Management of new onset atrial fibrillation Last literature review version 19.

2: maggio 2011 | This topic last updated: febbraio 16, 2011 (More) INTRODUCTION New onset atrial fibrillation (AF) is atrial fibrillation identified for the first time by an electrocardiogram or other electrocardiographic rhythm recording device, such as ambulatory or inpatient monitoring. There is overlap between new onset, acute, and first identified atrial fibrillation, but each represents a distinct clinical presentation with unique features mandating different assessments and management. Typical symptoms associated with new onset atrial fibrillation include palpitations, a sense of the heart racing, an irregular pulse, fatigue, lightheadedness, increased urination, weakness, and mild shortness of breath. More severe symptoms and signs include dyspnea, angina, hypotension, and presyncope. Infrequently, myocardial infarction, syncope, or pulmonary edema may occur. In addition, some patients present with an embolic event (particularly stroke) or the insidious onset of right-sided heart failure (as manifested by peripheral edema, weight gain, and ascites). Occasionally, the first detection of AF will occur incidentally and in the absence of symptoms at the time or during a routine examination or on an electrocardiogram obtained for other reasons, but such episodes may be present for extended periods or simply missed on prior examinations. Rarely, a patient with arterial thromboembolism is found only in retrospect to have new onset atrial fibrillation. Episodes at presentation can be paroxysmal and stop spontaneously, persistent and stop only with cardioversion, or permanent and present for prolonged periods. This topic will address the following management decisions, which need to be made soon after a patient presents with new onset AF: Is cardioversion indicated and if so should it be urgent? When and how should rate control be carried out? Who should be anticoagulated immediately and how? Does the patient need hospitalization? Are there any correctable causes of atrial fibrillation? What should be done with the patient who spontaneously converts to sinus rhythm?

More detailed discussions of these issues, as well as the causes, evaluation, and general management of AF, including the role of anticoagulation and rhythm versus rate control, particularly as they apply to patients with paroxysmal or permanent AF, are found elsewhere. (See "Epidemiology of and risk factors for atrial fibrillation" and "Overview of atrial fibrillation" and "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation" and "Rhythm control versus rate control in atrial fibrillation".)

Important first steps For those patients in whom the diagnosis of new onset atrial fibrillation is made in an office setting and who may need either urgent cardioversion (either electrical or chemical) or parenteral anticoagulant therapy, timely transfer to a facility with those capabilities should be carried out. A complete history and physical examination should be performed in all patients with new onset AF. Old records should be searched for evidence of a prior episode of AF or other atrial tachyarrhythmias. (See "The electrocardiogram in atrial fibrillation".) INDICATIONS FOR URGENT CARDIOVERSION Four circumstances for which urgent or emergent cardioversion may be needed (table 1 and algorithm 1) include: Active ischemia (symptomatic or electrocardiographic evidence) Evidence for organ hypoperfusion Severe manifestations of heart failure (HF) including pulmonary edema (see "Atrial fibrillation in patients with heart failure") The presence of a preexcitation syndrome, which may lead to an extremely rapid ventricular rate due to the presence of an accessory path. In a patient with any of these indications for urgent cardioversion, the need for restoration of normal sinus rhythm (NSR) takes precedence over the need for protection from thromboembolic risk. Intravenous anticoagulation with heparin should be started, but it should not cause a delay in emergent cardioversion. However, these four circumstances differ with regard to the urgency of cardioversion and in most cases rate control is possible as a temporizing measure. Further, indiscriminate cardioversion may have dire consequences or be futile if the cause for the initiation of the problem is not at least in part corrected (eg, immediate cardioversion in a patient with pulmonary edema will be dangerous to the patient and may not be effective without diuresis, oxygen, blood pressure control and other measures). Careful review of comorbidities and absolute need for immediate cardioversion must be weighed against its benefits as the atrial fibrillation may not be the cause but the consequence of the initiating process. Cardioversion of patients with AF is discussed elsewhere. (See "Restoration of sinus rhythm in atrial fibrillation", section on 'DC cardioversion'.) EVALUATION FOR AN UNDERLYING CAUSE When faced with a patient who presents with new onset AF (particularly if the ventricular response is rapid), there should be a quick assessment for an underlying cause, such as heart failure (HF), pulmonary problems, poorly controlled blood pressure, or hyperthyroidism. Therapy for a precipitating cause should be initiated prior to cardioversion in stable patients and may result in reversion to sinus rhythm. (See "Epidemiology of and risk factors for atrial fibrillation".)

The following tests, in addition to the electrocardiogram, should be performed on patients with new onset AF: Vital signs including oxygen saturation (in the ER setting and beyond) AF is rarely the only manifestation of an acute coronary syndrome, although AF with a rapid ventricular response and hypotension can provoke demand ischemia with or without angina. We suggest evaluation of myocardial infarction with serial troponin measurements, especially in patients with ECG changes, hypotension, symptoms, history or additional risk factors. Evaluation to rule out myocardial infarction may not be effective, however, or cost effective in patients without signs or symptoms present suggesting ischemia. Thyroid stimulating hormone (TSH) and free T4. These should be obtained even if there are no symptoms suggestive of hyperthyroidism (and if thyroid function has not been measured recently), since the risk of AF is increased up to threefold in patients with subclinical hyperthyroidism (figure 1). The latter disorder is characterized by low serum TSH (<0.5 mU/L with the newer sensitive assays) and normal serum free T4. (See "Subclinical hyperthyroidism".) Serum electrolytes and assessment of renal function Complete blood count A transthoracic echocardiogram should be performed to screen for cardiac causes of new onset atrial fibrillation, even in the face of a normal physical examination. Chest x-ray Other blood tests dependent on underlying comorbidities and based on medical therapies prescribed. ANTICOAGULATION This section will address the role of antithrombotic therapy in patients with new onset AF. The larger discussions of anticoagulation surrounding cardioversion and recommendations for the use of long-term antithrombotic therapy in patients with more than one episode of AF are found elsewhere. (See "Anticoagulation prior to and after restoration of sinus rhythm in atrial fibrillation" and "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation", section on 'Antithrombotic prevention'.) Patients requiring delayed cardioversion For most patients in whom the duration of new onset AF is suspected to be more than 48 hours (or when the duration is unknown), the risk of embolization is measurably increased. (See "Anticoagulation prior to and after restoration of sinus rhythm in atrial fibrillation", section on 'Left atrial thrombus'.) In these patients, it is preferable to anticoagulate and use transesophageal echo (TEE) to rule out left atrial thrombi. If TEE is not readily available, then anticoagulation for approximately three to four weeks is preferable before attempted cardioversion to allow any left atrial thrombi to resolve [1]. (See "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation" and "Anticoagulation prior to and after restoration of sinus rhythm in atrial fibrillation", section on 'AF of more than 48 hours duration'.)

This recommendation includes patients with a low CHADS2 score (0 or 1). While there is little published evidence that the risk of embolization after planned (either chemical or electric) cardioversion is greater than after spontaneous reversion, some of our authors and reviewers are concerned that delayed return of atrial mechanical function (atrial stunning) after electrical cardioversion could increase the risk of a thromboembolic event after this approach with cardioversion [2,3]. In this case, even with the lower CHADS2 score, oral anticoagulation is recommended for three to six weeks. Other patients for whom delayed cardioversion and anticoagulation is reasonable include those whose AF duration is less than 48 hours and who have: Associated mitral valve disease or significant cardiomyopathy or HF. A prior history of a thromboembolic event. Transesophageal echocardiography evidence of left atrial thrombus [4]. (See 'Role of TEE' below and "Role of echocardiography in atrial fibrillation".) When warfarin is chosen as the anticoagulant, the recommended target international normalized ratio (INR) is 2.5 (range 2.0 to 3.0) [5,6]. This issue is discussed in detail elsewhere. (See "Anticoagulation prior to and after restoration of sinus rhythm in atrial fibrillation".) Role of TEE Among patients with AF of recent onset (but more than 48 hours or unknown duration) who are not being anticoagulated, an alternative approach to three to four weeks of warfarin therapy (or dabigatran) before cardioversion is transesophageal echocardiography (TEE)-based screening with cardioversion performed if no thrombi are seen (table 2A-B) [5-8]. This regimen may be of particular use in the patient who requires hospitalization or has an increased risk of hemorrhagic complications during prolonged anticoagulant therapy [9,10]. (See "Anticoagulation prior to and after restoration of sinus rhythm in atrial fibrillation", section on 'TEE-based therapy'.) The ACUTE trial directly compared a TEE-guided strategy (anticoagulation with heparin immediately before TEE or with oral warfarin for five days [target INR 2.0 to 3.0] before TEE, followed by cardioversion and then warfarin for four weeks after cardioversion), with a conventional strategy (three weeks of anticoagulation before cardioversion, followed by four weeks of anticoagulation after cardioversion) in 1222 patients with AF of more than two days duration who were undergoing electrical cardioversion [8]. There was no difference between the two groups in the incidence of ischemic stroke, TIA, or all embolic events within eight weeks of cardioversion (0.8 versus 0.5 percent for the conventional strategy). However, patients undergoing the TEE-guided strategy had a lower, but not significant, incidence of hemorrhagic events (2.9 versus 5.5 percent) a shorter mean time to cardioversion (3 versus 30.6 days), and a greater incidence of successful reversion (71 versus 65 percent). Early cardioversion or spontaneous reversion There is only a small amount of observational evidence that can be used to formulate recommendations regarding the

approach to anticoagulation in patients who present with new onset AF of less than 48 hours duration. With the exception of certain high-risk patients, the embolic risk appears to be very low if cardioversion is performed within two days of the onset of AF. (See "Anticoagulation prior to and after restoration of sinus rhythm in atrial fibrillation", section on 'AF of less than 48 hours duration'.) Some experts have recommended cardioversion without anticoagulation or a transesophageal echocardiogram (TEE) prior to or following cardioversion in patients with new onset AF of less than 48 hours duration. The logic for doing so is that the risk of bleeding from anticoagulation is probably greater than the risk of embolization (particularly in those with CHADS2 scores of 0 or 1), and the risk of thromboembolic events from short duration of atrial fibrillation appears to be relatively low (but not zero). Others start intravenous heparin or low molecular weight heparin before cardioversion and continue it for at least 24 hours after the procedure. (See "Therapeutic use of heparin and low molecular weight heparin", section on 'Bleeding'.) In addition, our authors and reviewers differ on the approach to long-term anticoagulation in these patients, with some suggesting no oral anticoagulation for the first episode of AF (less than 48 hours duration) and others suggesting warfarin for patients with CHADS2 scores of two or greater. Guidelines from the American College of Cardiology/American Heart Association and the American College of Chest Physicians suggest periprocedural heparin in patients with new onset AF of less than 48 hours duration, but make weak recommendations against the use of prolonged anticoagulation (three weeks) [5,11,12]. The 2011 European Society of Cardiology guidelines for the management of AF make a weak recommendation for periprocedural heparin in all such patients, as well as long-term oral anticoagulant in patients at high risk of stroke [13]. Our authors and reviewers believe it is reasonable to defer cardioversion and start oral anticoagulation in selected patients with AF of less than 48 hours in whom cardioversion is planned. Longer duration of AF prior to cardioversion (for example 40 hours as opposed to 10 hours) or a higher CHADS2 score are two reasons to lower the threshold for the initiation of anticoagulation. INITIAL RATE CONTROL WITH MILD TO MODERATE SYMPTOMS Most patients with acute AF do not require urgent cardioversion. Initial treatment directed at slowing the ventricular rate will usually result in improvement or resolution of the associated symptoms. Even for patients with minimal symptoms, rate control should be carried out to block a more rapid ventricular response as a result of a new trigger, such as anxiety, caffeine, or hypovolemia. We believe that attempting to get the rate below 110 beats per minute is reasonable. (See "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy", section on 'Rate control goals'.) As noted above, this can be achieved with beta blockers, calcium channel blockers (primarily verapamil and diltiazem), and/or digoxin. Occasionally, IV amiodarone may be needed for

patients with poor left ventricular function. The drug selected and the route of administration (oral versus intravenous) are dictated by the clinical presentation (table 3A-B). (See "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy".) Diltiazem, a beta blocker, or verapamil is the preferred drug in the absence of HF, since digoxin is less likely to control the ventricular rate during exercise (when vagal tone is low and sympathetic tone is high), has little ability to terminate the arrhythmia, and often does not slow the heart rate in patients with recurrent AF. Intravenous amiodarone may help control rate when the other drugs are ineffective or cannot be given. Digoxin is the preferred drug ONLY in patients with AF due to HF. (See "Atrial fibrillation in patients with heart failure", section on 'Rate control'.) In addition to the direct vagotonic effect of digoxin on the atrioventricular (AV) node (which may require several hours to become apparent), the improvement in left ventricular function and systemic hemodynamics result in withdrawal of sympathetic tone and a further decrease in the ventricular rate. Not infrequently, the improvement in hemodynamics results in reversion of the arrhythmia. Digoxin can also be used in patients who cannot take or who respond inadequately to beta blockers or calcium channel blockers. The effect of digoxin is additive to both of these drugs. Procainamide IV is recommended for rate control and for attempt to cardiovert atrial fibrillation with preexcitation when urgent cardioversion is not available or recommended. Intravenous amiodarone is an alternative option. Intravenous AV nodal blockers, in particular digoxin and verapamil, are contraindicated in patients with atrial fibrillation and preexcitation. Beta blockers and nondihydropyridine calcium channel blockers are also effective if HF or hypotension is due to the rapid ventricular rates and should be given intravenously if rates exceed 140 beats/minute or are not well tolerated but not in need of urgent arrhythmic cardioversion. If, however, there is doubt about the origin of the HF, the initial dose should be small (since these drugs impair contractility), with upward titration based upon heart rate slowing, blood pressure, and symptomatic improvement. The decision between intravenous or oral therapy depends on the clinical presentation and the need and urgency for controlling the rate. The choice between a beta blocker, diltiazem, and verapamil is frequently based upon physician and patient preference, although it may be influenced by other problems that are present. As an example, beta blockers are particularly useful when the ventricular response increases to inappropriately high rates during exercise, after an acute MI, and when exerciseinduced angina pectoris is also present. Intravenous beta blockade is more effective than intravenous calcium channel blockade for rate control, but also for conversion to sinus rhythm especially after cardiac surgery. If there is a question about tolerance of the beta blocker, a short-acting drug with a short half-life would be recommended. On the other hand, a calcium

channel blocker is preferred in patients with chronic lung disease. The use of both a beta blocker and calcium channel blocker is reasonable when rate control is not adequate with single therapy. Careful monitoring is required to prevent excess AV nodal blockade, hypotension, and precipitation of heart failure. CARDIOVERSION The next step after control of the ventricular rate in patients with recent onset AF, who are hemodynamically stable (with only mild to moderate symptoms), is deciding whether an attempt will be made to cardiovert the patient and if so when. We believe that most patients with symptomatic new onset atrial fibrillation should have at least one attempt at cardioversion (either electrical or chemical) to sinus rhythm, particularly after reversible causes have been identified and corrected. The rationale for cardioversion is that some patients will never have a second episode, or will have very infrequent episodes; cardioversion will likely improve symptom status, particularly in young people. Circumstances in which it is reasonable to not attempt cardioversion in a patient with new onset AF include: Patients who are completely asymptomatic, particularly those who are very elderly (>80 years) with multiple comorbidities, where risks of undergoing cardioversion and/or pharmacologic rhythm control may outweigh the benefits of restoring sinus rhythm. A patient with a high CHADS2 (table 4) score who has a bleeding risk and cannot be anticoagulated during and after cardioversion. The timing of cardioversion (except in patients who are unstable) is determined in large measure by the duration of the episode. There is a low risk of systemic embolization if the duration of the arrhythmia is 24 hours or less (and the risks are acceptable up to 48 hours) and there are no cardiac abnormalities (particularly mitral valve disease or significant left ventricular enlargement due to a cardiomyopathy) on transthoracic echocardiography [14]. Most patients with new onset AF of longer than 48 hours duration should have cardioversion postponed. (See 'Early cardioversion or spontaneous reversion' above.) The choice of electrical or pharmacologic cardioversion depends upon the comfort of the clinician to use one or the other approach. Longer durations of the arrhythmia are less likely to respond to antiarrhythmic drug therapy for conversion (table 5). For patients with paroxysmal episodes of atrial fibrillation, drug therapy is preferred if they will have sinus rhythm maintained with long-term antiarrhythmic drug therapy, and as patients with paroxysmal atrial fibrillation will likely convert anyway with or without electrical cardioversion. For persistent episodes, electrical cardioversion is preferred. In some patients, antiarrhythmic drugs are administered prior to cardioversion to increase the chance of successful reversion and to prevent early, intermediate, and late recurrence (table 6). Our recommendations for cardioversion are found elsewhere. (See "Restoration of sinus rhythm in atrial fibrillation".) Antiarrhythmic therapy after reversion to sinus rhythm We agree with the American Association of Family Practice/American College of Physicians (AAFP/ACP) guideline

recommendation that maintenance antiarrhythmic drug therapy NOT be routinely used after cardioversion in patients with newly detected AF [15,16]. This issue is discussed separately. (See "Restoration of sinus rhythm in atrial fibrillation", section on 'Recurrence of AF after cardioversion'.) In addition, extensive attempts to maintain sinus rhythm are appropriate only in rare instances. (See "Rhythm control versus rate control in atrial fibrillation", section on 'Patients early in their natural history'.) Spontaneous reversion of AF New onset AF often spontaneously reverts to normal sinus rhythm, with the incidence of reversion related to the duration of the arrhythmia. This was illustrated in a study of 1822 patients admitted to the hospital because of AF: 356 had an arrhythmia duration less than 72 hours, 68 percent of whom spontaneously reverted to sinus rhythm [17]. Two-thirds of those with spontaneous reversion had AF duration of less than 24 hours, which was the only predictor of spontaneous reversion. (See "Paroxysmal atrial fibrillation".) The optimal antithrombotic therapy after spontaneous cardioversion of a first episode of AF (lasting less than 48 hours) in patients without structural heart disease is discussed above. (See 'Anticoagulation' above.) We do not recommend the initiation of drugs to maintain either rhythm or rate control, unless the patient is felt to be at high risk for recurrence and a rhythm control strategy has been chosen. (See 'Antiarrhythmic therapy after reversion to sinus rhythm' above.) INDICATIONS FOR HOSPITALIZATION Many patients with new onset AF, particularly those without spontaneous reversion, have often been admitted to the hospital. A frequent reason for admission is to "rule out" an acute myocardial infarction. AF is rarely the only manifestation of an acute coronary syndrome, although AF with a rapid ventricular response and hypotension can provoke angina. As a result, there is no reason to admit the patient unless there are other clinical reasons to consider an acute coronary syndrome such as ST segment elevation or major (>2 mm) ST segment depression [18]. In addition, the use of high-sensitivity troponins allows ruling out of MI in the emergency department within a few hours. (See "Epidemiology of and risk factors for atrial fibrillation", section on 'AF as a presentation of ACS'.) Several indications for hospitalization in patients with new onset AF are: Initiation of heparin or other anticoagulant therapy. Patients in whom ablation of an accessory pathway is being considered, particularly if the AF was highly symptomatic and associated with hemodynamic collapse and rapid ventricular response rate. Treatment of an associated medical problem, which is often the reason for the arrhythmia. Examples include the treatment of hypertension, infection, exacerbation of

chronic obstructive pulmonary disease (COPD), pulmonary embolism, persistent myocardial ischemia, or acute pericarditis. Treatment of elderly patients. The elderly are more likely to have a high risk of thromboembolism. There may also be difficulty in controlling the ventricular response rate without causing the development of sick sinus syndrome The elderly are more likely to have comorbidities that can complicate drug management in the treatment of atrial fibrillation, whether it be rate control or rhythm control approaches. A frequent reason for admission is to "rule out" an acute myocardial infarction. However, AF is rarely the only manifestation of an acute coronary syndrome, although AF with a rapid ventricular response and hypotension can provoke angina. As a result, there is no reason to admit the patient unless there are other clinical reasons to consider an acute coronary syndrome such as ST segment elevation or major (>2 mm) ST segment depression [18]. (See "Epidemiology of and risk factors for atrial fibrillation", section on 'AF as a presentation of ACS'.) Further management heart failure or hypotension after control of the rhythm or rate Initiation of antiarrhythmic drug therapy

The duration of hospitalization will depend on factors such as control of an underlying medical problem and time required to complete anticoagulation. DISCHARGE FROM THE EMERGENCY ROOM For those patients who do not have one of the above clear indications for hospitalization, an important initial issue is whether patients presenting with new onset AF (less than 48 hours duration) can be managed (including cardioversion) in the emergency department or an observational unit and then discharged [1922]. This issue was addressed in a study of 289 such patients who were stable, did not have heart disease, and did not have another indication for hospital admission [21]. Pharmacologic cardioversion was attempted in 62 percent and was successful in 50 percent; 28 percent underwent electric cardioversion with a success rate of 89 percent. Overall, 97 percent of patients were discharged home directly from the emergency department. (See "Restoration of sinus rhythm in atrial fibrillation", section on 'Antiarrhythmic drugs used in cardioversion'.) Similar results were noted in another report of 51 patients who underwent attempted pharmacologic cardioversion with intravenous ibutilide, followed by electrical reversion if AF was still present [22]. All patients were successfully reverted and discharged from the emergency department. Thus, emergency department or observational unit treatment of new onset AF in clinically stable patients, who have no other important comorbidities such as underlying structural heart disease, is safe and cost-effective [20]. The role of anticoagulation in such patients (ie, low risk and duration less than 48 hours) is discussed elsewhere. (See "Anticoagulation prior to and after restoration of sinus rhythm in atrial fibrillation", section on 'AF of less than 48 hours duration'.)

FOLLOW-UP Routine follow-up after an episode of acute atrial fibrillation is necessary to evaluate the safety and efficacy of antiarrhythmic and anticoagulant therapies, to reassess the need for these therapies, and to assess the functional status of the patient. INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5th to 6th 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 sophisticated, and more detailed. These articles are written at the 10th to 12th 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 information: Atrial fibrillation (The Basics)") Beyond the Basics topic (see "Patient information: Atrial fibrillation")

SUMMARY AND RECOMMENDATIONS New onset atrial fibrillation (AF) is atrial fibrillation identified for the first time by an electrocardiogram or other rhythm recording, such as ambulatory or inpatient monitoring. The early steps in the management of a patient with new onset atrial fibrillation (AF) involve an assessment of the need for cardioversion, rate slowing therapy, and antithrombotic therapy. The following summarizes that process: Patients in whom early cardioversion (within 48 hours) or parenteral anticoagulation are being considered should be transferred from an office setting to an acute care facility. (See 'Important first steps' above.) Urgent or emergent cardioversion should be considered for patients with active ischemia, significant hypotension, severe heart failure, or the presence of a preexcitation syndrome associated with rapid conduction using the accessory path. (See 'Indications for urgent cardioversion' above.) All patients should undergo an evaluation for precipitating cause. If found it should be corrected as soon as possible. (See 'Evaluation for an underlying cause' above.) Most patients with symptomatic new onset atrial fibrillation should have at least one attempt at cardioversion (either electrical or chemical) to sinus rhythm, particularly after reversible causes have been identified and corrected. The timing of cardioversion depends in large part on hemodynamic status and the duration of the AF episode. (See 'Cardioversion' above.) Most patients with new onset AF who have sinus rhythm restored do not need maintenance antiarrhythmic drug therapy. (See 'Antiarrhythmic therapy after reversion to sinus rhythm' above.)

The approach to decreasing the risk of embolization around the time of cardioversion in patients with new onset AF is nearly identical to that for patients with a prior episode in whom cardioversion is planned. (See 'Anticoagulation' above.)

Our specific recommendations as follows: We recommend rate control to improve symptoms and to reduce the risk of tachycardia-mediated cardiomyopathy for all patients who do not require urgent or emergent cardioversion. We believe a goal of less than 110 beats per minute is reasonable. (See 'Initial rate control with mild to moderate symptoms' above.) Beta blockers and nondihydropyridine calcium channel blockers are preferred as firstline agents in most patients. Intravenous preparations are preferred to oral preparations when rapid control of rate is necessary. (See 'Initial rate control with mild to moderate symptoms' above.) For patients with AF less than 48 hours in duration, the use of periprocedural heparin to reduce the risk of embolization can be considered. Our authors and reviewers believe there is insufficient evidence to make a recommendation for or against its use. (See "Therapeutic use of heparin and low molecular weight heparin", section on 'Bleeding'.) The decision to start long-term oral anticoagulation in these patients should be made based on an assessment of the long-term risk of embolization based on the CHADS2 score. For patients with AF of longer than 48 hours duration, we recommend four weeks of therapeutic oral anticoagulation prior to cardioversion, as opposed to immediate cardioversion. An alternative strategy is to perform a transesophageal echocardiogram to screen for atrial thrombi. (See 'Role of TEE' above.) Indications for hospitalization in patients with new onset AF include (but are not limited to) (See 'Indications for hospitalization' above.): Ablation of an accessory pathway Treatment of an associated medical problem, which is often the reason for the arrhythmia. Treatment of frail elderly patients. Further management of heart failure or hypotension after control of the rhythm or rate Initiation of antiarrhythmic drug therapy Initiation of heparin therapy

Rhythm control versus rate control in atrial fibrillation

Last literature review version 19.2: maggio 2011 | This topic last updated: febbraio 14, 2011 (More) INTRODUCTION Atrial fibrillation (AF) is the most common sustained arrhythmia. It may cause significant symptoms and impair both functional status and quality of life. Without therapeutic intervention, affected patients are at increased risk for mortality (1.5- to 1.9-fold in the Framingham study) and morbidity (thromboembolic events and limiting symptoms). In atrial fibrillation, the loss of the regular and organized contraction of the left atrium as well as the subsequent increase in ventricular rate, lead to both immediate and long-term adverse consequences: deterioration in hemodynamics secondary to increased heart rate and loss of atrioventricular (AV) synchrony, an increased risk for stroke and other embolic events from left atrial thrombi, and progressive dysfunction of the left atrium and left ventricle [1,2]. (See "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm" and "Tachycardia-mediated cardiomyopathy".) For each patient with AF, the two principal goals of therapy are symptom control and the prevention of thromboembolism. (See "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation" and "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm", section on 'Adverse hemodynamics in AF'.) Rate- and rhythm-control strategies improve symptoms, but neither has been conclusively shown to improve survival compared to the other. (See 'Definitions' below.) For each patient with AF, a decision should be made as to which approach will be used for long-term management. The following points should be kept in mind irrespective of strategy: Either strategy can fail both in the short and long terms. As a consequence many patients need to be reconsidered for the alternate strategy as the natural history of their disease progresses. All patients with AF, irrespective of strategy chosen, should have their thromboembolic risk assessed and be managed accordingly. (See 'Thromboembolic risk' below.) For patients who are managed with a rhythm-control strategy, rate control is necessary due to the possibility of the return of AF. The advantages and disadvantages of rhythm and rate control, as well as whether there are subgroups of patients in whom one or the other should be preferred, will be discussed here. The methods to achieve rhythm or rate control are discussed separately. (See "Drug therapy to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials" and "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations" and "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy" and "Control of ventricular rate in atrial fibrillation: Nonpharmacologic therapy".) Patients with recent onset In patients who present with recent onset AF, relatively rapid decisions, including the choice between rhythm and rate control, often need to be made. This issue is discussed in detail separately. (See "Management of new onset atrial fibrillation".)

DEFINITIONS A rhythm-control strategy uses antiarrhythmic drug therapy, radiofrequency catheter ablation, and/or a surgical procedure performed at the time of open heart surgery to maintain sinus rhythm. Many patients who remain in sinus rhythm require rate slowing drugs (in the event of return to AF) long term as well as antithrombotic therapy. (See 'Thromboembolic risk' below.) A rate-control strategy uses drugs that block (slow conduction through) the atrioventricular (AV) node such as beta blockers, rate-slowing calcium channel blockers, or digoxin. Atrioventricular (AV) nodal ablation plus ventricular pacing to control symptoms is also used when drug therapy is ineffective. Rate control goals are discussed elsewhere. (See "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy", section on 'Rate control goals'.) THROMBOEMBOLIC RISK Thromboembolism is the most important adverse outcome of AF. Unfortunately, maintaining sinus rhythm does not reduce the frequency of clinical thromboembolization. The AFFIRM and RACE trials demonstrated that embolic events occurred with equal frequency regardless of whether a rate control or rhythm-control strategy was pursued; furthermore, most embolic events (113 of 157 ischemic strokes in AFFIRM and 29 of 35 embolic events in RACE) occurred after warfarin had been stopped or when the International Normalized Ratio (INR) was subtherapeutic (less than 2.0) [3,4]. These findings indicate that high-risk patients in whom a rhythm-control strategy is pursued still require chronic anticoagulation, even if it seems that sinus rhythm is maintained. (See "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation".) There are at least two explanations for the failure of rhythm control to reduce embolic risk: Despite successful cardioversion and antiarrhythmic drug therapy, the recurrence rate of either intermittent (paroxysmal) or persistent (chronic) AF is 35 to 60 percent at one year with intermittent monitoring (figure 1) [5,6] and up to 88 percent with continuous monitoring (permanent pacemaker with AF detection function and electrogram storage) for more than 18 months [7]. In the AFFIRM trial described below, there was a high crossover rate from rhythm to rate control (17 and 38 percent of patients at one and five years), due primarily to inability to maintain sinus rhythm and drug intolerance [3].

Up to 90 percent of recurrences are asymptomatic [8] and asymptomatic episodes lasting more than 48 hours are not uncommon, occurring in 17 percent of patients in a report using continuous monitoring [7]. During these prolonged episodes of AF, thrombi can form that may cause clinical thromboembolism. The continuous monitoring study also showed that 40 percent of patients had episodes of AF-like symptoms in the absence of AF [7]. Even very brief episodes of AF can increase stroke risk. In a study using pacemakers for arrhythmia detection in patients without a history of AF, AF duration for greater than five minutes increased the risk of thromboembolic events sixfold compared to patients with similar or greater CHADS2 score and no detected AF [9].

Patients with nonvalvular AF that is not due to a reversible disease (eg, hyperthyroidism, cardiac surgery) often have other predisposing factors for embolism even when they are in sinus rhythm. These include complex aortic plaque and left ventricular systolic dysfunction. (See "Indications for anticoagulation in heart failure" and "Embolism from aortic plaque: Thromboembolism".)

Thus, the implementation of either strategy requires the assessment of the need for antithrombotic therapy. Issues related to risk stratification and the approach to antithrombotic therapy in patients with AF are discussed in detail separately. (See "Risk of embolization in atrial fibrillation" and "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation".) A separate issue from chronic antithrombotic therapy is anticoagulation related to cardioversion. The recommended approach to such patients is presented separately. (See "Anticoagulation prior to and after restoration of sinus rhythm in atrial fibrillation".) CLINICAL TRIALS At least seven randomized trials have compared rate and rhythm control approaches in the broad population of patients with AF and demonstrated equivalent outcomes (such as the rates of death or embolism) in both arms [3,4,10-12]. Two large trials, AFFIRM and RACE, will be discussed in detail. One trial demonstrated improved quality of life scores with rhythm control [13]. AFFIRM trial AFFIRM, the largest trial, randomly assigned 4060 patients with recurrent AF to rate control (using digoxin, beta blocker, and/or calcium channel blocker) and anticoagulation with warfarin or to rhythm control with the most effective antiarrhythmic drug, with the use of warfarin left up to the discretion of the investigator [3]. Patients had to be at least 65 years of age (mean age 70) or have other risk factors for stroke or death and there could be no contraindications to antiarrhythmic or anticoagulation therapy. All patients were initially anticoagulated, but those in the rhythm control arm who maintained NSR could be withdrawn from warfarin. In the rate control arm of the study, the goals were a ventricular rate of 80 beats per min at rest and 110 beats per minute during a six-minute walk test. At five years, 35 percent of patients were in sinus rhythm (compared to 63 percent with rhythm control), while over 80 percent of those still in AF had "adequate heart rate control." Over 85 percent of patients in the rate control arm were treated with warfarin. Radiofrequency ablation of the atrioventricular node was required in 105 patients (5 percent) (see "Control of ventricular rate in atrial fibrillation: Nonpharmacologic therapy"). In the rhythm control arm of the study, sinus rhythm was maintained in 82 and 63 percent of patients at one and five years; only 1 percent underwent nonpharmacologic therapy to maintain rhythm control. The most frequently used initial antiarrhythmic drugs were amiodarone (38 percent) and sotalol (31 percent). By the end of 3.5 years of follow-up, 63 percent of patients had had at least one trial of amiodarone.

Among patients initially assigned to rhythm control, crossover to rate control occurred in 17 and 38 percent of patients at one and five years, primarily due to inability to maintain sinus rhythm and drug intolerance. In those originally assigned to rate control, the crossover rate to rhythm control was lower at 8 and 15 percent, primarily due to failure to control symptoms due to AF and heart failure. After a mean follow-up of 3.5 years, the following findings were observed: There was an almost significant trend toward a decrease in the rate of occurrence of the primary endpoint (all-cause mortality) with rate control (21.3 versus 23.8 percent, hazard ratio [HR] 0.87, 95% CI 0.75-1.01) (figure 2). There was no difference between the two groups in the incidence of cardiac death, arrhythmic death, or deaths due to ischemic or hemorrhagic stroke [14]. Two prespecified subgroups had a significant reduction in mortality with rate control: those without a history of heart failure (adjusted HR 0.69) and those aged 65 years or older (HR 0.76) [15]. There was no significant difference in the composite secondary endpoint of death, ischemic stroke, anoxic encephalopathy, major bleeding, or cardiac arrest. There was no significant difference in global functional status or quality of life in the initial report. The number of patients requiring hospitalization during follow-up was significantly lower in the rate control group than in the rhythm control group (73 versus 80 percent). A subsequent report provided evidence that the trend toward increased mortality with rhythm control was due to the deleterious effects of antiarrhythmic drugs [16]. In this analysis, the use of antiarrhythmic drugs was associated with a significant increase in mortality (hazard ratio 1.49), while the presence of sinus rhythm was associated with a significant reduction in mortality (hazard ratio 0.53). It could not be determined if the latter effect was due to sinus rhythm itself or to AF being a marker for a confounding factor or factors that affect survival, such as heart failure [17]. RACE The RACE trial enrolled 522 patients (mean age 68) with recurrent persistent AF or atrial flutter less than one year in duration who had required one to two cardioversions within the prior two years [4]. (See "Overview of atrial fibrillation", section on 'Classification'.) Patients were randomly assigned to rate control using the same AV nodal blocking drugs as used in AFFIRM or to rhythm control. Successful rate control was defined as a ventricular rate below 100 beats/min and no symptoms. Initial therapy for rhythm control was sotalol. If AF recurred within six months, antiarrhythmic drug therapy was changed; if AF again recurred within six months, amiodarone was substituted. A late recurrence, after more than six months of therapy, was treated with repeat cardioversion and continuation of the same antiarrhythmic agent.

The primary endpoint was a composite of cardiovascular death, admission for heart failure, thromboembolic event, severe bleeding, pacemaker implantation, or severe side effects from antiarrhythmic drugs. After a mean 2.3-year follow-up, the following findings were observed: Significantly fewer patients were in sinus rhythm in the rate control group (10 versus 39 percent). There was an almost significant trend toward a lower incidence of the primary endpoint with rate control (17.2 versus 22.6 percent with rhythm control, hazard ratio 0.73, 90% CI 0.53-1.01) (figure 3). There was no difference in cardiovascular mortality (6.8 versus 7 percent). However, there was a trend toward a higher incidence of nonfatal endpoints among patients assigned to rhythm control, including heart failure, thromboembolism, pacemaker insertion, and adverse drug reactions. There were no significant differences in quality of life between the rate and rhythm control groups, a finding similar to that in AFFIRM [18]. Improvement in quality of life was associated with symptomatic AF at baseline, a short duration of AF, and the presence of sinus rhythm at the end of follow-up, rather than the assigned strategy. It has been thought that restoration and maintenance of sinus rhythm may be of particular importance in patients with cardiomyopathy and symptomatic heart failure who have AF, based upon the expectation that hemodynamics would improve and heart failure (HF) would be more easily controlled in such patients if they were in sinus rhythm. This issue is discussed in detail elsewhere. (See "Atrial fibrillation in patients with heart failure", section on 'Rhythm versus rate control'.) Limitations of trial data Limitations of the RACE and AFFIRM trials should be kept in mind: The mean age in AFFIRM and RACE was 70 and 68 years, respectively [3,4]. It is therefore uncertain if younger healthy patients might benefit from more aggressive rhythm control [19,20]. Approximately one-half of patients in AFFIRM who had a detailed history had symptomatic episodes of AF that occurred less often than once per month [21]. Such patients would be expected to derive little symptomatic benefit from rhythm control, and the results may not directly apply to patients with frequent episodes of symptomatic AF [17]. The use of antiarrhythmic drugs in AFFIRM was associated with a significant increase in mortality (hazard ratio 1.49), which was due to noncardiovascular causes, while the presence of sinus rhythm was associated with a significant reduction in mortality (hazard ratio 0.53) [14,16]. A similar benefit from being in sinus rhythm (relative risk 0.44) was noted in the DIAMOND trial that compared dofetilide to placebo in patients with reduced left ventricular function [22]. (See "Atrial fibrillation in patients with heart failure".)

One interpretation of these data is that maintenance of sinus rhythm might be beneficial if there were a safer and more effective approach than current antiarrhythmic drugs [17,23]. (See "Overview of atrial fibrillation", section on 'Long-term outcome'.) The AFFIRM and RACE data were largely gathered before catheter ablation was common. The potential impact of this procedure (versus chronic antiarrhythmic therapy) remains incompletely explored. CHOICE OF THERAPY The data from the clinical trials suggest that both rate and rhythm control are acceptable approaches, with comparable rates of mortality and stroke [10,11,18]. As discussed below, we prefer a rate-control strategy in most patients. However, an individual patient may do better with one or the other, and in many cases only after trying one strategy is utility known. When choosing a strategy, the major factors that should be considered are the relative ability of each strategy to control symptoms and the relative burdens imposed by each. Preference for rate control In most patients with AF, particularly recurrent AF, we prefer rate control as the initial approach [17,19,20,24]. This is based upon the following factors: The results from AFFIRM and RACE show equivalent and perhaps better outcomes with rate control (figure 2 and figure 3) as well as a similar requirement for anticoagulation [3,4]. A meta analysis of above five trials, in which AFFIRM accounted for 77 percent of the patients, found a strong trend toward a reduction in all-cause mortality with rate control (13.0 versus 14.6 percent with rhythm control, odds ratio 0.87, 95% CI 0.741.02) [25]. The proportion of patients who had an ischemic stroke was similar with the two approaches (3.5 versus 3.9 percent). Important side effects, especially proarrhythmia, are associated with antiarrhythmic drugs [16,26-28]. In addition pulmonary vein isolation using radiofrequency catheter ablation is associated with important complications. (See "Radiofrequency catheter ablation to prevent recurrent atrial fibrillation", section on 'Complications'.) There is an appreciable rate of recurrent AF and frequent crossover to a rate-control strategy when antiarrhythmic drugs are used for maintenance therapy after conversion to sinus rhythm. Recurrence is detected clinically in 20 to 60 percent at one year (figure 1) [29]. Furthermore, a continuous monitoring study found that recurrent episodes occurred in approximately 90 percent of patients; many of these episodes were asymptomatic, including some lasting more than 48 hours [7]. The risk of recurrent AF is highest in the patient who has hypertension, an enlarged left atrium (LA), AF for more than one year, or heart failure [30]. Rate control is generally preferred in patients with heart failure. This issue is discussed in detail separately. (See "Atrial fibrillation in patients with heart failure", section on 'Rhythm versus rate control'.)

Newly detected AF We agree with the American Academy of Family Practice/American College of Physicians guideline recommendation that maintenance antiarrhythmic drug therapy not be routinely used after cardioversion in patients with newly detected AF [19,24]. (See "Management of new onset atrial fibrillation", section on 'Antiarrhythmic therapy after reversion to sinus rhythm'.) Very elderly Patients over age 80 account for approximately 35 percent of patients with AF and the prevalence of AF is about 10 percent (figure 4) [31,32]. These individuals are underrepresented in clinical trials. Rhythm control is less often preferred in such patients for the following reasons [32]: They are more sensitive to the proarrhythmic effects of drugs AF is often permanent.

Preference for rhythm control While it seems intuitive that an individual patient would feel better in sinus rhythm than in AF (even with rate control) not all such patients feel better. Demonstrating that sinus rhythm improves symptoms and quality of life has been difficult for two reasons, related in large part by limitations of antiarrhythmic drug therapy: Limited efficacy: a substantial percentage of patients in whom a rhythm-control strategy is chosen continue to have AF. Side effects: proarrhythmia, and inconveniences (eg, monitoring tests and dose adjustments), that have a negative impact on quality of life. Among patients in whom sinus rhythm is successfully maintained, exercise capacity and quality of life are improved [33,34]. Thus, many experts see the failure to demonstrate improved outcomes with rhythm-control strategies as a reflection of the inadequacies of available therapies, rather than a clinical equivalence between AF with rate control and sinus rhythm. Despite the general preference for a rate-control strategy, and the difficulty in demonstrating improved outcomes with rhythm control, there are several situations in which rhythm control is preferable [19]. Failure of rate control There are two manifestations of failure of rate control: Persistent symptoms (palpitations, dyspnea, lightheadedness, angina, and near syncope) despite adequate rate control. (See "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm".) An inability to attain adequate rate control as defined above. In these patients, alternatives to rhythm control with antiarrhythmic drug therapy include radiofrequency ablation of the AV node with pacemaker insertion or radiofrequency catheter ablation. (See "Control of ventricular rate in atrial fibrillation: Nonpharmacologic therapy" and "Radiofrequency catheter ablation to prevent recurrent atrial fibrillation".)

Younger patients Younger individuals, or those who need to carry out activities requiring optimal cardiac performance, generally do not tolerate AF well. When antiarrhythmic drugs are used in this setting, patients should be well informed of the benefits and risks of this therapy. Patients early in their natural history There is some evidence that suggests it is easier to maintain sinus rhythm earlier in the natural history of AF than later [35]. Therefore, patients for whom a rhythm-control strategy is chosen should have AF restored to sinus rhythm early once adequate thromboembolic prophylaxis has been achieved. We consider cardioversion to sinus rhythm in most patients (particularly younger patients) with a first detected episode of AF in whom the arrhythmia is of recent onset and the risk for recurrence appears to be low based upon the following findings: LA size less than 4.5 to 5 cm A reversible underlying disorder such as hyperthyroidism, pericarditis, pulmonary embolism, or cardiac surgery No hypertension or hypertensive heart disease No left ventricular dysfunction or enlargement or heart failure.

Cardioversion should only be attempted when the risk of embolization has been lowered to an acceptable level. (See "Anticoagulation prior to and after restoration of sinus rhythm in atrial fibrillation".) Recommendations of others The 2010 European Society of Cardiology guidelines for the management of atrial fibrillation make the following recommendations for choosing between rhythm- or rate-control strategies [32]: Rate control is strongly preferred as the initial approach in elderly patients with minor symptoms. Rhythm control is strongly preferred in patients with symptoms despite rate control, including those with persistent symptoms of heart failure. Rhythm control is weakly preferred as an initial approach in young symptomatic patients. Rhythm controls is weakly preferred in patients with AF secondary to a trigger or substrate that has been corrected. The 2006 American College of Cardiology/American Heart Association/European Society of Cardiology guideline did not make specific recommendations regarding rhythm versus rate control, nor did the 2010 focused update [26,36]. INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5th to 6th 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 sophisticated, and more detailed. These articles are written at the 10th to 12th 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.) Beyond the Basics topic (see "Patient information: Atrial fibrillation")

SUMMARY AND RECOMMENDATIONS For each patient with AF, the two principal goals of therapy are symptom control and the prevention of thromboembolism. Therapies aimed at these two goals will improve survival, compared to no therapy. (See "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation" and "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm", section on 'Adverse hemodynamics in AF'.) A rhythm-control strategy uses either antiarrhythmic drug therapy, radiofrequency catheter ablation, or a surgical procedure performed at the time of open heart surgery to maintain sinus rhythm. Cardioversion may be necessary prior to an attempt to maintain sinus rhythm. Rate-slowing drugs are continued in many patients who remain in sinus rhythm (in the event of return to AF). (See 'Definitions' above.) A rate-control strategy generally uses drugs that block the atrioventricular (AV) node, such as beta blockers, rate-slowing calcium channel blockers, or digoxin. AV nodal ablation plus ventricular pacing is another option. Patients managed by either rate or rhythm control must be assessed for their thromboembolic risk. Therapy should be initiated when appropriate. (See 'Thromboembolic risk' above.) Rhythm- and rate-control strategies are associated with similar rates of mortality and serious morbidity, such as embolic risk. In addition, assessments of quality of life have not shown significant differences between the two in most studies. (See 'Clinical trials' above.). The principal reasons to prefer a rate-control strategy include simplification of the medical regimen, lower cost, and less concern about the risks of antiarrhythmic drug therapy (such as torsades de pointes) or radiofrequency catheter ablation. (See 'Preference for rate control' above.) For patients with AF who are 65 years or older, we suggest a rate-control as opposed to a rhythm-control strategy using medical therapy (Grade 2B). This recommendation places a high priority on concerns about side effects of antiarrhythmic drug therapy or radiofrequency catheter ablation. Older patients for whom a rhythm-control strategy

may be reasonable include those who continue with clinically significant symptoms on a rate-control strategy. (See 'Preference for rate control' above.) For most patients with AF younger than age 65, particularly those who are symptomatic, we suggest a rhythm control as opposed to a rate-control strategy (Grade 2B). This recommendation places a high priority on relief of symptoms as well as the potential, but as yet unproven benefit, from remaining in sinus rhythm over long periods of time. For younger, asymptomatic patients who are concerned about the potential side effects of antiarrhythmic drug therapy, and who are not inclined to undergo radiofrequency catheter ablation, a rate-control strategy is reasonable. In these patients an informed discussion of the benefits and risks of antiarrhythmic drug therapy is critically important. (See 'Preference for rhythm control' above.)