is usually influenced by practitioner familiarity. Amiodarone has very little negative inotropic activity and is usually more effective than digoxin. However, amiodarone and IV diltiazem can both cause hypotension. Amiodarone is associated with conversion to sinus rhythm in a small percent of patients, which is of concern if the patient is not anticoagulated. We usually avoid diltiazem due to its negative inotropic effect that might further compromise cardiac contractility. (See "Amiodarone: Clinical uses".) Amiodarone dosing for AF rate control in all patients and among critically ill patients is presented separately. Dosing is similar for AF in patients with HF. (See "Amiodarone: Clinical uses", section on 'Ventricular rate control in critically ill patients with atrial fibrillation and rapid ventricular response'.) Digoxin dosing for AF rate control usually includes IV loading followed by a maintenance oral dose. Oral loading is also possible. (See "Treatment with digoxin: Initial dosing, monitoring, and dose modification", section on 'Rapid digoxin loading'.) Diltiazem dosing in the acute setting is discussed separately. We generally avoid beta blocker therapy in patients with AF and acute decompensated HF. In such patients, the negative inotropic properties of a beta blocker may worsen the clinical condition. The use of beta blockers for long-term control of heart rate in AF is discussed separately. (See "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy", section on 'Urgent therapy' and 'Rate control in heart failure with reduced ejection fraction' below and 'Rate control in heart failure with preserved ejection fraction' below and "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy".) HF with preserved EF (HFpEF) In HFpEF patients who present with congestion or hypotension, rate control can be attempted first with IV diltiazem (which may be better tolerated in patients with borderline hypotension) or IV beta blockade. We consider these agents to be equally effective at rate control of AF in patients with HFpEF. With both medications, hypotension is a potential side effect. Diltiazem dosing in the acute setting is discussed separately. For the acute control of ventricular rate, IV beta blockade with metoprolol, propranolol, or esmolol can be effective. Specific dosing information for these medications is presented separately. Specific dosing information is discussed separately. https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 5/30 7/6/23, 3:10 PM The management of atrial fibrillation in patients with heart failure - UpToDate Correction of reversible causes In some patients, there is a reversible cause of AF, HF, or both. These are reviewed separately. (See "Pathophysiology of heart failure with preserved ejection fraction", section on 'Decompensated HFpEF' and "Overview of the management of heart failure with reduced ejection fraction in adults", section on 'Management of causes and associated conditions' and "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Triggers'.) Etiologies that are specific to AF and HF include: If a patient with existing AF develops new HF, a possible diagnosis to consider is arrythmia- induced cardiomyopathy from inadequate rate control. (See "Arrhythmia-induced cardiomyopathy".) If a patient develops new-onset AF and HF concurrently, thyrotoxicosis should be considered as a diagnostic possibility. (See "Cardiovascular effects of hyperthyroidism", section on 'Heart failure' and "Cardiovascular effects of hyperthyroidism", section on 'Atrial fibrillation'.) Role of cardioversion We rarely consider an initial cardioversion for treatment of patients with acute decompensated HF; there is a low probability of successful or durable cardioversion unless the HF decompensation is first corrected. However, cardioversion (generally electrical) may be helpful in the following circumstances: Initial attempts to decrease pulmonary congestion with diuretics, vasodilators, and rate control have failed. AF is thought to be the cause of acute HF decompensation, ie, the onset of AF has recently preceded the HF exacerbation. In such patients, even if the rate is well controlled, cardioversion may be helpful in managing HF. Patients with persistent evidence of myocardial ischemia. This scenario assumes that the patient does not require urgent reperfusion or other stabilizing therapies for acute coronary syndrome. (See "Overview of the acute management of ST-elevation myocardial infarction", section on 'Choosing and initiating reperfusion with PCI or fibrinolysis' and "Overview of the acute management of non-ST-elevation acute coronary syndromes", section on 'Choosing a revascularization strategy'.) In patients with HFpEF, it can be difficult to tell if the HF is predominantly due to AF or some other cause. https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 6/30 7/6/23, 3:10 PM The management of atrial fibrillation in patients with heart failure - UpToDate An important potential harm of cardioversion in this setting is the risk of a thromboembolic event in nonanticoagulated patients. We almost always avoid cardioversion (even in patients with hemodynamic instability or cardiogenic shock) if the patient is not adequately anticoagulated (ie, has not been on therapeutic, uninterrupted, chronic anticoagulation for at least one month prior). For patients in whom urgent cardioversion is being considered despite inadequate anticoagulation, a transesophageal echocardiogram should be considered to evaluate for a left atrial or left atrial appendage thrombus. (See 'Anticoagulation' above and "Role of echocardiography in atrial fibrillation", section on 'Transesophageal echocardiography'.) We avoid cardioversion in patients with long-standing persistent or permanent AF, who have failed cardioversion, or who have had early recurrence of AF after cardioversion with additional antiarrhythmic therapy. LONG-TERM MANAGEMENT Long-term anticoagulation We continue anticoagulation that was started during acute management, transitioning to oral anticoagulation as appropriate. If anticoagulation was not started during the acute management phase, and if there are no contraindications, we start anticoagulation. Because of the high risk of thromboembolism in these patients, we anticoagulate irrespective of ejection fraction (EF), whether or not a long-term rate or rhythm control management strategy is employed, and even if a patient has a CHA DS -VASc score of 1 2 2 [27]. (See "Atrial fibrillation in adults: Use of oral anticoagulants".) Novel oral anticoagulants, instead of warfarin, are often used for effective anticoagulation. There is increased risk of bleeding when these anticoagulants are used concomitantly with amiodarone or other medications [28-31]. Preference for rhythm over rate control Although the first management approach in acute decompensated AF with HF is often rate control, rhythm control is our preferred long-term management strategy for most patients. This includes patients with recent-onset AF, persistent HF even when rate controlled, or inadequate rate control. (See 'Acute decompensation' above.) Potential exceptions to this approach are noted below. (See 'Exceptions' below.) Evidence for cardiovascular benefit Specific reasons for returning the patient to sinus rhythm are to establish a symptom-rhythm correlation; this helps to establish if AF is a specific trigger or contributing factor for a patient's HF symptoms and/or worsening HF. A return to sinus rhythm can also improve cardiac function, increase exercise tolerance, and alleviate HF symptoms. https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 7/30 7/6/23, 3:10 PM The management of atrial fibrillation in patients with heart failure - UpToDate Some evidence suggests that early rhythm control (ie, within one year) is beneficial for improved five-year cardiovascular outcomes in patients with HF (either HF with preserved EF [HFpEF] or reduced EF [HFrEF]). In a prespecified subanalysis of the EAST-AFNET 4 randomized trial, over 750 patients with symptomatic HF were randomly assigned to early rhythm control or usual care (which included rhythm control for symptoms) [32]. The following was observed: The composite outcome of cardiovascular death, stroke, or hospitalization for HF or acute coronary syndrome occurred less often in patients in the early rhythm control versus usual care group (5.7 versus 7.9 per 100 patient-years; hazard ratio [HR] 0.74, 95% CI 0.56-0.97). Kaplan-Meier curves showed that event rates in the two treatment groups began to separate at six months. The two treatment groups had similar rates of all-cause mortality (9.9 versus 11.8 percent). Left ventricular EF (LVEF) improved in both groups (approximately 5 percent increase). The primary safety outcome (death, stroke, or serious adverse events related to rhythm control therapy) was similar between treatment groups (17.9 versus 21.6 percent, HR 0.85, 95% CI 0.62-1.17). Some limitations of EAST-AFNET 4 should be mentioned. The usual care assigned to the control group in EAST-AFNET 4 may not be generalizable, as it may not reflect standard treatment of AF in patients with HF. Also, patients assigned to rhythm control received a variety of therapies; only 19 percent received catheter ablation (CA). In the subsequent RAFT-AF trial, results were similar, although the trial was stopped early for futility and did not have statistically significant findings. Four hundred and eleven patients with HF and a high burden of AF were randomly assigned to either CA-based rhythm control or rate control and followed for mortality and HF events [33]. Patients assigned to rhythm control had a lower mortality and HF events compared with the rate control group, but the results were not statistically significant (23.4 versus 32.5 percent; HR 0.71, 95% CI 0.49-1.03). Patients in the rhythm control group also had greater improvements in LVEF (increase of 10 versus 4 percent), six-minute walk test, and HF- and AF-related quality of life. The CA-related adverse event rate was high at 11 percent. An additional limitation of this study was the lack of statistical power to detect a potential protective effect of therapy; the study was unable to recruit the anticipated number of participants due to restrictions on clinical research during the COVID-19 pandemic. Four small randomized trials, each with methodological limitations, and one observational study have compared CA with rate control in patients with HF and also found benefit [34-38]. (See "Atrial fibrillation: Catheter ablation", section on 'Efficacy' and 'Catheter ablation' below.) https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 8/30 7/6/23, 3:10 PM The management of atrial fibrillation in patients with heart failure - UpToDate A previous trial (AF-CHF) did not find a significant benefit for long-term pharmacologic rhythm control compared with rate control in patients with HFrEF and AF [39,40]. It is important to recognize that CA was not a strategy tested in the AF-CHF trial, whereas 19 percent of patients in the rhythm control arm had CA in the EAST-AFNET 4 trial. Furthermore, in AF-CHF, the patients all had severe LV systolic dysfunction. These key differences may underline why the results in AF- CHF were null in contrast to the EAST-AFNET 4 trial described above, in which early rhythm control was beneficial. Exceptions A rate control strategy may be preferred in patients with longstanding AF or severe left atrial enlargement. In these cases, the cardioversion is much less likely to be successful or durable. Also, for patients with severe valvular disease (such as severe mitral regurgitation), cardioversion is less likely to be successful in maintaining sinus rhythm and reducing symptoms. A rate control strategy may also be reasonable in an older patient who is unwilling to undergo the burdens of a rhythm control strategy, particularly if they tolerate AF well. Some patients will not want to be placed on antiarrhythmic medications or undergo invasive procedures. In these patients, a rate control strategy may be pursued. If a patient has a contraindication to anticoagulation, a rate control strategy may also be preferred. Heart failure with reduced ejection fraction Rhythm control Conversion to and maintenance of sinus rhythm can be achieved with electrical cardioversion, antiarrhythmic drug therapy, CA, or surgical ablation [21]. Generally, we approach attempts at rhythm control in a step-wise fashion as outlined in the sections that follow. (See 'Preference for rhythm over rate control' above.) Rhythm control is less effective in patients with persistent AF (which is common among patients with HF) or with severe left atrial enlargement (a marker of AF chronicity). Electrical cardioversion For nearly all patients, we first try electrical cardioversion (this can be done in conjunction with antiarrhythmic medication, which can increase the likelihood of maintaining sinus rhythm, or it can be performed without such a medication). We generally perform the initial electrical cardioversion without an antiarrhythmic medication if this is the first episode of AF, if AF is well tolerated, if HF is not difficult to manage, and if there is no hemodynamically significant mitral regurgitation or left atrial enlargement. Patients require appropriate anticoagulation prior to, during, and after cardioversion. (See 'Anticoagulation' above.) https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 9/30 7/6/23, 3:10 PM The management of atrial fibrillation in patients with heart failure - UpToDate Electrical cardioversion is not appropriate in those who have short episodes of paroxysmal AF and for those in whom HF exacerbation is unlikely to be due to the AF. However, we use cardioversion if paroxysmal AF episodes last days, if there is precipitous change in condition, and if patients do not respond to an antiarrhythmic drug. After initial cardioversion, the majority of patients will have recurrent AF unless it was due to an acute precipitant that is no longer present (eg, acute pulmonary edema, myocardial infarction, pulmonary embolus, cardiac surgery). If a patient reverts to AF after cardioversion, we may try another cardioversion, this time with an antiarrhythmic medication (initiated prior to cardioversion) in order to help the patient maintain sinus rhythm. In some patients, we attempt cardioversion multiple times. Considerations include the likelihood of maintaining sinus rhythm, the time course of AF recurrence, patient symptom burden, and need for improvement of patient hemodynamics. We also try to balance these with the patient's overall preference to be in sinus rhythm. For example, if AF seems to be related to acute HF decompensation or other adverse event, repeat cardioversions are appropriate. If repeat cardioversions are not successful, we may use antiarrhythmic drugs and/or CA to maintain sinus rhythm. Antiarrhythmic drugs In nearly all patients with HFrEF who have recurrent AF after cardioversion, we use an antiarrhythmic drug to help maintain sinus rhythm or to facilitate cardioversion if the cardioversion is not successful in achieving sinus rhythm. We always ensure the patient is appropriately anticoagulated. (See 'Anticoagulation' above.) We use dofetilide, sotalol, or amiodarone as the initial antiarrhythmic medication in patients with persistent AF and HF. Some experts prefer to try dofetilide first, especially in patients who are younger and have preserved kidney dysfunction. Other experts prefer to use amiodarone, given its ease of use. Dofetilide is more likely to cause the potentially life-threatening ventricular arrhythmia "torsades de pointes" in patients with HF with severe systolic dysfunction than amiodarone and in those with acute decompensation. Therefore, dofetilide is safer to use in patients with HF and milder systolic dysfunction, as well as those patients who have an implantable cardiac defibrillator, as these devices can prevent sudden cardiac arrest from ventricular arrhythmia. Prior to using dofetilide, during its initiation, and subsequent to initiation, measurements of QT intervals are necessary. (See "Clinical use of dofetilide", section on 'Safety' and "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Sotalol can worsen HF in those with HFrEF due to the beta-blocking effects and is not recommended for patients with markedly impaired LV function and acute decompensated https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 10/30 7/6/23, 3:10 PM The management of atrial fibrillation in patients with heart failure - UpToDate HF. Sotalol can cause the potentially life-threatening arrythmia torsade de pointes, and thus prior to using the drug and after it is initiated, measurements of QT intervals are necessary. If the baseline QTc is greater than 450 msec, sotalol is contraindicated. Other details regarding sotalol initiation and QTc monitoring are discussed separately. (See "Clinical uses of sotalol", section on 'Dosing' and "Clinical uses of sotalol", section on 'Proarrhythmia'.) We avoid propafenone, dronedarone, and flecainide because of worse outcomes in HFrEF patients. The following provides evidence for the efficacy of specific pharmacotherapy in AF and HF: Dofetilide Dofetilide, a class III antiarrhythmic drug, can be effective and safe for preventing recurrent persistent AF in patients with HF. It may also be used to convert patients to sinus rhythm. The recommended dose of dofetilide is 500 micrograms twice daily in the absence of renal insufficiency, but it is adjusted based on renal function. Patients need to be hospitalized for dofetilide initiation. Further information regarding the initiation protocol and safety of dofetilide is discussed separately. (See "Clinical use of dofetilide".) In the DIAMOND-CHF trial, 390 patients with AF and symptomatic HF were randomly assigned to dofetilide or placebo [41]. Dofetilide was more likely to be associated with conversion to sinus rhythm at one month (12 versus 1 percent) and maintenance of sinus rhythm at one year (44 versus 13 percent; HR 0.35, 95% CI 0.22-0.57). Mortality did not differ between treatment groups (41 versus 42 percent; HR 0.95, 95% CI 0.81-1.11). In a separate investigation, among 500 patients with HFrEF and AF in the DIAMOND-HF and DIAMOND-MI studies, dofetilide was more likely than placebo to lead to conversion to sinus rhythm (59 versus 34 percent) and to maintain sinus rhythm at one year (79 versus 42 percent; relative risk 0.30, 95% CI 0.19-0.48) [42]. (See "Clinical use of dofetilide".) The most important side effect of dofetilide was torsades de pointes, which was seen in 25 cases (3.3 percent); three-quarters of episodes occurred within the first three days while the patient was in the hospital [42]. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes", section on 'Definitions'.) Amiodarone When used for preventing recurrence of AF, advantages of low-dose amiodarone include no negative inotropic effect and little or no proarrhythmia. Advantages of amiodarone compared with dofetilide include the ability to start therapy as an outpatient (for AF), once-a-day dosing, and a lower risk of torsades de pointes. In addition, https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 11/30 7/6/23, 3:10 PM The management of atrial fibrillation in patients with heart failure - UpToDate since amiodarone has non-competitive beta-blocking and calcium channel antagonist activity, the ventricular rate is usually slow and well tolerated if AF does recur. The recommended dose of amiodarone is 400 mg/day. Occasionally, less than 200 mg/day is used (eg, for patients at high risk of side effects or toxicities). (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring", section on 'Adverse drug interactions'.) Its use in HF patients does not necessarily require hospitalization, but careful monitoring of the prothrombin time international normalized ratio is necessary, as amiodarone can potentiate the effects of warfarin. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring", section on 'Adverse drug interactions'.) The efficacy of amiodarone in AF and HF was illustrated in a subset analysis from the CHF- STAT trial of over 660 patients in which 15 percent of patients had AF at baseline [43]. Among these 103 patients, 51 were randomly assigned to amiodarone and 52 to placebo. Patients assigned to amiodarone had a higher likelihood of converting to sinus rhythm (31 versus 8 percent). Patients who converted to sinus rhythm with amiodarone had a lower mortality than those who did not. However, it is not clear if reductions in mortality were because patients who converted were less sick to begin with or if restoration of sinus rhythm was causative. Complications associated with amiodarone loading and long-term therapy in patients with HFrEF and AF include bradycardia requiring permanent pacemaker, hypothyroidism, and neurotoxicity [44]. Side effects with maintenance therapy are less likely with lower doses but still occur. Sotalol Sotalol should be used with caution in patients with HF who have poor LV function (LVEF <30 percent) based on increased risk for torsades de pointes [45]. This is especially true if there are marked fluctuations in electrolyte levels, acute or decompensated HF, or renal dysfunction. (See "Drugs that should be avoided or used with caution in patients with 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 7/6/23, 3:10 PM 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 7/6/23, 3:10 PM 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 7/6/23, 3:10 PM 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