Atrial Fibrillation

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Practice Essentials

Atrial fibrillation (AF) has strong associations with other cardiovascular diseases, such as heart failure, coronary artery disease (CAD), valvular heart disease, diabetes mellitus, and hypertension. It is characterized by an irregular and often rapid heartbeat (see the first image below). The exact mechanisms by which cardiovascular risk factors predispose to AF are not understood fully but are under intense investigation. Catecholamine excess, hemodynamic stress, atrial ischemia, atrial inflammation, metabolic stress, and neurohumoral cascade activation are all purported to promote AF.



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Ventricular rate varies from 130-168 beats per minute. Rhythm is irregularly irregular. P waves are not discernible.



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The image on the right is a reconstructed 3-dimensional image of the right atrium in a patient undergoing atrial fibrillation ablation. The figure on the left was created with a mapping catheter using Endocardial Solutions mapping technology. It represents the endocardial shell of the right atrium and is used as the template during left atrial ablation procedures.

Signs and symptoms

The clinical presentation of AF spans the entire spectrum from asymptomatic AF with rapid ventricular response to cardiogenic shock or devastating cerebrovascular accident (CVA). Unstable patients requiring immediate direct current (DC) cardioversion include the following:

Initial history and physical examination include the following:

Clinical Presentation

Diagnosis

Findings from 12-lead electrocardiography (ECG) usually confirm the diagnosis of AF and include the following:

Transthoracic echocardiography (TTE) is helpful for the following applications:

Transesophageal echocardiography (TEE) is helpful for the following applications:

Workup

Management

The cornerstones of AF management are rate control and anticoagulation,[1] as well as rhythm control for those symptomatically limited by AF. The clinical decision to use a rhythm-control or a rate-control strategy requires integrated consideration of the following:

Anticoagulation

The 2014 American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society (HRS) guidelines on anticoagulation for patients with nonvalvular AF include the following[1] :

Risk factors for thromboembolism in AF are as follows:

Anticoagulation is indicated as follows:

Newer oral anticoagulants that have been approved by the US Food and Drug Administration (FDA) include the following:

Risk of bleeding

Optimal long-term strategies for AF management should be based on a thoroughly integrated consideration of patient-specific factors and the likelihood of success. Selection of an appropriate antithrombotic regimen should be balanced between the risk of stroke and the risk of bleeding.

Factors that increase the risk of bleeding with anticoagulation include the following:

For patients with clinical indications for anticoagulation who are at an unacceptably high risk of clinically significant bleeding, two treatment alternatives exist:

Rate control strategies

Rhythm control strategies

Catheter ablation is recommended in the 2014 ACC/AHA/HRS AF guidelines for the following indications[1] :

See Treatment and Medication for more detail.

Background

Classification of atrial fibrillation (AF) begins with distinguishing a first detectable episode, irrespective of whether it is symptomatic or self-limited. Published guidelines from an American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society (HRS) committee of experts on the treatment of patients with atrial fibrillation recommend classification of AF into the following three patterns (also see the image below)[1] :



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Classification scheme for patients with atrial fibrillation (AF).

This classification schema pertains to cases that are not related to a reversible cause of AF (eg, thyrotoxicosis, electrolyte abnormalities, acute ethanol intoxication). In current clinical practice, atrial fibrillation secondary to acute myocardial infarction, cardiac surgery, pericarditis, sepsis, pulmonary embolism, or acute pulmonary disease is considered separately. This is because, in these situations, AF is thought to be less likely to recur once the precipitating condition has been treated adequately and has resolved.

However, data from the Framingham Heart Study suggest that over 60% of the participants with secondary AF developed recurrent AF over 15-years of follow-up.[2] Furthermore, the long-term risks of stroke and all-cause mortality were similar between participants without a secondary precipitant and those with secondary precipitants. Thus, long-term AF screening strategies can be considered in these patients similar to the current standard of practice for patients with cryptogenic stroke.[3]

Paroxysmal AF

Atrial fibrillation is considered to be recurrent when a patient has two or more episodes. If recurrent AF terminates spontaneously, it is designated as paroxysmal.

Some patients with paroxysmal AF, typically younger patients, have been found to have distinct electrically active foci within their pulmonary veins. These patients generally have many atrial premature beats noted on Holter monitoring. Isolation or elimination of these foci can lead to elimination of the trigger for paroxysms of AF.

Paroxysmal AF may progress to persistent AF, and aggressive attempts to restore and maintain sinus rhythm may prevent comorbidities associated with AF.

Persistent AF

If recurrent AF is sustained, it is considered persistent, irrespective of whether the arrhythmia is terminated by either pharmacologic therapy or electrical cardioversion.

Persistent AF may be either the first presentation of AF or the result of recurrent episodes of paroxysmal AF. Patients with persistent AF also include those with longstanding AF in whom cardioversion has not been indicated or attempted, often leading to permanent AF.

Patients can also have AF as an arrhythmia secondary to cardiac disease that affects the atria (eg, congestive heart failure, hypertensive heart disease, rheumatic heart disease, coronary artery disease). These patients tend to be older, and AF is more likely to be persistent.

Persistent AF with an uncontrolled, rapid ventricular heart rate response can cause a dilated cardiomyopathy and can lead to electrical remodeling in the atria (atrial cardiomyopathy). Therapy, such as drugs or atrioventricular nodal modification and permanent pacemaker implantation, to control the ventricular rate can improve left ventricular function and improve quality-of-life scores.

Long-standing persistent AF

Permanent AF is recognized as the accepted rhythm, and the main treatment goals are rate control and anticoagulation. Although it is possible to reverse the progression from paroxysmal to persistent and to long-standing persistent, this task can be challenging.

Lone atrial fibrillation

In addition to the above schema, the term "lone atrial fibrillation" has been used to identify AF in younger patients without structural heart disease, who are at a lower risk for thromboembolism. The definition of lone AF remains controversial, but it generally refers to paroxysmal, persistent, or permanent AF in younger patients (< 60 y) who have normal echocardiographic findings.[4]  The most recent ACC/AHA/HRS guidelines recommend against using “lone AF” as a separate entity and utilizing the standard AF management tools for all patients.[1]

For patient education resources, see Heart Health Center and Brain and Nervous System Center, as well as Atrial Fibrillation (AFib), Arrhythmias (Heart Rhythm Disorders), Stroke, and Supraventricular Tachycardia (SVT, PSVT).

Pathophysiology

Three forms of atrial remodeling during a progression of atrial fibrillation (AF) have been described: electrical, contractile, and structural.[5] Electrical remodeling is a consequence of high atrial rates and includes shortening of the refractory period of atrial myocytes and slowing of atrial conduction velocity.[6] Structural remodeling is characterized both by changes in atrial myocytes[7, 8] in the interstitium,[9, 10] and by changes in extracellular matrix composition and deposition of fibrotic tissue.[11]  Changes at the level of atrial myocytes include the loss of contractile structures and expression of fetal-like proteins, and accumulation of glycogen in the atrial interstitium.[12]  

Changes in the interstitium are primarily manifested by the deposition of collagen fibers around cardiomyocytes.[13] Contractile remodeling is caused mainly by impaired calcium handling and may result in atrial mechanical dysfunction that may be transient or progress to irreversible dysfunction. Impaired contractility results from local changes in cell physiology and also from structural remodeling of atrial myocytes (loss of gap junctions).

Another observed morphologic feature related to AF is the presence of inflammatory cells in the atrial myocardium.[8] The role of inflammation and myocardial inflammatory infiltrate was suggested by morphologic studies on atrial tissue removed at the time of cardiac surgery and by clinical studies that monitored serum levels of inflammatory cytokines in patients with AF.[14, 15] Despite the observed association between elevated plasma levels of inflammatory markers and AF, it remains unknown whether inflammation is a systemic or local phenomenon reflecting an active inflammatory process in the atria.[14] It is also not known whether the inflammatory cells are a marker of local reaction to tissue injury caused by factors leading to AF or whether they actively participate in the maintenance of AF due to direct cytotoxic or profibrotic effects or due to indirect effects from released cytokines that may promote arrhythmogenesis.[16]

AF shares strong associations with other cardiovascular diseases, such as heart failure, coronary artery disease (CAD), valvular heart disease, diabetes mellitus, and hypertension.[17] These factors have been termed upstream risk factors, but the relationship between comorbid cardiovascular disease and AF is incompletely understood and more complex than this terminology implies. The exact mechanisms by which cardiovascular risk factors predispose to AF are not understood fully but are under intense investigation. Catecholamine excess, hemodynamic stress, atrial ischemia, atrial inflammation, metabolic stress, and neurohumoral cascade activation are all purported to promote AF.

Because diabetes mellitus and obesity are increasing in prevalence and are associated with an elevated risk of AF, Fontes et al examined whether insulin resistance is an intermediate step for the development of AF. In a community-based cohort that included 279 patients who developed AF within 10 years of follow-up, no significant association was observed between insulin resistance and incident AF.[18]

Although the precise mechanisms that cause atrial fibrillation are incompletely understood, AF appears to require both an initiating event and a permissive atrial substrate. The importance of focal pulmonary vein triggers has been highlighted in multiple studies, but alternative and nonmutually exclusive mechanisms have also been evaluated.[19] These mechanisms include multiple wavelets, mother waves, fixed or moving rotors, and macro-reentrant circuits.[19] In a given patient, multiple mechanisms may coexist at any given time. The automatic focus theory and the multiple wavelet hypothesis appear to have the best supporting data.

Automatic focus

A focal origin of AF is supported by several experimental models showing that AF persists only in isolated regions of atrial myocardium. This theory has garnered considerable attention, as studies have demonstrated that a focal source of AF can be identified in humans and that isolation of this source can eliminate AF.

The pulmonary veins appear to be the most frequent source of these automatic foci, but other foci have been demonstrated in several areas throughout the atria. Cardiac muscle in the pulmonary veins appears to have active electrical properties that are similar, but not identical, to those of atrial myocytes. Heterogeneity of electrical conduction around the pulmonary veins is theorized to promote reentry and sustained AF. Thus, pulmonary vein automatic triggers may provide the initiating event, and heterogeneity of conduction may provide the sustaining conditions in many patients with AF.

Multiple wavelet

The multiple wavelet hypothesis proposes that fractionation of wave fronts propagating through the atria results in self-perpetuating "daughter wavelets." In this model, the number of wavelets is determined by the refractory period, conduction velocity, and mass of atrial tissue. Increased atrial mass, shortened atrial refractory period, and delayed intra-atrial conduction increase the number of wavelets and promote sustained AF. This model is supported by data from patients with paroxysmal AF demonstrating that widespread distribution of abnormal atrial electrograms predicts progression to persistent AF.[20] Intra-atrial conduction prolongation has also been shown to predict recurrence of AF.[21] Together, these data highlight the importance of atrial structural and electrical remodeling in the maintenance of AF[19] —hence the phrase "atrial fibrillation begets atrial fibrillation."

Etiology

Atrial fibrillation (AF) is strongly associated with the following risk factors:

Hemodynamic stress

Increased intra-atrial pressure results in atrial electrical and structural remodeling and predisposes to AF. The most common causes of increased atrial pressure are mitral or tricuspid valve disease and left ventricular dysfunction. Systemic or pulmonary hypertension also commonly predisposes to atrial pressure overload, and intracardiac tumors or thrombi are rare causes.

Atrial ischemia

Coronary artery disease infrequently leads directly to atrial ischemia and AF. More commonly, severe ventricular ischemia leads to increased intra-atrial pressure and AF.

Inflammation

Myocarditis and pericarditis may be idiopathic or may occur in association with collagen vascular diseases; viral or bacterial infections; or cardiac, esophageal, or thoracic surgery.

Noncardiovascular respiratory causes

Pulmonary embolism, pneumonia, lung cancer, and hypothermia have been associated with AF.

Drug and alcohol use

Stimulants, alcohol, and cocaine can trigger AF. Acute or chronic alcohol use (ie, holiday or Saturday night heart, also known as alcohol-related cardiomyopathy) and illicit drug use (ie, stimulants, methamphetamines, cocaine) have been specifically found to be related to AF. Whereas the association of more than moderate chronic alcohol use and AF has been reported in multiple studies previously, a more recent community-based study found an association with even moderate alcohol use with an increased risk of AF.[22]

Endocrine disorders

Hyperthyroidism, diabetes, and pheochromocytoma have been associated with AF.

Neurologic disorders

Intracranial processes such as subarachnoid hemorrhage or stroke can precipitate AF.

Familial AF

A history of parental AF appears to confer increased likelihood of AF (and occasional family pedigrees of AF are associated with defined ion channel abnormalities, especially sodium channels).[23] One cohort study suggests that familial AF is associated with an increased risk of AF. This increase was not lessened by adjustment for genetic variants and other AF risk factors.[24]

Advancing age

AF is strongly age-dependent, affecting 4% of individuals older than 60 years and 8% of persons older than 80 years.

Other

In a 15-year prospective cohort study of 132,250 Japanese subjects, Xu et al found that anemia and chronic kidney disease, alone and in combination, were associated with an increased risk of new-onset AF.[25, 26] During a mean follow-up of 13.8 years in 1232 patients with new-onset AF, multivariate analysis showed that those with an estimated glomerular filtration rate (eGFR) lower than 60 mL/min/1.73 m2 were 2.56 times more likely to experience new-onset AF compared with patients with normal kidney function; those whose hemoglobin levels were lower than 13 g/dL had a 1.5 times increased risk of new-onset AF relative to patients with normal hemoglobin levels (P< 0.0001 for both analyses).[25, 26] Patients with CKD and anemia had a threefold higher incidence of AF.[26]

Epidemiology

Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia.[19] It affects more than 2.7 to 6.1 million persons in the United States.[27] AF is strongly age-dependent, affecting 4% of individuals older than 60 years and 8% of persons older than 80 years. Approximately 25% of individuals aged 40 years and older will develop AF during their lifetime.[28]

The prevalence of AF is 0.1% in persons younger than 55 years, 3.8% in persons 60 years or older, and 10% in persons 80 years or older. With the projected increase in the elderly population in the United States, the prevalence of AF is expected to more than double by the year 2050. AF is uncommon in childhood except after cardiac surgery.[29]

The incidence of AF is significantly higher in men than in women in all age groups, although this effect may be mediated through the difference in average height between men and women.[30] AF appears to be more common in white individuals than in black persons, with black individuals have less than half the age-adjusted risk of developing AF.

In 10-15% of cases of AF, the disease occurs in the absence of comorbidities. However, AF is often associated with other cardiovascular diseases, including hypertension; heart failure; diabetes-related heart disease; ischemic heart disease; and valvular, dilated, hypertrophic, restrictive, and congenital cardiomyopathies.[28] The Atherosclerosis Risk in Communities (ARIC) Study suggests reduced kidney function and presence of albuminuria are strongly associated with AF.[31]

The rate of ischemic stroke in patients with nonrheumatic AF averages 5% a year, which is somewhere between 2 and 7 times the rate of stroke in patients without AF. The risk of stroke is not due solely to AF; it increases substantially in the presence of other cardiovascular diseases.[32] The prevalence of stroke in patients younger than 60 years is less than 0.5%; however, in those older than 70 years, the prevalence doubles with each decade.[33] The attributable risk of stroke from AF is estimated to be 1.5% for those aged 50-59 years, and it approaches 30% for those aged 80-89 years. Women are at a higher risk of stroke due to AF than men and some have suggested this may be due to undertreatment with warfarin. However, one study of patients 65 years or older with recently diagnosed AF found warfarin use played no part in the increased risk of stroke among female patients.[34]

Prognosis

Atrial fibrillation (AF) is associated with a 1.5- to 1.9-fold higher risk of death, which is in part due to the strong association between AF and thromboembolic events, according to data from the Framingham heart study.[35]

Medical therapies aimed at rhythm control offered no survival advantage over rate control and anticoagulation, according to the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial. The study addressed whether rate control and anticoagulation are sufficient goals for asymptomatic, elderly patients.[36]

AF is associated with increased morbidity and mortality, in part due to the risk of thromboembolic disease, particularly stroke, in AF and in part due to its associated risk factors. Studies have shown that individuals in sinus rhythm live longer than individuals with AF. Disruption of normal atrial electromechanical function in AF leads to blood stasis. This, in turn, can lead to development of thrombus, most commonly in the left atrial appendage. Dislodgement or fragmentation of a clot can then lead to embolic phenomena, including stroke.

Development of AF predicts heart failure and is associated with a worse New York Heart Association Heart Failure classification. AF may also worsen heart failure in individuals who are dependent on the atrial component of the cardiac output. Those with hypertensive heart disease and those with valvular heart disease are particularly at high risk for developing heart failure when AF occurs. In addition, AF may cause tachycardia-mediated cardiomyopathy if adequate rate control is not established.

In critically ill patients, new-onset AF is independently associated with in-hospital and post-ICU risk of death.[37]

Findings from the observational multicenter PLECTRUM study that evaluated the thromboembolic risk regarding the type and site of mechanical prosthetic heart valves, as well as the quality of anticoagulation and risk factors associated with thromboembolism, found that there was a low rate of bleeding and thromboembolic events in patients with these valves, even when anticoagulation control was suboptimal.[38]  There was no association between the thromboembolic risk and low time in therapeutic range, but the presence of AF and a history of thromboembolism and of mitral prosthesis were independent risk factors for thromboembolism.[38]

In a systematic review (13 studies) and meta-analysis (10 eligible studies) of death and adverse outcomes in 54,587 patients with AF and concomitant heart failure, investigators reported a significantly higher all-cause mortality in AF patients with reduced ejection fraction compared to those with preserved ejection fraction.[39] However, the rates of stroke and hospitalizations were similar between the groups.

The risk of stroke from AF that lasts longer than 24 hours is a major concern and is usually addressed by prescribing a blood thinner (warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban). The CHADS2 prognostic scoring system was originally derived to estimate the risk of ischemic stroke in patients with AF. A higher CHADS2 score implies a higher risk of ischemic stroke; in older guidelines, a CHADS2 score of 2 or greater was considered an indication for using blood thinners.[40]  However, the CHADS2 score appears to underestimate the risk of embolic stroke in patients older than 75 years.[41]  Furthermore the CHADS2 score does not include some of the other risk factors associated with ischemic stroke in AF patients, such as female sex and vascular disease.

An analysis of the AFNET (Central Registry of the German Competence NETwork on Atrial Fibrillation) registry of 8847 patients with nonvalvular AF indicated that the CHA2 DS2-VASc score is more sensitive than the CHADS2 score for risk stratification of thromboembolic events (ischemic stroke, transient ischemic attack [TIA], systemic embolism), particularly in patients with a CHADS2 score of 0 or 1 who would have otherwise not received prescribed anticoagulation therapy on the basis of previous guidelines.[42, 43]  However, CHA2 DS2-VAScc scoring—which adds age 65-74 years, arterial disease, and female sex as stroke risk factors to the CHADS2 score[43] —placed 30.3% of those classified as CHADS2 0 or 1 into CHA2 DS2-VASc 1 or 2 and higher, groups in which oral anticoagulation is now recommended.

In another investigation of over 47,000 participants with a CHADS2  score of 0 to 1 who were not on anticoagulation therapy, Olesen et al reported a serial increase in the risk of stroke/thromboembolism with an increase in CHA2 DS2-VASc score.[44] Furthermore, a regression model with the CHA2 DS2-VASc score showed higher discrimination for predicting stroke than the model with the CHADS2 score.[44]

A post-hoc analysis of the ONTARGET and TRANSCEND studies, which evaluated the efficacy of treatment with ramipril plus telmisartan or telmisartan alone in reducing cardiovascular disease, used the Mini–Mental State Examination (MMSE) to measure the cognitive function of participants at baseline and after two and five years. Results show that AF is associated with an increased risk of cognitive decline, new dementia, loss of independence in performing activities of daily living and admission to long-term care facilities.[45]

Atrial fibrillation in association with acute myocardial infarction

AF is a common finding in patients presenting with an acute myocardial infarction. A meta-analysis pooled data from 43 studies and more than 278,800 patients.[46] The study found that AF in the setting of acute myocardial infarction was associated with 40% increase in mortality compared to patients in sinus rhythm with acute myocardial infarction. The causes of death were unclear, but may be related to triple anticoagulation therapy with aspirin, clopidogrel, and warfarin, or may be related to hemodynamic consequences associated with the loss of atrial contraction. Whether AF is a complication of myocardial infarction or a marker for myocardial infarction severity is unclear.

A study by van Diepen et al suggests that patients with heart failure or atrial fibrillation have a significantly higher risk of noncardiac postoperative mortality than patients with coronary artery disease; thus, patients and physicians should consider this risk, even if a minor procedure is planned.[47]

Catheter ablation in association with mortality and stroke

A systemic review and meta-analysis comprising 30 studies and 78,966 patients (about one third receiving AF ablation and two thirds on medical therapy) with 233,990 patient-years of follow-up found a survival benefit for AF ablation relative to medical treatment alone, but these findings were only supported in the setting of heart faiure and left ventricular systolic dysfunction.[48]

History

Clinical presentation spans the entire spectrum from asymptomatic atrial fibrillation (AF) with rapid ventricular response to cardiogenic shock or devastating cerebrovascular accident (CVA).

Initial evaluation of the patient with new-onset atrial fibrillation should focus on the patient's hemodynamic stability. Care of hemodynamically unstable patients is guided by Advanced Cardiac Life Support (ACLS) protocols, including immediate direct current (DC) cardioversion.[49] Symptomatic patients may benefit from intravenous (IV) rate-controlling agents, either calcium-channel blockers or beta-adrenergic blockers.

Although up to 90% of AF episodes may not cause symptoms,[50] many patients experience a wide variety of symptoms, including palpitations, dyspnea, fatigue, dizziness, angina, and decompensated heart failure. In addition, AF can be associated with hemodynamic dysfunction, tachycardia-induced cardiomyopathy, and systemic thromboembolism.

Unstable patients requiring immediate DC cardioversion include the following:

Less severe symptoms and patient complaints include the following:

In addition to eliciting the symptoms above, history taking of any patient presenting with suspected AF should include questions relevant to temporality, precipitating factors (including hydration status, recent infections, alcohol use), history of pharmacologic or electric interventions and responses, and presence of heart disease. An effort should also be made to evaluate for potential comorbid diseases that contribute to initiation or maintenance of AF. Occasionally, a patient may have a clear and strong belief about the onset of symptoms that may be helpful in determining a course of action.

Initial history includes the following:

Documentation of clinical type of AF (paroxysmal, persistent, long-standing persistent, or permanent) (See Diagnostic Considerations.)

Documentation of any previous surgical or percutaneous AF ablation procedures

Physical Examination

Physical examination always begins with airway, breathing, and circulation (ABCs) and vital signs, as these guide the pace of the intervention. The physical examination also provides information on underlying causes and sequelae of atrial fibrillation.

Vital signs

Heart rate, blood pressure, respiratory rate, and oxygen saturation are particularly important in evaluating hemodynamic stability and adequacy of rate control in AF.

Patients will have an irregularly irregular pulse and will commonly be tachycardic, with heart rates typically in the 110- to 140-range, but rarely over 160-170. Patients who are hypothermic or who have cardiac drug toxicity may present with bradycardic atrial fibrillation.

Head and neck

Examination of the head and neck may reveal exophthalmos, thyromegaly, elevated jugular venous pressures, or cyanosis. Carotid artery bruits suggest peripheral arterial disease and increase the likelihood of comorbid coronary artery disease.

Pulmonary

The pulmonary examination may reveal evidence of heart failure (eg, rales, pleural effusion). Wheezes or diminished breath sounds are suggestive of underlying pulmonary disease (eg, chronic obstructive pulmonary disease [COPD], asthma).

Cardiac

The cardiac examination is central to the physical examination of the patient with AF. Thorough palpation and auscultation are necessary to evaluate for valvular heart disease or cardiomyopathy. A displaced point of maximal impulse or S3 suggests ventricular enlargement and elevated left ventricular pressure. A prominent P2 points to the presence of pulmonary hypertension.

Abdomen

The presence of ascites, hepatomegaly, or hepatic capsular tenderness suggests right ventricular failure or intrinsic liver disease. Left upper quadrant pain may suggest splenic infarct from peripheral embolization.

Lower extremities

Examination of the lower extremities may reveal cyanosis, clubbing, or edema. A cool or cold pulseless extremity may suggest peripheral embolization, and assessment of peripheral pulses may lead to the diagnosis of peripheral arterial disease or diminished cardiac output.

Neurologic

Signs of a transient ischemic attack or cerebrovascular accident may be discovered. Evidence of prior stroke and increased reflexes is suggestive of hyperthyroidism.

Approach Considerations

When atrial fibrillation (AF) is suspected during auscultation of the heart with irregularly irregular beats, obtaining a 12-lead electrocardiogram (ECG) is the next step. Because AF is due to irregular atrial activation at a rate of 350-600 bpm with irregular conduction through the atrioventricular (AV) node, it appears on ECG as irregularly irregular narrow complex tachycardia. Fibrillatory (F) waves may be evident or may be absent. Unless the heart is under excess sympathetic or parasympathetic stimulation, the ventricular rate is usually between 80 and 180 bpm.

With an abnormality in the intraventricular conduction system, the QRS complexes may become wide. It is important to pay attention to the electrocardiographic signs of associated cardiac diseases, such as left ventricular hypertrophy (LVH) and preexcitation.

Various cardiac diseases, including ischemic heart disease, valvular diseases, and cardiomyopathy, are associated with AF. Therefore, after the diagnosis of AF is confirmed with ECG, an evaluation of serum cardiac biomarkers and B-type natriuretic peptide (BNP) is usually required to investigate for underlying heart disease. More invasive cardiac tests (eg, cardiac catheterization) may be required depending on signs and symptoms and findings on initial tests. The ECG is also necessary to monitor the QT and QRS intervals of patients receiving anti-arrhythmic medications for AF.

Chest radiographic findings are usually normal in patients with AF. However, chest radiography may provide evidence of congestive heart failure, as well as signs of lung or vascular pathology (eg, chronic obstructive pulmonary disease, pulmonary embolism, pneumonia). In addition, many other noncardiac diseases, such as hyperthyroidism, and many infections and inflammatory diseases, have been associated with AF. Accordingly, chest radiography, thyroid function tests, complete blood cell (CBC) count, and serum chemistry may be helpful, and other tests should be considered, depending on the patient’s presentation. If a reversible cause of AF (eg, hyperthyroidism) is found, it should be treated and the patient should be reassessed afterward.

Electrocardiography

Electrocardiographic (ECG) findings usually confirm the diagnosis of atrial fibrillation (AF) and include the following:

QRS duration appears to be an independent predictor of incident AF among women, but not in men, based on findings from 15,314 participants from the Atherosclerosis Risk in Communities (ARIC) study.[51]  The underlying mechanism for the difference between men and women is not yet clear.

Laboratory Studies

Laboratory studies in patients with atrial fibrillation (AF) are aimed at uncovering underlying disorders, which may be particularly important to address when ventricular rate is difficult to control. One study suggests that minor elevations in troponin I levels upon hospital admission is associated with higher mortality and cardiac events, which may be useful for risk stratification.[52]

Laboratory studies indicated include the following:

Relatively recent studies indicate that increased plasma trimethylamine-N-oxide (TMAO) levels are associated with incident AF independent of traditional AF risk factors and of dietary choline intake.[53] More studies are needed to evaluate endogenous metabolic factors that impact the relationship between TMAO and cardiovascular disease.

Echocardiography

Echocardiography may be used to evaluate for valvular heart disease, left and right atrial size, left ventricular (LV) size and function, left ventricular hypertrophy (LVH), and pericardial disease. Transthoracic echocardiography has low sensitivity in detecting left atrial (LA) thrombus, and transesophageal echocardiography is the modality of choice for this purpose.[54]

Transthoracic echocardiography (TTE) is helpful for making the following determinations:

Transesophageal echocardiography (TEE) is helpful for making the following determinations:

CT Scanning and MRI

In patients with atrial fibrillation (AF) and a positive D-dimer result, chest computed tomography angiography (CTA) may be necessary to rule out pulmonary embolus.

Three-dimensional imaging technologies (CT scan or MRI) are often helpful to evaluate atrial anatomy if AF ablation is planned. Imaging data can be processed to create anatomic maps of the left atrium and pulmonary veins.

Preablation delayed-enhancement magnetic resonance imaging (DE-MRI) in patients with AF may be an important tool to not only determine the extent of atrial disease but also to predict treatment outcome.[55, 56]  In the international multicenter Delayed Enhancement-MRI Determinant of Successful Catheter Ablation of Atrial Fibrillation (DECAAF) trial, DE-MRI prior to ablation therapy for atrial fibrillation was able to stage atrial fibrosis and predict ablation success.[55, 56]  Moreover, the greater the extent of fibrotic tissue ablated during the procedure, the better the outcome.

The investigators reported that preablation stage of atrial fibrosis and postablation residual fibrosis were independent predictors of successful ablation or recurrent symptoms.[55, 56]  However, ablation of the pulmonary veins, the standard of care in AF ablation candidates, was not a significant predictor of treatment success.[55, 56]

The DECAAF-II study is under way; this trial will compare the outcomes of patients who undergo index AF ablation using conventional methods to those of patients who undergo ablation that targets areas of left atrial fibrosis as identified on DE-MRI.

Other Studies

Six-minute walk test or exercise testing

Six-minute walk or exercise testing can help assess the adequacy of rate control (eg, target heart rate of 110 bpm or less during a 6-minute walk) in patients with suspected atrial fibrillation (AF).[36]  Exercise testing can exclude ischemia prior to treatment of patients with class Ic antiarrhythmic drugs and can be used to reproduce exercise-induced AF.

Holter monitoring or event recording

Holter monitoring and event recording may be helpful to establish a diagnosis (eg, in cases of paroxysmal AF not evident upon presentation) and evaluate rate control (eg, target average rate of 100 bpm or less).

Electrophysiology studies

Electrophysiology studies may help identify the mechanism of a wide-QRS tachycardia, a predisposing arrhythmia, or sites for curative ablation or AV node ablation.

Approach Considerations

The cornerstones of atrial fibrillation (AF) management are rate control and anticoagulation[1, 19]  and rhythm control for those symptomatically limited by AF.[19] The clinical decision to use a rhythm-control or rate-control strategy requires an integrated consideration of several factors, including degree of symptoms, likelihood of successful cardioversion, presence of comorbidities, and candidacy for AF ablation (eg, catheter-based pulmonary vein electric isolation or surgical ablation).

Restoration of sinus rhythm with regularization of the heart's rhythm improves cardiac hemodynamics and exercise tolerance. By maintaining the atrial contribution to cardiac output, symptoms of heart failure and overall quality of life can improve. As AF contributes to pathologic atrial and ventricular remodeling, restoration of sinus rhythm can slow or, in some cases, reverse atrial dilatation and left ventricular dysfunction. For these reasons, most clinicians focus initially on restoration and maintenance of sinus rhythm in patients with new-onset AF and opt for a rate-control strategy only when rhythm control fails.

However, several randomized controlled trials have demonstrated that a strategy aimed at restoring and maintaining sinus rhythm neither improves survival nor reduces the risk of stroke in patients with AF.

In the AFFIRM study (Atrial Fibrillation Follow-up Investigation of Rhythm Management), an insignificant trend toward increased mortality was noted in the rate control group, and importantly, no evidence suggested that the rhythm-control strategy protected patients from stroke. In the study, 4060 subjects aged 65 years or older whose AF was likely to be recurrent and who were at risk for stroke were randomized to a strategy of rhythm control (cardioversion to sinus rhythm plus drugs to maintain sinus rhythm) versus a strategy of rate control (in which no attempt was made to restore or maintain normal sinus rhythm).[36] Clinically silent recurrences of AF in the rhythm-control group are theorized to be responsible for the increased rates of thromboembolic events and mortality noted in this cohort. This underscores the importance of anticoagulation in both rhythm-control and rate-control patients.

New developments aimed at curing AF are being explored actively. By reducing the critical mass required to sustain AF through either surgical or catheter-based compartmentalization of the atria (ie, maze procedure), fibrillatory wavelets collide with fixed anatomic obstacles, such as suture lines or complete lines of ablation, thus eliminating or reducing the development of permanent AF. One concern is that an extensive maze procedure can render the atrial severely hypocontractile, which may elevate the risk of embolic stroke even if AF is substantively suppressed. Some patients with focal origins of their AF also may be candidates for catheter ablation. Simple electric isolation of the origins of the pulmonary veins has proven roughly up to 80% successful in substantially reducing frequency and duration of AF in patients who do not tolerate AF well.

AF ablation methods continue to be studied and modified and thus may be considered as a work in progress rather than a mature primary therapy. Go to Catheter Ablation for complete information on this topic.

2019 ACC/AHA/HRS updated guidelines

A focused update of the American College of Cardiology/American Heart Association (ACC/AHA) Task Force on Clinical Practice Guidelines and the Heart Rhythm Society (HRS) 2014 guidelines for the management of patients with atrial fibrillation (AF) was released in January 2019.[57, 58, 59]

Selecting an anticoagulant regimen

For patients with AF and an elevated CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism [doubled], vascular disease, age 65-74 years, sex category) score of 2 or greater in men or 3 or greater in women, oral anticoagulants are recommended.

Female sex, in the absence of other AF risk factors (CHA2DS2-VASc score of 0 in males and 1 in females), carries a low stroke risk that is similar to males. Adding female sex to the CHA2DS2-VASc score matters for age >65 years or ≥2 non–sex-related stroke risk factors.

Non-vitamin K oral anticoagulants (NOACs) (dabigatran, rivaroxaban, apixaban, and edoxaban) are recommended over warfarin in NOAC-eligible patients with AF (except those with moderate-to-severe mitral stenosis or a mechanical heart valve).

In patients with AF (except those with moderate-to-severe mitral stenosis or a mechanical heart valve), the CHA2DS2-VASc score is recommended for assessment of stroke risk. For patients with AF who have mechanical heart valves, warfarin is recommended.

Renal and hepatic function should be evaluated before initiation of a NOAC, and both should be reevaluated at least annually.

Aspirin is no longer recommended for patients with low CHA2DS2-VASc scores. For patients with AF (except those with moderate-to-severe mitral stenosis or a mechanical heart valve) and a CHA2DS2-VASc score of 1 in men or 2 in women, clinicians may consider prescribing an oral anticoagulant to reduce the risk of thromboembolic stroke.

Interruption and bridging anticoagulation

Idarucizumab is recommended for dabigatran reversal in the event of life-threatening bleeding or an urgent procedure. Andexanet alfa can be useful for rivaroxaban and apixaban reversal in the event of life-threatening or uncontrolled bleeding.

Percutaneous approaches to occlude the LAA

Percutaneous left atrial appendage (LAA) occlusion may be considered in patients with AF at an increased risk of stroke who have contraindications to long-term anticoagulation.

Prevention of thromboembolism

For patients with AF or atrial flutter of at least 48 hours, or when the AF duration is unknown, anticoagulation with warfarin (international normalized ratio [INR] 2.0-3.0), a factor Xa inhibitor, or direct thrombin inhibitor is recommended for at least 3 weeks before and at least 4 weeks after cardioversion, regardless of the CHA2DS2-VASc score or the method (electrical or pharmacologic) used to restore sinus rhythm.

Catheter ablation in HF

AF catheter ablation may be reasonable in selected patients with symptomatic AF and heart failure (HF) with reduced left ventricular (LV) ejection fraction (HFrEF) to potentially lower the mortality rate and reduce hospitalization for HF.

AF complication ACS

In patients with AF at increased risk of stroke (based on CHA2DS2-VASc risk score of ≥2) who have undergone percutaneous coronary intervention (PCI) with stenting for acute coronary syndrome (ACS), the following is reasonable to reduce the risk of bleeding as compared with triple therapy (oral anticoagulant, aspirin, and P2Y12 inhibitor):

If triple therapy is prescribed for patients with AF who are at an increased risk of stroke (based on CHA2DS2-VASc risk score of ≥2) and who have undergone PCI with stenting (drug eluting or bare metal) for ACS, clinicians may consider a transition to double therapy (oral anticoagulant and P2Y12 inhibitor) at 4-6 weeks.

Weight loss in patients with AF

For overweight and obese patients with AF, weight loss, combined with risk factor modification, is recommended.

Risk-Management Decisions

One of the major management decisions in atrial fibrillation (AF) (and atrial flutter) is determining the risk of stroke and appropriate anticoagulation regimen for low-, intermediate-, and high-risk patients. For each anticoagulant, the benefit in terms of stroke reduction must be weighed against the risk of clinically significant bleeding.

Overall, approximately 15-25% of all strokes in the United States (75,000/y) can be attributed to AF. Known risk factors for stroke in patients with AF include advancing age, female sex, hypertension, diabetes, heart failure, prior history of stroke/transient ischemic attack (TIA)/thromboembolism, coronary artery disease, peripheral arterial disease, and valvular heart disease (rheumatic valvular disease).[1]

At least four large clinical trials have clearly demonstrated that anticoagulation with warfarin decreases the risk of stroke by 50-80%. In relatively recent trials, the newer oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban) have proven to be similarly effective (dabigatran 110 mg, rivaroxaban, or edoxaban) or superior (dabigatran 150 mg or apixaban) to warfarin for prevention of stroke and thromboembolism.[60] However, although anticoagulants reduce 30-day mortality from ischemic stroke, these agents increase intracranial hemorrhage–related mortality.[61] If warfarin is chosen for anticoagulation, a target international normalized ratio (INR) of 2-3 is traditionally used in this cohort, as this limits the risk of hemorrhage while providing protection against thrombus formation. Warfarin is also superior to clopidogrel or a combination of clopidogrel and aspirin in the prevention of embolic events in higher-risk patients.

Most clinicians agree that the risk-benefit ratio of anticoagulants in low-risk patients with AF is not advantageous. The appropriate treatment regimen for patients with AF at intermediate risk is controversial. In this population, clinicians should assess risk factors for thromboembolic disease, patient preference, risk of bleeding, risk of falls or trauma, and likelihood of medication adherence.[62]

Note that treatment risks exist with concomitant antiplatelet therapy with oral anticoagulation in patients with AF. A study analyzing concomitant use of aspirin and its association with clinical outcomes among AF patients treated with oral anticoagulation found a significantly increased risk for bleeding among those receiving both therapies.[63] Hospitalizations for bleeding events were also increased in the group treated with this treatment combination.

Of the 7347 AF patients on oral anticoagulation therapy who participated in the study, 2543 (35%) also received aspirin.[63] Among the patients treated with aspirin, 39% did not have a history of atherosclerotic disease and 17% had elevated ATRIA bleeding risk scores. Compared with patients receiving oral anticoagulation alone, those receiving concomitant aspirin had a significantly higher risk of major bleeding (adjusted hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.20-1.96) and bleeding hospitalizations (adjusted HR 1.52, 95% CI 1.17-1.97).[63]

Results from a retrospective study by Sjalander et al of 115,185 Swedish patients with AF indicated that aspirin as monotherapy not only did not protect against stroke, but it was also associated with an increased risk of ischemic stroke and thromboembolic events in elderly patients, as compared with no antithrombotic treatment.[64] In the study, 58,671 patients received aspirin monotherapy, whereas 56,514 did not receive any antithrombotic treatment at baseline; mean follow-up was 1.5 years.

Several risk factor assessment algorithms have been developed to aid the clinician on decisions on anticoagulation for patients with AF. The CHADS2 index (Cardiac failure, Hypertension, Age ≥75 years, Diabetes, Stroke or transient ischemic attack [TIA]) was widely used previously[65] ; however, multiple more recent studies have proven the superiority of the CHA2DS2-Vasc score over the CHADS2 score in predicting the risk of thromboembolism in patients with AF, particularly for participants with low to intermediated CHADS2 scores (0-1).[44, 66]

The CHA2DS2-Vasc score uses a point system to determine yearly thromboembolic risk. Two points are assigned for a history of stroke or TIA, thromboembolism, or age of 75 years or older, and one point is given for age 65-74 years or a history of hypertension, diabetes, heart failure, arterial disease (coronary artery disease, peripheral arterial disease, or aortic plaque), or female sex. The predictive value of this scoring system was evaluated in 90,490 elderly patients with nonvalvular AF who were taking warfarin therapy.[67] An increase in CHA2 DS2-VASc score was associated with serial increase in the risk of stroke (see Table 1 below).

Table 1. Stroke Rate in Patients with Nonvalvular Atrial Fibrillation not Treated with Anticoagulation[67]



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See Table

Recommendations on anticoagulation for patients with nonvalvular AF have been based on the 2014 American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society (HRS) task force guidelines on the management of patients with AF (see Table 2 below).[1]

Table 2. Recommendations for Antithrombotic Therapy in Patients with Nonvalvular Atrial Fibrillation



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See Table

Management of New-Onset AF

Results from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study and similar findings from the smaller Rate Control Versus Electrical Cardioversion (RACE) trial[68]  led to the development of consensus guidelines that recommend an initial rate-control strategy for the majority of asymptomatic patients with atrial fibrillation (AF).

Rate control

Regardless of the long-term management strategy chosen, control of ventricular rate is a critical component of management of new-onset AF. The main determinants of the ventricular rate during AF are those intrinsic and extrinsic factors that influence atrioventricular (AV) conduction. Foremost among these are the intrinsic AV nodal conduction properties. Underlying sympathetic and parasympathetic tone also influences AV nodal conduction. Rate-controlling agents act primarily by increasing AV nodal refractoriness.

Beta-blockers and calcium channel blockers are first-line agents for rate control in AF. These drugs can be administered either intravenously or orally. They are effective at rest and with exertion. Intravenous diltiazem or metoprolol are commonly used for AF with a rapid ventricular response. Caution should be exercised in patients with reactive airway disease who are given beta-blockers.

Digoxin can be used in the acute setting but does little to control the ventricular rate in active patients. As such, it is rarely used as monotherapy. Caution should be exercised in elderly patients and those with renal failure receiving digoxin. Digoxin is indicated in patients with heart failure and reduced left ventricular function.

A large study of elderly persons with nonvalvular AF or atrial flutter indicated that digoxin therapy can increase the risk that a patient will die within approximately 3 years by more than 20%.[69, 70] The study, The Retrospective Evaluation and Assessment of Therapies in AF (TREAT-AF), involved more than 122,000 elderly US veterans (mean age 72 years) with newly diagnosed AF or atrial flutter, almost a quarter of whom underwent early therapy with digoxin. After a follow-up period of about 3 years, the multivariate-adjusted hazard ratio for patient mortality was calculated to be 1.26 in the digoxin group. According to the investigators, the increased mortality risk was not associated with drug adherence, concomitant treatment, comorbid cardiovascular disorders, or renal function.[69, 70]

Amiodarone has a class IIa recommendation from the 2014 American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society (HRS) for use as a rate-controlling agent for patients who are intolerant of or unresponsive to other agents, such as patients with congestive heart failure (CHF) who may otherwise not tolerate diltiazem or metoprolol.[1] Caution should be exercised in those who are not receiving anticoagulation, as amiodarone can promote cardioversion.

Extreme care must be taken in patients with preexcitation syndrome and AF. Blocking the AV node in some of these patients may lead to AF impulses that are transmitted exclusively down the accessory pathway, and this can result in ventricular fibrillation. (If this happens, the patient will require immediate defibrillation.) Beta-blockers, non-dihydropyridine calcium channel blockers, digoxin, and intravenous amiodarone are contraindicated in these patients; flecainide or amiodarone can be used instead.[1, 71]

Anticoagulation

One of the most important considerations in the acute management of atrial fibrillation is the need for anticoagulation (see the image below). Acute cardioversion for AF carries a risk of thromboembolism unless anticoagulation therapy is initiated prior to the procedure and continued post procedure. Risk of thromboembolism is similar in patients undergoing either pharmacologic or electrical cardioversion. The risk of thromboembolic events is greatest when AF has been present for longer than 48 hours.

Transesophageal echocardiography (TEE) is a good predictor of acute risk. If no thrombus is seen in the cardiac chambers, particularly the left atrial appendage, and dense spontaneous echo contrast is not seen, cardioversion has low acute risk of stroke. Effective anticoagulation in patients with AF reduces the risk of stroke 3-fold after 4-6 weeks.



View Image

Patient management for newly diagnosed atrial fibrillation (Afib). *Therapeutic anticoagulation implies either treatment with warfarin with a therapeu....

Patients with newly diagnosed AF and patients awaiting electrical cardioversion can be started on intravenous heparin (activated partial thromboplastin time [aPTT] of 45-60 seconds) or low-molecular-weight heparin (LMWH) (1 mg/kg twice daily [BID]).

Patients can be started concomitantly on warfarin in an inpatient setting while awaiting a therapeutic international normalized ratio [INR] value (2-3). Many practices have developed specialized anticoagulation clinics to monitor INR values closely. Newer oral anticoagulants are attractive alternatives to warfarin in patients with nonvalvular AF. These agents include dabigatran, rivaroxaban, apixaban, and edoxaban, and they can be started without the need for an anticoagulation bridge with heparin or LMWH before cardioversion.

Cardioversion

Cardioversion may be performed electively or emergently to restore sinus rhythm in patients with new-onset AF. Cardioversion is most successful when initiated within 7 days after onset of AF. The need for cardioversion may be acute when AF is responsible for hypotension, heart failure, or angina.

Pharmacologic agents or direct current energy can be used to cardiovert patients with AF. Pharmacologic cardioversion has the advantage of not requiring sedation or anesthesia, but the major disadvantage is the risk of ventricular tachycardia and other serious arrhythmias.

Long-Term Management

Long-term management of atrial fibrillation (AF) is focused on reducing the likelihood of AF recurrence, reducing AF-related symptoms, control of ventricular rate, and reducing stroke risk. As discussed previously, AF is often the result of established cardiovascular risk factors. Appropriate management of these risk factors will reduce the likelihood of future episodes of AF and AF-related morbidity and mortality. Anticoagulation with either aspirin or warfarin should be initiated for all individuals with AF, except in those with contraindications. Selection of the appropriate antithrombotic regimen for a given patient should be balanced between the risk of stroke and the risk of bleeding. Antiarrhythmic therapy can aid in maintenance of sinus rhythm in certain patients but requires close monitoring.

Optimal long-term strategies for AF management should be based on a thoroughly integrated consideration of patient-specific factors and likelihood of success. As a rule, younger patients with more severe symptoms and fewer comorbidities tend to derive greater benefit from a long-term focus on rhythm control. Older patients with structural heart disease (eg, left ventricular hypertrophy, prior myocardial infarction, depressed ejection fraction, atrial dilatation) are less likely to remain in sinus rhythm and are more likely to have serious side effects from antiarrhythmic drugs. In this cohort, most clinicians focus on long-term rate control.

Because of the electrophysiologic and structural remodeling caused by AF, many patients with paroxysmal AF will progress to persistent and long-standing persistent AF. The degree to which this reflects the continuing influence of underlying cardiovascular risk factors as opposed to a direct effect of AF is unknown. Regardless, clinicians need to reevaluate their management strategies frequently, as AF burden and comorbidities increase with time.

Anticoagulation

The goal of long-term anticoagulation in AF is to reduce the risk of thromboembolism. Patients in AF have a risk of stroke or peripheral embolism that is approximately five times that of individuals in sinus rhythm. Recommendations for anticoagulation for patients with nonvalvular AF are based on guidelines from a 2014 American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society (HRS) task force on the management of patients with AF.[1]  Currently approved anticoagulants include warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban.

Warfarin

Anticoagulation therapy with warfarin is significantly more effective than antiplatelet therapy (relative risk of 40%) if the international normalized ratio (INR) is adjusted. The INR goal in AF is usually between 2 and 3, except in patients who are at a significant risk for stroke (eg, patients with artificial valves, those with rheumatic heart disease, and those at a high risk for AF with recurrent prior strokes), in whom the INR should be maintained between 2.5 and 3.5. A lower INR goal (1.8-2) may be considered in elderly patients who are at high risk for a fall.

Anticoagulation clinics have shown more success and a lower complication rate than primary care physicians in controlling patients’ INR. In addition, one study reported that patients who used an Internet-based program for patient self-management of oral anticoagulant therapy achieved a higher mean time in the therapeutic range than patients whose INR was controlled by an established anticoagulation clinic.[72] Similar programs alone or in combination with regular care provided by anticoagulation clinics may improve the mean time that patients are in the therapeutic range and may further reduce the risk of stroke.

As patients with AF age, the relative efficacy of oral anticoagulation appears not to decrease, whereas the efficacy of antiplatelet therapy does appear to decrease.[73] A mutation in coagulation factor IX may cause spontaneous bleeding, even with an INR in the therapeutic range. Adverse effects of warfarin therapy are not limited to bleeding, however; other important side effects include skin necrosis within the first few days of therapy and cholesterol embolization to the skin or visceral organs in the first few weeks of therapy.

Several scoring systems have been developed to estimate risk-benefit for warfarin use in AF (summarized below).

The major adverse effect of anticoagulation therapy with warfarin is bleeding. Factors that increase this risk include the following:

Several risk models have been introduced. The risk model called HEMORR2HAGES assigns points to risk factors, as follows[74] :

Using this scoring, the risks of a major bleeding event per 100 patient-years of warfarin therapy are as follows:

When the bleeding risk outweighs the benefit, avoidance of anticoagulation therapy in AF should be considered. In addition, because of its teratogenic effects, anticoagulation with warfarin is contraindicated in pregnant women, especially in the first trimester.

Dabigatran

Dabigatran (Pradaxa) is a direct oral thrombin inhibitor. The RE-LY study evaluated the efficacy and safety of two different doses of dabigatran relative to warfarin in more than 18,000 patients with AF. Patients were randomized to one of three arms: (1) adjusted-dose warfarin, (2) dabigatran 110 mg twice daily (BID), or (3) dabigatran 150 mg BID. Dabigatran 110 mg was noninferior to warfarin for the primary efficacy endpoint of stroke or systemic embolization, whereas dabigatran 150 mg was significantly more effective than warfarin or dabigatran 110 mg. Major bleeding occurred significantly less often with dabigatran 110 mg than with warfarin; dabigatran 150 mg had similar bleeding to that of warfarin.[75, 76]

A meta-analysis by Uchino and Hernandez evaluated the risk of myocardial infarction or acute coronary syndrome (ACS) with the use of dabigatran. The results suggest the risk of myocardial infarction or ACS was similar when using revised RE-LY trial results. Dabigatran is associated with an increased risk of myocardial infarction or ACS in an extensive range of patients when tested against different controls.[77]

A different meta-analysis involving more than 1000 patients found that major bleeding complications were generally less critical and more manageable in patients being treated with dabigatran than in those on warfarin therapy. For example, in patients treated with dabigatran, the worst major bleeds tended to be gastrointestinal, whereas in patients treated with warfarin, most of the worst bleeds were intracranial and therefore more difficult to treat. In addition, among patients with major bleeds, the dabigatran patients spent less time in intensive care and had a lower mortality rate than did the warfarin patients.[78, 79]

The US Food and Drug Administration (FDA) has approved the 150 mg BID dose—but not the 110 mg BID dose—of dabigatran for the management of patients with AF. The 75 mg BID dose has also been approved for patients with moderate renal failure (creatinine clearance of 15-29 mL/min). Patients with AF who are not candidates for dabigatran include those with prosthetic heart valves or hemodynamically significant valve disease, severe renal failure (creatinine clearance ≤15 mL/min), or advanced liver disease.

Rivaroxaban

Rivaroxaban (Xarelto) was approved by the FDA in November 2011 for nonvalvular AF.[80] It is a highly selective direct factor Xa inhibitor with high oral bioavailability, and with rapid onset of action. Clinical trial data have shown that it allows predictable anticoagulation with no need for dose adjustments and routine coagulation monitoring.[81]

Approval of rivaroxaban was based on the ROCKET-AF multinational, double-blind trial, in which the risk of major bleeding was similar for rivaroxaban and warfarin, but a significantly lower risk of intracranial hemorrhage and fatal bleeding was seen with rivaroxaban when compared with warfarin.[82]  The study included over 14,000 patients who were randomized to either rivaroxaban or warfarin; rivaroxaban 20 mg once daily was used for patients with normal renal function and 15 mg once daily for patients with mild renal failure (creatinine clearance of 30-49 mL/min). In the primary analysis of this study, rivaroxaban was found to be noninferior to warfarin for prevention of stroke or systemic embolism in patients with nonvalvular AF.[82] During the approval process, there was concern expressed over the amount of time the warfarin-treated patients spent at the optimal INR during the study (57.8%), which was lower than in other trials with warfarin (eg, RE-LY trial for Dabigatran).[75] Also, the participants of the ROCKET-AF trial had higher mean CHADS2 scores (3.67) when compared to those of the RE-LY trial (2.1).

Apixaban

Another factor Xa inhibitor, apixaban (Eliquis), was approved by the FDA in December 2012. Approval was based on two clinical trials: ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in AF) and AVERROES (Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in AF Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment). (Patients with serum creatinine of 2.5 mL/dL or greater were excluded from both apixaban trials.)

The ARISTOTLE  trial compared apixaban with warfarin for the prevention of stroke or systemic embolism in 18,201 patients with AF and found that apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality.[83, 84, 85]

The AVERROES trial, which compared apixaban with aspirin in 5599 patients with AF for whom warfarin therapy was considered unsuitable, was stopped early (after 1.1 year) after an interim analysis because apixaban showed a significant reduction in stroke and systemic embolism compared with aspirin.[86] A modest increase of major bleeding was observed with apixaban compared with aspirin.[86]

Edoxaban

Edoxaban (Savaysa) was approved for the prevention of thromboembolism in AF by the FDA in January 2015 on the basis of results from the ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction Study 48) trial.[87] This double-blind, noninferiority trial randomized 21,105 patients with nonvalvular AF to high-dose edoxaban (60 mg daily), low-dose edoxaban (30 mg daily), or warfarin (creatinine clearance up to 30 mL/min was an exclusion criterion). Mean CHADS2 score for the subjects in this trial was 2.8. In intention-to-treat analyses, both doses of edoxaban were noninferior to warfarin for prevention of the stroke and systemic embolic events; however, there was a trend toward superiority for high-dose edoxaban (embolic risk of 1.57% with high-dose edoxaban compared to 1.8% with warfarin; P = 0.08).[87]

Of note, in participants with a creatinine clearance of 95 mL/min or greater, the hazard ratios (HRs) for developing embolic events were similar between the high-dose edoxaban and the warfarin groups.[87] Consequently, the FDA recommends avoiding edoxaban in patients with a creatinine clearance of 95 mL/min.[88] Both doses of edoxaban were reported to be superior to warfarin for all types of bleeding, except gastrointestinal bleeding wherein low-dose edoxaban was superior (HR: 0.67 (ie, 33% lower risk of bleeding); P< 0.001), whereas high-dose edoxaban was inferior to warfarin (HR: 1.23 [ie, 23% higher risk of bleeding]; P = 0.03).

A meta-analysis of four randomized trials involving 42,411 patients who received newer anticoagulants and 29,272 who received warfarin showed that, in patients with AF, the newer oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban protected against stroke or systemic embolism better than warfarin and had comparable safety profiles.[87, 89, 90, 91]

The newer anticoagulants also significantly reduced the incidence of all-cause mortality and intracranial hemorrhage, but increased gastrointestinal bleeding. Median follow-up periods ranged from 1.8 years to 2.8 years. The risk of stroke or systemic embolic events was reduced by 19% with the newer anticoagulants compared with warfarin; hemorrhagic strokes accounted for a large proportion of the reduction. Compared with warfarin, low-dose new anticoagulant regimens showed similar overall reductions in stroke or systemic embolic events and a more favorable bleeding profile, but significantly more ischemic strokes.[87, 89, 90, 91]

Newer oral anticoagulants versus warfarin

There are several advantages of using the newer oral anticoagulants over warfarin, including the following:

Disadvantages of the newer oral anticoagulants include the following:

Reversal of anticoagulation

In the presence of acute major bleeding, emergent reversal of anticoagulation is required. Fresh frozen plasma is often utilized to reverse the effects of warfarin, but it takes 6-24 hours to achieve compete reversal. In more emergent settings, prothrombin complex concentrates (PCCs) can be used, because they provide complete reversal of anticoagulation in 15-20 minutes.[94]

For patients taking newer oral anticoagulants, several reversal agents have been developed; however, it should be noted that these newer anticoagulants have short half-lives (5-17 hours), and reversal is rarely indicated. Idarucizumab (Praxbind) is a monoclonal antibody fragment which binds with high affinity to dabigatran. Its efficacy was studied in the RE-VERSE AD trial (Reversal Effects of Idarucizumab on Active Dabigatran) in which 90 patients who were taking dabigatran and presented with serious bleeding or had a need for an urgent invasive procedure (< 8 hours) were given two doses of idarucizumab 15 minutes apart. As measured by laboratory testing, idarucizumab completely normalized coagulation parameters in 90% of patients within the first 10-30 minutes. Five thrombotic events and 18 deaths were reported, but there was no control group to compare the relative risk of thrombosis and death.[92]

Andexanet alfa targets and sequesters factor Xa inhibitors (rivaraoxaban, apixaban, edoxaban). This agent is currently under clinical trials and is not FDA approved.[93, 95]

Recommendations from the American Academy of Neurology (AAN)

In 2014, the AAN released level B and C recommendations on the prevention of stroke in patients with nonvalvular AF. The level B recommendations included the following[96, 97] :

Postoperative and postdischarge anticoagulation therapy

Anticoagulation prior to and during an elective surgery may be continued or stopped depending on the patient’s risk of bleeding and risk of thromboembolism. If the risk of thromboembolism is high (stratified by the CHA2DS2-Vasc score) and the risk of bleeding is low, anticoagulation should be continued with the INR in the low therapeutic range. However, a high risk of bleeding during the procedure should prompt discontinuation of warfarin for 3-5 days prior to surgery. These patients should then be treated with heparin prior to and following the operation to allow discontinuation of anticoagulation if bleeding occurs. Newer anticoagulants can generally be discontinued 1-2 days before the surgery and do not require bridging with heparin or low molecular-weight heparin (LMWH). 

In general, patients who develop AF only postoperatively do not need anticoagulation. Administration of preoperative and postoperative beta-blockers is usually sufficient, as postoperative AF is usually paroxysmal and tends to terminate spontaneously. The Colchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS) AF Substudy found that the administering of colchicine appears to be safe and efficacious in the reduction of postoperative AF, which could potentially halve the complication and reduce the time a patient stays in the hospital.[98]

Research has shown that the administration of colchicine in patients who underwent pulmonary vein isolation helped to prevent early recurrences of paroxysmal AF.[99, 100] This process appeared to be mediated through a postablation reduction in inflammation.

A large cohort study in Denmark compared the bleeding risk of anticoagulants prescribed upon hospital discharge for AF: During mean follow-up (3.3 years), 11.4% of patients experienced a nonfatal or fatal bleeding episode.[101] The highest incidence for bleeding was observed for dual therapy with warfarin and clopidogrel and for triple therapy with warfarin, aspirin, and clopidogrel (3-fold higher risk) compared with single agent use.[101]

Omega-3 fatty acids

Several small trials have suggested that treatment for paroxysmal AF with prescription omega-3 fatty acids may provide a safe and effective treatment option. However, no benefit has been found to date.[102, 103]

Angiotensin-converting enzyme (ACE) inhibitors and ACE-receptor blockers (ARB)

Trials examining the incidence of AF in patients with heart failure who are treated with ACE inhibitors or ARBs have demonstrated a potential beneficial effect on AF recurrence. This recurrence is thought to be mediated by blocking the rennin-angiotensin-aldosterone system and the downstream effects on atrial mechanical and electrical remodeling.[104, 105, 106]

A study by Yusuf et al examined the effects of irbesartan in patients with permanent AF or at least two episodes of paroxysmal AF in the previous 6 months.[107] Irbesartan did not demonstrate a benefit in patients with AF who were already receiving an ACE inhibitor or patients in sinus rhythm. No reduction in cardiovascular death, stroke, or myocardial infarction was noted in the patient population studied.

Rate control

As discussed previously, several trials have validated the noninferiority of an initial rate-control strategy. Many clinicians believe, however, that an attempt at a rhythm-control strategy should be made in most patients. Older patients with comorbid cardiovascular disease have a lower likelihood of successful long-term rhythm control, and thus, these patients are often managed using a rate-control strategy. Some patients managed initially with a rhythm-control strategy will progress to recurrent or persistent AF. Clinicians often switch to a rate-control strategy as the AF burden increases.

Effectiveness of rate control should be assessed both at rest and with exertion, especially in patients who experience primarily exertional AF-related symptoms. Twenty-four hour Holter monitoring or exercise-treadmill testing can be helpful in evaluating heart rate variability.

Adequate rate control was previously defined as a heart rate of 60-80 bpm at rest and 90-115 bpm with moderate exercise. However, the ACC/AHA/HRS guidelines on the management of AF now advise that there is no benefit in achieving strict heart rate control (< 80 bpm at rest, < 110 bpm after a 6-minute walk) relative to more lenient rate control (< 110 bpm at rest). Strict rate control in patients with stable ventricular function is no longer recommended.[1]

AV nodal blocking medications are the cornerstone of rate control in long-standing AF. In the absence of an accessory pathway, oral beta-blockers, non-dihydropyridine calcium channel blockers, and digoxin are effective. Generally, coadministration of beta-blockers and calcium channel blockers is reserved for patients in whom adequate rate control cannot be achieved with a single agent.

Digoxin can be effective in sedentary patients (especially in those with heart failure) but requires close monitoring of drug levels, serum electrolytes (potassium, magnesium), and renal function. Combinations of rate-control medications (eg, beta-blocker and digoxin) may be superior to individual agents in some patients.

Amiodarone may contribute to ventricular rate control. However, antiarrhythmic agents may organize AF to a potentially life-threatening atrial flutter with 1:1 AV conduction. Particularly with class IC agents, maintenance of effective AV nodal rate control is essential in most patients. Therefore, administration of a beta-blocker or calcium channel blocker is recommended before class IC drugs are initiated.

In the presence of tachycardia-mediated cardiomyopathy or inadequate ventricular rate control despite drug therapy, AV nodal ablation and permanent pacemaker implantation may be considered.

Rhythm control

Maintenance of sinus rhythm requires treatment of cardiovascular risk factors and any underlying disorder (eg, hyperthyroidism, sleep apnea) that may have triggered AF. As mentioned previously, several antiarrhythmic drugs (flecainide, propafenone, dofetilide, amiodarone) have an established efficacy in the pharmacologic conversion of AF to sinus rhythm. The noncardiac adverse effects and contraindications of each drug should be checked prior to administration.

Amiodarone, as a part of a strategy to achieve sinus rhythm, appears to be safe and effective in patients with persistent AF, according to Doyle and Ho. However, in their study, intolerable adverse effects were more common with amiodarone than with placebo or rate-control drugs.[108] Nevertheless, in patients with cardiac disease such as coronary artery disease or systolic or diastolic heart failure, amiodarone becomes the drug of choice because of its decreased proarrhythmic effects compared with other antiarrhythmic drugs.[71]

Amiodarone was also found to be more effective at maintaining sinus rhythm than other drugs in the Canadian Trial of Atrial Fibrillation (CTAF) and the Sotalol Amiodarone Atrial Fibrillation Efficacy Trial (SAFE-T).[109, 110]

Dronedarone is structurally similar to amiodarone, but it lacks amiodarone's iodine moieties. Although the lack of iodine moieties reduces the incidence of adverse events, dronedarone is less effective for rhythm control than amiodarone.[111] Dronedarone has been found to be associated with increased mortality in patients with permanent AF. The randomized, double-blind, phase III Permanent Atrial fibriLLation Outcome Study Using Dronedarone on Top of Standard Therapy (PALLAS) trial was halted following a preliminary review that revealed that dronedarone was associated with a 2-fold rise in risk of death.[112] Two-fold increases in two other endpoints, stroke and hospitalization for heart failure, were also noted when compared with placebo.

The FDA advises healthcare professionals not to prescribe dronedarone to patients with permanent AF. A separate study by Connolly et al also found that dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent AF who were at risk for major vascular events; the authors of that study suggested that dronedarone should not be used in this group of patients.[113]  The 2014 ACC/AHA/HRS guidelines for the management of AF advise against using dronedarone for patients with New York Heart Association (NYHA) class III and IV heart failure or for patients who have had an episode of decompensated heart failure in the past 4 weeks.[1]

Several distinct agents, most notably sotalol, are used for the long-term maintenance of sinus rhythm. Sotalol is efficacious, but as with other class III drugs, it requires close monitoring of the QT interval and serum electrolyte levels. Sotalol is associated with the risk of QT interval prolongation and torsade de pointes. The proarrhythmic effect of sotalol is increased in patients with congestive heart failure (unlike dofetilide and amiodarone), so it is generally contraindicated in such patients or in those with a prolonged QT interval. Hypokalemia should be corrected and monitored prior to administration of sotalol because it may also prolong the QT interval. Sotalol can be used in patients with coronary artery disease.[71]

In a study of 99 consecutive patients with persistent AF, atrial flutter, or both, patients whose AF responded to chemical cardioversion with dofetilide were particularly vulnerable to proarrhythmias.[114, 115] Of the 99 patients, 46 had successful cardioversion after an average of 2.2 doses of dofetilide, and 53 required electrical cardioversion after an average of 4.7 doses. Of the 21 patients who chemically converted with only one dose of dofetilide, 15 developed QT prolongation and had to either adjust their dose or discontinue treatment. In contrast, only one patient in the electrical conversion group had to discontinue treatment because of QT prolongation. In all, 2% of the patients in the electrical conversion group and 17% of those in the dofetilide-sensitive group had to discontinue treatment because of QT prolongation (P = 0.007).[114, 115]

Class III agents (sotalol, amiodarone) also have some beta-blocking effect and should be used with caution in patients with a history of bradycardia.

Class Ic drugs (flecainide, propafenone) increased the mortality risk in patients with coronary artery disease during the Cardiac Arrhythmia Suppression Trial (CAST) and therefore should not be used in these patients.[116]

Class Ic drugs increased the mortality risk in patients with coronary artery disease during the Cardiac Arrhythmia Suppression Trial (CAST) and therefore should not be used in these patients.[110]

Ablation (catheter based, surgical, or hybrid) for AF can also be performed for achieving rhythm-control. The ACC/AHA/HRS guidelines recommend catheter ablation in the following settings[1] :

Surgical ablation of AF is also an option for patients with AF undergoing other cardiac surgery and for those patients in whom pharmacologic and catheter-based procedures are ineffective or contraindicated. AF ablation may be superior to AV nodal ablation and biventricular pacing in heart failure patients but is technically difficult and demanding, and the widespread applicability of ablation in this population of patients is uncertain.

In the first randomized clinical trial comparing the efficacy and safety of catheter ablation versus minimally invasive surgical ablation during a 12-month follow-up, Boersma et al found that patients with AF who had a dilated left atrium and hypertension or who failed prior AF catheter ablation, surgical ablation was superior in achieving freedom from left atrial arrhythmias after 12 months of follow-up; however, the procedural adverse event rate was found to be significantly higher with surgical ablation than for catheter ablation, primarily postoperative pneumothorax, major bleeding, and an increased need for permanent pacing.[117]

Go to Catheter Ablation for complete information on this topic.

New medical and device-based rhythm-control therapies are being explored actively. Experimental and clinical data suggest that renin-angiotensin system (RAS) antagonists and HMG-CoA-reductase inhibitors (statins) may decrease the incidence of AF and increase the likelihood of successful cardioversion.[118, 119, 120, 121] Device-based therapies under investigation include single- and dual-site atrial pacemakers to prevent AF, as well as atrial defibrillators to rapidly restore sinus rhythm. Invasive (surgical and catheter-based) therapies to compartmentalize the atria and localize focal triggers (in the pulmonary veins) are being evaluated and refined.

Electrical cardioversion

Patients who are hemodynamically unstable, who have severe dyspnea or chest pain with AF, or who have preexcited AF should undergo urgent cardioversion.[71] In stable patients with symptomatic new-onset AF, the rate-control strategy may be considered first to control the ventricular rate. If rate-control treatment does not elicit a response or if echocardiography does not reveal any valvular or functional abnormality of the heart, cardioversion is indicated.

Direct current (DC) cardioversion is the delivery of electrical current that is synchronized to the QRS complexes; it can be delivered in monophasic or biphasic waveforms. The required energy for cardioversion is usually 100-200 J (sometimes higher energy is required) for monophasic waveforms and less for biphasic waveforms. The patient should be sedated. In patients with AF of relatively short duration in whom the left atrium is not significantly large, the success rate of cardioversion exceeds 75% (ie, the size of the left atrium and the duration of AF inversely correlate with the success rate of cardioversion).

Embolization is the most important complication of cardioversion. Accordingly, thrombus in the heart should be ruled out with transesophageal echocardiography (TEE), or anticoagulation should be provided for 3-4 weeks before cardioversion is performed. Stunning of the atria and stasis can occur after cardioversion, and this can lead to thrombus formation even though the patient is in sinus rhythm. Therefore, the patient should receive anticoagulants for at least 4 weeks following the procedure.

Other complications of electrical cardioversion may include pulmonary edema, hypotension, myocardial dysfunction, and skin burns, which may be avoided with the use of steroid cream and proper technique. Electrical cardioversion is also associated with some ST- and T-wave changes on electrocardiography (ECG) and may elevate levels of serum cardiac biomarkers. Synchronization prevents serious ventricular arrhythmias.

Placement of pads or paddle positions include anterior-lateral (ventricular apex and right infraclavicular) and anterior-posterior (sternum and left scapular), with at least one study suggesting increased efficacy with the anterior-posterior (AP) method.

Biphasic waveforms are proved to convert AF at lower energies and higher rates than monophasic waveforms. Strategies include dose escalation (70, 120, 150, 170 J for biphasic or 100, 200, 300, 360 J for monophasic) versus beginning with single high energy/highest success rate for single shock delivered. Patients who are stable and/or awake and can tolerate sedation should be pretreated, with typical regimens involving midazolam, fentanyl, and propofol.

Cardioversion of patients with implanted pacemakers and defibrillator devices is safe when appropriate precautions are taken. Keeping the cardioversion pads in an AP orientation ensures that the shocks are not directly over the generator. Alteration in pacer-programmed data has been reported, as well as heart block and elevated enzymes if the current is conducted through a pacer lead.

Pharmacologic cardioversion

Although pharmacologic cardioversion may be used as the first-line strategy, it is used mainly if DC cardioversion fails or, in some cases, as a precardioversion strategy.

Out-of-hospital self-administration of either flecainide 300 mg or propafenone 600 mg (weight-based dosages if >70 kg) was determined to be successful in terminating AF in 94% of episodes (mean time to symptom resolution of 133 minutes) by Alboni et al. The investigators studied outpatient treatment of AF with a “pill-in-the-pocket” approach in 268 patients with little or no structural heart disease presenting to the emergency department with symptomatic AF.[122]

Pretreatment with amiodarone, flecainide, ibutilide, propafenone, or sotalol has been shown to increase the success rate of DC cardioversion.[4] This strategy is also recommended when DC cardioversion fails and prior to repeat DC cardioversion.[4] Intravenous amiodarone is typically given as a 150-mg bolus over 10-15 minutes, followed by a continuous infusion of 1 mg/min for 6 hours and then 0.5 mg/min.

Hemodynamically unstable patients (eg, those with hypotension) may not tolerate antiarrhythmic drugs, and the adverse effects and contraindications of each antiarrhythmic drug should be considered carefully before administration. Because of possible proarrhythmic adverse effects of antiarrhythmic drugs, these patients should be monitored for at least 24 hours, requiring hospitalization in most cases.

The FDA mandates inpatient monitoring for dofetilide initiation. Patients who start sotalol usually require inpatient monitoring (for torsade de pointes), although patients with no heart disease, with a QT interval less than 450 msec, and with normal electrolyte levels should be started on outpatient medications.

Special considerations

Postoperative AF is common, and perioperative beta-blockers are recommended in all patients undergoing cardiac surgery unless contraindicated.[123] Preoperative administration of amiodarone and sotalol may reduce the incidence of AF in patients undergoing cardiac surgery. As such, these agents may be used as prophylactic therapy in those at high risk for postoperative AF.

Postoperative AF was reduced by treatment with landiolol hydrochloride.[124] Amelioration of ischemia, an anti-inflammatory effect, and inhibition of sympathetic hypertonia by landiolol presumably reduced the occurrence of AF. Hypotension or bradycardia did not develop in any of the patients, indicating the safety of this beta-blocker. These findings suggest that landiolol hydrochloride could be useful in the perioperative management of patients undergoing cardiac surgery.[124]

Retrospective data suggest that atrial-based pacing (AAI, DDD modes) reduces the risk of developing AF and increases the interval between episodes in patients with sick sinus syndrome.[125]

Overview of Surgical and Catheter Ablation

The goal of catheter ablation and surgical treatment of atrial fibrillation (AF) is to disconnect triggers and/or to modify the substrate for AF. Mapping and radiofrequency (RF) ablation of AF is one of the most complex ablation procedures. Numerous approaches are used depending on the expertise of the cardiac electrophysiologist and characteristics of the AF.

Paroxysmal AF is usually caused by triggered and ectopic activity in pulmonary veins, and ablation around the veins terminates the arrhythmia. In persistent AF, triggering foci and reentry circuits may coexist in the atrial tissue, requiring more extensive mapping and ablation to terminate the AF; this yields a lower success rate than ablation used to treat paroxysmal AF.

Antiarrhythimic drug treatment for 6 weeks after ablation of paroxysmal AF was shown to be well tolerated, to reduce the incidence of clinically significant atrial arrhythmias, and to reduce the need for cardioversion or hospital admission during that period, according to Roux et al.[126] Class IC drugs were used as the first line of therapy, and sotalol was the most commonly used drug in cases of left ventricular dysfunction or coronary artery disease. Measured outcomes included atrial arrhythmias lasting more than 24 hours; atrial arrhythmias associated with severe symptoms that required hospitalization, cardioversion, or initiation/change of antiarrhythmic drug therapy; and intolerance to antiarrhythmic agent requiring drug cessation.[126]

Hussein et al performed a registry study that examined controls and patients with mitral valve replacement who underwent AF ablation.[127] No cases of catheter entrapment or stroke were reported. Although most patients required more than one ablation, at last follow-up, 69% were arrhythmia-free and no longer taking antiarrhythmic medications. This provides evidence that AF ablation is safe in this group of patients. Of note, many patients had flutter and creation of a flutter line was one of the keys to success.[127]

Compartmentalization of the Atria

Two approaches to compartmentalization of the atria are surgical, by which multiple cuts are made to the atria, and radiofrequency ablation (RFA).

Surgical compartmentalization of the atria (maze procedure)

Since its inception, surgical compartmentalization of the atria, or the “maze” procedure, has evolved as an exciting approach with the potential to cure atrial fibrillation (AF). The procedure involves making a series of small endocardial incisions in the right and left atria to isolate the pulmonary veins and interrupt potential reentrant pathways required for AF maintenance. Early experience showed that atrial transport is restored postoperatively and that long-term anticoagulation is not required.

The downside remains the need for an open chest procedure; however, thoracoscopic approaches have been developed which reduce the duration of hospitalization and recovery times. The maze procedure remains an attractive procedure for patients with AF who are undergoing concomitant mitral valve procedures. Its role as a primary therapy for AF is doubtful. The role of lesion sets on outcome after maze procedure was studied; the addition of right-sided ablation was found to improve clinical and electrophysiologic results after maze procedure.[128]

Compartmentalization of the atria with continuous ablation lines of blockage

As a parallel to the maze procedure, electrophysiologists have attempted to mimic surgical suture lines with radiofrequency (RF) lesions. The procedures tend to last many hours, and success rates have been somewhat disappointing (50-60%), with the occurrence of left atrial reentrant tachycardias and left atrial flutters (requiring further ablation procedures).[129]

Researchers are uncertain which areas of the atria are necessary to sustain AF. Purely right-sided lesions are not sufficient to eliminate AF, making left atrial procedures necessary. In addition, gaps in linear lesions can be difficult to find.

Research currently focuses on catheter design to deliver linear continuous lesions. Additionally, alternative energy sources (eg, cryotherapy, laser, ultrasonography) may improve the ability to deliver transmural lesions in the left atrium.

Catheter Ablation of Focal Triggers of AF

In some patients, atrial fibrillation (AF) appears to be triggered by electrically active pulmonary vein foci.[130] These patients typically have an abundance of ectopic atrial beats noted on 24-hour Holter monitoring. Electrical isolation of individual pulmonary veins, and thus the ectopic foci, is performed successfully at many centers, and patient selection is key to success.

In a study by Santangeli and colleagues, 59% of patients with paroxysmal AF who underwent a single pulmonary vein antrum isolation (PVAI) procedure were arrhythmia free by 10-year follow-up.[131]  The study involved 513 adult patients with drug-refractory paroxysmal AF, all of whom underwent catheter ablation extended to the posterior wall between the pulmonary veins.

Among those patients who underwent multiple procedures for recurrent arrhythmia, Santangeli et al reported that 87% were arrhythmia free by the 10-year mark and that the rate of late recurrence of AF was lower than those reported for segmental and less-extensive antral isolation procedures.[131]  However, nonpulmonary vein triggers causing very late recurrence of atrial arrhythmia developed in a significant number of patients.

In a follow-up study, these researchers reported similar findings: 58.7% of patients with paroxysmal AF who underwent the single procedure remained arrhythmia free survival after 12 years, with the highest rate of recurrent arrhythmia in the year 1 (21%) and the lowest rate between years 6 and 12 of follow-up (5.3%).[132] Nearly three quarters of the patients (74%) required repeat procedures, with nearly one third of these (31%) undergoing reconnection in the pulmonary vein antrum after a single procedure and none after two procedures, and another approximate 14% who developed recurrent owing to new non-pulmonary vein triggers. Overall, after multiple procedures, 87% of patients achieved freedom from recurrent AF/atrial tachycardia.[132]

Two major catheter-based modalities for isolating pulmonary venous triggers currently exist: radiofrequency ablation (RFA) and cryoballoon ablation. Cryoballoon ablation offers significantly shorter fluoroscopy and procedures times with similar efficacy as RFA in patients with paroxysmal AF.[133] Patients with persistent AF often require left atrial compartmentalization and ablation of nonpulmonary vein triggers; RFA is preferred in these scenarios.

Chest computed tomography (CT) scanning or magnetic resonance imaging (MRI) can be used to recreate 3-dimensional anatomy in the left atrium, thus aiding in mapping and creating contiguous lines in the left atrium.



View Video

The image on the right is a reconstructed 3-dimensional image of the right atrium in a patient undergoing atrial fibrillation ablation. The figure on the left was created with a mapping catheter using Endocardial Solutions mapping technology. It represents the endocardial shell of the right atrium and is used as the template during left atrial ablation procedures.

The AF cure rate after pulmonary vein isolation may be influenced by sinus node function in both the early and late stages. Although further examinations are required, pulmonary vein isolation may be an adequate treatment for persistent/permanent AF in patients with normal sinus node function.[134]

Patients with paroxysmal AF in whom antiarrhythmic drug therapy does not elicit a response are potential candidates for ablation of AF. The threshold for catheter ablation has fallen over the years and is likely to continue to fall. Ablation of persistent AF is more complex and yields lower success rates. Therefore, RFA is generally considered only if antiarrhythmic drugs fail in patients with persistent AF who remain severely symptomatic despite adequate ventricular rate control.[135]

The success rate of catheter ablation in the treatment of AF varies depending on the type and duration of AF (ie, paroxysmal vs persistent), structural remodeling of the heart, and the technique and expertise of the cardiac electrophysiologist, but it usually ranges from 60-80% over 1-2 years of follow-up.

Patients opting for AF ablation should be told to expect to undergo repeat ablations because these are not uncommon and they improve overall success.[136] In a randomized, clinical trial, a repeat pulmonary vein isolation procedure was more effective than the use of antiarrhythmic drugs in preventing recurrences of paroxysmal AF.[137, 138] The results of the trial further suggested that switching to antiarrhythmic drugs may give the AF time to worsen.

In this study, 154 patients with a 4- to 5-year history of symptomatic AF before the first ablation were randomized to antiarrhythmics or to repeat pulmonary vein isolation.[138] By 3 months, the AF burden was significantly lower in the repeat pulmonary vein isolation group than in the antiarrhythmics group (1.9% vs 3.3%). The AF burden then began to rise in the antiarrhythmics group, reaching 18.8% by 36 months. In contrast, the AF burden did not begin to rise in the reablation group until 15 months after the procedure, reaching just 5.6% at 36 months.

Complications are rarely seen with catheter ablation of AF, but they can include cardiac perforation, pericardial effusion, cardiac tamponade, vascular access complications (bleeding, pseudoaneurysms), pulmonary vein stenosis, thromboembolism, atrioesophageal fistula, left atrial flutter/tachycardia, and phrenic nerve injury (which is more common with cryoballoon ablation). Pulmonary vein stenosis develops in about 6% of patients and may cause dyspnea, chest pain, cough, and hemoptysis.[4] If pulmonary vein stenosis is suspected following catheter ablation, further diagnostic workup with transesophageal echocardiography (TEE), spiral CT scanning, or MRI is recommended. MRI is the most accurate test in diagnosing this complication. Patients with pulmonary vein stenosis should undergo percutaneous angioplasty, which can significantly improve pulmonary blood flow and the patient's symptoms.

Go to Catheter Ablation for complete information on this topic.

AV Node Modification and Permanent Pacemakers

Atrioventricular (AV) node modification may be an alternative in patients with persistent atrial fibrillation (AF) and an uncontrolled ventricular response despite aggressive medical therapy. Catheter ablation of the AV junction permanently interrupts conduction from the atria to the ventricles.

Because the result is permanent AV block, a permanent ventricular pacemaker is required. AF may still be present, but the pacemaker governs the ventricular response. The risk of thromboembolism is unchanged, and patients still require anticoagulation; however, most patients are relieved of their symptoms. During the first 1-3 months, the pacing rate must be programmed in the 80- to 90-beat range to prevent torsade de pointes, which presumably occurs because of slow ventricular rates and early after-depolarizations. In patients with ventricular dysfunction (left ventricular ejection fraction < 50%) and permanent ventricular pacing, a biventricular device may be appropriate.[139] Improvements in left ventricular size and function, functional class, and quality-of-life scores have been demonstrated.[140]

Left Atrial Appendage Percutaneous Closure

The majority of embolic stroke in patients with nonvalvular atrial fibrillation (AF) are associated with left atrial appendage (LAA) thrombi. LAA closure may be a suitable alternative to long-term warfarin therapy for stroke prophylaxis in patients with nonvalvular AF.[141]  Currently available devices for LAA closure/ligation include the WATCHMAN device, WAVECREST device, AMPLATZER cardiac plug (ACP) or amulet, and LARIAT endocardial/epicardial suture.[142]

Two randomized trials have assessed the efficacy and safety of LAA closure using the WATCHMAN device. The PROTECT-AF (Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) trial randomized 707 patients with nonvalvular AF and at least one additional risk factor for stroke to either warfarin or LAA closure.[141] Patients who received the WATCHMAN device received 45 days of warfarin and aspirin therapy after implantation. If there was an adequate seal (ie, no leaks >5 mm around the device on TEE performed 45 days after implantation), patients were transitioned to aspirin and clopidogrel for 6 months, followed by lifelong aspirin .

The WATCHMAN device was found to be noninferior to warfarin therapy for the composite primary end-point of stroke, systemic embolism, and cardiovascular or unexplained death.[141] Furthermore, the risk of hemorrhagic stroke was significantly lower in group implanted with the WATCHMAN device compared to the group who received warfarin therapy. However, up to 5% of patients who received the WATCHMAN device developed serious pericardial effusions.

Due to this safety concern, the PREVAIL (Prospective Randomized Evaluation of the Watchman LAA Closure Device in Patients with Atrial Fibrillation Versus Long-Term Warfarin Therapy) trial was undertaken, in which only 2.2% of the participants developed pericardial effusion.[143] This trial randomized 407 patients to receive WATCHMAN device or warfarin therapy, wherein the presence of more than one risk factor for stroke was required, the mean CHADS2 score for the participants was 2.6, and 25% of the operators had to be new operators.

In a patient-level meta-analysis utilizing data from the PROTECT and the PREVAIL studies, as well as follow-up registry data (2406 patients with average duration of follow-up 2.7 years), Holmes et al reported that the WATCHMAN device was associated with a nearly 80% reduction in the risk of hemorrhagic stroke, and a 50% reduction in the risk of cardiovascular/unexplained death, when compared to warfarin therapy.[144] However, the risk of ischemic stroke with the WATCHMAN device was significantly higher than with warfarin therapy.

On the basis of the published trial data, the WATCHMAN device implantation seems to be reasonable alternative to warfarin therapy when there is contraindications for long-term anticoagulation with warfarin. Large clinical trials for the WAVECREST and AMPLATZER devices are under way.

As compared to the other three percutaneous LAA closure devices, LARIAT is an endocardial/epicardial suturing system for ligation of LAA. An epicardial approach is utilized to deliver a pretied suture over a snare, and this is facilitated by an endocardial magnetic-tip guide wire. In a multicenter series, major bleeding was reported in 9% of the patients who underwent LARIAT procedure.[145] However, unlike with the WATCHMAN device, there is no need for postprocedure anticoagulation. Larger studies with long-term follow-up to assess the efficacy and safety of LARIAT device are also under way.

Consultations

Consultation with a cardiac electrophysiologist or knowledgeable clinician is recommended prior to antiarrhythmic drug initiation in patients with atrial fibrillation (AF).

A cardiologist may be consulted emergently if complicating factors are present or if the patient is experiencing ongoing cardiac ischemia or infarction not treatable with direct current (DC) cardioversion, rate-reduction measures, and standard chest pain protocols.[146] A patient with acute myocardial infarction (AMI) and new-onset AF who is stable may benefit from simple rate-control measures (eg, intravenous beta-blockers) while being prepared for the catheterization laboratory and while intravenous nitrates, heparin, and aspirin are initiated. In the patient with an ST elevation MI (STEMI), the main emphasis, however, is to minimize door-to-open-artery time.

A patient's cardiologist plays a vital role in determining the most appropriate long-term strategy for a patient with AF and provides crucial follow-up care.

Long Term Monitoring

Catheter ablation of atrial fibrillation (AF)

Patients who undergo AF catheter ablation should be monitored for the signs and symptoms of potential complications, such as the following:

In addition, AF can recur and most episodes are asymptomatic. Therefore, it is important to monitor for signs and symptoms of recurrent AF in follow-up visits and to administer appropriate diagnostic tests if recurrence is suspected. In a prospective study (2011-2014)  that evaluated conventional intermittent Holter and electrocardiographic (ECG) monitoring for recurrent AF following surgical ablation with continuous monitoring via an implantable loop recorder (ILR) in 47 patients, compliance at 12 months was 93% for IRL, 76% for Holter monitoring, and 85% for ECG monitoring.[147] Moreover, detection of atrial tachyarrhythmias was equivalent between continuous monitoring with ILR and intermittent Holter and ECG monitoring. However, the investigators cautioned that these data were limited for broad use of continuous monitoring owing to a high rate of false-positive results (54%) and a limited number of events available for review (11%).[147]

Further outpatient care

Assessment and reassessment of thromboembolic risk is necessary, and periodic ECG monitoring (especially when taking antiarrhythmic agents) and Holter monitoring are often necessary to assess for paroxysmal AF and/or rate control.

Deterrence/prevention

Experimental and clinical data suggest that renin-angiotensin system (RAS) antagonists and HMG-CoA reductase inhibitors (statins) may decrease the incidence of AF and increase the likelihood of successful cardioversion.[118, 119, 120, 121]

In addition, treatment of underlying cardiovascular risk factors such as hypertension, coronary artery disease (CAD), valvular heart disease, obesity, sleep apnea, diabetes, and heart failure is likely to decrease the incidence of AF. Fish oil preparations have also been shown to reduce ventricular arrhythmias in at-risk populations (CAD) and may also protect against AF.

Atrial Fibrillation Classification

Guideline contributor: Noel G Boyle, MB, BCh, MD, PhD, Professor of Medicine, UCLA Cardiac Arrhythmia Center, Ronald Reagan UCLA Medical Center.

Atrial fibrillation classification

In 2014, the American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) released updated guidelines for the management of patients with atrial fibrillation (AF). These guidelines supersede the AF guideline published in 2006 and updated in 2011. The guidelines provide the following revised classification schema, based on duration of episodes[1]

It is further noted that episodes often increase in frequency and duration over time. In addition, the term “lone AF” to identify AF in typically younger patients without structural heart disease, hypertension, or diabetes mellitus is deemed potentially confusing and should not be used to guide treatment decisions.[1]

The European Society of Cardiology (ESC) utilizes a similar classification schema published in its 2010 guidelines. The ESC included one additional characterization, silent AF (asymptomatic), which can manifest as AF-related complications such as ischemic stroke or tachycardiomyopathy, or is diagnosed incidentally on electrocardiography (ECG). Any form of AF may be silent or asymptomatic.[148]

Stroke Risk Assessment

Guidelines have been issued by the following organizations for prevention of stroke in atrial fibrillation (AF) patients:

All major guidelines note that one of the major management decisions in AF is determining the risk of stroke and the appropriate anticoagulation regimen for low-, intermediate-, and high-risk patients. For each anticoagulant, the benefit in terms of stroke reduction must be weighed against the risk of serious bleeding, with the risk-benefit ratio generally considered not advantageous in low-risk patients with AF. Thus, the guidelines stress that clinical judgment and patient preferences should play a major role in shared decision making.[1, 97, 149, 150]

The CHADS2 score (Cardiac failure, Hypertension, Age >75 years, Diabetes, prior Stroke or TIA [transient ischemic attack]) is the most widely used algorithm to determine yearly thromboembolic risk. Two points are assigned for a history of stroke or TIA, and 1 point is given for age older than 75 years or a history of hypertension, diabetes, or heart failure.[65]

The ACCP bases its recommendations for antithrombotic therapy in patients with nonvalvular atrial fibrillation (NVAF) on the CHADS2 score, as follows[150] :

However, the 2014 AHA/ACC/HRS and 2012 updated ESC guidelines both recommend that the CHADS2 score be replaced with the more comprehensive CHA2DS2-VASc score.[1, 149] In this scoring system, points are assigned as follows[66] :

The AHA/ACC/HRS further recommends that antithrombotic therapy should be based on the risk of thromboembolism irrespective of whether the AF pattern is paroxysmal, persistent or permanent.[1]

In 2014, the American Heart Association (AHA) also issued joint guidelines with the American Stroke Association (ASA) for the primary prevention of stroke, which included specific recommendations for stroke prevention in patients with AF. The main advantage of the CHA2DS2-VASc score (range, 0-9) is that it provides significantly improved risk prediction for individuals at low to moderate risk compared with the CHADS2 (scores of 0 or 1), particularly for elderly women.[151]

The AHA/ACC/HRS recommendations for antithrombotic therapy in patients with AF, based on CHA2DS2-VASc scores, are as follows[1] :

The ESC offers varying recommendations for patients with AF based on CHA2DS2-VASc scores, as follows[149] :

The shift from the CHADS2 score to the CHA2DS2-VASc score has not been without controversy. The number of patients eligible for oral anticoagulant therapy in the United States is estimated to increase by nearly 1 million, raising concerns about the associated increase in bleeding complications. An analysis by O’Brien and colleagues concluded that using the 2014 AHA/ACC/HRS recommendations to guide the management of AF would result in 98.5% of patients 65 years of age and older and 97.7% of women with AF receiving a definitive recommendation for oral anticoagulant therapy.[152]

The 2014 AAN revised guidelines for stroke prevention in NVAF recommend use of risk stratification to aid in clinical decision making, but do not recommend the use of any specific tool. Furthermore, the guidelines caution against use of strictly interpreted thresholds as definitive indicators for which patients require anticoagulation therapy. Additional recommendations for patient selection included the following[97] :

Antithrombotic Therapy

The major guidelines vary considerably in their recommendations for antithrombotic therapy. See the table below.

Table. Antithrombotic Therapy Recommendations for Atrial Fibrillation



View Table

See Table

Rate Control

The 2017 American Academy of Family Physicians updated guidelines on the pharmacologic management of newly diagnosed atrial fibrillation (AF) include the following recommendations for patients with AF[153] :

The 2014 American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society (HRS) guidelines include the following recommendations for control of ventricular rate in patients with AF[1] :

Cardioversion

The 2014 American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society (HRS) guidelines provide the following recommendations regarding cardioversion of atrial fibrillation (AF)[1] :

NOTE: Repeated cardioversions may be undertaken in patients with persistent AF, provided that sinus rhythm can be maintained for a clinically meaningful period between cardioversion procedures; severity of AF symptoms and patient preference should be considered before initiation of a strategy requiring serial cardioversions

In general, the European Society of Cardiology (ESC) recommendations for cardioversion concur with the AHA/ACC/HRS guidelines. Many of the differences between the guidelines involve the use of vernakalant, which was approved for use in European Union in 2010 but has not been approved by the US Food and Drug Administration. Additional and/or variant ESC recommendations include the following[149] :

The ESC guidelines note that vernakalant is contraindicated in patients with any of the following:

Maintaining Sinus Rhythm

The 2014 American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society (HRS) guidelines include the following recommendations for the prevention of atrial fibrillation (AF) and maintenance of sinus rhythm[1] :

The European Society of Cardiology (ESC) recommendations for maintenance of sinus rhythm are similar to those in the AHA/ACC/HRS.[149]

Catheter Ablation

Both the 2014 American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society (HRS) and 2012 European Society of Cardiology updated guidelines suggest a more prominent role for radiofrequency ablation in the treatment of atrial fibrillation (AF), including its use as first-line therapy in recurrent symptomatic paroxysmal or persistent AF.[1, 149]

According to AHA/ACC/HRS guidelines, AF catheter ablation is contraindicated for patients who cannot be treated with anticoagulant therapy during and after the procedure and should not be performed with the sole intent of eliminating the need for anticoagulation.[1]

The 2017 HRS/EHRA/ECAS/APHRS/SOLAECE (HRS, European Heart Rhythm Association, European Cardiac Arrhythmia Society, Asia Pacific Heart Rhythm Society, and the Latin American Society of Cardiac Stimulation and Electrophysiology (Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología [SOLAECE]) expert consensus statement on catheter and surgical ablation of AF completely supersedes the 2012 HRS/EHRA/ECAS expert consensus statement. It provides updated definitions, mechanisms, and rationale for AF ablation and consensus recommendations concerning indications, strategies, techniques, and endpoints, technology and tools, and follow-up considerations for AF ablation.

Key points of this document include the following[154] :

The 2019 ACC/AHA/HRS focused update on the management of patients with AF indicates that AF catheter ablation may be reasonable in selected patients with symptomatic AF and heart failure (HF) with reduced left ventricular (LV) ejection fraction (HFrEF) to potentially lower the mortality rate and reduce hospitalization for HF.[57]

Supraventricular Arrhythmias Guidelines

In August 2019, the European Society of Cardiology (ESC) in collaboration with the Association for European Paediatric and Congenital Cardiology (AEPC) released recommendations on the management of supraventricular tachycardia.[155, 156] Previous related guidelines include, but are not limited to, the 2017 European Heart Rhythm Association[157] guidelines for the management of supraventricular tachycardia which includes specific recommendations for both acute and ongoing management of atrial tachycardia. These guidelines are summarized in the following sections.

2019 ESC/AEPC Guidelines for the Management of Supraventricular Tachycardia

Supraventricular Tachycardia Clinical Practice Guidelines (2019)

Several changes from the previous guidelines (2003) include revised drug grades as well as medications that are no longer considered, and changes to ablation techniques and indications.[155, 156]

Table. Medications, Strategies, and Techniques Specified or Not Mentioned in the 2019 Guidelines



View Table

See Table

2019 New Recommendations

For detailed recommendations on specific types of SVTs, please consult the original guidelines as listed under the references.

Class I (recommended or indicated)

For conversion of atrial flutter: Intravenous (IV) ibutilide, or IV or oral (PO) (in-hospital) dofetilide

For termination of atrial flutter (when an implanted pacemaker or defibrillator is present): High-rate atrial pacing

For asymptomatic patients with high-risk features (eg, shortest pre-excited RR interval during atrial fibrillation [SPERRI] ≤250 ms, accessory pathway [AP] effective refractory period [ERP] ≤250 ms, multiple APs, and an inducible AP-mediated tachycardia) as identified on electrophysiology testing (EPS) using isoprenaline: Catheter ablation

For tachycardia responsible for tachycardiomyopathy that cannot be ablated or controlled by drugs: Atrioventricular nodal ablation followed by pacing (“ablate and pace”) (biventricular or His-bundle pacing)

First trimester of pregnancy: Avoid all antiarrhythmic drugs, if possible

Class IIa (should be considered)

Symptomatic patients with inappropriate sinus tachycardia: Consider ivabradine alone or with a beta-blocker

Atrial flutter without atrial fibrillation: Consider anticoagulation (initiation threshold not yet established)

Asymptomatic preexcitation: Consider EPS for risk stratification

Asymptomatic preexcitation with left ventricular dysfunction due to electrical dyssynchrony: Consider catheter ablation

Class IIb (may be considered)

Acute focal atrial tachycardia: Consider IV ibutilide

Chronic focal atrial tachycardia: Consider ivabradine with a beta-blocker

Postural orthostatic tachycardia syndrome: Consider ivabradine

Asymptomatic preexcitation: Consider noninvasive assessment of the AP conducting properties

Asymptomatic preexcitation with low-risk AP at invasive/noninvasive risk stratification: Consider catheter ablation

Prevention of SVT in pregnant women without Wolff-Parkinson-White syndrome: Consider beta-1 selective blockers (except atenolol) (preferred) or verapamil

Prevention of SVT in pregnant women without Wolff-Parkinson-White syndrome and without ischemic or structural heart disease: Consider flecainide or propafenone

Class III (not recommended)

IV amiodarone is not recommended for preexcited atrial fibrillation.

2017 EHRA Consensus Document on the Management of Supraventricular Arrhythmias

The European Heart Rhythm Association (EHRA) published its consensus document on the management of supraventricular arrhythmias, which has been endorsed by Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardiaca y Electrofisiologia (SOLAECE).[157]

Acute Management (without established diagnosis)

In the setting of hemodynamically unstable supraventricular tachycardia (SVT), synchronized electrical cardioversion is recommended.

In the setting of hemodynamically stable SVT, vagal maneuvers, preferably in the supine position, or adenosine are recommended. Intravenous (IV) diltiazen or verapamil, or beta blockers, may be considered.

Sinus Tachycardia

Inappropriate sinus tachycardia

Sinus nodal reentrant tachycardia

Focal Atrial Tachycardia

Acute therapy

Chronic therapy

Atrial Flutter (AFL)/ Macroreentrant tachycardia (MRT)

Acute therapy

Chronic therapy

Stroke prevention

AV Nodal Reentrant Tachycardia (AVNRT)

Acute therapy

Chronic therapy

Focal Junctional Tachycardia

In the setting of acute therapy, IV propranolol with or without procainamide, verapamil, or flecainide may be considered.

In the setting of chronic therapy, beta blockers and, in the absence of ischemic or structural heart disease, flecainide or propafenone may be considered. Catheter ablation may be considered, but there is a risk of AV block.

AV Reentrant Tachycardia (AVRT) Due to Manifest/Concealed Accessory Pathways

Acute therapy

Chronic therapy

Asymptomatic Preexcitation

Patients with asymptomatic ventricular preexcitation: Consider electrophysiologic (EP) testing for risk stratification.

Asymptomatic patients with preexcited ECG: Consider screening programs for risk stratification.

Catheter ablation of accessory pathways may be considered in asymptomatic patients with accessory pathways with an antegrade refractory period of less than 240 ms, inducible AVRT triggering preexcited AF, and multiple accessory pathways.

Observation without treatment may be reasonable in asymptomatic Wolff-Parkinson-White patients who are considered to be at low risk following an EP study or due to intermittent preexcitation.

SVTs in Patients With Adult Congenital Heart Disease

Acute therapy

Hemodynamically stable SVT (NOTE: Use caution in those with sinus node dysfunction and impaired ventricular function with a need for chronotropic or inotropic support.)

Hemodynamically stable AVNRT/AVRT

Hemodynamically stable AFL / atrial tachycardia

Chronic therapy

Recurrent symptomatic SVT

Planned surgical repair and symptomatic SVT

SVT During Pregnancy

Acute therapy

Chronic therapy

Resources

For more information, please go to Atrial Tachycardia, Atrial Flutter, and Atrioventricular Nodal Reentry Tachycardia.

For more Clinical Practice Guidelines, please go to Guidelines.

Medication Summary

The goals of medical therapy for patients with atrial fibrillation (AF) are to maintain sinus rhythm, avoid the risk of complications (eg, stroke), and minimize symptoms. Warfarin represents the cornerstone of anticoagulant therapy for patients at moderate to high risk of thromboembolic events. Some patients may not be able to take anticoagulants because of contraindications or comorbidities.

Warfarin is associated with approximately 30% of reported anticoagulant-related errors. In an effort to improve patient safety, Schillig et al implemented an inpatient Pharmacist-Directed Anticoagulation Service (PDAS) to help patients reduce the risks associated with initiation of Coumadin when transitioning from the inpatient to the outpatient setting. This included appropriate enrollment in the anticoagulation clinic, documented inpatient-to-outpatient provider contact, documented inpatient provider-to-anticoagulation clinic communication, and patient follow-up with the anticoagulation clinic within 5 days of discharge. The results suggest PDAS may improve quality of care.[158]

In patients unable to take warfarin, the addition of clopidogrel to aspirin was shown to reduce the risk of major vascular events, especially stroke, when compared with placebo and aspirin in the ACTIVE (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) trial; however, increased risk for major hemorrhage was more prevalent in the clopidogrel plus aspirin group than the placebo and aspirin group. The ACTIVE trial studied 7554 patients with AF with the intent to determine whether adding clopidogrel to aspirin therapy would reduce the risk for acute vascular events (ie, stroke, myocardial infarction [MI], non-central nervous system [CNS] systemic embolism, or death from vascular event).[159]

In another study, among AF patients treated with concomitant aspirin and oral anticoagulation, there was also a significantly increased risk for bleeding.[63] Hospitalizations for bleeding events were also increased in those receiving this treatment combination.

Clopidogrel has been suggested to be less effective in reducing the rate of cardiovascular events in individuals who carry the loss-of-function CYP2C19 alleles. However, a 2010 study concluded that patients with acute coronary syndromes or AF respond well to clopidogrel, regardless of CYP2C19 loss-of-function carrier status.[160]

The goal of antiarrhythmic drug therapy is to reduce the duration and frequency of atrial fibrillation episodes, thus improving patient quality of life and symptoms. If successful, rhythm control can eliminate or delay the need for long-term anticoagulation with warfarin in some patients.

Several antiarrhythmic drugs are commonly used to prevent atrial fibrillation recurrence, such as quinidine, flecainide, propafenone, sotalol, and dofetilide. Other antiarrhythmic agents, such as amiodarone, are used in an off-label fashion with great clinical efficacy. Use of antiarrhythmic drugs requires caution because they are proarrhythmic. These agents can exacerbate preexisting arrhythmias and generate arrhythmia de novo. Tachyarrhythmias and bradyarrhythmias generated by these agents can be of ventricular or atrial origin. Drug-drug interactions and extracardiac side effects are common. Consultation with a cardiac electrophysiologist or knowledgeable clinician is recommended prior to antiarrhythmic drug initiation.

If maintenance of sinus rhythm is the goal, the American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society (HRS) have jointly developed guidelines for the long-term antiarrhythmic treatment in the maintenance of sinus rhythm.[1] These guidelines are intended to help clinicians tailor antiarrhythmic therapy on an individual basis for their patients.

The following algorithm incorporates clinical trial data on the safety and efficacy of antiarrhythmic agents:



View Image

Antiarrhythmic drug algorithm for the medical management of sinus rhythm in patients with atrial fibrillation.

For patients with no evidence of structural heart disease, flecainide, propafenone and sotalol should be considered first-line agents, and amiodarone and dofetilide can be considered as alternative agents. Amiodarone is considered a reasonable first-line agent for patients with substantial left ventricular hypertrophy (LVH). Dofetilide and sotalol are first-line therapy for patients with coronary artery disease (CAD), and amiodarone is considered a second-line agent in this population. For patients with heart failure, amiodarone and dofetilide are first-line agents.

The Atrial arrhythmia Conversion Trial (ACT) I and the open-label ACT IV trials suggest that intravenous vernakalant hydrochloride can quickly convert recent-onset AF to sinus rhythm. This is potentially an important therapeutic option for the treatment of patients with AF seen in the emergency department, as the treatment was well tolerated.[161]

Current practice constraints mandate that clinicians carefully consider patient populations at low and acceptable risks for outpatient antiarrhythmic drug initiation. Proarrhythmia is the most common adverse effect of antiarrhythmics during the loading phase. Although the proarrhythmic effect of these drugs extends into the maintenance phase, a monitored inpatient setting is generally recommended for drug initiation, especially for those patients with structural heart disease or substantial comorbidities. Nevertheless, certain antiarrhythmic drugs have established and acceptable safety profiles when used in outpatients without structural heart disease or other risk factors.

Schmidt et al found that the use of non-aspirin nonsteroidal anti-inflammatory agents (NSAIDs) is associated with an increased risk of AF or flutter, suggesting a need to add this caution when prescribing this course of medication.[162]

Diltiazem (Cardizem)

Clinical Context:  Diltiazem is the drug of choice for rate control in many cases. During depolarization, it inhibits calcium ions from entering the slow channels or voltage-sensitive areas of vascular smooth muscle and myocardium.

Verapamil (Calan, Isoptin, Verelan)

Clinical Context:  Verapamil can diminish PVCs associated with perfusion therapy and can decrease the risk of ventricular fibrillation and ventricular tachycardia. During depolarization, verapamil inhibits calcium ions from entering the slow channels or voltage-sensitive areas of vascular smooth muscle and myocardium.

Class Summary

Calcium channel blockers are more effective than digoxin when given orally for long-term rate control and should be the initial drug of choice. They reduce the rate of AV nodal conduction and control ventricular response. Intravenous formulations control severe symptoms related to rapid ventricular rates in emergent situations.

Esmolol (Brevibloc)

Clinical Context:  Esmolol is an ultra–short-acting beta-adrenergic receptor blocker. It selectively blocks beta-1 receptors, with little or no effect on beta-2 receptor types. It is particularly useful in patients with elevated arterial pressure, especially if surgery is planned. It has been shown to reduce episodes of chest pain and clinical cardiac events compared with placebo. It can be discontinued abruptly if necessary. It is useful in patients at risk for experiencing complications from beta-blockade, particularly those with reactive airway disease, mild-to-moderate LV dysfunction, and/or peripheral vascular disease. A short half-life of 8 min allows for titration to the desired effect and quick discontinuation if needed.

Propranolol (Inderal)

Clinical Context:  Propranolol is a nonselective beta-adrenergic receptor blocker as well as a class II antiarrhythmic, with membrane-stabilizing activity that decreases the automaticity of contractions.

Atenolol (Tenormin)

Clinical Context:  Atenolol selectively blocks beta-1 receptors, with little or no effect on beta-2 types. Atenolol is excellent for use in patients at risk for experiencing complications from beta-blockade, particularly those with reactive airway disease, mild-to-moderate LV dysfunction, and/or peripheral vascular disease.

Metoprolol (Lopressor)

Clinical Context:  Metoprolol is a selective beta-1 adrenergic receptor blocker that decreases the automaticity of contractions. During intravenous administration, carefully monitor blood pressure, heart rate, and ECG.

Class Summary

These agents slow the sinus rate and decrease AV nodal conduction. Beta-blockers now have more of a secondary role in AF rate control. Carefully monitor blood pressure.

Digoxin (Lanoxin)

Clinical Context:  Digoxin slows the sinus node and AV node via vagomimetic effects and is not very effective if sympathetic tone is increased. It is generally not recommended unless depressed LV function is present. Digoxin can be effective in sedentary patients (especially in those with heart failure) but requires close monitoring of drug levels and renal function. Combinations of rate-control medications (eg, a beta-blocker and digoxin) may be superior to individual agents in some patients.

Class Summary

These drugs slow AV nodal conduction primarily by increasing vagal tone. They are used primarily in the setting of AF with CHF.

Quinidine (Cardioquin, Quinalan, Quinidex, Quinaglute)

Clinical Context:  Of Vaughn-Williams class IA agents, only quinidine is FDA approved for atrial fibrillation. As with all class IA agents, QRS and QTc prolongation are the main ECG manifestations. It should not be used in patients with a prolonged QTc baseline (>460 milliseconds). Quinidine has generally fallen out of favor as a first- or second-line agent for the treatment of atrial fibrillation.

Procainamide (Procanbid, Pronestyl)

Clinical Context:  Procainamide is not FDA approved for the treatment of atrial fibrillation; however, many use this agent for acute cardioversion (eg, postoperatively) and because it can be administered intravenously. Intravenous administration is useful for acute conversion, and it can subsequently be converted to an oral dose. It is a negative inotropic agent and vasodilator, and care must be taken when administering to patients with reduced LV function. It is generally considered a second-line agent.

Disopyramide (Norpace)

Clinical Context:  Disopyramide is not commonly used to treat atrial fibrillation because it has adverse anticholinergic effects and because it is a strongly negative inotropic agent, which may precipitate CHF and cardiogenic shock in patients with reduced LV function. It may be useful in vagally mediated syncope.

Class Summary

Quinidine, procainamide, and disopyramide are class IA antiarrhythmic agents used to maintain sinus rhythm. Generally, start administration in the hospital because of the high risk of adverse effects. All patients treated with class IA agents should be treated concomitantly with AV nodal blocking agents. Some patients demonstrate a slowing in the atrial rate and an increase in AV conduction, with rapid ventricular rates, when treated with class IA agents alone. They are fading as first-line drugs for AF.

Propafenone (Rythmol)

Clinical Context:  It is indicated for documented life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia. It appears to be effective in the treatment of supraventricular tachycardias, including atrial fibrillation and flutter. It is not recommended in patients with less severe ventricular arrhythmias, even if symptomatic. Use it in conjunction with AV nodal blocking agents when administered to patients in atrial fibrillation, because conversion to AFL with 1:1 conduction (producing fast ventricular rates) has been noted.

Flecainide (Tambocor)

Clinical Context:  It is indicated for the treatment of paroxysmal atrial fibrillation/flutter associated with disabling symptoms and paroxysmal supraventricular tachycardias, including AV nodal reentrant tachycardia, AV reentrant tachycardia, and other supraventricular tachycardias of unspecified mechanism associated with disabling symptoms in patients without structural heart disease. It is also indicated for the prevention of documented life-threatening ventricular arrhythmias (eg, sustained ventricular tachycardia). It is not recommended in less severe ventricular arrhythmias even if patients are symptomatic. Use flecainide in conjunction with AV nodal blocking agents when given to patients in atrial fibrillation, because conversion to AFL with 1:1 conduction (producing fast ventricular rates) can occur.

Class Summary

These agents are indicated for patients with AF and supraventricular tachycardia without structural heart disease. Given the results of the CAST I and II trials (increased mortality), class IC agents are generally not used in patients with concomitant LV dysfunction and/or CAD. The applicability of the CAST results to other populations (eg, patients without recent MI) is uncertain. Many specialists initiate class IC antiarrhythmic agents in an outpatient setting for patients with paroxysmal AF and no associated structural heart disease. Regardless, close patient follow-up is mandated, with frequent ECG monitoring or via transtelephonic monitoring for potential signs of proarrhythmia.

Amiodarone (Cordarone)

Clinical Context:  Amiodarone has antiarrhythmic effects that overlap all 4 Vaughn-Williams antiarrhythmic classes. It has a low risk of proarrhythmia, and any proarrhythmic reactions generally are delayed. It is used in patients with structural heart disease. Most clinicians are comfortable with inpatient or outpatient loading with 400 mg PO tid for 1 wk because of low proarrhythmic effect, followed by weekly reductions, with a goal of the lowest dose with desired therapeutic benefit (usual maintenance dose for atrial fibrillation is 200 mg/d). During loading, patients must be monitored for bradyarrhythmias.

Sotalol (Betapace atrial fibrillation)

Clinical Context:  Sotalol is a class III agent with beta-blocking effects. It is effective in the maintenance of sinus rhythm, even in patients with underlying structural heart disease. Inpatient loading is FDA mandated.

Dofetilide (Tikosyn)

Clinical Context:  Dofetilide is approved by the FDA for maintenance of sinus rhythm, as well as for the conversion of atrial fibrillation to sinus rhythm (approximately 50%) in patients with persistent atrial fibrillation. It has no effect on cardiac output, cardiac index, stroke volume index, or systemic vascular resistance in patients with ventricular tachycardia, mild to moderate CHF, angina, and either normal or reduced LVEF. It has not shown evidence of any negative inotropic effects.

Ibutilide (Corvert)

Clinical Context:  Ibutilide is indicated for conversion of recent-onset atrial fibrillation or atrial flutter (3 h to 90 d). It prolongs repolarization by increasing the slow inward sodium current and by blocking the delayed rectifier current with rapid onset.

Class Summary

Currently, the class III antiarrhythmic agents sotalol and dofetilide are FDA approved for use in treating atrial arrhythmias; however, amiodarone is also used widely for maintenance of sinus rhythm in patients with AF. Dofetilide must be initiated in an inpatient setting. Sotalol is also initiated in an inpatient setting.

Dronedarone (Multaq)

Clinical Context:  It is indicated to reduce the risk for cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation or atrial flutter, with a recent episode of atrial fibrillation/atrial flutter and associated cardiovascular risk factors (ie, age >70 y, hypertension, diabetes, history of CVA, LAD >50 mm or LVEF < 40%) who are in sinus rhythm or who will be cardioverted.

Important to note, however, is that dronedarone was found to be associated with increased mortality in patients with permanent atrial fibrillation. A recent randomized, double-blind, phase III trial, the Permanent Atrial fibriLLation Outcome Study Using Dronedarone on Top of Standard Therapy (PALLAS) study, was halted following a preliminary review that revealed that dronedarone was associated with a 2-fold rise in risk of death. Two-fold increases in 2 other endpoints, stroke and hospitalization for heart failure, were also noted when compared with placebo. Healthcare professionals are advised by the FDA not to prescribe dronedarone to patients with permanent atrial fibrillation.

Class Summary

Dronedarone is an antiarrhythmic agent with properties belonging to all 4 Vaughn-Williams antiarrhythmic classes.

Heparin

Clinical Context:  Heparin augments the activity of antithrombin III and prevents the conversion of fibrinogen to fibrin. It does not actively lyse but is able to inhibit further thrombogenesis. It prevents reaccumulation of clot after spontaneous fibrinolysis.

Enoxaparin Sodium (Lovenox)

Clinical Context:  Enoxaparin is a low molecular weight heparin. It augments the activity of antithrombin III and prevents the conversion of fibrinogen to fibrin. It does not actively lyse but is able to inhibit further thrombogenesis. It prevents reaccumulation of clot after spontaneous fibrinolysis.

Warfarin (Coumadin)

Clinical Context:  Warfarin interferes with the hepatic synthesis of vitamin K–dependent coagulation factors. It is used for the prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Tailor the dose to maintain an INR of 2-3.

Dabigatran (Pradaxa)

Clinical Context:  Competitive, direct thrombin inhibitor. Thrombin enables fibrinogen conversion to fibrin during the coagulation cascade, thereby preventing thrombus development. Inhibits both free and clot-bound thrombin and thrombin-induced platelet aggregation. Indicated for prevention of stroke and thromboembolism associated with nonvalvular atrial fibrillation.

Rivaroxaban (Xarelto)

Clinical Context:  Factor Xa inhibitor indicated reduce risk of stroke and systemic embolism with nonvalvular atrial fibrillation. Dose is adjusted according to estimated creatinine clearance.

Apixaban (Eliquis)

Clinical Context:  Apixaban is a Factor Xa inhibitor that inhibits platelet activation by selectively and reversibly blocking the active site of Factor Xa without requiring a cofactor (eg, antithrombin III) for activity. It inhibits free and clot-bound Factor Xa, and prothrombinase activity. Although this agent has no direct effect on platelet aggregation, it does indirectly inhibit platelet aggregation induced by thrombin. Apixaban is indicated to reduce risk of stroke and systemic embolism associated with nonvalvular atrial fibrillation.

Edoxaban (Savaysa)

Clinical Context:  Edoxaban is a factor Xa inhibitor that inhibits platelet activation by blocking the active site of factor Xa without requiring a cofactor (eg, antithrombin III) for activity. Edoxaban is indicated to reduce the risk of stroke and systemic embolism associated with nonvalvular atrial fibrillation. Use is not recommended in patients with creatinine clearance ≥95 mL/min or ≤30 mL/min.

Class Summary

Anticoagulants are used to prevent thromboembolic complications.

Clopidogrel (Plavix)

Clinical Context:  Clopidogrel selectively inhibits adenosine diphosphate (ADP) binding to the platelet receptor and subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. It is indicated for reduction of atherothrombotic events following recent stroke.

Aspirin (Bayer Aspirin, Ecotrin)

Clinical Context:  Aspirin irreversibly inhibits platelet aggregation by inhibiting platelet cyclooxygenase. This, in turn, inhibits conversion of arachidonic acid to PGI2 (potent vasodilator and inhibitor of platelet activation) and thromboxane A2 (potent vasoconstrictor and platelet aggregate). Platelet-inhibition lasts for the life of the cell (approximately 10 d). It may be used at a low dose to inhibit platelet aggregation and improve complications of venous stases and thrombosis. It reduces the likelihood of myocardial infarction. It is also very effective in reducing the risk of stroke. Anticoagulation with either aspirin or warfarin should be initiated for all individuals with AF, except those with lone AF or contraindications.

Class Summary

Some patients may not be able to take anticoagulants such as warfarin because of contraindications or comorbidities. In patients unable to take warfarin, the addition of clopidogrel to aspirin has been shown to reduce the risk of major vascular events.

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stroke and how do they affect atrial fibrillation (Afib) (AF) anticoagulation management decisions?What is the efficacy of anticoagulation with warfarin to decrease stroke risk associated with atrial fibrillation (Afib) (AF)?When are anticoagulants indicated in low-risk patients with atrial fibrillation (Afib) (AF)?What are the risks of concomitant antiplatelet therapy with oral anticoagulation in patients with atrial fibrillation (Afib) (AF)?What effect does aspirin as monotherapy for atrial fibrillation (Afib) (AF) have on the risk of stroke?Which risk factor assessment algorithms have been developed to aid in making anticoagulation decisions for patients with atrial fibrillation (Afib) (AF)?What are the ACC/AHA guidelines on anticoagulation for patients with nonvalvular atrial fibrillation (Afib) (AF)?What are guidelines for the initial treatment of asymptomatic patients with atrial fibrillation (Afib) (AF)?What are the determinants of the ventricular rate during atrial fibrillation (Afib) (AF)?What are the first-line agents for rate control in patients with atrial fibrillation (Afib) (AF)?When is digoxin indicated for rate control in patients with atrial fibrillation (Afib) (AF)?When is amiodarone recommended by guidelines for rate control in patients with atrial fibrillation (Afib) (AF)?Which agents are contraindicated in patients with preexcitation syndrome and atrial fibrillation (Afib) (AF)?What is the most important consideration for the acute management of atrial fibrillation (Afib) (AF)?Which transesophageal echocardiography findings predict low acute risk of stroke in patients with atrial fibrillation (Afib) (AF)?Which anticoagulation treatments can be administered to patients with atrial fibrillation (Afib) (AF) awaiting electrical cardioversion?When and how is cardioversion performed in patients with new-onset atrial fibrillation (Afib) (AF)?When is inpatient monitoring necessary for pharmacologic cardioversion in atrial fibrillation (Afib) (AF)?What is the focus of the long-term management of patients with atrial fibrillation (Afib)(AF)?What is the basis of clinical decisions for long-term management in patients with atrial fibrillation (Afib) (AF)?What is the goal of long-term anticoagulation in atrial fibrillation (Afib) (AF) and which anticoagulants are approved?Why and how should the international normalized ratio (INR) be adjusted for anticoagulation therapy with warfarin in patients with atrial fibrillation (Afib) (AF)?How does efficacy of anticoagulation and antiplatelet therapies change as patients with atrial fibrillation (Afib) (AF) age?Which factors affect bleeding risk during anticoagulation therapy with warfarin in patients with atrial fibrillation (Afib) (AF)?What is the HEMORR2HAGES risk model and how is it scored?What is the efficacy and safety of dabigatran (Pradaxa) use in patients with atrial fibrillation (Afib) (AF)?What is the efficacy and safety of rivaroxaban (Xarelto) use in patients with atrial fibrillation (Afib) (AF)?What is the efficacy and safety of apixaban (Eliquis) use in patients with atrial fibrillation (Afib) (AF)?What is the efficacy and safety of edoxaban (Savaysa) use in patients with atrial fibrillation (Afib) (AF)?What are the advantages and disadvantages of newer oral anticoagulants for treatment of atrial fibrillation (Afib) (AF)?When is reversal of anticoagulation required and how is it achieved in patients with atrial fibrillation (Afib) (AF)?What are the AAN guidelines for stroke prevention in patients with nonvalvular atrial fibrillation (Afib) (AF)?What factors should be considered when deciding whether to stop anticoagulation prior to elective surgery in patients with atrial fibrillation (Afib) (AF)?Do patients who develop atrial fibrillation (Afib) (AF) postoperatively need anticoagulation?When is colchicine indicated in the treatment of atrial fibrillation (Afib) (AF)?What is the bleeding risk of anticoagulants prescribed upon hospital discharge for atrial fibrillation (Afib) (AF)?What is the efficacy and safety of omega-3 fatty acids as treatment for paroxysmal atrial fibrillation (Afib) (AF)?What is the efficacy and safety of ACE inhibitors and ACE-receptor blockers (ARB) to reduce recurrence of atrial fibrillation (Afib) (AF) in patients with heart failure?What is the efficacy and safety of an initial rate-control strategy for treatment of patients with atrial fibrillation (Afib) (AF)?How should rate control be monitored in patients with atrial fibrillation (Afib)?What drugs can be used to achieve rate control in patients with atrial fibrillation (Afib) (AF)?What treatments are used to maintain sinus rhythm control in patients with atrial fibrillation (Afib) (AF)?What is the efficacy and safety of amiodarone for sinus rhythm control in patients with atrial fibrillation (Afib) (AF)?What is the efficacy and safety of dronedarone for sinus rhythm control in patients with atrial fibrillation (Afib) (AF)?What is the efficacy and safety of sotalol for sinus rhythm control in patients with atrial fibrillation (Afib) (AF)?What is the rate of proarrhythmias in patients with atrial fibrillation (Afib) (AF) taking dofetilide for cardioversion?When are class III agents and class Ic drugs contraindicated for long-term management of atrial fibrillation (Afib) (AF)?What are the guidelines for catheter ablation to achieve rhythm control in patients with atrial fibrillation (Afib) (AF)?What new medical and device-based rhythm-control therapies are being evaluated for atrial fibrillation (Afib) (AF)?When is cardioversion necessary for patients with atrial fibrillation (Afib) (AF)?What is direct current cardioversion for atrial fibrillation (Afib) (AF)?What are the complications of cardioversion for atrial fibrillation (Afib) (AF)?Which is the best method of cardioversion for patients with atrial fibrillation (Afib) (AF)?What measures increase the safety of cardioversion in patients with implanted pacemakers and defibrillator devices?When is pharmacologic cardioversion used for atrial fibrillation (Afib) (AF)?What is the efficacy of self-administration of pharmacologic cardioversion for atrial fibrillation (Afib) (AF)?What pretreatment medications are effective for DC cardioversion in atrial fibrillation (Afib) (AF)?Should antiarrhythmic drugs be used in hemodynamically unstable patients?How can postoperative atrial fibrillation (Afib) (AF) be prevented?What is the goal of catheter ablation and surgical treatment for atrial fibrillation (Afib) (AF)?How does ablation treat paroxysmal atrial fibrillation (Afib) (AF)?What is the role of antiarrhythmic drug treatment after ablation of paroxysmal atrial fibrillation (Afib) (AF)?What is the efficacy and safety of atrial fibrillation (Afib) (AF) ablation in patients with mitral valve replacement?How is the atria compartmentalized in patients with atrial fibrillation (Afib) (AF)?What is the maze procedure method of surgical compartmentalization of the atria in atrial fibrillation (Afib) (AF)?What is the role of radiofrequency (RF) lesions in the surgical compartmentalization of the atria in atrial fibrillation (Afib) (AF)?How effective is electrical isolation of individual pulmonary veins in patients with atrial fibrillation (Afib) (AF)?What are catheter-based modalities for isolating pulmonary venous triggers and when are they indicated in atrial fibrillation (Afib) (AF)?What is the role of chest CT scanning or MRI in imaging pulmonary veins in atrial fibrillation (Afib) (AF)?How does sinus node function influence the atrial fibrillation (Afib) (AF) cure rate after pulmonary vein isolation?What is the success rate of ablation of atrial fibrillation (Afib) (AF) and who are potential candidates?After atrial fibrillation (Afib) (AF) ablation, what is the likelihood that the patient will undergo repeat ablations?What are the complications associated with catheter ablation of atrial fibrillation (Afib) (AF)?When should atrioventricular (AV) node modifications be considered for atrial fibrillation (Afib) (AF) and how should pacemakers be programmed?What is the efficacy and safety of devices for left atrial appendage (LAA) closure/litigation in atrial fibrillation (Afib) (AF)?What consultations are recommended for atrial fibrillation (Afib) (AF)?What long-term monitoring is required for patients who undergo atrial fibrillation (Afib) (AF) catheter ablation?What long-term monitoring is required for patients with atrial fibrillation (Afib) (AF)?How do guidelines classify atrial fibrillation (Afib) (AF)?What are the guidelines for the prevention of stroke in patients with atrial fibrillation (Afib) (AF)?What are the differences in guidelines recommendations for antithrombotic therapy in patients with atrial fibrillation (Afib) (AF)?What are the guidelines for rate control in patients with atrial fibrillation (Afib) (AF)?What are the guidelines for cardioversion of atrial fibrillation (Afib) (AF)?What are the guidelines for maintaining sinus rhythm in patients with atrial fibrillation (Afib) (AF)?What are the guidelines for catheter ablation for atrial fibrillation (Afib) (AF)?What is the goals of medical therapy for atrial fibrillation (Afib) (AF)?How safe is warfarin in patients with atrial fibrillation (Afib) (AF)?How safe is clopidogrel and aspirin in patients with atrial fibrillation (Afib) (AF)?What is the goal of antiarrhythmic drug therapy in atrial fibrillation (Afib) (AF) and which drugs are used?Which medications in the drug class Calcium Channel blockers are used in the treatment of Atrial Fibrillation?Which medications in the drug class Beta-adrenergic Receptor Blockers are used in the treatment of Atrial Fibrillation?Which medications in the drug class Cardiac glycosides are used in the treatment of Atrial Fibrillation?Which medications in the drug class Antiarrhythmics, class IA are used in the treatment of Atrial Fibrillation?Which medications in the drug class Antiarrhythmics, class IC are used in the treatment of Atrial Fibrillation?Which medications in the drug class Antiarrhythmics, class III are used in the treatment of Atrial Fibrillation?Which medications in the drug class Antiarrhythmic Agent, Miscellaneous are used in the treatment of Atrial Fibrillation?Which medications in the drug class Anticoagulants are used in the treatment of Atrial Fibrillation?Which medications in the drug class Antiplatelet Agents are used in the treatment of Atrial Fibrillation?

Author

Lawrence Rosenthal, MD, PhD, FACC, FHRS, Associate Professor of Medicine, Director, Section of Cardiac Pacing and Electrophysiology, Director of EP Fellowship Program, Division of Cardiovascular Disease, University of Massachusetts Memorial Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

David D McManus, MD, MSc, FACC, FHRS, Director, Atrial Fibrillation Program, Assistant Professor of Medicine and Quantitative Health Sciences, University of Massachusetts Medical School

Disclosure: Nothing to disclose.

Mayank Sardana, MBBS, Fellow in Cardiovascular Medicine, University of Massachusetts Medical School

Disclosure: Nothing to disclose.

Chief Editor

Jeffrey N Rottman, MD, Professor of Medicine, Department of Medicine, Division of Cardiovascular Medicine, University of Maryland School of Medicine; Cardiologist/Electrophysiologist, University of Maryland Medical System and VA Maryland Health Care System

Disclosure: Nothing to disclose.

Additional Contributors

Mariclaire Cloutier, Freelance editor, Medscape Drugs & Diseases

Disclosure: Nothing to disclose.

Acknowledgements

Pierre Borczuk, MD Assistant Professor of Medicine, Harvard Medical School; Associate in Emergency Medicine, Massachusetts General Hospital

Pierre Borczuk, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

David FM Brown, MD Associate Professor, Division of Emergency Medicine, Harvard Medical School; Vice Chair, Department of Emergency Medicine, Massachusetts General Hospital

David FM Brown, MD is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Abraham G Kocheril, MD, FACC, FACP, FHRS Professor of Medicine, University of Illinois College of Medicine

Abraham G Kocheril, MD, FACC, FACP, FHRS is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Heart Association, American Medical Association, Cardiac Electrophysiology Society, Central Society for Clinical Research, Heart Failure Society of America, and Illinois State Medical Society

Disclosure: Nothing to disclose.

William Lober, MD, MS Associate Professor, Health Informatics and Global Health, Schools of Medicine, Nursing, and Public Health, University of Washington

Disclosure: Nothing to disclose.

Brian Olshansky, MD Professor of Medicine, Department of Internal Medicine, University of Iowa College of Medicine

Brian Olshansky, MD is a member of the following medical societies: American College of Cardiology, American Heart Association, Cardiac Electrophysiology Society, and Heart Rhythm Society

Disclosure: Guidant/Boston Scientific Honoraria Speaking and teaching; Medtronic Honoraria Speaking and teaching; Guidant/Boston Scientific Consulting fee Consulting

Gary Setnik, MD Chair, Department of Emergency Medicine, Mount Auburn Hospital; Assistant Professor, Division of Emergency Medicine, Harvard Medical School

Gary Setnik, MD is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians, and Society for Academic Emergency Medicine

Disclosure: SironaHealth Salary Management position; South Middlesex EMS Consortium Salary Management position; ProceduresConsult.com Royalty Other

Ali A Sovari, MD, FACP Clinical and Research Fellow in Cardiovascular Medicine, Section of Cardiology, University of Illinois College of Medicine; Staff Physician and Hospitalist, St John Regional Medical Center, Cogent Healthcare, Inc

Ali A Sovari, MD, FACP is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Heart Association, American Medical Association, American Physiological Society, and Heart Rhythm Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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Ventricular rate varies from 130-168 beats per minute. Rhythm is irregularly irregular. P waves are not discernible.

The image on the right is a reconstructed 3-dimensional image of the right atrium in a patient undergoing atrial fibrillation ablation. The figure on the left was created with a mapping catheter using Endocardial Solutions mapping technology. It represents the endocardial shell of the right atrium and is used as the template during left atrial ablation procedures.

Classification scheme for patients with atrial fibrillation (AF).

Ventricular rate varies from 130-168 beats per minute. Rhythm is irregularly irregular. P waves are not discernible.

Patient management for newly diagnosed atrial fibrillation (Afib). *Therapeutic anticoagulation implies either treatment with warfarin with a therapeutic international normalized ratio (INR) (2-3) or with newer oral anticoagulants (dabigatran, rivaroxaban, apixaban, or edoxaban). Transesophageal echocardiography (TEE)/cardioversion should be performed with an anticoagulation strategy using either low molecular-weight heparin (LMWH) 1 mg/kg twice daily as a bridge, with initiation of warfarin (INR 2-3) or newer oral anticoagulants.

The image on the right is a reconstructed 3-dimensional image of the right atrium in a patient undergoing atrial fibrillation ablation. The figure on the left was created with a mapping catheter using Endocardial Solutions mapping technology. It represents the endocardial shell of the right atrium and is used as the template during left atrial ablation procedures.

Antiarrhythmic drug algorithm for the medical management of sinus rhythm in patients with atrial fibrillation.

Ventricular rate varies from 130-168 beats per minute. Rhythm is irregularly irregular. P waves are not discernible.

Classification scheme for patients with atrial fibrillation (AF).

Patient management for newly diagnosed atrial fibrillation (Afib). *Therapeutic anticoagulation implies either treatment with warfarin with a therapeutic international normalized ratio (INR) (2-3) or with newer oral anticoagulants (dabigatran, rivaroxaban, apixaban, or edoxaban). Transesophageal echocardiography (TEE)/cardioversion should be performed with an anticoagulation strategy using either low molecular-weight heparin (LMWH) 1 mg/kg twice daily as a bridge, with initiation of warfarin (INR 2-3) or newer oral anticoagulants.

Antiarrhythmic drug algorithm for the medical management of sinus rhythm in patients with atrial fibrillation.

The image on the right is a reconstructed 3-dimensional image of the right atrium in a patient undergoing atrial fibrillation ablation. The figure on the left was created with a mapping catheter using Endocardial Solutions mapping technology. It represents the endocardial shell of the right atrium and is used as the template during left atrial ablation procedures.

CHA2 DS2-VASc Score Unadjusted Stroke Rate (%/y)
00.2
10.6
22.2
33.2
44.8
57.2
69.7
711.2
810.8
912.2
CHA2 DS2-VASc Score Recommended Therapy
0No therapy
1No therapy, or aspirin 81-325 mg daily, or anticoagulation therapy



(eg, warfarin [international normalized ratio (INR) goal 2-3], dabigatran, rivaroxaban, apixaban, edoxaban)



≥2Anticoagulation therapy (eg, warfarin [INR goal 2-3], dabigatran, rivaroxaban, apixaban, edoxaban)
Issuing OrganizationYearPatient GroupsAntithrombotic Therapy
American Heart Association/American College of Cardiology/ Heart Rhythm Society (AHA/ACC/HRS)[1] 2014
  • AF with mechanical heart valve
  • With prior stroke, TIA or CHA2DS2-VASc score ≥2
  • NVAF and CHA2DS2-VASc score ≥2
  • NVAF with CHA2DS2-VASc score ≥2 and end-stage CKD or on hemodialysis
  • NVAF with CHA2DS2-VASc score ≥2 and moderate to severe CKD
  • All patients
  • Warfarin therapy; target INR, 2.0-3.0 or 2.5-3.5 based on type and location of prosthesis
  • Bridging therapy with unfractionated heparin or LMWH for patients undergoing procedures that require interruption of warfarin. Decisions on bridging therapy should balance the risks of stroke and bleeding.
  • Oral anticoagulants: Warfarin (INR 2.0-3.0), dabigatran, apixaban, or rivaroxaban
  • Warfarin (INR 2.0-3.0); if unable to maintain a therapeutic INR level with warfarin, use of a direct thrombin or factor Xa inhibitor (dabigatran, rivaroxaban, or apixaban)
  • Warfarin (INR 2.0-3.0); direct thrombin or factor Xa inhibitors are not recommended
  • Reduced doses of direct thrombin or factor Xa inhibitors may be considered (eg, dabigatran, rivaroxaban, apixaban), but safety and efficacy have not been established
  • In patients receiving warfarin, the INR should be determined at least weekly during initiation of antithrombotic therapy and at least monthly when anticoagulation (INR in range) is stable
  • Periodic reevaluation of the need and choice of anti-thrombotic therapy to reassess stroke and bleeding risks
American Heart Association/American Stroke Association (AHA/ASA)[151] 2014
  • Valvular AF/ CHA2DS2-VASc score ≥2
  • NVAF// CHA2DS2-VASc score ≥2 and low risk for hemorrhagic complications
  • NVAF, CHA2DS2-VASc score = 1, and low risk for hemorrhagic complications
  • Warfarin therapy; target INR, 2.0-3.0
  • Oral anticoagulant (warfarin, dabigatran, apixaban, or rivaroxaban) individualized based on patient risk factors (particularly risk for intracranial hemorrhage), cost, tolerability, patient preference, potential for drug interactions, and other clinical characteristics.
  • No antithrombotic therapy, anticoagulant therapy, or aspirin therapy may be considered
American Academy of Neurology (AAN)[97] 2014
  • NVAF and history of TIA or stroke; age >75 years, if no history of unprovoked bleeding or intracranial hemorrhage; patients with dementia or occasional falls; however in patients with moderate to severe dementia or frequent falls, risk-benefit ratio is uncertain
  • Patients at moderate stroke risk in developing countries where newer anticoagulants are unavailable
  • Warfarin, target INR 2.0 to 3.0
  • Dabigatran, rivaroxaban, or apixaban (preferred) if at high risk for intracranial bleeding or unable to submit to frequent periodic INR testing
  • Apixaban, if at increased risk for gastrointestinal bleeding
  • Triflusal 600 mg/day plus moderate-intensity anticoagulation (INR 1.25–2.0) with acenocoumarol is likely more effective than acenocoumarol alone at the higher INR (2.0-3.0)
American College of Chest Physicians (ACCP)[150] 2012NVAF intermediate risk (CHADS2 score = 1) or high risk (CHADS2 score ≥2)
  • Oral anticoagulants: dabigatran 150 mg BID preferred over warfarin (target INR range, 2.0-3.0)
  • Patients who are unsuitable for or choose not to take an oral anticoagulant (for reasons other than concerns about major bleeding): combination therapy with aspirin and clopidogrel
European Society of Cardiology (ESC)[149] 2012
  • CHA2DS2-VASc score = 0, and females aged < 65 years with CHA2DS2-VASc score = 1
  • CHA2DS2-VASc score = 1
  • CHA2DS2-VASc score ≥2
  • All patients
  • Patients who refuse oral anticoagulants
  • No antithrombotic therapy
  • Oral anticoagulants: Warfarin (INR 2.0-3.0) or dabigatran or rivaroxaban or apixaban based on assessment of risk of bleeding
  • Oral anticoagulants: Dabigatran or rivaroxaban or apixaban preferred over warfarin (INR 2.0-3.0)
  • When dabigatran is considered, 150 mg BID preferred; 110 mg BID is preferred for ages ≥80 years, concomitant use of interacting drugs, high bleeding risk or moderate renal impairment
  • When rivaroxaban is considered, 20 mg OD preferred; 15 mg OD is preferred for those with high bleeding risk or moderate renal impairment
  • Baseline and subsequent annual assessment of renal function (by CrCl) is recommended in patients following initiation of any novel oral anticoagulant (dabigatran, rivaroxaban, and apixaban), and 2-3 times per year in those with moderate renal impairment; novel oral anticoagulants are not recommended in patients with severe renal impairment (CrCl < 30 mL/min)
  • Antiplatelet therapy should be considered, using combination therapy with aspirin 75–100 mg plus clopidogrel 75 mg daily (where there is a low risk of bleeding) or—less effectively—aspirin 75–325 mg daily
Note: Edoxaban was approved by the FDA in January 2015 for use as an oral anticoagulant in atrial fibrillation.



AF = atrial fibrillation; BID = twice daily; CKD = chronic kidney disease; CrCl = creatinine clearance; INR = international normalized ratio; LMWH = low-molecular-weight heparin; NVAF = nonvalvular atrial fibrillation; OD = before bedtime; TIA = transient ischemic attack.



Type of Tachycardia Treatment (Grade) Not Mentioned in 2019 Guidelines
Narrow QRS tachycardias Verapamil and diltiazem; beta-blockers (now all are grade IIa)Amiodarone, digoxin
Wide QRS tachycardias Procainamide, adenosine (both grade IIa); amiodarone (IIb)Sotalol, lidocaine
Inappropriate sinus tachycardia Beta-blockers (IIa)Verapamil/diltiazem, catheter ablation
Postural orthostatic tachycardia syndrome Salt and fluid intake (IIb)Head-up tilt sleep, compression stockings, selective beta-blockers, fludrocortisone, clonidine, methylphenidate, fluoxetine, erythropoietin, ergotaminel octreotide, phenobarbitone
Focal atrial tachycardia Acute: beta-blockers (IIa); flecainide/propafenone, amiodarone (IIb)Acute: procainamide, sotalol, digoxin
Chronic: beta-blockers; verapamil and diltiazem (all IIa)Chronic: amiodarone, sotalol, disopyramide
Atrial flutter Acute: ibutilide (I); verapamil and diltiazem, beta-blockers (all IIa); atrial or transesophageal pacing (IIb); flecainide/propafenone (III)Acute: digitalis
Chronic: —Chronic: dofetilide, sotalol, flecainide, propafenone, procainamide, quinidine, disopyramide
Atrioventricular nodal re-entrant tachycardia (AVNRT) Acute: —Acute: amiodarone, sotalol, flecainide, propafenone
Chronic: verapamil and diltiazem; beta-blockers (all IIa)Chronic: amiodarone, sotalol, flecainide, propafenone, “pill-in-the-pocket” approach
Atrioventricular re-entrant tachycardia (AVRT) Beta-blockers (IIa); flecainide/propafenone (IIb)Amiodarone, sotalol, “pill-in-the-pocket” approach
SVT in pregnancy Verapamil (IIa); catheter ablation (IIa when fluoroless ablation is available)Sotalol, propafenone, quinidine, procainamide
Adapted from Brugada J, Katritsis DG, Arbelo E, et al, for the ESC Scientific Document Group. 2019 ESC Guidelines for the management of patients with supraventricular tachycardia. The Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J. 2019 Aug 31;ehz467. https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehz467/5556821