Management of Patients with Atrial Fibrillation

Publication Date: November 30, 2023
Last Updated: April 4, 2024

Overview

Overview

Top 10 Take-Home Messages for Atrial Fibrillation

  1. Stages of atrial fibrillation (AF): The previous classification of AF, which was based only on arrhythmia duration, although useful, tended to emphasize therapeutic interventions. The new proposed classification, using stages, recognizes AF as a disease continuum that requires a variety of strategies at the different stages, from prevention, lifestyle and risk factor modification (LRFM), screening, and therapy.
  2. AF risk factor modification and prevention: This guideline recognizes lifestyle and risk factor modification as a pillar of AF management to prevent onset, progression, and adverse outcomes. The guideline emphasizes risk factor management throughout the disease continuum and offers more prescriptive recommendations, accordingly, including management of obesity, weight loss, physical activity, smoking cessation, alcohol moderation, hypertension, and other comorbidities.
  3. Flexibility in using clinical risk scores and expanding beyond CHA2DS2-VASc for prediction of stroke and systemic embolism: Recommendations for anticoagulation are now made based on yearly thromboembolic event risk using a validated clinical risk score, such as CHA2DS2-VASc. However, patients at an intermediate annual risk score who remain uncertain about the benefit of anticoagulation can benefit from consideration of other risk variables to help inform the decision, or the use of other clinical risk scores to improve prediction, facilitate shared decision making, and incorporate into the electronic medical record.
  4. Consideration of stroke risk modifiers: Patients with AF at intermediate to low (<2%) annual risk of ischemic stroke can benefit from consideration of factors that might modify their risk of stroke, such as the characteristics of their AF (eg, burden), nonmodifiable risk factors (sex), and other dynamic or modifiable factors (blood pressure control) that may inform shared decision-making (SDM) discussions.
  5. Early rhythm control: With the emergence of new and consistent evidence, this guideline emphasizes the importance of early and continued management of patients with AF that should focus on maintaining sinus rhythm and minimizing AF burden.
  6. Catheter ablation of AF receives a Class 1 indication as first-line therapy in selected patients: Recent randomized studies have demonstrated the superiority of catheter ablation over drug therapy for rhythm control in appropriately selected patients. In view of the most recent evidence, we upgraded the Class of Recommendation.
  7. Catheter ablation of AF in appropriate patients with heart failure (HF) with reduced ejection fraction (EF) receives a Class 1 indication: Recent randomized studies have demonstrated the superiority of catheter ablation over drug therapy for rhythm control in patients with heart failure and reduced ejection failure. In view of the data, we upgraded the Class of Recommendation for this population of patients.
  8. Recommendations have been updated for device-detected AF: In view of recent studies, more prescriptive recommendations are provided for patients with device-detected AF that consider the interaction between episode duration and the patient's underlying risk for thromboembolism. This includes considerations for patients with AF detected via implantable devices and wearables.
  9. Left atrial appendage occlusion (LAAO) devices receive higher level Class of Recommendation: In view of additional data on safety and efficacy of left atrial appendage occlusion devices, the Class of Recommendation has been upgraded to 2a compared to the 2019 AF Focused Update for use of these devices in patients with long-term contraindications to anticoagulation.
  10. Recommendations are made for patients with AF identified during medical illness or surgery (precipitants): Emphasis is made on the risk of recurrent AF after AF is discovered during noncardiac illness or other precipitants, such as surgery.

2. Background and Pathophysiology 
2.1. Epidemiology

  • Atrial fibrillation is the most sustained common arrhythmia, and its incidence and prevalence are increasing in the United States and globally (Figure 1; Figure 2; Figure 3).
  • AF is associated with a 1.5- to 2-fold increased risk of death.

Introduction

Introduction

Note: The numbering of the following tables and figures may differ from that of the Clinical Practice Guideline.
Colors in tables and figures correspond to Class of Recommendations and Level of Evidence tables.

Figure 1. Temporal Trends in Counts and Age-Standardized Rates of AF-Prevalent Cases by Social Demographic Index (SDI) Quintile for Both Sexes Combined, 1990 to 2017

Trends in counts of AF-prevalent cases by Social Demographic Index quintile, 1990 to 2017.

SDI was made up of the geometric mean of three common indicators: the lag distributed income per capita, mean educational achievement for those aged 15 years or older, and total fertility rate under 25 years. SDI ranged from 0 to 1, where 0 represents the theoretical minimum level of development, whereas 1 represents the theoretical maximum level of development.

Modified from Dai H, et al. by permission of Oxford University Press on behalf of the European Society of Cardiology. Copyright 2020, Oxford University Press.

Figure 2. Prevalence of AF Among Medicare Beneficiaries, 1993–2007

(A) In the overall cohort, (B) by age group, (C) by sex, and (D) by race. The dashed lines in panel A represent 95% confidence intervals (CIs).

Reproduced with permission from Piccini JP, et al. [Circulation: Cardiovascular Quality and Outcomes. 2012;5:85–93] Copyright 2012, American Heart Association, Inc.

Figure 2. Prevalence of AF Among Medicare Beneficiaries, 1993–2007 (cont'd)

(A) In the overall cohort, (B) by age group, (C) by sex, and (D) by race. The dashed lines in panel A represent 95% confidence intervals (CIs).

Reproduced with permission from Piccini JP, et al. [Circulation: Cardiovascular Quality and Outcomes. 2012;5:85–93] Copyright 2012, American Heart Association, Inc.

Figure 3. Age-Standardized Global Prevalence Rates of AF and Atrial Flutter (AFL) per 100,000, Both Sexes, 2020

During each annual Global Burden of Disease (GBD) Study cycle, population health estimates are produced for the full-time series. Improvements in statistical and geospatial modeling methods and the addition of new data sources may lead to changes in past results across the GBD Study cycle.

Modifed with permission from Tsao CW, et al. Copyright 2023, American Heart Association, Inc. Modifed Source: Institute for Health Metrics Evaluation. Used with permission. All rights reserved.

2.1.2. Risk Factors and Associated Heart Disease

Table 3. Risk Factors for Diagnosed AF

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Condition Study type Effect on risk of AF Summary risk of incident AF Effect of LRFM
Risk factors Advancing age
  • Systematic review (SR)/ meta-analysis (MA)
  • Age per 5 y: ↑ risk hazard ratio (HR, 1.43–1.66)
↑ risk Not applicable (N/A)
Risk factors Advancing age
  • Mendelian randomization (MR)
  • Accelerated epigenetic age by MR: no association
↑ risk Not applicable (N/A)
Risk factors Smoking
  • Single study
  • Current smoking: ↑ risk (9.8%)
↑ risk N/A
Risk factors Smoking
  • SR/MA
  • Smoking: ↑ risk (HR, 1.21–1.43)
↑ risk N/A
Risk factors Smoking
  • MR
  • Smoking initiation: ↑ risk odds ratio (OR, 1.11)
↑ risk N/A
Risk factors Physical activity
  • SR/MA
  • Sedentary lifestyle: ↑ risk (OR, 2.47)
  • Guideline-recommended physical activity: ↓ risk (HR, 0.94)
  • Elite athletes vs. nonathletes: ↑ risk (OR, 2.46)
U curve: Sedentary lifestyle and elite/extreme exercise: ↑ risk Exercise: ↓ AF burden, recurrence, symptoms; ↑ quality of life (QOL), functional capacity
Risk factors Alcohol
  • Single studies
  • Risk of AF episode within 4 h of 1 drink: ↑ risk (OR, 2.02)
  • Greater access to alcohol law: ↑ risk
↑ risk
  • Randomized abstinence: ↓ AF recurrence and burden
  • N-of-1 studies of alcohol avoidance: ↓ near-term AF
  • Alcohol avoidance or reduction as part of a comprehensive LRFM program: ↓ AF burden, symptoms, progression of AF
Risk factors Alcohol
  • SR/MA
  • Dose response (#drinks/day): ↑ risk relative risk (RR)
  • 1: 1.08; 2: 1.17; 3: 1.33; 4: 1.36; 5: 1.47
↑ risk
  • Randomized abstinence: ↓ AF recurrence and burden
  • N-of-1 studies of alcohol avoidance: ↓ near-term AF
  • Alcohol avoidance or reduction as part of a comprehensive LRFM program: ↓ AF burden, symptoms, progression of AF
Risk factors Alcohol
  • MR
  • Genetically predicted heavy alcohol consumption (>35 U/week for women and >50 U/week for men): ↑ risk (OR, 1.11)
↑ risk
  • Randomized abstinence: ↓ AF recurrence and burden
  • N-of-1 studies of alcohol avoidance: ↓ near-term AF
  • Alcohol avoidance or reduction as part of a comprehensive LRFM program: ↓ AF burden, symptoms, progression of AF
Risk factors Adiposity markers: weight, body mass index (BMI), obesity
  • Single study
  • Obesity: population attributable fraction 12.7%–16.9%
↑ risk
  • Weight loss in overweight or obese patients with AF as part of a comprehensive LRFM program: ↓ AF symptoms, burden, recurrence, progression
  • Bariatric surgery in class III obesity: associated with reversal of AF type, ↑ sinus rhythm postablation
  • Weight loss in long-lasting persistent AF and obesity: ↔
Risk factors Adiposity markers: weight, body mass index (BMI), obesity
  • SR/MA
  • BMI: RR, 1.28 per 5-unit ↑ in BMI
  • Weight: HR, 1.12 per 15 kg ↑
↑ risk
  • Weight loss in overweight or obese patients with AF as part of a comprehensive LRFM program: ↓ AF symptoms, burden, recurrence, progression
  • Bariatric surgery in class III obesity: associated with reversal of AF type, ↑ sinus rhythm postablation
  • Weight loss in long-lasting persistent AF and obesity: ↔
Risk factors Adiposity markers: weight, body mass index (BMI), obesity
  • MR
  • Obesity
  • Birthweight: 1.26 per SD ↑
  • Childhood BMI, (OR, 1.18)
  • BMI 1.31 per unit BMI
↑ risk
  • Weight loss in overweight or obese patients with AF as part of a comprehensive LRFM program: ↓ AF symptoms, burden, recurrence, progression
  • Bariatric surgery in class III obesity: associated with reversal of AF type, ↑ sinus rhythm postablation
  • Weight loss in long-lasting persistent AF and obesity: ↔
Risk factors Height
  • MA
  • Height per 10 cm: ↑ risk (HR, 1.28)
↑ risk N/A
Risk factors Height
  • SR/MA
  • Increasing height: ↑ risk
↑ risk N/A
Risk factors Height
  • MR
  • Increasing height: ↑ risk (OR per unit, 1.33)
↑ risk N/A
Risk factors Hypertension and blood pressure (BP)
  • Single studies
  • Elevated BP: ↑ risk, population attributable fraction, 21.6%
  • Presence of hypertension treatment: ↑ risk (HR, 1.35–1.68), incidence 9.8%–19.5%; both AF and systolic blood pressure (SBP) decreased over time
  • Hypertension: ↑ risk
  • SBP: ↑ risk
  • DBP: ↑↓↔ risk
  • Renal denervation: ↓AF postablation
  • Mineralocorticoid receptor antagonists (MRAs): ↓AF burden
  • BP control postablation: ↔
Risk factors Hypertension and blood pressure (BP)
  • MA
  • BP: SBP: ↑ risk (HR per 20 mm Hg, 1.22); diastolic blood pressure (DBP) per 10 mmHg ↓ risk (HR, 0.90); use of BP medications ↑ risk (HR, 1.42)
  • Hypertension: ↑ risk
  • SBP: ↑ risk
  • DBP: ↑↓↔ risk
  • Intensive BP control to SBP <120 mmHg in patients with HTN at high risk for cardiovascular disease (CVD): ↓ AF risk
  • BP control as part of a comprehensive LRFM program: ↓ AF burden
Risk factors Hypertension and blood pressure (BP)
  • SR/MA
  • Hypertension: ↑ risk
  • Hypertension: ↑ risk
  • SBP: ↑ risk
  • DBP: ↑↓↔ risk
  • Intensive BP control to SBP <120 mmHg in patients with HTN at high risk for cardiovascular disease (CVD): ↓ AF risk
  • BP control as part of a comprehensive LRFM program: ↓ AF burden
Risk factors Hypertension and blood pressure (BP)
  • MR
  • SBP ↑ risk; DBP mixed results ↔↑ risk; pulse pressure ↑ risk
  • Hypertension: ↑ risk
  • SBP: ↑ risk
  • DBP: ↑↓↔ risk
  • Intensive BP control to SBP <120 mmHg in patients with HTN at high risk for cardiovascular disease (CVD): ↓ AF risk
  • BP control as part of a comprehensive LRFM program: ↓ AF burden
Risk factors Resting heart rate
  • SR/MA
  • Resting heart rate: J-shaped relationship with incident AF. Lowest risk at 68–80 beats per minute (bpm); <70 bpm, (RR, 1.09 per 10 bpm ↓ ); >70 bpm (RR, per 10 bpm ↑ RR 1.06)
  • Slow heart rate: ↑ ↓ variable risk
  • Higher heart rate: ↑ ↓ variable risk
N/A
Risk factors Resting heart rate
  • MR
  • Heart rate: <65 bpm slower HR ↑ risk; (HR per 5 bpm ↑, 0.82)
  • Slow heart rate: ↑ ↓ variable risk
  • Higher heart rate: ↑ ↓ variable risk
N/A
Risk factors Diabetes mellitus (DM)
  • Single study
  • DM: ↑ risk, population attributable fraction 3.1%
  • DM: ↑ risk, population attributable fraction ↑ over time 3.2%–5.9%
↑ risk
  • Optimal glycemic control preablation may ↓ AF recurrence postablation
Risk factors Diabetes mellitus (DM)
  • MA
  • DM: ↑ risk (HR, 1.27 [95% CI, 1.10–1.46])
↑ risk Optimal glycemic control preablation may ↓ AF recurrence postablation
Risk factors Diabetes mellitus (DM)
  • SR/MA
  • DM: ↑ risk (RR, 1.28, excluding large outlying study)
  • Pre-DM: ↑ risk (RR, 1.20)
  • Blood glucose; ↑ risk (RR per 20 mg/dL ↑ , 1.11)
↑ risk Optimal glycemic control preablation may ↓ AF recurrence postablation
Cardiovascular disease HF or coronary artery disease (CAD)
  • Single study
  • HF or CAD: population attributable fraction 5.4%
↑ risk N/A
Cardiovascular disease HF
  • Single studies
  • HF: ↑ risk but population attributable fraction ↓ d over time 7.8%–1.4%
  • Bidirectional relation between AF and HF
↑ risk N/A
Cardiovascular disease HF
  • MA
  • History of HF: ↑ risk (HR, 2.02)
↑ risk N/A
Cardiovascular disease HF
  • MR
  • Genetically predicted HF: ↑ risk (OR, 1.86)
↑ risk N/A
Cardiovascular disease CAD
  • Single study
  • Myocardial infarction (MI): Population attributable fraction 3.6%
↑ risk N/A
Cardiovascular disease CAD
  • MA
  • History of MI: (HR, 1.64)
↑ risk N/A
Cardiovascular disease CAD
  • MR
  • Genetically predicted CAD: (OR, 1.18)
↑ risk N/A
Cardiovascular disease Valvular heart disease (VHD)
  • Single studies
  • Significant heart murmur: ↑ risk (HR, 2.38)
  • Significant heart murmur (any diastolic and grade ≥3/6 systolic murmur): ↑ risk, population attributable fraction 21.9% ↓ d over time to 3.1%
↑ risk N/A
Cardiovascular disease Valvular heart disease (VHD)
  • Single studies
  • Significant heart murmur: ↑ risk (HR, 2.38)
  • Significant heart murmur (any diastolic and grade ≥3/6 systolic murmur): ↑ risk, population attributable fraction 21.9% ↓ d over time to 3.1%
↑ risk N/A
Cardiovascular disease Valvular heart disease (VHD)
  • MR
  • Genetically predicted risk of AF in individuals of European ancestry: associated with VHD with rheumatic fever, (OR, 1.26) and nonrheumatic VHD, (OR, 1.27)
↑ risk N/A
Cardiovascular disease Cardiac surgery
  • Single study
  • Multicenter validated risk prediction model: ↑ risk AF after coronary artery bypass graft surgery CABG
↑ risk
  • Prophylactic amiodarone, beta blockers: ↓ ↔ postop AF
  • Posterior left pericardiotomy during CABG, aortic valve, ascending aortic aneurysm surgery: ↓ postop AF
Cardiovascular disease Cardiac surgery
  • SR/MA
  • Postop AF incidence: 23.7%–25.5% of cardiac surgery patients
↑ risk
  • Prophylactic amiodarone, beta blockers: ↓ ↔ postop AF
  • Posterior left pericardiotomy during CABG, aortic valve, ascending aortic aneurysm surgery: ↓ postop AF
Other conditions Chronic kidney disease (CKD)
  • SR/MA
  • CKD: ↑ risk (HR, 1.47)
↑ ↔ risk N/A
Other conditions Chronic kidney disease (CKD)
  • MR
  • Bidirectional relation between CKD and AF
  • AF causal for CKD; CKD not causal for AF
↑ ↔ risk N/A
Other conditions Obstructive sleep apnea
  • SR/MA
  • Obstructive sleep apnea (OSA): ↑ risk (OR, 1.71), with potential dose response relation by severity
↑ risk
  • Observational studies of sleep-disordered breathing (SDB) treatment: ↓ AF burden
  • Small randomized controlled trial(s) (RCTs) of SDB treatment: ↔
Other conditions Obstructive sleep apnea
  • MR
  • Genetically predicted OSA:
    ↑ risk (OR, 1.21)
↑ risk
  • Observational studies of sleep-disordered breathing (SDB) treatment: ↓ AF burden
  • Small randomized controlled trial(s) (RCTs) of SDB treatment: ↔
Other conditions Thyroid disease
  • SR/MA
  • Clinical hyperthyroidism: risk ↑ (RR, 2.35)
↑ risk
Other conditions Thyroid disease
  • MR
  • Hyperthyroidism: ↑ risk (OR, 1.31)
↑ risk
Other conditions Sepsis
  • Single study
  • Severe sepsis: ↑ risk (OR, 6.82); Medicare population
↑ risk N/A
Other conditions Sepsis
  • SR/MA
  • Sepsis severity: ↑ risk
↑ risk N/A
Electrocardiogram (ECG) markers PR interval
  • SR/MA
  • Prolonged PR: ↑ risk (RR, 1.45)
  • Prolonged PR:
    ↑ risk
  • PR interval polygenic risk score: ↓ risk
  • PR interval risk SNPs: variable
    ↑ ↓ risk
N/A
Electrocardiogram (ECG) markers PR interval
  • MR
  • Polygenic risk score PR interval prolongation: ↓ AF risk, (OR, 0.95; P=4.30×10−8) with some variants associated with ↑ and some with ↓ AF risk
  • Prolonged PR:
    ↑ risk
  • PR interval polygenic risk score: ↓ risk
  • PR interval risk SNPs: variable
    ↑ ↓ risk
N/A
Electrocardiogram (ECG) markers Left ventricular (LV) hypertrophy
  • Single study
  • ECG left ventricular hypertrophy (LVH): Population attributable fraction 10.4% ↓ d over time to 1.8%
↑ risk N/A
Electrocardiogram (ECG) markers Left ventricular (LV) hypertrophy
  • SR/MA
  • LVH: ↑ risk (RR, 1.46)
↑ risk N/A
Biomarkers Natriuretic peptides
  • MA
  • Brain naturiuretic peptide BNP: ↑ risk, (HR per 1-SD ln-BNP, 1.66)
↑ ↔ risk N/A
Biomarkers Natriuretic peptides
  • MR
  • Natriuretic peptides not associated
↑ ↔ risk N/A
Biomarkers Inflammatory markers
  • SR/MA
  • CRP: ↑ risk standardized mean difference (SMD, 0.95)
  • IL-6: ↑ risk (SMD, 0.89)
  • TNF- α: ↑ risk (SMD, 2.20)
  • CRP, IL-6, TNF-α DUSP13, FKBP7, Spondin-1: ↑ risk
  • IL-6R, TNFS12:
    ↓ risk
N/A
Biomarkers Inflammatory markers
  • MR
  • DUSP13, FKBP7, Spondin-1
    ↑ risk
  • IL-6R, TNFS12 ↓ risk
  • CRP, IL-6, TNF-α DUSP13, FKBP7, Spondin-1: ↑ risk
  • IL-6R, TNFS12:
    ↓ risk
N/A
Biomarkers Lp(a)
  • SR/MA
  • Lp(a): (HR, 1.03); only 39% of Lp(a) risk mediated via atherosclerotic cardiovascular disease ASCVD
↑ risk N/A
Biomarkers Lp(a)
  • MR
  • Genetically predicted ↑ Lp(a): ↑ risk (HR per 23 mg/dL genetically predicted ↑ Lp(a), 1.04)
↑ risk N/A
Imaging markers Left atrial size or function
  • Single studies
  • Left atrium (LA) anterior-posterior dimension: ↑ risk (HR per 5 mm ↑ , 1.39)
  • End diastolic LA volume (min): ↑ risk (HR, 1.12)
  • LA emptying fraction: ↑ risk (HR, 1.03)
LA size, emptying fraction: ↑ risk Surgical LA reduction in conjunction with cardiac surgery or surgical AF ablation in patients with persistent AF may ↑ rates of sinus rhythm
Imaging markers Left atrial size or function
  • MR
  • Genetic susceptibility to AF (independent measure) is associated with ↑ indexed LA size and ↓ LA ejection fraction (dependent measures)
LA size, emptying fraction: ↑ risk Surgical LA reduction in conjunction with cardiac surgery or surgical AF ablation in patients with persistent AF may ↑ rates of sinus rhythm
Imaging markers LV wall thickness
  • Single study
  • LV posterior wall thickness: ↑ risk (HR per 4 mm ↑ , 1.28)
↑ risk N/A
Imaging markers LV wall thickness
  • SR/MA
  • LVH: ↑ risk (RR, 1.46)
↑ risk N/A
Social determinants of health Education
  • Single studies
  • Higher education: ↑ lifetime risk of AF (U.S.-based ARIC study)
  • Higher education in young individuals: ↓ risk of AF diagnosis (Danish study)
Variable ↑ ↓ risk N/A
Social determinants of health Education
  • MR
  • AF risk related but largely mediated via BMI (57.5%), type 2 DM (9.8%), SBP (18.7%), and smoking (7.1%)
Variable ↑ ↓ risk N/A
Social determinants of health Income
  • Single studies
  • Higher income: ↑ lifetime risk of AF (U.S.-based ARIC study)
  • Higher income in young individuals: ↓ risk of AF diagnosis (Danish study)
Variable ↑ ↓ risk N/A
Social determinants of health Socioeconomic status
  • Single studies
  • Cumulative socioeconomic disadvantage: ↑ risk (HR, 1.57)
  • Individual’s poorest areas: 12% ↑ d risk
Low SES: ↑ ↔ risk N/A
Social determinants of health Socioeconomic status
  • SR/MA
  • Heterogeneous results
Low SES: ↑ ↔ risk N/A
Genetics Family history/ heritability
  • Single studies
  • Family history of AF: ↑ risk
↑ risk N/A
Genetics Family history/ heritability
  • MR
  • Proportion heritability explained by loci in European ancestry analysis, 42%
↑ risk N/A
Genetics Genome-wide association study (GWAS)
  • MA
  • Number of AF risk loci ↑s with ↑ number of subjects studied. In 2018, 97–111 loci explained ~11%–42% of the heritability of AF in individuals of European ancestry
↑ risk N/A
↓ indicates decreased; ↑, increased; ↔ no significant change in risk;
Population attributable fraction: the proportional disease incidence in the population that is estimated to be due to the risk factor.
Statistically significant associations reported, unless otherwise indicated.

2.2. Atrial Arrhythmia Classification and Definitions

Figure 4. AF Stages: Evolution of Atrial Arrhythmia Progression

* Heart failure, valve disease, CAD, hypertrophic cardiomyopathy (HCM), neuromuscular disorders, thyroid disease.

(Original figure created by the Atrial Fibrillation Guideline Writing Committee.)

Figure 5. Pillars for AF Management

Table 4. Definitions

Having trouble viewing table?
Term Definition
Atrial fibrillation
  • A supraventricular tachyarrhythmia with uncoordinated atrial activation and ineffective atrial contraction.
  • ECG characteristics include (a) irregular R-R intervals (when atrioventricular [AV] conduction is present), (b) absence of distinct P waves, and (c) irregular atrial activity also known as fibrillatory waves. AF can be documented by 12 lead ECG, rhythm strips, wearables, intracardiac electrograms, etc. but will always require visual confirmation that the diagnosis is accurate.
Clinical AF With the increasing availability of wearable devices and other continuous monitoring technologies, the distinction between clinical and subclinical AF has become increasingly blurred thus the writing group felt the term clinical AF has become less useful. Yet, the term was kept since most of the evidence from randomized trials that have led to guideline recommendations for the treatment of AF refer to “clinical AF.” These trials required ECG documentation of the arrhythmia for inclusion and a majority of patients presented for clinical evaluation and/or therapy of the arrhythmia.
Subclinical AF Subclinical AF refers to this arrhythmia identified in individuals who do not have symptoms attributable to AF and in whom there are no prior ECGs documenting AF.
This includes AF identified by implanted devices (pacemakers, defibrillators, or implantable loop recorders) or wearable monitors.
Atrial high-rate episodes (AHRE) These are defined as atrial events exceeding the programmed detection rate limit set by the device. These are recorded by implanted devices but require visual inspection to confirm AF and exclude other atrial arrhythmias, artifact or oversensing.
AF burden AF burden encompasses both frequency and duration and refers to the amount of AF that an individual has. AF burden has been defined differently across studies. For the purpose of this guideline, AF burden will be defined as the durations of an episode or as a percentage of AF duration during the monitoring period depending on how it was defined in the individual studies.
First detected AF The first documentation of AF, regardless of prior symptoms
Paroxysmal AF AF that is intermittent and terminates within ≤7 days of onset
Persistent AF AF that is continuous and sustains for >7 days and requires intervention. Of note, patients with persistent AF who with therapy become paroxysmal should still be defined as persistent as this reflects their original pattern and is a more useful to predict outcomes and define substrate.
Long-standing persistent AF AF that is continuous for >12 months in duration
Permanent AF A term that is used when the patient and clinician make a joint decision to stop further attempts to restore and/or maintain sinus rhythm
Acceptance of AF represents a therapeutic decision and does not represent an inherent pathophysiological attribute of AF
Terms considered obsolete
Chronic AF This historical term has had variable definitions and should be abandoned. It has been replaced by the “paroxysmal, persistent, long-standing persistent and permanent” terminology.
Valvular and Nonvalvular AF The distinction between “valvular” and “non-valvular” AF remains a matter of debate. Their definitions may be confusing. Recent trials comparing vitamin K antagonists with non-vitamin K antagonist oral anticoagulants (OACs) in AF were performed among patients with so-called “non-valvular’’ AF. These trials have all allowed native valvular heart disease other than mitral stenosis (mostly moderate and severe) and prosthetic heart valves to be included. We should no longer consider the classification of AF as ‘‘valvular’’ or “non-valvular” for the purpose of defining the etiology of AF, since the term was specific for eligibility of stroke risk reduction therapies. Valvular and nonvalvular terminology should be abandoned.
Lone AF This term has been used in the past to identify AF in younger patients without structural heart disease who are at a lower risk for thromboembolism. This term does not enhance patient care, is not currently used and should be abandoned.

2.2.2. Associated Arrhythmias

Figure 6. Types of Atrial Flutter and Macroreentrant Atrial Tachycardia

Fl indicates flutter; MRT, macroreentrent.

The typical, reverse typical, and the lower-loop flutter all have the low right atrial isthmus incorporated in the flutter circuit. Other macroreentrant flutters include scar-mediated reentrant tachycardia and left mitral isthmus flutter. Modified with permission from Wellens HJJ.

Copyright 2002, American Heart Association, Inc. Illustration courtesy of Dr F. Cosio.

2.3. Mechanisms and Pathophysiology

Figure 7. Mechanisms and Pathways Leading to AF

The pathways that contribute to the development of AF create a substrate for re-entry and provide triggers that can initiate arrhythmic activity.

2.3.3. Role of the Autonomic Nervous System (ANS)

Figure 8. Contemporary Summary of the Role of the ANS in AF

Created by the Atrial Fibrillation Guideline Writing Committee.

2.5. Addressing Health Inequities and Barriers to AF Management

1. Patients with AF, regardless of sex and gender diversity, race and ethnicity, or adverse social determinants of health (SDOH),* should be equitably offered guideline-directed stroke risk reduction therapies as well as rate or rhythm control strategies and LRFM as indicated to improve QOL and prevent adverse outcomes. (1, B-NR)
* Including lower income, lower education, inadequate or lack of insurance coverage, or rurality.
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3. Shared Decision-Making in AF Management

1. In patients with AF, the use of evidence-based decision aids might be useful to guide stroke reduction therapy treatment decisions throughout the disease course to improve engagement, decisional quality, and patient satisfaction. (2b, B-R)
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Table 5. Table of Publicly Available Decision Aids

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Agency Website Link Focus Area
American College of Cardiology
Colorado Program for Patient Centered Decisions
https://patientdecisionaid.org/icd/atrial-fibrillation/ Stroke risk reduction therapies
Anticoagulation Choice Decision Aid https://anticoagulationdecisionaid.mayoclinic.org/ Stroke risk reduction therapies
Ottawa Hospital Research Institute
Developer Healthwise
https://decisionaid.ohri.ca/AZlist.html AF ablation
Stroke risk reduction
Stanford https://afibguide.com/ Stroke risk reduction therapies

Management

Management

4. Clinical Evaluation
4.1. Risk Stratification and Population Screening

Table 6. CHARGE-AF Risk Score for Detecting Incident AF*

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Variable (X) Estimated β coefficient (SE) HR (95% CI)
Age (per 5-y increment) 0.508 (0.022) 1.66 (1.59–1.74)
White Race 0.465 (0.093) 1.59 (1.33–1.91)
Height (per 10-cm increment) 0.248 (0.036) 1.28 (1.19–1.38)
Weight (per 15-kg increment) 0.115 (0.033) 1.12 (1.05–1.20)
Systolic BP (per 20-mm Hg increment) 0.197 (0.033) 1.22 (1.14–1.30)
Diastolic BP (per 10-mm Hg increment) -0.101 (0.032) 0.90 (0.85–0.96)
Smoking (current versus former/never) 0.359 (0.063) 1.42 (1.25–1.60)
Diabetes (yes) 0.237 (0.073) 1.27 (1.64–2.48)
Myocardial infarction (yes) 0.496 (0.089) 1.64 (1.38–1.96)
* Five-year risk is given by: 1 – 0.9718412736exp(ΣβX – 12.4411305), where β is the regression coefficient (column 2) and X is the level of each variable risk factor.
Table 6 does not encompass all complications.

Table 7. C2HEST Risk Score for Detecting Incident AF*

Having trouble viewing table?
Acronym Risk Factor Points
C2 CAD/chronic obstructive pulmonary disease (COPD) 1–2
H Hypertension 1
E Elderly (age ≥75 y) 2
S Systolic heart failure 2
T Thyroid disease (hyperthyroidism) 1
* Total points 0–8. For the C2HEST score, the C statistic was 0.749, with 95% CI of 0.729 to 0.769. The incident rate of AF increased significantly with higher C2HEST scores.
The C2HEST score: C2, coronary artery disease or chronic obstructive pulmonary disease [1 point each]; H, hypertension [1 point]; E, elderly [age ≥75 y, 2 points]; S, systolic HF [2 points]; T, thyroid disease [hyperthyroidism, 1 point])

4.2. Basic Evaluation

4.2.1. Basic Clinical Evaluation

1. In patients with newly diagnosed AF, a transthoracic echocardiogram to assess cardiac structure, laboratory testing to include a complete blood count, metabolic panel, and thyroid function, and testing to assess for other medical conditions associated with AF are recommended to determine stroke and bleeding risk factors, as well as underlying conditions that will guide further management. (1, B-NR)
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2. In patients with newly diagnosed AF, protocolized testing for ischemia, acute coronary syndrome (ACS), and pulmonary embolism (PE) should not routinely be performed to assess the etiology of AF unless there are additional signs or symptoms to indicate those disorders. (3 - No Benefit, B-NR)
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4.2.2. Rhythm Monitoring Tools and Methods

1. Among individuals without a known history of AF, it is recommended that an initial AF diagnosis be made by a clinician using visual interpretation of the electrocardiographic signals, regardless of the type of rhythm or monitoring device. (1, B-NR)
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2. In patients with an intracardiac rhythm device capable of a diagnosis of AF, such as from an atrial pacemaker lead, a diagnosis of AF should only be made after it is visually confirmed by reviewing intracardiac tracings in order to exclude signal artifacts and other arrhythmias. (1, B-NR)
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3. For patients who have had a systemic thromboembolic event without a known history of AF and in whom maximum sensitivity to detect AF is sought, an implantable cardiac monitor is reasonable. (2a, B-R)
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4. Among patients with a diagnosis of AF, it is reasonable to infer AF frequency, duration, and burden using automated algorithms available from electrocardiographic monitors, implantable cardiac monitors, and cardiac rhythm devices with an atrial lead, recognizing that periodic review can be required to exclude other arrythmias. (2a, B-NR)
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5. Among patients with AF in whom cardiac monitoring is advised, it is reasonable to recommend use of a consumer-accessible electrocardiographic device that provides a high-quality tracing to detect recurrences.

(2a, B-R)
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5. Lifestyle and Risk Factor Modification for AF Management

5.1. Primary Prevention

1. Patients at increased risk of AF should receive comprehensive guideline-directed LRFM for AF, targeting obesity, physical inactivity, unhealthy alcohol consumption, smoking, diabetes, and hypertension. (1, B-NR)
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5.2. Secondary Prevention: Management of Comorbidities and Risk Factors

5.2.1. Weight Loss in Individuals Who Are Overweight or Obese

1. In patients with AF who are overweight or obese (with BMI >27 kg/m2), weight loss is recommended, with an ideal target of at least 10% weight loss to reduce AF symptoms, burden, recurrence, and progression to persistent AF. (1, B-R)
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5.2.2. Physical Fitness

1. In individuals with AF,* moderate to vigorous exercise training to a target of 210 minutes per week is recommended to reduce AF symptoms and burden, increase maintenance of sinus rhythm, increase functional capacity, and improve QOL. (1, B-R)
* In patients without AF related to excessive exercise training.
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5.2.3. Smoking Cessation

1. Patients with a history of AF who smoke cigarettes should be strongly advised to quit smoking and should receive guideline-directed management and therapy (GDMT) for tobacco cessation to mitigate increased risks of AF-related cardiovascular complications and other adverse outcomes. (1, B-NR)
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5.2.4. Alcohol Consumption

1. Patients with AF seeking a rhythm-control strategy should minimize or eliminate alcohol consumption to reduce AF recurrence and burden. (1, B-R)
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5.2.5. Caffeine Consumption

1. For patients with AF, recommending caffeine abstention to prevent AF episodes is of no benefit, although it may reduce symptoms in patients who report caffeine triggers or worsens AF symptoms. (3 - No Benefit, B-NR)
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5.2.8. Treatment of Hypertension

1. For patients with AF and hypertension, optimal BP control is recommended to reduce AF recurrence and AF-related cardiovascular events. (1, B-NR)
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5.2.9. Sleep

1. Among patients with AF, it may be reasonable to screen for obstructive sleep apnea, given its high prevalence in patients with AF, although the role of treatment of SDB to maintain sinus rhythm is uncertain. (2b, B-NR)
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5.2.10. Comprehensive Care

1. Patients with AF should receive comprehensive care addressing guideline-directed LRFM, AF symptoms, risk of stroke, and other associated medical conditions to reduce AF burden, progression, or consequences. (1, A)
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2. In patients with AF, use of clinical care pathways, such as nurse-led AF clinics, is reasonable to promote comprehensive, team-based care and to enhance adherence to evidence-based therapies for AF and associated conditions. (2a, B-R)
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6. Prevention of Thromboembolism

6.1. Risk Stratification Schemes

1. Patients with AF should be evaluated for their annual risk of thromboembolic events using a validated clinical risk score, such as CHA2DS2-VASc. (1, B-NR)
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2. Patients with AF should be evaluated for factors that specifically indicate a higher risk of bleeding, such as previous bleeding and use of drugs that increase bleeding risk, in order to identify possible interventions to prevent bleeding on anticoagulation. (1, B-NR)
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3. Patients with AF at intermediate annual risk of thromboembolic events by risk scores (eg, equivalent to CHA2DS2-VASc score of 1 in men or 2 in women), who remain uncertain about the benefit of anticoagulation, can benefit from consideration of factors that might modify their risk of stroke to help inform the decision.* (2a, C-LD)
* Factors may include AF burden or other features in Table 3.
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4. In patients who are deemed at high risk for stroke, bleeding risk scores should not be used in isolation to determine eligibility for oral anticoagulation but instead to identify and modify bleeding risk factors and to inform medical decision-making. (3 - No Benefit, B-NR)
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Table 8. Three Validated Risk Models for Stroke

Having trouble viewing table?
Risk Factor CHA2DS2-VASc ATRIA GARFIELD
Age ≥85 y 6 0.98
Age ≥75 y 2 5 0.59
Age 65–74 y 1 3 0.20
Female sex 1 1
Hypertension 1 0.16
Renal disease 1 0.35
Diabetes 1 1 0.21
Current smoking 0.48
Congestive heart failure 1 1 0.23
Prior stroke or transient ischemic attack (TIA) 2 2–8* 0.80
Vascular disease 1 0.20
Dementia 0.51
Prior bleeding 0.30
Proteinuria 1
Low risk score 0 0–5 0—0.89
Intermediate risk score 1 6 0.90—1.59
High risk score ≥2 7–15 ≥1.60
C-index (11)
C-index (13) 0.67 0.71
* 8 points if age <65 y; 2 points if age 75–84 y; and 3 points if ≥85 y

Figure 9. Rates of Stroke by Stroke Risk Score Levels in Different Cohorts

Table 9. Some Best Known Published Clinical Scores With Potential Advantages

Having trouble viewing table?
Year of Publication
Score Name
Score Components Potential Advantages No. of Validation Studies Hyperlink to Online Score Calculator if Available
2001
Congestive heart failure, hypertension, age >75 years, diabetes mellitus, stroke/transient ischemia attack/ thromboembolism (CHADS2)
Congestive heart failure (CHF), hypertension, age (≥65 y = 1 point, ≥75 y = 2 points), diabetes, stroke/TIA (2 points) CHADS2 was superior to existing risk classification schemes.
AFI scheme: C-statistic = 0.68 (0.65–0.71)
SPAF-III scheme: C-statistic = 0.74 (0.71–0.76)
CHADS2 score: C-statistic = 0.82 (0.80–0.84)
46 https://www.mdcalc.com/calc/40/chads2-score-atrial-fibrillation-stroke-risk
2010
CHA2DS2-VASc
CHF, hypertension, age ≥75 y, diabetes, stroke or TIA, vascular disease, age 65–74 y, female sex Most commonly used and studied, superior to CHADS2.
C-statistic = 0.606 (0.513–0.699) for CHA2DS2-VASs versus 0.561 (0.450–0.672) for CHADS2
Improved compared with original CHADS2 score.
82 https://www.mdcalc.com/calc/801/cha2ds2-vasc-score-atrial-fibrillation-stroke-risk#next-steps
2013
ATRIA
Age (65–74 y = 3 points, 75–84 y = 5 points, ≥85 y = 6 points), hypertension, diabetes, CHF, proteinuria, GFR <45 mL/min/1.73 m2, sex Includes more age categories, renal function, and proteinuria.
More patients were classified as low or high risk but not as well tested in general.
11 https://www.mdcalc.com/calc/1842/atria-stroke-risk-score
2017
GARFIELD-AF
Web-based, uses routinely collected clinical data, and includes a total of 16 questions Web-based tool for predicting stroke and mortality, includes the effect of the different anticoagulants, bleeding risk and mortality to facilitate shared decision-making on the potential benefits/risks of anticoagulation 4 https://af.garfieldregistry.org/garfield-af-risk-calculator
2016
MCHA2DS2-VASc
Expanded lower threshold for age to 50 y (1 point for age 50–74 y) Validated in Asian cohort.
Can further identify Asian AF patients who may derive benefits from stroke prevention. In one study, MCHA2DS2-VASc was superior to CHA2DS2-VASc.
C-statistics = 0.708 (0.703–0.712) vs. 0.689 (0.684–0.694)
1

Table 10. Risk Factor Definitions for CHA2DS2-VASc Score as in the Original Article

Having trouble viewing table?
C Heart Failure The presence of signs and symptoms of either right (elevated central venous pressure, hepatomegaly, dependent edema) or left ventricular failure (exertional dyspnea, cough, fatigue, orthopnea, paroxysmal nocturnal dyspnea, cardiac enlargement, rates, gallop rhythm, pulmonary venous congestion) or both, confirmed by noninvasive or invasive measurements demonstrating objective evidence of cardiac dysfunction.
H Hypertension A resting blood pressure >140 mm Hg systolic and/or >90 mm Hg diastolic on at least 2 occasions or current antihypertensive pharmacological treatment.
A2 Age, additional risk/point Age ≥75 y
D Diabetes Fasting plasma glucose level ≥7.0 mmol/L (126 mg/dL) or treatment with hypoglycemic agent and/or insulin.
S2 Thromboembolism Either an ischemic stroke, transient ischemic attack, peripheral embolism, or pulmonary embolism.
V Vascular Disease Coronary artery disease (prior myocardial infarction, angina pectoris, percutaneous coronary intervention (PCI), or coronary artery bypass surgery) or peripheral vascular disease (the presence of any of the following: intermittent claudication, previous surgery or percutaneous intervention on the abdominal aorta or the lower extremity vessels, abdominal or thoracic vascular surgery, arterial and venous thrombosis.)
A Age standard risk/weight Age 65–74 y
Sc Sex Category Female sex
Modified with permission from Lip GY, et al. Copyright 2010, with permission from Elsevier.

Table 11. Factors That Increase the Risk of Stroke

  • Higher AF burden/Long duration
  • Persistent/permanent AF versus paroxysmal
  • Obesity (body mass index ≥30 kg/m2)
  • HCM
  • Poorly controlled hypertension
  • Estimated glomerular filtration rate (eGFR) (<45 mL/h)
  • Proteinuria (>150 mg/24 h or equivalent)
  • Enlarged LA volume (≥73 mL) or diameter (≥4.7 cm)

Table 12. Thromboembolic Event Rates by Point Score for ATRIA, CHADS2, and CHA2DS2-VASc Risk Scores*

Having trouble viewing table?
Points ATRIA
Events
ATRIA
Person-years
ATRIA
Rate per 100 Person-years
CHADS2
Events
CHADS2
Person-years
CHADS2
Rate per 100 Person-years
CHA2DS2-VASc
Events
CHA2DS2-VASc
Person-years
CHA2DS2-VASc
Rate per 100 Person-years
0 2 2652 0.08 22 6126 0.36 1 2493 0.04
1 12 2819 0.43 121 10, 084 1.20 21 3806 0.55
2 14 1419 0.99 253 9757 2.59 46 5560 0.83
3 13 1780 0.73 178 4782 3.72 121 7305 1.66
4 19 2960 0.64 81 1309 6.19 193 6898 2.80
5 36 3614 0.99 19 450 4.23 175 4057 4.31
6 83 4346 1.91 11 101 10.84 85 1783 4.77
7 119 4768 2.50 24 498 4.82
8 151 3913 3.86 14 179 7.82
9 104 2400 4.33 5 30 16.62
10 75 1181 6.35
11 31 501 6.18
12 20 183 10.95
13 4 53 7.52
14 2 12 16.36
15 0 7 0
All 685 32, 609 2.10
* Black lines identify thresholds for low-, moderate-, and high-risk categories for the 3 stroke risk point scores using published cut points.
The CHADS2 score assigns points as follows: 1 point each for the presence of congestive heart failure, hypertension, age ≥75 y, and diabetes mellitus and 2 points for history of stroke/transient ischemic attack.
The CHA2DS2-VASc score assigns points as follows: 1 point each for congestive heart failure/left ventricular dysfunction, hypertension, diabetes mellitus, vascular disease, age 65 to 74 y, and female sex, and 2 points each for age ≥75 years and stroke/transient ischemic attack/thromboembolism.

Reproduced with permission from Singer DE, et al. Copyright 2013, The Authors.
Published on behalf of the American Heart Association, Inc., by Wiley-Blackwell.

6.2. Risk-Based Selection of Oral Anticoagulation: Balancing Risks and Benefits

1. In patients diagnosed with AF who have an estimated annual risk of stroke or thromboembolic events ≥2%, selection of therapy to reduce the risk of stroke should be based on the risk of thromboembolism, regardless of whether the AF pattern is paroxysmal, persistent, long-standing persistent, or permanent. (1, B-R)
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2. In patients with AF at risk for stroke, reevaluation of the need for and choice of stroke risk reduction therapy at periodic intervals is recommended to reassess stroke and bleeding risk, net clinical benefit, and proper dosing.

(1, B-NR)
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6.3. Oral Anticoagulants

6.3.1. Antithrombotic Therapy

1. For patients with AF and an estimated annual thromboembolic risk of ≥2%/year (eg, CHA2DS2-VASc score of ≥2 in men and ≥3 in women), anticoagulation is recommended to prevent stroke and systemic thromboembolism. (1, A)
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2. In patients with AF who do not have a history of moderate to severe rheumatic mitral stenosis or a mechanical heart valve, and who are candidates for anticoagulation, direct oral anticoagulants (DOACs) are recommended over warfarin to reduce the risk of mortality, stroke, systemic embolism, and intracranial hemorrhage (ICH). (1, A)
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3. For patients with AF and an estimated annual thromboembolic risk of ≥1% but <2%/year (equivalent to CHA2DS2-VASc score of 1 in men and 2 in women), anticoagulation is reasonable to prevent stroke and systemic thromboembolism. (2a, A)
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4. In patients with AF who are candidates for anticoagulation and without an indication for antiplatelet therapy (APT), aspirin either alone or in combination with clopidogrel as an alternative to anticoagulation is not recommended to reduce stroke risk. (3 - Harm, B-R)
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5. In patients with AF without risk factors for stroke, aspirin monotherapy for prevention of thromboembolic events is of no benefit. (3 - No Benefit, B-NR)
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Figure 10. Antithrombotic Options in Patients with AF

Table 13. OACs Pharmacokinetic Characteristics and Dosing

Having trouble viewing table?
Name
(Class)
Warfarin
(Vitamin K antagonist (VKA))
Dabigatran
(Direct Thrombin Inhibitor)
Rivaroxaban
(Factor Xa Inhibitor)
Apixaban
(Factor Xa Inhibitor)
Edoxaban
(Factor Xa Inhibitor)
Metabolism S-isomer: CYP2C9
R-isomer: CYP2C19, CYP3A4
Minimal CYP3A4/5 CYP3A4 Minimal CYP3A4
P-glycoprotein substrate No Yes Yes Yes Yes
Excretion 0% renal; very little warfarin excreted unchanged in urine 80% renal 66% renal, 28% feces 27% renal, 73% biliary and intestinal 50% renal, 50% liver and biliary/intestinal
Half-life 20–60 h 12–17 h 5–9 h 12 h 10–14 h
Renal dosing adjustment based on actual body weight N/A
  • Creatinine clearance (CrCl) >30 mL/min
    • 150 mg twice daily
  • CrCl 15–30 mL/min
    • 75 mg twice daily
  • CrCl >50 mL/ min
    • 20 mg daily with the biggest meal*
  • CrCl 15–50 mL/min
    • 15 mg daily with the biggest meal*
  • 5 mg twice daily
  • If any 2 of the following: age ≥80 y, body weight ≤60 kg, SCr ≥1.5 mg/ dL
    • 2.5 mg twice daily
  • CrCl >50 to ≤95 mL/ min
    • 60 mg once daily
  • CrCl 15–50 mL/min
    • 30 mg once daily
Drug interaction management based on concomitant therapy of CYP3A4 inhibitors/p-glycoprotein inhibitors Adjust dose based on INR trends CrCl 30–50 mL/ min with concomitant use of dronedarone or systemic ketoconazole: 75 mg twice daily

CrCl < 30 mL/min: avoid dabigatran use concomitantly with dronedarone or systemic ketoconazole
Avoid rivaroxaban use with concomitant therapy of combined p-glycoprotein and strong CYP3A4 inhibitors (eg, systemic ketoconazole and ritonavir)

No dose adjustment required with clarithromycin

Avoid rivaroxaban use in patients with CrCl 15 to < 80 mL/min receiving combined p-glycoprotein and moderate CYP3A4 inhibitors (eg, erythromycin)
In patients receiving apixaban 5 mg twice daily, reduce dose to 2.5 mg twice daily when combined p-glycoprotein and strong CYP3A4 inhibitors (eg, itraconazole, systemic ketoconazole, ritonavir) are concomitantly used

If patients already receiving apixaban 2.5 mg twice daily, avoid apixaban use if combined p-glycoprotein and strong CYP3A4 inhibitors are concomitantly used
No dose adjustment is required
Drug interaction management based on concomitant therapy of p-glycoprotein/ CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin, St. John’s wort) Adjust dose based on INR trends Avoid use Avoid use Avoid use Avoid use with rifampin. No study evaluated the effect of other p-glycoprotein/ CYP3A4 inducers on edoxaban drug levels
Appropriate use based on liver function (Child-Pugh score)
Child-Pugh A (mild)
Not mentioned in the labeling No dose adjustment needed No dose adjustment needed No dose adjustment needed No dose adjustment needed
Child-Pugh B (moderate) Not mentioned in the labeling Use with caution Avoid use Use with caution Use with caution
Child-Pugh C (severe) Not mentioned in the labeling Avoid use Avoid use Avoid use Avoid use
*The effect of food (high-fat, high-calorie meal) on bioavailability for 10- and 20-mg tablet was evaluated in 24 subjects under fed and fasting conditions. After a single oral 20-mg dose, area under the curve was increased by 39%, and Cmax was increased by 76% under fed condition, but area under the curve and Cmax were similar between fasting and fed conditions.

Child-Pugh scoring: the severity of liver disease, primarily cirrhosis. Child-Pugh A (mild): 5 to 6 points; Child-Pugh B (moderate): 7 to 9 points; Child-Pugh C (severe): 10 to 15 points. The score is based on the 5 variables: encephalopathy (none=1 point, grade 1 and 2=2 points, grade 3 and 4=3 points); ascites (none=1 point, slight=2 points, moderate=3 points); total bilirubin (<2 mg/mL=1 point, 2-3 mg/mL=2 points, >3 mg/mL=3 points); albumin (>3.5 mg/mL=1 point, 2.8-3.5 mg/mL=2 points, <2.8 mg/mL=3 points); INR (<1.7=1 point, 1.7-2.2=2 points, >2.2=3 points).

Information obtained from manufacturer package inserts. Adapted with permission from pgs. 28–31 of Kido K. Copyright 2021, American College of Clinical Pharmacy

Figure 11. DOAC Laboratory Monitoring

CrCL indicates creatinine clearance based on actual body weight; INR, international normalized ratio. Developed by Atrial Fibrillation Guideline Writing Committee. 2022.

* HAS-BLED scoring (low risk=score 0, moderate risk=score 1–2, high risk=score ≥3): uncontrolled hypertension (systolic blood pressure >160 mm Hg)=1 point; abnormal renal (serum creatinine >2.26 mg/dL, dialysis, or kidney transplant) or hepatic function (bilirubin >2 times upper limit normal, alanine aminotransferase/aspartate aminotransferase/alkaline phosphatase >3 times upper limit normal, or cirrhosis)=1 or 2 points; stroke (hemorrhagic or ischemic)=1 point; bleeding history or predisposition=1 point; labile INR (time in therapeutic range <60%)=1 point; elderly age >65 years=1 point; drugs (antiplatelet agents or nonsteroidal anti-inflammatory drugs) or excessive alcohol intake (8 units/week)=1 or 2 points.

Child-Pugh scoring: the severity of liver disease, primarily cirrhosis in patients with documented liver disease. Child-Pugh A (mild): 5 to 6 points; Child-Pugh B (moderate): 7 to 9 points; Child-Pugh C (severe): 10 to 15 points. The score is based on the 5 variables: encephalopathy (none=1 point, grade 1 and 2=2 points, grade 3 and 4=3 points); ascites (none=1 point, slight=2 points, moderate=3 points); total bilirubin (<2 mg/mL=1 point, 2–3 mg/mL=2 points, >3 mg/mL=3 points); albumin (>3.5 mg/mL=1 point, 2.8–3.5 mg/mL=2 points, <2.8 mg/mL=3 points); INR (<1.7=1 point, 1.7–2.2=2 points, >2.2=3 points).

6.3.1.1. Considerations in Managing Anticoagulants

1. For patients with AF receiving DOACs, optimal management of drug interactions is recommended for those receiving concomitant therapy with interacting drugs, especially CYP 3A4 and/or p-glycoprotein inhibitors or inducers (see Table 13). (1, C-LD)
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2. For patients with AF receiving warfarin*, a target INR between 2 and 3 is recommended, as well as optimal management of drug-drug interactions, consistency in vitamin K dietary intake, and routine INR monitoring to improve time in therapeutic range and to minimize risks of preventable thromboembolism or major bleeding. (1, B-R)
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3. For patients with AF, nonevidence-based doses of DOACs should be avoided to minimize risks of preventable thromboembolism or major bleeding and to improve survival. (3 - Harm, B-NR)
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* Excludes patients with mechanical valves.

6.4. Silent AF and Stroke of Undetermined Cause

1. In patients with stroke or TIA of undetermined cause, initial cardiac monitoring, and, if needed, extended monitoring with an implantable loop recorder are reasonable to improve detection of AF. (2a, B-R)
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6.4.1. Oral Anticoagulation for Device-Detected Atrial High-Rate Episodes Among Patients Without a Prior Diagnosis of AF

1. For patients with a device-detected atrial high-rate episode (AHRE) lasting ≥24 hours and with a CHA2DS2-VASc score ≥2 or equivalent stroke risk, it is reasonable to initiate oral anticoagulation within a SDM framework that considers episode duration and individual patient risk. (2a, B-NR)
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2. For patients with a device-detected AHRE lasting between 5 minutes and 24 hours and with a CHA2DS2-VASc score ≥3 or equivalent stroke risk, it may be reasonable to initiate anticoagulation within a SDM framework that considers episode duration and individual patient risk. (2b, B-NR)
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3. Patients with a device-detected AHRE lasting <5 minutes and without another indication for oral anticoagulation should not receive oral anticoagulation. (3 - No Benefit, B-NR)
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Figure 12. Consideration of Oral Anticoagulation for Device-Detected AHREs According to Patient Stroke Risk by CHA2DS2-VASc Score and Episode Duration 

ARTESiA, Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Subclinical Atrial Fibrillation trial; COMMANDER HF, A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants With Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure; COMPASS, Cardiovascular Outcomes for People Using Anticoagulation Strategies; NOAH, Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes Trial; and OAC, oral anticoagulation.

A potential approach to patients with SCAF could consider both patient risk (as gauged by the CHA2DS2-VASc score) and SCAF burden/duration.
Circle A indicates patients at low risk or with short and infrequent AHREs do not require anticoagulation; Circle B, patients with intermediate risk and AHREs lasting >6 min to 24 h are an uncertain population but are currently under study in 2 prospective randomized controlled trials; and Circle C, patients at high risk with longer episodes could be considered reasonable candidates for anticoagulation, although the precise threshold for SCAF duration remains uncertain.

Reproduced with permission from Noseworthy PA, et al. Copyright 2019 American Heart Association, Inc.
Modified from Freedman B et al. Copyright 2017 Springer Nature Limited.

6.5.1. Percutaneous Approaches to Occlude the Left Atrial Appendage (LAA)

1. In patients with AF, a moderate to high risk of stroke (CHAD2DS2-VASc score ≥2), and a contraindication (Table 14) to long-term oral anticoagulation due to a nonreversible cause, percutaneous LAAO (pLAAO) is reasonable. (2a, B-NR)
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2. In patients with AF and a moderate to high risk of stroke and a high risk of major bleeding on oral anticoagulation, pLAAO may be a reasonable alternative to oral anticoagulation based on patient preference, with careful consideration of procedural risk and with the understanding that the evidence for oral anticoagulation is more extensive. (2b, B-R)
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Table 14. Situations in Which Long-Term Anticoagulation Is Contraindicated and Situations When It Remains Reasonable

Long-Term Anticoagulation Contraindicated
  • Severe bleeding due to a nonreversible cause involving the gastrointestinal, pulmonary, or genitourinary systems
  • Spontaneous intracranial/intraspinal bleeding due to a nonreversible cause
  • Serious bleeding related to recurrent falls when cause of falls is not felt to be treatable

Long-Term Anticoagulation is Still Reasonable
  • Bleeding involving the gastrointestinal, pulmonary, or genitourinary systems that is treatable
  • Bleeding related to isolated trauma
  • Bleeding related to procedural complications

6.5.2. Cardiac Surgery — LAA Exclusion/Excision

1. In patients with AF undergoing cardiac surgery with a CHAD2DS2-VASc score ≥2 or equivalent stroke risk, surgical LAA exclusion, in addition to continued anticoagulation, is indicated to reduce the risk of stroke and systemic embolism. (1, A)
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2. In patients with AF undergoing cardiac surgery and LAA exclusion, a surgical technique resulting in absence of flow across the suture line and a stump of <1 cm as determined by intraoperative transesophageal echo should be used. (1, A)
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3. In patients with AF undergoing cardiac surgery with CHAD2DS2-VASc score ≥2 or equivalent stroke risk, the benefit of surgical LAA exclusion in the absence of continued anticoagulation to reduce the risk of stroke and systemic embolism is uncertain. (2b, A)
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6.6 Active Bleeding on Anticoagulant Therapy and Reversal Drugs

1. In patients with AF receiving dabigatran who develop life-threatening bleeding, treatment with idarucizumab is recommended to rapidly reverse dabigatran’s anticoagulation effect. (1, B-NR)
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2. In patients with AF receiving dabigatran who develop life-threatening bleeding, treatment with activated prothrombin complex concentrate (PCC) is reasonable to reverse dabigatran’s anticoagulation effect if idarucizumab is not available. (2a, C-LD)
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3. In patients with AF receiving factor Xa inhibitors who develop life-threatening bleeding, treatment with
either andexanet alfa (apixaban or rivaroxaban*, edoxaban) (1, B-NR)
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or 4-factor prothrombin complex concentrate. (1, C-LD)
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is recommended to rapidly reverse factor Xa inhibitor’s anticoagulation effect.
4. In patients with AF receiving warfarin who develop life-threatening bleeding, treatment with 4-factor prothrombin complex concentrate (if available) in addition to intravenous (IV) vitamin K is recommended to rapidly achieve INR correction over fresh frozen plasma and intravenous vitamin K treatment. (1, A)
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5. In patients with AF who develop major GI bleeding, resumption of oral anticoagulation therapy may be reasonable after correction of reversible causes of bleeding and reassessment of its long-term benefits and risks with a multidisciplinary team approach during SDM with patients. (2b, B-NR)
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Table 15. Reversal Agents for Oral Anticoagulants 

Having trouble viewing table?
Idarucizumab Andexanet alfa 4-Factor PCC Activated PCC
Class Humanized monoclonal antibody fragment binding to dabigatran and neutralizing anticoagulation effects A recombinant modified human factor Xa protein binding and sequestering the factor Xa inhibitors Prothrombin complex concentrate: coagulation factors II, VII, IX, and X

Anticoagulation proteins C and S
Nonactivated factors II, IX, and X Activated VII
US Food and Drug Administration (FDA) indications Reversal of dabigatran effects
  • For emergent surgery/ urgent procedures
  • Life-threatening or uncontrolled bleeding
Reversal of apixaban or rivaroxaban
  • For life-threatening or uncontrolled bleeding
The urgent reversal for acute major bleeding or need for an urgent surgery/invasive procedure in patients receiving vitamin K antagonists Control and prevention of bleeding episodes, perioperative management, prophylaxis to prevent or reduce bleeding frequency in hemophilia A and B patients
Off-label indications N/A Edoxaban-associated life-threatening bleeding Reversal of factor Xa inhibitors in patients requiring urgent procedure or with life-threatening bleeding Dabigatran- associated life-threatening bleeding
Dosing 5-g (2 separate vials of 2.5 g/vial) intravenous infusion over 5 minutes. Additional 5 g may be given if reappearance of bleeding with elevated coagulation parameters have been observed or patients require second emergent surgery/procedure and elevated coagulation parameters Low-dose regimen: 400-mg bolus at a target rate of 30 mg/min followed by 4 mg/min for up to 120 min
High-dose regimen: 800-mg bolus at a target rate of 30 mg/min followed by 8 mg/min for up to 120 min
The recommended dosing is based on apixaban or rivaroxaban, dose, and time since the patient’s last dose of apixaban or rivaroxaban
Warfarin reversal based on pretreatment INR (units of factor IX):
1. INR 2 to <4: 25 units/kg (up to 2500 units)
2. INR 4 to 6: 35 units/kg (up to 3500 units)
3. INR 6<: 50 units/kg (up to 5000 units)
Oral factor Xa inhibitors: 2000 units once or 25 to 50 units/kg
Dabigatran- associated life-threatening bleeding: 50 units/kg once
Onset Within 5 min Within 2 min Within 10 min Within 30 min
Duration 12–24 h 2 h 8 h 12 h
Monitoring Coagulation parameters (activated partial thromboplastin time [aPTT], diluted thrombin time, or ecarin clotting time) between 12–24 h to assess redistribution of dabigatran from peripheral to plasma Current commercial anti-Xa activity assays are not suitable for measuring factor Xa activities after andexanet alfa use Warfarin reversal: Repeat INR within 30 min after the administration N/A
Others Risk of serious reactions (hypoglycemia, hypophosphatemia, metabolic acidosis, increase in uric acid, acute liver failure) in patients with hereditary fructose intolerance (due to sorbitol excipient 4 g in each 5 g of idarucizumab)
No procoagulant effect based on endogenous thrombin potential
No FDA indication for other factor Xa inhibitors other than apixaban or rivaroxaban
Andexanet alfa may interfere with the anticoagulation effect of heparin
US Black Box warning: Serious and life-threatening adverse events (arterial and venous thromboembolism, myocardial infarction, ischemic stroke, cardiac arrest, sudden deaths)
May not be indicated for patients with thromboembolic events in the prior 3 mon
It includes heparin
Administer intravenous vitamin K 10 mg over 10–20 min in addition to 4-factor PCC
It does not include heparin
Coagulation parameters do not correlate with the drug’s efficacy
Not effective to reverse factor Xa inhibitors
Information in table was obtained from manufacturer package inserts.

Figure 13. Active Bleeding Associated with Oral Anticoagulant

Figure 14. Forms of ICH, Classified by Mechanism

6.6.1. Management of Patients with AF and Intracranial Hemorrhage

1. In patients with AF and conditions associated with very high risk of thromboembolic events (>5%/year), such as rheumatic heart disease or a mechanical heart valve, early (1–2 weeks) resumption of anticoagulation after ICH is reasonable to reduce the risk of thromboembolic events. (2a, C-LD)
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2. In patients with AF and ICH, delayed (4-8 weeks) resumption of anticoagulation may be considered to balance the risks of thromboembolic and hemorrhagic complications after careful risk benefit assessment. (2b, C-LD)
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3. In patients with AF and conditions associated with high risk of recurrent ICH (eg, cerebral amyloid angiopathy) anticoagulation-sparing strategies (eg, LAAO) may be considered to reduce the risk of recurrent hemorrhage. (2b, B-NR)
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Table 16. Bleeding Events (Precent/Year) in Direct Oral Anticoagulant Pivotal Clinical Trials

Having trouble viewing table?
Study RE-LY (n=18,113) ARISTOTLE (n=18,201) ENGAGE-AF TIMI 48 (n=21,105) ROCKET-AF (n=14,264)
Major bleeding
  • Dabigatran 150 mg 3.11% (RR, 0.93, 95% CI, 0.81–1.07; P=0.31)
  • Dabigatran 110 mg 2.71% (RR, 0.80, 95% CI, 0.69–0.93; P=0.003)
  • Warfarin 3.36%
  • Apixaban 2.13% (HR, 0.69, 95% CI, 0.60–0.80; P<0.001)
  • Warfarin 3.09%
  • Edoxaban 60 mg 2.75% vs. warfarin 3.43% (HR, 0.80, 95% CI, 0.71–0.91; P<0.001)
  • Edoxaban 30 mg 1.61% vs. warfarin 3.43% (HR, 0.47, 95% CI, 0.41–0.55; P<0.001)
Rivaroxaban 3.6% vs. warfarin 3.4% (HR, 1.04, 95% CI, 0.90–1.20; P=0.58)
GI bleeding
  • Dabigatran 150 mg 1.51% vs. warfarin 1.02% (RR, 1.50, 95% CI, 1.19–1.89; P<0.001)
  • Dabigatran 110 mg 1.12% vs. warfarin 1.02% (RR, 1.10, 95% CI, 0.86–1.41; P=0.43)
  • Apixaban 0.76% (HR, 0.89, 95% CI, 0.70–1.15; P=0.37)
  • Warfarin 0.86%
  • Edoxaban 60 mg 1.51% (HR, 1.23, 95% CI, 1.02–1.50; P=0.03)
  • Edoxaban 30 mg 0.82% (HR, 0.67, 95% CI, 0.53–0.83; P<0.001)
  • Warfarin 1.23%
  • Rivaroxaban 3.2% (HR not reported, P<0.001)
  • Warfarin 2.2%
Intracranial bleeding
  • Dabigatran 150 mg 0.30% (RR, 0.40, 95% CI, 0.27–0.60; P<0.001)
  • Dabigatran 110 mg 0.23% (RR, 0.31, 95% CI, 0.20–0.47; P<0.001)
  • Warfarin 0.74%
  • Apixaban 0.33% (HR, 0.42, 95% CI, 0.30–0.58; P<0.001)
  • Warfarin 0.80%
  • Edoxaban 60 mg 0.39% (HR, 0.47, 95% CI, 0.34–0.63; P<0.001)
  • Edoxaban 30 mg 0.26% (HR, 0.30, 95% CI, 0.21–0.43; P<0.001)
  • Warfarin 0.85%
  • Rivaroxaban 0.80% (HR, 0.67, 95% CI, 0.47–0.93; P=0.02)
  • Warfarin 1.20%
HR indicates hazard ratio; and RR, relative risk.
Adapted with permission from pgs. 32-33 of Kido K.22 Copyright 2021 American College of Clinical Pharmacy.

Table 17. Risk Factors for Thromboembolic Complications and Recurrent ICH

Factors Associated With High Risk of Thromboembolism
  • Mechanical heart valve
  • Rheumatic valve disease
  • Previous history of stroke/ thromboembolism
  • Hypercoagulable state (eg, active malignancy, genetic thrombophilia)
  • High CHA2DS2-VASc score (>5)

Factors Associated With High Risk of Recurrent ICH
  • Suspected cerebral amyloid angiopathy
  • Lobar intraparenchymal hemorrhage (IPH)
  • Older age
  • >10 cerebral microbleeds on MRI
  • Disseminated cortical superficial siderosis on MRI
  • Poorly controlled hypertension
  • Previous history of spontaneous ICH
  • Genetic/acquired coagulopathy
  • Untreated symptomatic vascular malformation or aneurysm

6.7. Periprocedural Management

1. In patients with AF (excluding those with recent stroke or TIA, or a mechanical valve) and on oral anticoagulation with
either warfarin*
(1, B-R)
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or DOAC
(1, B-NR)
and who are scheduled to undergo an invasive procedure or surgery, temporary cessation of oral anticoagulation without bridging anticoagulation is recommended.
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2. In patients with AF on warfarin anticoagulation and an annual predicted risk of thromboembolism of ≥5% undergoing PM or defibrillator implantation or generator change, continued anticoagulation is recommended in preference to interruption of warfarin and bridging anticoagulation with heparin to reduce the risk of pocket hematoma. (1, A)
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3. In patients with AF with CHA2DS2-VASc score ≥2 or equivalent risk of stroke, on DOAC anticoagulation and undergoing PM or defibrillator implantation or generator change, either uninterrupted or interrupted DOAC is reasonable. (2a, A)
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4. In patients with AF on DOAC anticoagulation and scheduled to undergo an invasive procedure or surgery that cannot be performed safely on uninterrupted anticoagulation, the timing of interruption of DOAC should be guided by the specific agent, renal function, and the bleeding risk of the procedure (Table 18). (1, B-NR)
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5. In patients with AF on DOAC anticoagulation that has been interrupted for an invasive procedure or surgery, in general, resumption of anticoagulation the day after low bleeding risk surgery and between the evening of the second day and the evening of the third day after high bleeding risk surgery is reasonable, as long as hemostasis has been achieved and further bleeding is not anticipated. (2a, B-NR)
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6. In patients with AF on warfarin anticoagulation, who are undergoing surgeries or procedures for which they are holding warfarin, except in patients with mechanical valve or recent stroke or TIA, bridging anticoagulation with low-molecular-weight heparin should not be administered. (3 - Harm, B-R)
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Figure 15. Flowchart: Management of Periprocedural Anticoagulation in Patients With AF

Table 18. Timing of Discontinuation of Oral Anticoagulants in Patients With AF Scheduled to Undergo an Invasive Procedure or Surgery in Whom Anticoagulation is to Be Interrupted

Having trouble viewing table?
Anticoagulant Low Bleeding Risk Procedure High Bleeding Risk Procedure
Apixaban (CrCl >25 mL/min)* 1 d 2 d
Dabigatran (CrCl >50 mL/min) 1 d 2 d
Dabigatran (CrCl 30-50 mL/min) 2 d 4 d
Edoxaban (CrCl >15 mL/min) 1 d 2 d
Rivaroxaban (CrCl >30 mL/min) 1 d 2 d
Warfarin 5 d for a target INR <1.5
2-3 d for a target INR <2
5 d
CrCl indicates creatinine clearance; and INR, international normalized ratio.
* For patients on DOAC with creatinine clearance lower than the values in the table, few clinical data exist: consider holding for an additional 1 to 3 days, especially for high bleeding risk procedures.
The number of days is the number of full days before the day of surgery in which the patient does not take any dose of anticoagulant. The drug is also not taken the day of surgery. For instance, in the case of holding a twice daily drug for 1 day, if the drug is taken at 8 pm, and surgery is at 8 am, at the time of surgery it will be 36 hours since the last dose was taken.

6.8. Anticoagulation in Specific Populations

6.8.1. AF Complicating Acute Coronary Syndrome or Percutaneous Coronary Intervention

1. In patients with AF and an increased risk for stroke who undergo PCI, DOACs are preferred over VKAs in combination with APT to reduce the risk of clinically relevant bleeding. (1, A)
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2. In most patients with AF who take oral anticoagulation and undergo PCI, early discontinuation of aspirin (1–4 wk) and continuation of dual antithrombotic therapy (DAT) with OAC and a P2Y12 inhibitor is preferred over triple therapy (OAC, P2Y12 inhibitor, and aspirin) to reduce the risk of clinically relevant bleeding. (1, A)
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6.8.2. Chronic Coronary Disease (CCD)

1. In patients with AF and CCD (beyond 1 year after revascularization or CAD not requiring coronary revascularization) without history of stent thrombosis, oral anticoagulation monotherapy is recommended over the combination therapy of OAC and single APT (aspirin or P2Y12 inhibitor) to decrease risk of major bleeding. (1, B-R)
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6.8.3. Peripheral Artery Disease (PAD)

1. In patients with AF and concomitant stable PAD, monotherapy oral anticoagulation is reasonable over dual therapy (anticoagulation plus aspirin or P2Y12 inhibitors) to reduce the risk of bleeding. (2a, B-NR)
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6.8.4. Chronic Kidney Disease/Kidney Failure

1. For patients with AF at elevated risk for stroke and CKD stage 3, treatment with warfarin or, preferably, evidence-based doses of direct thrombin or factor Xa inhibitors (Table 19) is recommended to reduce the risk of stroke. (1, B-R)
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2. For patients with AF at elevated risk for stroke and CKD stage 4, treatment with warfarin or labeled doses of DOACs is reasonable to reduce the risk of stroke. (2a, B-NR)
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3. For patients with AF at elevated risk for stroke and who have end-stage CKD (CrCl <15 mL/min) or are on dialysis, it might be reasonable to prescribe warfarin (INR 2.0–3.0) or evidence-based dose of apixaban for oral anticoagulation to reduce the risk of stroke. (2b, B-NR)
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Table 19. Recommended Doses of Currently Approved DOACs According to Renal Function

Having trouble viewing table?
DOAC CrCl (mL/min) >95 mL/min CrCl (mL/min)
51–95
CrCl (mL/min)
31–50
CrCl (mL/min)
15–30
CrCl (mL/min)
<15 or on dialysis
Apixaban 5 or 2.5 mg twice daily* 5 or 2.5 mg twice daily* 5 or 2.5 mg twice daily* 5 or 2.5 mg twice daily* 5 or 2.5 mg twice daily*
Dabigatran 150 mg twice daily 150 mg twice daily 150 mg twice daily 75 mg twice daily Contraindicated
Edoxaban Contraindicated 60 mg once daily 30 mg once daily 30 mg once daily Contraindicated
Rivaroxaban 20 mg once daily 20 mg once daily 15 mg once daily 15 mg once daily 15 mg once daily

Note that other, nonrenal considerations such as drug interactions may also apply.
The gray area indicates doses not studied in the pivotal clinical trials of these agents.
* If at least 2 of the following are present: serum creatinine ≥1.5 mg/dL, age ≥80 years, or body weight ≤60 kg, the recommended dose is 2.5 mg twice daily. The ARISTOTLE trial excluded patients with either a creatinine of >2.5 mg/dl or a calculated CrCl <25 mL/min.
Rivaroxaban is not recommended for other indications in patients with a CrCl <15 mL/min, but such a recommendation is not made for the AF indication. However, pharmacokinetic data are limited.

6.8.5. AF in Valvular Heart Disease

1. In patients with rheumatic mitral stenosis or mitral stenosis of moderate or greater severity and history of AF, long-term anticoagulation with warfarin is recommended over DOACs, independent of the CHA2DS2-VASc score to prevent cardiovascular events, including stroke or death. (1, B-R)
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2. In patients with AF and valve disease other than moderate or greater mitral stenosis or a mechanical heart valve, DOACs are recommended over VKAs. (1, B-NR)
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6.8.6. Anticoagulation of Typical Atrial Flutter

1. For patients with AFL, anticoagulant therapy is recommended according to the same risk profile used for AF. (1, B-NR)
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2. In patients with AFL who undergo successful cardioversion or ablation resulting in restoration of sinus rhythm, anticoagulation should be continued for at least 4 weeks postprocedure. (1, C-LD)
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3.L who have undergone successful cavotricuspid isthmus (CTI) ablation and have had AFL ablation should receive ongoing oral anticoagulation postablation as indicated for AF. (1, A)
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4. Patients with typical AFL who have undergone successful CTI ablation and are deemed to be at high thromboembolic risk, without any known prior history of AF, should receive close follow-up and arrhythmia monitoring to detect silent AF if they are not receiving ongoing anticoagulation in view of significant risk of AF. (1, B-NR)
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5.L who have undergone successful CTI ablation without any known prior history of AF who are at high risk for development of AF (eg, LA enlargement, inducible AF, COPD, HF), it may be reasonable to prescribe long-term anticoagulation if thromboembolic risk assessment suggests high risk (>2% annual risk) for stroke. (2b, B-NR)
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* This section refers to typical right-sided (CTI-dependent) AFL. Left-Ls or ATs that develop after ablation of AF should be anticoagulated and managed in a manner similar to AF.
Define typical and atypical AFL elsewhere:
  • “Typical” AFL is defined as either typical counterclockwise AFL when the macroreentrant circuit is dependent on the CTI using the isthmus from the patient’s right to left or typical clockwise AFL when the macroreentrant circuit is dependent on the CTI and uses this isthmus from the patient’s left to right.
  • “Atypical” AFL is not dependent on the CTI and may arise from a macroreentrant circuit in the LA, such as perimitral or LA roof flutter or could be dependent on scar from prior ablation or surgery.

7. Rate Control

Figure 16. Anticoagulation for Typical (CTI-Dependent) AFL

* Intraprocedural documentation of bidirectional block.
For example, left atrial enlargement, inducible AF, chronic obstructive pulmonary disease, concomitant heart failure.

7.1. Broad Considerations for Rate Control

1. In patients with AF, SDM with the patient is recommended to discuss rhythm- vs. rate-control strategies (taking into consideration clinical presentation, comorbidity burden, medication profile, and patient preferences), discuss therapeutic options, and for assessing long-term benefits. (1, B-NR)
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2. In patients with AF without HF who are candidates for select rate-control strategies, heart rate target should be guided by underlying patient symptoms, in general aiming at a resting heart rate of <100 to 110 bpm. (2a, B-R)
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Table 20. Clinical Presentations and Objectives of Heart Rate Control

Having trouble viewing table?
Presentation Objective
Symptomatic atrial fibrillation To reduce symptoms
Tachycardia-induced cardiomyopathy To improve heart function or reduce the risk of recurrent cardiomyopathy
Implantable cardioverter-defibrillator use To reduce risk of inappropriate shock
Cardiac resynchronization therapy (CRT) use To enhance biventricular pacing (BiVP), likelihood of myocardial recovery, and/or preservation of function
Tachycardia-bradycardia form of sick sinus syndrome among those with a pacemaker To reduce the risk of hospitalization

Table 21. Pharmacological Agents for Rate Control in Patients With Atrial Fibrillation - Beta Blockers

Having trouble viewing table?
Intravenous Administration Oral Maintenance Dose Elimination Half-Life Notes
Metoprolol tartrate 2.5–5 mg bolus over 2 min; up to 3 doses 25–200 mg twice daily 3–4 h
Metoprolol succinate N/A 50–400 mg daily 3–7 h
Atenolol N/A 25–100 mg daily 6–7 h Predominantly renally eliminated
Bisoprolol N/A 2.5–10 mg daily 9–12 h
Carvedilol N/A 3.125–25 mg twice daily 7–10 h
Esmolol 500 µg/kg bolus over 1 min; then 50–300 µg/kg/min N/A 9 min
Nadolol N/A 10–240 mg daily 20–24 h
Propranolol 1 mg over 1 min; repeat as needed every 2 min; up to 3 doses 10–40 mg 3–4 times daily IV: 2.4 h
Oral: 3–6 h
Extended release (ER:) 8–20 h

Table 21. Pharmacological Agents for Rate Control in Patients With Atrial Fibrillation - Nondihydropyridine Calcium Channel Blockers

Having trouble viewing table?
Intravenous Administration Oral Maintenance Dose Elimination Half-Life Notes
Diltiazem 0.25 mg/kg (actual body weight) IV over 2 min
May repeat 0.35 mg/kg over 2 min; then 5–15 mg/h continuous infusion
120–360 mg daily (ER) IV: 3–5 h
Oral immediate release: 3–4.5 h
ER: 4–9.5 h
Avoid in heart failure with reduced ejection fraction (HFrEF)
Verapamil 5–10 mg over ≥2 min (may repeat twice); then 5 mg/h continuous infusion (max 20 mg/h) 180–480 mg daily (ER) IV: 6–8 h
Oral: 2–7 h
ER: 12–17 h
Avoid in HFrEF

Table 21. Pharmacological Agents for Rate Control in Patients With Atrial Fibrillation - Digitalis Glycoside

Having trouble viewing table?
Intravenous Administration Oral Maintenance Dose Elimination Half-Life Notes
Digoxin 0.25–0.5 mg over several min; repeat doses of 0.25 mg every 6 h (maximum 1.5 mg/24 h) 0.0625–0.25 mg daily 1–2 d Renally eliminated

Increased mortality at plasma concentrations exceeding 1.2 ng/mL

Table 21. Pharmacological Agents for Rate Control in Patients With Atrial Fibrillation - Other

Having trouble viewing table?
Intravenous Administration Oral Maintenance Dose Elimination Half-Life Notes
Amiodarone 150–300 mg IV over 1 h, then 10–50 mg/h over 24 h 100–200 mg daily (generally IV form used for rate control) IV: 9–36 d
Oral: 26–107 d
Loading dose 6–10 g administered over 2–4 wk; can combine IV and oral dosing to complete

7.2.1. Acute Rate Control

1. In patients with AF with rapid ventricular response who are hemodynamically stable, beta blockers or nondihydropyridine calcium channel blockers (verapamil, diltiazem, provided that EF >40%) are recommended for acute rate control (Figure 17). (1, B-R)
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2. In patients with AF with rapid ventricular response in whom beta blockers and nondihydropyridine calcium channel blockers are ineffective or contraindicated, digoxin can be considered for acute rate control, either alone or in combination with the aforementioned agents. (2a, B-R)
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3. In patients with AF with rapid ventricular response, the addition of intravenous magnesium to standard rate-control measures is reasonable to achieve and maintain rate control. (2a, A)
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4. In patients with AF with rapid ventricular response who are critically ill and/or in decompensated HF in whom beta blockers and nondihydropyridine calcium channel blockers are ineffective or contraindicated, intravenous amiodarone may be considered for acute rate control.* (2b, B-NR)
* Consider the risk of cardioversion and stroke when using amiodarone as a rate-control agent.
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5. In patients with AF with rapid ventricular response and known moderate or severe LV systolic dysfunction with or without decompensated HF, intravenous nondihydropyridine calcium channel blockers should not be administered. (3 - Harm, B-NR)
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Figure 17. Acute Rate Control in AF With Rapid Ventricular Response (RVR)

* Note: Contraindicated in patients with moderate-severe LV dysfunction regardless of decompensated HF.

7.2.2. Long-Term Rate Control

1. In patients with AF, beta blockers or nondihydropyridine calcium-channel blockers (diltiazem, verapamil) are recommended for long-term rate control with the choice of agent according to underlying substrate and comorbid conditions. (1, B-NR)
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2. For patients with AF in whom measuring serum digoxin levels is indicated, it is reasonable to target levels <1.2 ng/mL. (2a, B-NR)
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3. In patients with AF and HF symptoms, digoxin is reasonable for long-term rate control in combination with other rate-controlling agents, or as monotherapy if other agents are not preferred, not tolerated, or contraindicated. (2a, B-R)
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4. In patients with AF and left ventricular ejection fraction (LVEF) <40%, nondihydropyridine calcium channel-blocking drugs should not be administered given their potential to exacerbate HF. (3 - Harm, C-LD)
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5. In patients with permanent AF who have risk factors for cardiovascular events, dronedarone should not be used for long-term rate control. (3 - Harm, B-R)
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Figure 18. AF Long-Term Rate Control

7.3. Atrioventricular Nodal Ablation (AVNA)

1. In patients with AF and a persistently rapid ventricular response who undergo AVNA, initial PM lower rate programming should be 80 to 90 bpm to reduce the risk of sudden death. (1, C-LD)
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2. In patients with AF and uncontrolled rapid ventricular response refractory to rate-control medications (who are not candidates for or in whom rhythm control has been unsuccessful), AVNA can be useful to improve symptoms and QOL. (2a, B-R)
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4. In patients with AF with normal EF undergoing AVNA, conduction system pacing (CSP) of the His bundle or left bundle area may be reasonable. (2b, C-LD)
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8. Rhythm Control

8.1. Goals of Therapy With Rhythm Control

1. In patients with reduced LV function and persistent (or high burden) AF, a trial of rhythm control should be recommended to evaluate whether AF is contributing to the reduced LV function. (1, B-R)
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2. In patients with symptomatic AF, rhythm control can be useful to improve symptoms. (2a, B-R)
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3. In patients with a recent diagnosis of AF (<1 year), rhythm control can be useful to reduce hospitalizations, stroke, and mortality. (2a, B-R)
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4. In patients with AF and HF, rhythm control can be useful for improving symptoms and improving outcomes, such as mortality and hospitalizations for HF and ischemia. (2a, B-R)
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5. In patients with AF, rhythm-control strategies can be useful to reduce the likelihood of AF progression. (2a, B-NR)
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6. In patients with AF where symptoms associated with AF are uncertain, a trial of rhythm control (eg, cardioversion or pharmacological therapy) may be useful to determine what if any symptoms are attributable to AF. (2b, C-LD)
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7. In patients with AF, rhythm-control strategies may be useful to reduce the likelihood of development of dementia or worsening cardiac structural abnormalities.

(2b, B-NR)
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Figure 19. Patient and Clinical Considerations for Choosing Between Rhythm Control and Rate Control

Patient and clinical considerations for deciding between rhythm- and rate-control strategies in a patient with a high burden of AF.

Figure 20. Flowchart for Treatment Choices When Required to Decrease AF Burden

* Younger with few comorbidities.
Flowchart outlining overall strategy and treatment options for patient with AF in whom rhythm-control therapy is required.

8.2. Electrical and Pharmacological Cardioversion

8.2.1. Prevention of Thromboembolism in the Setting of Cardioversion

1. In patients with AF duration of ≥48 hours, a 3-week duration of uninterrupted therapeutic anticoagulation or imaging evaluation to exclude intracardiac thrombus is recommended before elective cardioversion. (1, B-R)
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2. In patients with AF undergoing cardioversion, therapeutic anticoagulation should be established before cardioversion and continued for at least 4 weeks afterwards without interruption to prevent thromboembolism.

(1, B-NR)
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3. In patients with AF in whom cardioversion is deferred due to LAA thrombus detected on precardioversion imaging, therapeutic anticoagulation should be instituted for at least 3 to 6 weeks, after which imaging should be repeated before cardioversion. (1, C-LD)
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4. In patients with AF and prior LAAO who are not on anticoagulation, imaging evaluation to assess the adequacy of LAAO and exclude device-related thrombosis before cardioversion may be reasonable.

(2b, B-NR)
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5. In patients with AF and prior LAAO with residual leak, pericardioversion anticoagulation may be considered and continued thereafter. (2b, C-LD)
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6. In patients with reported AF duration of <48 hours (not in the setting of cardiac surgery) and who are not on anticoagulation, precardioversion imaging to exclude intracardiac thrombus may be considered in those who are at elevated thromboembolic risk (CHA2DS2-VASc score ≥2 or equivalent).

(2b, C-LD)
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7. In patients with low thromboembolic risks (CHA2DS2-VASc 0–1 or equivalent) and AF duration of <12 hours, the benefit of precardioversion imaging or pericardioversion anticoagulation is uncertain given the low incidence of pericardioversion thromboembolic events in this population. (2b, C-LD)
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Figure 21. Patients With Hemodynamically Stable AF Planned for Cardioversion

8.2.2. Electrical Cardioversion

1. In patients with hemodynamic instability attributable to AF, immediate electrical cardioversion should be performed to restore sinus rhythm. (1, C-LD)
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2. In patients with AF who are hemodynamically stable, electrical cardioversion can be performed as initial rhythm-control strategy or following failed pharmacological cardioversion. (1, B-R)
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3. In patients with AF undergoing electrical cardioversion, energy delivery should be confirmed to be synchronized to the QRS to reduce the risk of inducing ventricular fibrillation (VF). (1, C-LD)
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4. For patients with AF undergoing elective electrical cardioversion, the use of biphasic energy of at least 200 J as initial energy can be beneficial to improve success of initial electrical shock. (2a, B-R)
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5. In patients with AF undergoing elective cardioversion, with longer duration of AF or failed initial shock, optimization of electrode vector, use of higher energy, and pretreatment with AADs can facilitate success of electrical cardioversion. (2b, C-LD)
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6. In patients with obesity and AF, use of manual pressure augmentation and/or further escalation of electrical energy may be beneficial to improve success of electrical cardioversion.

(2b, C-LD)
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8.2.3. Pharmacological Cardioversion

1. For patients with AF, pharmacological cardioversion is reasonable as an alternative to electrical cardioversion for those who are hemodynamically stable or in situations when electrical cardioversion is preferred but cannot be performed. (2a, C-LD)
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2. For patients with AF, ibutilide is reasonable for pharmacological cardioversion for patients without depressed LV function (LVEF <40%). (2a, A)
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3. For patients with AF, intravenous amiodarone is reasonable for pharmacological cardioversion, although time to conversion is generally longer than with other agents (8–12 hours). (2a, A)
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4. For patients with recurrent AF occurring outside the setting of a hospital, the “pill-in-the-pocket” (PITP) approach with a single oral dose of flecainide or propafenone, with a concomitant AV nodal blocking agent, is reasonable for pharmacological cardioversion if previously tested in a monitored setting.

(2a, A)
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5. For patients with AF, use of intravenous procainamide may be considered for pharmacological cardioversion when other intravenous agents are contraindicated or not preferred. (2b, B-R)
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Table 22. Drugs for Pharmacological Conversion of Atrial Fibrillation to Sinus Rhythm

Having trouble viewing table?
Drug Route of Administration Loading Dose Maintenance Dose Approximate Time to Conversion to Sinus Rhythm Primary Route(s) of Elimination Elimination Half-Life Major Adverse Effects
Amiodarone IV 5–7 mg/kg or 300 mg* 1200–3000 mg via continuous infusion over 24 h 8–12 h Liver metabolism
Biliary excretion
9–36 d Bradycardia
Hypotension
QT prolongation
Phlebitis
Torsades de pointes (TdP)
Flecainide Oral N/A 200 mg if <70 kg, 300 mg if >70 kg, single dose 3–8 h Liver (70%)
Kidney (30%)
12–27 h Atrial flutter
AV block
Dizziness
Dyspnea
Exacerbation of HFrEF
Headache
Nausea
QT prolongation
Ventricular tachycardia (VT)
Visual disturbances
Ibutilide IV ≥60 kg: 1 mg over 10 min
<60 kg: 0.01 mg/kg over 10 min
If arrhythmia does not terminate within 10 min after the end of the first infusion, may administer a second dose, equal to the first dose
N/A 30–90 min Liver 2–12 h Nonsustained VT
QT prolongation
TdP
Procainamide IV 1 g over 30 min 2 mg/min continuous infusion over 1 hour 30–60 min Liver (16–33%)
Kidney (50–65%)
3–4 h (parent)
7 h (NAPA)
Agranulocytosis
AV block
Exacerbation of HFrEF
Hypotension
Neutropenia
QT prolongation
Rash
Thrombocytopenia
TdP
Propafenone Oral N/A 450 mg if <70 kg, 600 mg if >70 kg, single dose 3–8 h Liver 9 h Atrial flutter
AV block
Dizziness
Dyspnea
Exacerbation of HFrEF
Nausea
Taste disturbances
VT
Visual disturbances
* Some studies have administered intravenous amiodarone for 24 hours followed by oral administration.
Flecainide is available in an intravenous dosage form in Europe.
% of a dose excreted unchanged in urine.

Figure 22. Treatment Algorithm for Pharmacological Conversion of AF to Sinus Rhythm

* In the absence of pre-excitation.

Amiodarone requires several hours for efficacy; ibutilide is generally effective in 30–90 minutes, but carries a higher risk of QT interval prolongation and torsades de pointes.

Recommend avoidance of intravenous procainamide for patients initially treated with amiodarone or ibutilide, to avoid excessive QT interval prolongation and torsades de pointes; rather, procainamide may be considered for patients for whom amiodarone and ibutilide are not considered optimal as first-line drugs.

§ First dose should be administered in a facility that can provide continuous ECG monitoring and cardiac resuscitation, due to the potential for proarrhythmia or post-conversion bradycardia.

8.3. AADs for Maintenance of Sinus Rhythm

8.3.1. Specific Drug Therapy for Long-Term Maintenance of Sinus Rhythm

1. For patients with AF and HFrEF (≤40%), therapy with

dofetilide*

(2a, A)
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amiodarone

(2a, B-NR)
is reasonable for long-term maintenance of sinus rhythm.
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2. For patients with AF and no prior MI, or known or suspected significant structural heart disease, or ventricular scar or fibrosis, use of flecainide or propafenone is reasonable for long-term maintenance of sinus rhythm. (2a, A)
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3. For patients with AF without recent decompensated HF or severe LV dysfunction, use of dronedarone is reasonable for long-term maintenance of sinus rhythm. (2a, A)
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4. For patients with AF without significant baseline QT interval prolongation, uncorrected hypokalemia or hypomagnesemia, use of dofetilide is reasonable for long-term maintenance of sinus rhythm, with proper dose selection based on kidney function and close monitoring of the QT interval, serum potassium and magnesium concentrations, and kidney function. (2a, A)
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5. For patients with AF and normal LV function, use of low-dose amiodarone (100–200 mg/d) is reasonable for long-term maintenance of sinus rhythm, but in view of its adverse effect profile should be reserved for patients in whom other rhythm control strategies are ineffective, not preferred, or contraindicated. (2a, A)
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6. For patients with AF without significant baseline QT interval prolongation, hypokalemia, hypomagnesemia, or bradycardia, use of sotalol may be considered for long-term maintenance of sinus rhythm, with proper dose selection based on kidney function and close monitoring of the QT interval, heart rate, serum potassium and magnesium concentrations, and kidney function. (2b, A)
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7. In patients with prior MI and/or significant structural heart disease, including HFrEF (LVEF ≤40%), flecainide and propafenone should not be administered to due to the risk of worsening HF, potential proarrhythmia, and increased mortality.

(3 - Harm, B-R)
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8. For patients with AF, dronedarone should not be administered for maintenance of sinus rhythm to those with New York Heart Association (NYHA) class III and IV HF or patients who have had an episode of decompensated HF in the past 4 weeks, due to the risk of increased early mortality associated with worsening HF. (3 - Harm, B-R)
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Figure 23. Treatment Algorithm for Drug Therapy for Maintenance of Sinus Rhythm

In each box, drugs are listed in alphabetical order. Significant structural heart disease with scar or fibrosis.

Table 23. Specific Drug Therapy for Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation

Having trouble viewing table?
Drug Loading Dose Maintenance Dose Primary Route(s) of Elimination Elimination Half-Life Mechanism of Action Major Adverse Effects Important Pharmacokinetic Drug Interactions
Amiodarone Total loading dose 6–10 g, given 400–800 mg daily in 2–4 divided doses for 1–4 wk 200 mg once daily Liver metabolism

Biliary excretion
14–59 d Inhibits IKr, IKs, INa, IKur, Ito, ICa-L, IKAch

Noncompetitive betablocker
AV block
Bradycardia
Corneal microdeposits
Elevation in transaminases
Hepatotoxicity
Hyperthyroidism
Hypothyroidism
Nausea
QT prolongation
Peripheral neuropathy
Photosensitivity
Pulmonary fibrosis
Skin pigmentation (blue-grey)
TdP
Moderate* inhibitor of CYP2C9, weak inhibitor of CYP2D6
Some inhibition of CYP3A
Increases plasma concentrations of warfarin, lovastatin, simvastatin,§ cyclosporine

Inhibits p-gp
Increases plasma concentrations of digoxin
Dofetilide N/A CrCl > 60 mL/min: 500 µg twice daily
CrCl 40–60 mL/min: 250 µg twice daily
CrCl 20–40 mL/min: 125 µg twice daily
CrCl < 20 mL/min: Contraindicated
Kidney 10 h Inhibits IKr and augments late INa QT prolongation
TdP
Dofetilide is renally excreted via the renal cation transport system. The following drugs inhibit renal cation transport, increase plasma dofetilide concentrations, and are contraindicated in patients taking dofetilide:
Cimetidine
Dolutegravir
Ketoconazole
Megestrol
Prochlorperazine
Trimethoprim (alone or in combination with sulfamethoxazole)
Verapamil

In addition, hydrochlorothiazide (alone or in combination with triamterene) increases plasma dofetilide concentrations and should not be coadministered with dofetilide
Dronedarone N/A 400 mg twice daily Liver metabolism 13–19 h Inhibits IKr, IKs, INa, IKur, Ito, ICa-L, IKAch
Noncompetitive betablocker
Abdominal pain
Asthenia
Bradycardia
Diarrhea
Nausea and vomiting
QT prolongation
Rash
TdP
Dronedarone is a substrate for CYP3A and is a moderate inhibitor of CYP3A and CYP2D6
Dronedarone is also a substrate for, and inhibitor of, p-gp

Dronedarone may increase plasma concentrations of:
Dabigatran
Digoxin
Simvastatin||
Sirolimus
Tacrolimus
Warfarin

The following drugs may increase plasma dronedarone concentrations:
Grapefruit juice

The following drugs may decrease plasma dronedarone concentrations:
CYP 3A inducers including St. John’s wort, rifampin, and phenytoin
Flecainide N/A 50–300 mg/d PO divided q 8–12 h Liver (70%)
Kidney (30%)¶
12–27 h Inhibits INa Atrial flutter
AV block
Dizziness
Dyspnea
Exacerbation of HFrEF
Headache
Nausea
QT prolongation
VT
Visual disturbances
Flecainide is a substrate for CYP2D6

The following drugs may increase plasma flecainide concentrations:
Amiodarone
Duloxetine
Fluoxetine
Paroxetine
Propafenone N/A 150–300 mg/ PO q 8 h, ER 225–425 PO q 12 h Liver 9 h Inhibits INa Atrial flutter
Bradycardia
AV block
Dizziness
Dyspnea
Exacerbation of HFrEF
Nausea
Taste disturbances
VT
Visual disturbances
Propafenone is a substrate for CYP 2D6
The following drugs may increase plasma propafenone concentrations:
Fluoxetine
Paroxetine

Propafenone may increase plasma digoxin concentrations

Propafenone may increase plasma warfarin concentrations
Sotalol CrCl >60 mL/min: 40–80 mg twice daily for 3 d
CrCl: 40–60 mL/min: 80 mg once daily for 3 d
CrCl <40 mL/min: Contraindicated
CrCl >60 mL/min: 80–160 mg twice daily
CrCl: 40-60 mL/min: 80–160 mg once daily
CrCl <40 mL/min: Contraindicated
Kidney 12 h Inhibits IKr
Betablocker d-Sotalol augments late INa
AV block
Bradycardia
Bronchospasm
Diarrhea
Exacerbation of HFrEF
Fatigue
Nausea and vomiting
QT prolongation
TdP
None
* Moderate inhibitor: causes a 2-fold to <5-fold increase in AUC or a 50% to 80% decrease in clearance.
Mild inhibitor: causes a ≥1.25-fold but <2-fold increase in AUC or a 20% to 50% decrease in clearance.
Lovastatin doses should not exceed 40 mg daily in patients taking amiodarone.
§ Simvastatin doses should not exceed 20 mg daily in patients taking amiodarone.
|| Simvastatin doses should not exceed 10 mg daily in patients taking dronedarone.
% of a dose excreted unchanged in urine.

8.3.2. Inpatient Initiation of Antiarrhythmic Agents

1. Patients with AF who are initiating, increasing the dose of, or reinitiating dofetilide therapy should be admitted for a minimum of 3 days to a facility that can provide continuous electrocardiographic monitoring, calculations of CrCl, and cardiac resuscitation, given the potential for proarrhythmia. (1, A)
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2. In patients with AF, it is reasonable to initiate sotalol therapy in a facility that can provide continuous electrocardiographic monitoring, calculations of CrCl, and cardiac resuscitation, given the potential for proarrhythmia and bradycardia. (2a, B-R)
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3. In patients with AF who are initiating PITP dosing of flecainide and propafenone with concomitant AV nodal blocking drugs, it is reasonable to receive the first dose in a facility that can provide continuous electrocardiographic monitoring, given the potential for proarrhythmia. (2a, B-NR)
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Table 24. Recommended Monitoring for Patients Taking Oral Amiodarone

Having trouble viewing table?
Adverse Effect Baseline Testing Initial Follow-Up Testing Additional Follow-Up Testing
Hypo- or hyperthyroidism TSH (T4 and T3 if TSH abnormal) 3–6 mo Every 6 mo
Hepatotoxicity AST, ALT 3–6 mo Every 6 mo
QT interval prolongation ECG Annually
Interstitial lung disease Chest x-ray: Recommended

CT chest: not recommended
Chest x-ray: Unexplained cough or dyspnea or other signs/symptoms suspicious for interstitial lung disease CT chest: As indicated to follow-up ongoing symptoms or chest x-ray findings
Corneal microdeposits (epithelial keratopathy) Not recommended Development of visual abnormalities which may indicate optic neuropathy
Dermatologic (blue-grey skin discoloration), photosensitivity Not recommended Physical examination annually Development of skin discoloration, severe sunburn
Neurological Not recommended Physical examination annually Development of peripheral neuropathy or other neurological abnormalities

Table 25. Recommended Monitoring for Patients Taking Other Antiarrhythmic Drugs

Having trouble viewing table?
Drug Baseline Testing Follow-Up Testing Additional Follow-Up Testing
Dofetilide 12-lead ECG*

Continuous ECG monitoring during 3-d hospitalization for dofetilide initiation

Serum potassium and magnesium concentration

Serum creatinine for estimation of CrCl
In 3–6 mo: 12-lead ECG*

Serum potassium and magnesium concentration

Serum creatinine for estimation of CrCl
Every 3–6 mo (more frequently for patients concomitantly taking other QT interval-prolonging drugs or with changing kidney function): 12-lead ECG*

Serum potassium and magnesium concentration

Serum creatinine for estimation of CrCl
Dronedarone 12-lead ECG*
AST
ALT
Within first 6 mo:
AST
ALT
Ibutilide 12-lead ECG*

Determination of serum potassium and magnesium concentrations and correction of hypokalemia and/or hypomagnesemia is recommended prior to initiation of the infusion
Continuous ECG monitoring for assessment of QTc interval duration is recommended for at least 4 h following infusion or until the QTc has returned to baseline to minimize the risk of ibutilide-associated TdP
Procainamide 12-lead ECG*
Blood pressure
ECG monitoring for assessment of rhythm, QRS width and QTc interval is recommended during the infusion to minimize the risk of procainamide-associated ventricular proarrhythmia, including TdP

Blood pressure monitoring is recommended during the infusion to detect clinically relevant hypotension
Sotalol 12-lead ECG*
Continuous ECG monitoring during 3-d hospitalization for sotalol initiation

Serum potassium and magnesium concentration

Serum creatinine for estimation of CrCl
In 3-6 mo:
12-lead ECG*

Serum potassium and magnesium concentration

Serum creatinine for estimation of CrCl
Every 3–6 mo (more frequently for patients concomitantly taking other QT interval-prolonging drugs or with changing kidney function):
12-lead ECG*

Serum potassium and magnesium concentration

Serum creatinine for estimation of CrCl
* Assess rhythm and calculate QTc.
To facilitate early detection of potential dronedarone-associated hepatotoxicity.

8.3.4. Upstream Therapy

8.4. AF Catheter Ablation

1. In patients with symptomatic AF in whom AADs have been ineffective, contraindicated, not tolerated or not preferred, and continued rhythm control is desired, catheter ablation is useful to improve symptoms. (1, A)
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2. In selected patients (generally younger with few comorbidities) with symptomatic paroxysmal AF in whom rhythm control is desired, catheter ablation is useful as first-line therapy to improve symptoms and reduce progression to persistent AF. (1, A)
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3. In patients with symptomatic or clinically significant AFL, catheter ablation is useful for improving symptoms. (1, A)
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4. In patients who are undergoing ablation for AF, ablation of additional clinically significant supraventricular arrhythmias can be useful to reduce the likelihood of future arrhythmia.

(2a, B-NR)
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5. In patients (other than younger with few comorbidities) with symptomatic paroxysmal or persistent AF who are being managed with a rhythm-control strategy, catheter ablation as first-line therapy can be useful to improve symptoms. (2a, B-R)
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6. Catheter ablation for symptomatic AF provides intermediate economic value compared with AAD therapy (Cost Value Statement: Intermediate). (, B-R)
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7. In selected* patients with asymptomatic or minimally symptomatic AF, catheter ablation may be useful for reducing progression of AF and its associated complications. (2b, B-NR)
* Younger patients with few comorbidities and a moderate to high burden of AF or persistent AF* Younger patients with few comorbidities and a moderate to high burden of AF or persistent AF and AFL.
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8.4.1. Patient Selection

8.4.2. Techniques and Technologies for AF Catheter Ablation

1. In patients undergoing ablation for AF, pulmonary vein isolation (PVI) is recommended as the primary lesion set for all patients unless a different specific trigger is identified. (1, A)
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2. In patients undergoing ablation for AF, the value of other endpoints beyond PVI such as noninducibility and ablation of additional anatomic ablation targets (eg, posterior wall, sites, low voltage areas, complex fractionated electrograms, rotors) is uncertain. (2b, B-R)
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8.4.3. Management of Recurrent AF After Catheter Ablation

1. In patients with recurrent symptomatic AF after catheter ablation, repeat catheter ablation or AAD therapy is useful to improve symptoms and freedom from AF. (1, B-NR)
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2. In some patients who have undergone catheter ablation of AF, short-term AAD therapy after ablation can be useful to reduce early recurrences of atrial arrhythmia and hospitalization. (2a, A)
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8.4.4. Anticoagulation Therapy Before and After Catheter Ablation

1. In patients undergoing catheter ablation of AF on warfarin, catheter ablation should be performed on uninterrupted therapeutic anticoagulation with a goal INR of 2.0 to 3.0. (1, B-NR)
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2. In patients on a DOAC undergoing catheter ablation of AF, catheter ablation should be performed with either continuous or minimally interrupted oral anticoagulation. (1, A)
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3. In patients who have undergone catheter ablation of AF, oral anticoagulation should be continued for at least 2 to 3 months after the procedure with a longer duration determined by underlying risk. (1, B-NR)
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4. In patients who have undergone catheter ablation of AF, continuation of longer-term oral anticoagulation should be dictated according to the patients’ stroke risk (eg, CHA2DS2-VASc score ≥2). (1, B-NR)
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8.4.5. Complications Following AF Catheter Ablation

Table 26 . Complications After Atrial Fibrillation Catheter Ablation

Having trouble viewing table?
Complication Frequency of Complication Timing of Complication Signs and Symptoms Diagnosis Treatment
LA-esophageal fistula 0.2% 1–4 wk Chest pain, pain with swallowing, fever, stroke symptoms CT scan of chest Surgery
Cardiac perforation w/ tamponade 0.4%–1.5% During procedure Hypotension Echocardiography Pericardiocentesis
CVA/TIA 0.1%–1.0% During procedure and up to 1 wk Neurological findings MRI or CT scan Anticoagulate when safe
Pulmonary vein (PV) stenosis 0.1%–0.8% Months Dyspnea, hemoptysis MRI or CT Scan Stent
Phrenic nerve paralysis 0.2%–0.4% During procedure Dyspnea Fluoroscopy Time
Vascular access complications 1%–7% During procedure and up to 1 mon Pain, swelling at access site Ultrasound or CT scan Observation
Vascular access complications requiring surgery 0.1%–0.3% During procedure and up to 1 mon Pain and swelling at access site Ultrasound or CT scan Surgery
Death 0.1%–0.4% During procedure
Pneumonia 0.4%–1.0% Days Cough, fever Chest x-ray Antibiotics

8.5. Role of Pacemakers and Implantable Cardioverter-Defibrillators for the Prevention and Treatment of AF

1. In patients with bradycardia requiring cardiac-implanted electronic devices who have normal AV conduction, device selection and programming strategies to maintain AV synchrony and minimize ventricular pacing should be used to reduce the incidence and progression of AF. (1, A)
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2. In selected patients with a pacemaker and symptomatic atrial tachyarrhythmias, antitachycardia atrial pacing and ventricular pacing minimization may be useful for reducing symptoms. (2b, B-NR)
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3. In patients with AF who require significant ventricular pacing, conduction system pacing may be useful to reduce progression of AF. (2b, C-LD)
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4. In patients with AF, specialized atrial pacing algorithms designed to suppress AF are not useful for reducing the incidence or slowing the progression of AF. (3 - No Benefit, B-R)
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8.6. Surgical Ablation

1. For patients with AF who are undergoing cardiac surgery, concomitant surgical ablation can be beneficial to reduce the risk of recurrent AF. (2a, B-R)
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2. In patients undergoing surgical ablation, anticoagulation therapy is reasonable for at least 3 months after the procedure to reduce the risk of stroke or systemic embolism. (2a, B-NR)
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3. For patients with symptomatic, persistent AF refractory to AAD therapy, a hybrid epicardial and endocardial ablation might be reasonable to reduce the risk of recurrent atrial arrhythmia. (2b, B-R)
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9. Management of Patients With HF
9.1. General Considerations for AF and HF

9.2. Management of AF in Patients With HF*

1. In patients who present with a new diagnosis of HFrEF and AF, arrhythmia-induced cardiomyopathy should be suspected, and an early and aggressive approach to AF rhythm control is recommended. (1, B-NR)
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2. In appropriate patients with AF and HFrEF who are on GDMT, and with reasonable expectation of procedural benefit (Figure 24), catheter ablation is beneficial to improve symptoms, QOL, ventricular function, and cardiovascular outcomes. (1, A)
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3. In appropriate patients with symptomatic AF and heart failure with preserved ejection fraction (HFpEF) with reasonable expectation of benefit, catheter ablation can be useful to improve symptoms and improve QOL. (2a, B-NR)
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4. In patients with AF and HF, digoxin is reasonable for rate control, in combination with other rate-controlling agents or as monotherapy if other agents are not tolerated. (2a, B-R)
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5. In patients with AF and HF with rapid ventricular rates in whom beta blockers or calcium channel blockers are contraindicated or ineffective, intravenous amiodarone is reasonable for acute rate control. (2a, B-NR)
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6. In patients with AF, HFrEF (LVEF <50%), and refractory rapid ventricular response who are not candidates for or in whom rhythm control has failed, AVNA and biventricular pacing therapy can be useful to improve symptoms, QOL, and EF. (2a, B-R)
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7. In patients with AF, HF, and implanted biventricular pacing therapy in whom an effective pacing percentage cannot be achieved with pharmacological therapy, AVNA can be beneficial to improve functional class, reduce the risk of ICD shock, and improve survival. (2a, B-NR)
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8. In patients with AF-induced cardiomyopathy who have recovered LV function, long-term surveillance can be beneficial to detect recurrent AF in view of the high risk of recurrence of arrhythmia-induced cardiomyopathy. (2a, B-NR)
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9. In patients with suspected AF-induced cardiomyopathy or refractory HF symptoms undergoing pharmacological rate-control therapy for AF, a stricter rate-control strategy (target heart rate <80 bpm at rest and <110 bpm during moderate exercise) may be reasonable. (2b, B-NR)
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10. In patients with AF and HFrEF who undergo AVNA, conduction system pacing of the His bundle or left bundle branch area may be reasonable as an alternative to biventricular pacing to improve symptoms, QOL, and LV function. (2b, C-LD)
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11. In patients with AF and known LVEF <40%, nondihydropyridine calcium channel-blocking drugs should not be administered given their potential to exacerbate HF. (3 - Harm, B-R)
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12. For patients with AF, dronedarone should not be administered for maintenance of sinus rhythm to those with NYHA class III and IV HF or patients who have had an episode of decompensated HF in the past 4 weeks, due to the risk of increased early mortality associated with worsening HF. (3 - Harm, B-R)
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* Please see other recommendations on anticoagulation in AF (Section 8.4.4, “Anticoagulation Therapy Before and After Catheter Ablation”), rate control in HF (Section 7, “Rate Control”), and agents for pharmacological cardioversion (Section 7.2, “Specific Pharmacological Agents for Rate Control”) and maintenance of sinus rhythm (Section 8.3.1, “Specific Drug Therapy for Long-Term Maintenance of Sinus Rhythm”).

Consider the risk of cardioversion and stroke when using amiodarone as a rate-control agent.

10. AF and Specific Patient Groups

Figure 24. Management of Patients with HF and AF

10.1. Management of Early Onset AF, Including Genetic Testing

1. In patients with an onset of unexplained AF before the age of 30 years, electrophysiologic study to evaluate and treat reentrant supraventricular tachyarrhythmias with a targeted ablation may be reasonable in view of the high prevalence of reentrant arrhythmias in this group. (2b, B-NR)
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2. In patents with an onset of AF before the age of 45 years without obvious risk factors for AF, referral for genetic counseling, genetic testing for rare pathogenic variants, and surveillance for cardiomyopathy or arrhythmia syndromes may be reasonable. (2b, B-NR)
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10.2. Athletes

1. In athletes who develop AF, catheter ablation with PVI is a reasonable strategy for rhythm control in view of its effectiveness and low risk of detrimental effect on exercise capacity. (2a, B-NR)
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10.3. Management Considerations in Patients With AF and Obesity 

10.4. Anticoagulation Considerations in Patients With Class III Obesity

1. In patients with AF and class III obesity (BMI ≥40 kg/m2 ), DOACs are reasonable to choose over warfarin for stroke risk reduction. (2a, B-NR)
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2. In patients with AF who have undergone bariatric surgery, warfarin may be reasonable to choose over DOACs for stroke risk reduction in view of concerns about DOAC drug absorption. (2b, C-LD)
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10.5. AF and VHD


10.6. Wolff-Parkinson-White (WPW) and Pre-Excitation Syndromes

1. Patients with AF with rapid anterograde conduction (preexcited AF), and hemodynamic instability should be treated with electrical cardioversion. (1, B-NR)
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2. For patients with AF with rapid anterograde conduction (pre-excited AF), catheter ablation of accessory pathways (APs) is recommended. (1, B-NR)
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3. In patients with AF with rapid anterograde conduction (preexcited AF) and hemodynamic stability, pharmacological cardioversion with intravenous ibutilide or intravenous procainamide is recommended as an alternative to elective cardioversion. (1, C-LD)
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4. For patients with AF with anterograde accessory pathway conduction (pre-excited AF), pharmacological agents that block AV nodal conduction (verapamil, diltiazem, amiodarone, digoxin, adenosine, or beta blockers) are contraindicated due to risk of precipitating VF or hemodynamic deterioration. (3 - Harm, B-NR)
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10.7. HCM


10.8. Adult Congenital Heart Disease (ACHD)

1. In adults with ACHD and AF, it is recommended to evaluate for and treat precipitating factors and reversible causes of AF, recognizing that residual hemodynamic sequalae may contribute to the occurrence of the arrhythmia. (1, B-NR)
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2. In adults with AF and moderate or complex congenital heart disease, electrophysiological procedures should be performed by operators with expertise in ACHD procedures and in collaboration with an ACHD cardiologist, ideally in specialized centers, when available. (1, C-LD)
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3. In adults with congenital heart disease and symptomatic or hemodynamically significant paroxysmal or persistent AF, an initial strategy of rhythm control is recommended regardless of lesion severity as AF in this population is often poorly tolerated. (1, C-LD)
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4. In symptomatic patients with simple congenital heart disease with AAD-refractory AF, it is reasonable to choose ablation over long-term antiarrhythmic therapies. (2a, B-NR)
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5. In ACHD patients with AF undergoing PVI, it may be reasonable to include an ablative strategy in the right atrium directed at reentrant arrhythmia secondary to atriotomy scars and the CTI. (2b, C-LD)
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6. In adults with AF and moderate or severe forms of congenital heart disease, particularly those with low-flow states such as Fontan circulation, blind-ending cardiac chambers, and cyanosis, it may be reasonable to treat with anticoagulation independent of conventional risk score to reduce risk of thromboembolic events. (2b, C-LD)
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10.9. Prevention and Treatment After Cardiac Surgery

10.9.1. Prevention of AF After Cardiac Surgery

1. In patients undergoing cardiac surgery at high risk for postoperative AF, it is reasonable to administer short-term prophylactic beta blockers or amiodarone to reduce the incidence of postoperative AF. (2a, B-R)
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2. In patients undergoing CABG, aortic valve, or ascending aortic aneurysm operations, it is reasonable to perform concomitant posterior left pericardiotomy to reduce the incidence of postoperative AF. (2a, B-R)
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Figure 25. Prevention of AF After Cardiac Surgery

10.9.2. Treatment of AF After Cardiac Surgery

1. In postoperative cardiac surgery patients,
beta blockers* are recommended to achieve rate control for AF, (1, A)
unless contraindicated or ineffective, in which case
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a nondihydropyridine calcium channel blocker is recommended. (1, B-R)
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2. In hemodynamically stable cardiac surgery patients with postoperative AF, rate-control (target heart rate <100 bpm) and/or rhythm- control medications are recommended as initial therapy, with the choice of strategy according to patient symptoms, hemodynamic consequences of the arrhythmia, and physician preference. (1, B-R)
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3. In patients who develop poorly tolerated AF after cardiac surgery, DCCV in combination with AAD therapy is recommended, with consideration of imaging to rule out left appendage thrombus before cardioversion in those patients in whom AF has been present >48 hours and who have not been on anticoagulation. (1, B-R)
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4. In patients who develop postoperative AF after cardiac surgery, it is reasonable to administer anticoagulation when deemed safe in regards to surgical bleeding for 60 days after surgery unless complications develop, and to reevaluate the need for longer term anticoagulation at that time. (2a, B-NR)
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5. In patients who develop AF after cardiac surgery and who are treated with rate-control strategy, at 30- to 60-day follow-up it is reasonable to perform rhythm assessment and, if AF does not revert to sinus rhythm spontaneously, consider cardioversion after an adequate duration of anticoagulation. (2a, C-LD)
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Figure 26. Treatment of AF After Cardiac Surgery

10.10. Acute Medical Illness or Surgery (Including AF in Critical Care)

1. Patients with AF identified in the setting of acute medical illness or surgery should be counseled about the significant risk of recurrent AF after the acute illness is resolved. (1, B-NR)
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2. In patients with AF identified in the setting of acute medical illness or surgery, outpatient follow-up for thromboembolic risk stratification and decision-making on OAC initiation or continuation, as well as AF surveillance, can be beneficial given a high risk of AF recurrence. (2a, B-NR)
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3. In patients with AF identified in the setting of critical illness due to sepsis, the benefits of anticoagulation for stroke prevention are uncertain. (2b, B-NR)
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Figure 27. Unadjusted Cumulative Risk of AF Recurrence

Unadjusted curves displaying cumulative risk of recurrent AF, generated using Kaplan-Meier method.

(A) Overall risk of recurrent AF among individuals with and without acute precipitants. (B) Overall risk of recurrent AF among individuals with infection, cardiac surgery, and noncardiothoracic surgery, as compared with no precipitant. These 3 precipitants were selected for display because the risk of recurrent AF was significantly lower as compared with the referent group without precipitants in multivariable adjusted models. Individuals with other AF precipitants were excluded from this plot for clarity. CT, cardiothoracic.

Reproduced with permission from Wang EY, et al. Copyright 2020, American Heart Association, Inc

Figure 28. Acute Medical or Surgical Illness

Adapted with permission from Chyou JY, et al. Copyright 2023, American Heart Association, Inc.

10.11. Hyperthyroidism

1. In patients with hyperthyroidism and AF who have an elevated risk of stroke based on a standard clinical risk score, anticoagulation is recommended until thyroid function has returned to normal and sinus rhythm can be maintained. (1, B-NR)
3594638

10.12. Pulmonary Disease

1. In patients with AF and COPD, it is reasonable to use cardioselective beta blockers for rate control of AF, especially where other indications exist, such as MI and HF. (2a, B-R)
3594638
2. In patients with pulmonary hypertension with pulmonary vascular disease (PHPVD) and AF In patients with pulmonary hypertension with pulmonary vascular disease (PHPVD) and AF or AFL, a rhythm-control strategy is reasonable to improve functional status and potentially prolong survival. (2a, B-NR)
3594638

10.13. Pregnancy

1. In pregnant patients with AF, DCCV is safe to the patient and fetus and should be performed in the same manner as in patients who are not pregnant. (1, B-NR)
3594638
2. In pregnant individuals with structurally normal hearts and hemodynamically stable AF, pharmacological cardioversion with agents with history of safe use in pregnancy, such as intravenous procainamide, may be considered. (2b, C-LD)
3594638
3. In pregnant individuals with AF and without structural heart disease, antiarrhythmic agents with history of safe use in pregnancy, such as flecainide and sotalol, are reasonable for maintenance of sinus rhythm. (2a, C-LD)
3594638
4. In pregnant individuals with persistent AF, rate-control agents with a record of safety in pregnancy, such as beta blockers (eg, propranolol or metoprolol) and digoxin, either alone or in combination with beta blockers, are reasonable as first-line agents. (2a, B-NR)
3594638
5. Pregnant individuals with AF and elevated risk of stroke may be considered for anticoagulation with the recognition that no anticoagulation strategy is completely safe for both the mother and fetus, and an SDM discussion should take place regarding risks to both mother and fetus (see Table 28). (2b, C-LD)
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Table 28. Anticoagulation Strategies During Pregnancy - Antenatal Options

Having trouble viewing table?
Method 1 Method 2 Method 3 Alternative Method 4
1st trimester Warfarin ≤5 mg LMWH UFH LMWH
2nd trimester Warfarin Warfarin Warfarin LMWH
3rd trimester Warfarin Warfarin Warfarin LMWH
Adapted with permission from Otto CM, et al. Copyright 2021, American Heart Association, Inc. and American College of Cardiology Foundation.

Table 28. Anticoagulation Strategies During Pregnancy - Delivery Planning

Having trouble viewing table?
Method 1 Method 2
1 wk prior Discontinue warfarin → continuous IV UFH Dose-adjusted LMWH
36 h prior Continuous IV UFH Switch to continuous IV UFH
4–6 h prior Stop IV heparin Stop IV heparin

Table 29. Medical Cancer Therapy Associated With Increased Risk of AF (>1%)

Having trouble viewing table?
Cancer Therapy Frequency Reported in Clinical Trials and Observational Studies

Common: Incidence 1%–10%
Frequency Reported in Clinical Trials and Observational Studies

Frequent: >10%
Comments
Anthracyclines
Doxorubicin, epirubicin, idarubicin, mitoxantrone
× AF may be a secondary result of anthracycline cardiotoxicity; studies in different populations demonstrate variable risk of AF
Antimetabolites × ×
Clofarabine combined with cytarabine ×
5 fluorouracil (5FU) ×
Cepecitabine
Gemcitabine
Alkylating agents
Cyclophosphamide
Melphalan + stem cell transplantation
× ×* * Stem cell transplantation is associated with an increased risk of AF, and the risk may be higher with melphalanassociated regimens
Immunomodulatory drugs × Given rates reported from patients with multiple myeloma, AF due to underlying cardiac AL amyloid may contribute
Lenalidomide ×
Interleukin-2
Tyrosine kinase inhibitors (TKIs) × × Reported AF rates with ibrutinib have varied across trials (4%–18%), partly related to varying duration of follow-up and patient factors. Second-generation BTKis have more selective Bruton’s tyrosine kinase (BTK) activity and are associated with a lower incidence of AF than ibrutinib

Based on US FDA adverse event reporting system
Ibrutinib (Bruton’s kinase inhibitor [BTKi]) ×
Acalbrutinib (2ndgeneration BTKi) ×
Zanubrutinib (2ndgeneration BTKi) ×
Ponatinib (BCRABL TKI) and other TKIs (eg, trametinib, osimertinib, nilotinib, ribociclib) ×
VEGF inhibitor
Sorafenib in combination with 5FU
BRAF inhibitor
Vemurafenib
Chimeric antigen receptor (CAR) T-cell therapy
Tisagenlecleucel
Axicabtagene ciloleucel
×
Monoclonal antibodies
Rituximab
×
Table developed by Atrial Fibrillation Guideline Writing Committee. Data extracted from Buza V et al. Circ Arrhythm Electrophysiol. 2017;10:e005443, Fradley MG et al. Circulation. 2021;144:e41-e55.

10.14. Cardio-Oncology and Anticoagulation Considerations

1. In patients with cancer and AF, multidisciplinary communication including cardiology, oncology and other clinicians, and SDM with the patient is recommended to optimize cancer and AF treatment and to reduce the risk of drug-drug interactions, QTc prolongation, proarrhythmia, bleeding, and thromboembolism. (1, C-LD)
3594638
2. In patients who are to be initiated on cancer therapies associated with an increased risk of developing AF, increased vigilance for incident AF and treatment of contributing factors is reasonable to decrease morbidity. (2a, C-LD)
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3. In most patients with AF and cancer (remote history or receiving active cancer treatment), DOACs are reasonable to choose over VKAs for stroke risk reduction. (2a, B-NR)
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Table 30. Special Considerations for Anticoagulation in Patients With AF on Active Cancer Treatment

Having trouble viewing table?
Increased bleeding risk High bleeding risk estimators (eg, HAS-BLED)
Thrombocytopenia (platelet <50,000/uL)
Intracranial malignancy
Gastrointestinal malignancy
History of major bleeding
Severe kidney dysfunction (eGFR <30 mL/min/1.73m2)
Drug interactions P-glycoprotein inducers or inhibitors
CYP 3A4 inducers or inhibitors

10.15. CKD and Kidney Failure


10.16. Anticoagulation Use in Patients With Liver Disease

1. For patients with AF at increased risk of systemic thromboembolism and mild or moderate liver disease (Child-Pugh* class A or B), OAC therapy is reasonable in the absence of clinically significant liver disease-induced coagulopathy or thrombocytopenia. (2a, B-NR)
* Child-Pugh scoring: the severity of liver disease, primarily cirrhosis in patients with diagnosed liver disease. Child-Pugh A (mild): 5–6 points; Child-Pugh B (moderate): 7–9 points; Child-Pugh C (severe): 10–15 points.
The score is based on the 5 variables: encephalopathy (none=1 point, grade 1 and 2=2 points, grade 3 and 4= 3 points); ascites (none=1 point, slight=2 points, moderate=3 points); total bilirubin (<2 mg/mL=1 point, 2–3 mg/mL=2 points, >3 mg/mL=3 points); albumin (>3.5 mg/mL=1 point, 2.8–3.5 mg/mL=2 points, <2.8 mg/mL=3 points); INR (<1.7=1 point, INR 1.7–2.2=2 points, INR >2.2=3 points).
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2. For patients with AF at increased risk of systemic thromboembolism and mild or moderate liver disease (ChildPugh class A or B) who are deemed to be candidates for anticoagulation, it is reasonable to prescribe DOACs (ChildPugh class A: any DOAC; Child-Pugh class B: apixaban, dabigatran, or edoxaban) over warfarin. (2a, B-NR)
3594638
3. For patients with AF and moderate liver disease (Child-Pugh class B) at increased risk of systemic thromboembolism, rivaroxaban is contraindicated due to the potentially increased risk of bleeding. (3 - Harm, C-LD)
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Recommendation Grading

Abbreviations

  • ACE: Angiotensin-converting Enzyme
  • ACS: Acute Coronary Syndrome
  • AF: Atrial Fibrillation
  • ARB: Angiotensin Receptor Blocker
  • AV: Atrioventricular
  • BID: Two Times A Day
  • CAD: Coronary Artery Disease
  • CKD: Chronic Kidney Disease
  • COPD: Chronic Obstructive Pulmonary Disease
  • COR: Class Of Recommendation
  • CPR: Cardiopulmonary Resuscitation
  • CT: Computed Tomography
  • CrCl: Creatinine Clearance
  • ECG: Electrocardiogram
  • EF: Ejection Fraction
  • ER: Extended Release
  • GI: Gastrointestinal
  • HCM: Hypertrophic Cardiomyopathy
  • HCTZ: Hydrochlorthiazide
  • HF: Heart Failure
  • HFpEF: Heart Failure With Preserved Ejection Fraction
  • INR: International Normalized Ratio
  • IV: Intravenous
  • LA: Left Atrium/atrial
  • LAA: Left Atrial Appendage
  • LMWH: Low Molecular Weight Heparin
  • LOE: Level Of Evidence
  • LV: Left Ventricular
  • LVEF: Left Ventricular Ejection Fraction
  • MRI: Magnetic Resonance Imaging
  • N/A: Not Applicable
  • NSAIDs: Non-Steroidal Anti-Inflammatory Drugs
  • PAD: Peripheral Artery Disease
  • QD: Once Daily
  • QID: Four Times A Day
  • RA: Right Atrium/atrial
  • RAAS: Renin-angiotensin-aldosterone System
  • RV: Right Ventricular
  • RVR: Rapid Ventricular Response
  • TE: Thromboembolic Events
  • TEE: Transesophageal Echocardiography
  • TTE: Transthoracic Echocardiogram
  • UFH: Unfractionated Heparin
  • VHD: Valvular Heart Disease
  • WPW: Wolff-Parkinson-White
  • bpm: Beats Per Minute

Source Citation

Joglar JA, Chung MK, Armbruster AL, Benjamin EJ, Chyou JY, Cronin EM, Deswal A, Eckhardt L, Goldberger ZD, Gopinathannair R, Gorenek B, Hess PL, Hlatky M, Hogan G, Ibeh C, Indik JH, Kido K, Kusumoto F, Link MS, Linta KT, Marcus GM, McCarthy PM, Patel N, Patton KK, Perez MV, Piccini JP, Russo AM, Sanders P, Streur MM, Thomas KL, Times SS, Tisdale JE, Valente AM, Van Wagoner DR. 2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. [published online ahead of print Nov 30, 2023].
J Am Coll Cardiol. doi: 10.1016/j.jacc.2023.08.017

Copublished in Circulation. doi: 10.1161/CIR.0000000000001193

Disclaimer

This resource is for informational purposes only, intended as a quick-reference tool based on the cited source guideline(s), and should not be used as a substitute for the independent professional judgment of healthcare providers. Practice guidelines are unable to account for every individual variation among patients or take the place of clinician judgment, and the ultimate decision concerning the propriety of any course of conduct must be made by healthcare providers after consideration of each individual patient situation. Guideline Central does not endorse any specific guideline(s) or guideline recommendations and has not independently verified the accuracy hereof. Any use of this resource or any other Guideline Central resources is strictly voluntary.

Codes

CPT Codes

Code Descriptor
71048 Radiologic examination
33256 Operative tissue ablation and reconstruction of atria
84442 Thyroxine binding globulin (TBG)
93016 Cardiovascular stress test using maximal or submaximal treadmill or bicycle exercise
93000 Electrocardiogram, routine ECG with at least 12 leads; with interpretation and report
84439 Thyroxine; free
93313 Echocardiography
93312 Echocardiography
84479 Thyroid hormone (T3)
93017 Cardiovascular stress test using maximal or submaximal treadmill or bicycle exercise
84443 Thyroid stimulating hormone (TSH)
71045 Radiologic examination
78454 Myocardial perfusion imaging
93010 Electrocardiogram, routine ECG with at least 12 leads; interpretation and report only
33266 Endoscopy
93227 External electrocardiographic recording up to 48 hours by continuous rhythm recording and storage; review and interpretation by a physician or other qualified health care professional
78453 Myocardial perfusion imaging
93270 External patient and
33250 Operative ablation of supraventricular arrhythmogenic focus or pathway (eg
84432 Thyroglobulin
80076 Hepatic function panel
33251 Operative ablation of supraventricular arrhythmogenic focus or pathway (eg
93271 External patient and
78452 Myocardial perfusion imaging
93226 External electrocardiographic recording up to 48 hours by continuous rhythm recording and storage; scanning analysis with report
93314 Echocardiography
93355 Echocardiography
84445 Thyroid stimulating immune globulins (TSI)
93268 External patient and
93229 External mobile cardiovascular telemetry with electrocardiographic recording
33340 Percutaneous transcatheter closure of the left atrial appendage with endocardial implant
93618 Induction of arrhythmia by electrical pacing
93272 External patient and
78451 Myocardial perfusion imaging
93225 External electrocardiographic recording up to 48 hours by continuous rhythm recording and storage; recording (includes connection
93224 External electrocardiographic recording up to 48 hours by continuous rhythm recording and storage; includes recording
93228 External mobile cardiovascular telemetry with electrocardiographic recording
33265 Endoscopy
93005 Electrocardiogram, routine ECG with at least 12 leads; tracing only, without interpretation and report
33254 Operative tissue ablation and reconstruction of atria
92961 Cardioversion
80069 Renal function panel
71046 Radiologic examination
71047 Radiologic examination
93015 Cardiovascular stress test using maximal or submaximal treadmill or bicycle exercise
92960 Cardioversion
33255 Operative tissue ablation and reconstruction of atria
84436 Thyroxine; total

ICD-10 Codes

Code Descriptor Documentation Concepts Quality/Performance
I15.1 Hypertension secondary to other renal disorders Type Due to Caused by
E05.20 Thyrotoxicosis with toxic multinodular goiter without thyrotoxic crisis or storm
E05.00 Thyrotoxicosis with diffuse goiter without thyrotoxic crisis or storm
Z86.73 Personal history of transient ischemic attack (TIA), and cerebral infarction without residual deficits
I50.31 Acute diastolic (congestive) heart failure Type
I48.11 Longstanding persistent atrial fibrillation Type Temporal parameter HCC96, RXHCC193
R00.1 Bradycardia, unspecified Symptom
Z79.02 Long term (current) use of antithrombotics/antiplatelets
I50.30 Unspecified diastolic (congestive) heart failure Type
E05.01 Thyrotoxicosis with diffuse goiter with thyrotoxic crisis or storm
E05.21 Thyrotoxicosis with toxic multinodular goiter with thyrotoxic crisis or storm
I47.2 Ventricular tachycardia Anatomic location Complicating factors HCC96
I15.0 Renovascular hypertension Type Due to Caused by
I42.1 Obstructive hypertrophic cardiomyopathy Type Causation HCC85, RXHCC186
I12.9 Hypertensive chronic kidney disease with stage 1 through stage 4 chronic kidney disease, or unspecified chronic kidney disease Type
E05.10 Thyrotoxicosis with toxic single thyroid nodule without thyrotoxic crisis or storm Type, anatomical location, with or without, caused by due to
I50.21 Acute systolic (congestive) heart failure Type
J44.9 Chronic obstructive pulmonary disease, unspecified Severity, Temporal parameters, Complication, Contributing factors HCC111,, RXHCC226
I48.0 Paroxysmal atrial fibrillation Anatomic location Complicating factors HCC96, RXHCC193
I48.20 Chronic atrial fibrillation, unspecified Type Temporal parameter HCC96, RXHCC193
I50.40 Unspecified combined systolic (congestive) and diastolic (congestive) heart failure Type
E05.30 Thyrotoxicosis from ectopic thyroid tissue without thyrotoxic crisis or storm
I11.0 Hypertensive heart disease with heart failure Type HCC85, RXHCC186
E05.31 Thyrotoxicosis from ectopic thyroid tissue with thyrotoxic crisis or storm
I48.21 Permanent atrial fibrillation Type Temporal parameter HCC96, RXHCC193
I50.41 Acute combined systolic (congestive) and diastolic (congestive) heart failure Type
I13.0 Hypertensive heart and chronic kidney disease with heart failure and stage 1 through stage 4 chronic kidney disease, or unspecified chronic kidney disease Type HCC85, RXHCC186
I48.1 Persistent atrial fibrillation Anatomic location Complicating factors HCC96, RXHCC193
I50.20 Unspecified systolic (congestive) heart failure Type
E05.11 Thyrotoxicosis with toxic single thyroid nodule with thyrotoxic crisis or storm Type, anatomical location, with or without, caused by due to

ICD-10 Complexities

Code Descriptor
I69.859 Hemiplegia and hemiparesis following other cerebrovascular disease affecting unspecified side
I69.361 Other paralytic syndrome following cerebral infarction affecting right dominant side
I69.232 Monoplegia of upper limb following other nontraumatic intracranial hemorrhage affecting left dominant side
I69.398 Other sequelae of cerebral infarction
I69.818 Other symptoms and signs involving cognitive functions following other cerebrovascular disease
I69.320 Aphasia following cerebral infarction
I69.265 Other paralytic syndrome following other nontraumatic intracranial hemorrhage, bilateral
I69.834 Monoplegia of upper limb following other cerebrovascular disease affecting left non-dominant side
I69.249 Monoplegia of lower limb following other nontraumatic intracranial hemorrhage affecting unspecified side
I69.863 Other paralytic syndrome following other cerebrovascular disease affecting right non-dominant side
I69.033 Monoplegia of upper limb following nontraumatic subarachnoid hemorrhage affecting right non-dominant side
I69.80 Unspecified sequelae of other cerebrovascular disease
I69.064 Other paralytic syndrome following nontraumatic subarachnoid hemorrhage affecting left non-dominant side
I69.822 Dysarthria following other cerebrovascular disease
I69.121 Dysphasia following nontraumatic intracerebral hemorrhage
I69.910 Attention and concentration deficit following unspecified cerebrovascular disease
I69.013 Psychomotor deficit following nontraumatic subarachnoid hemorrhage
I69.290 Apraxia following other nontraumatic intracranial hemorrhage
I69.044 Monoplegia of lower limb following nontraumatic subarachnoid hemorrhage affecting left non-dominant side
I69.228 Other speech and language deficits following other nontraumatic intracranial hemorrhage
I69.814 Frontal lobe and executive function deficit following other cerebrovascular disease
I69.951 Hemiplegia and hemiparesis following unspecified cerebrovascular disease affecting right dominant side
I69.052 Hemiplegia and hemiparesis following nontraumatic subarachnoid hemorrhage affecting left dominant side
I69.843 Monoplegia of lower limb following other cerebrovascular disease affecting right non-dominant side
I69.269 Other paralytic syndrome following other nontraumatic intracranial hemorrhage affecting unspecified side
I69.992 Facial weakness following unspecified cerebrovascular disease
I69.091 Dysphagia following nontraumatic subarachnoid hemorrhage
I69.212 Visuospatial deficit and spatial neglect following other nontraumatic intracranial hemorrhage
I69.253 Hemiplegia and hemiparesis following other nontraumatic intracranial hemorrhage affecting right non-dominant side
I69.341 Monoplegia of lower limb following cerebral infarction affecting right dominant side
I69.069 Other paralytic syndrome following nontraumatic subarachnoid hemorrhage affecting unspecified side
I69.252 Hemiplegia and hemiparesis following other nontraumatic intracranial hemorrhage affecting left dominant side
I69.244 Monoplegia of lower limb following other nontraumatic intracranial hemorrhage affecting left non-dominant side
I69.028 Other speech and language deficits following nontraumatic subarachnoid hemorrhage
I69.213 Psychomotor deficit following other nontraumatic intracranial hemorrhage
I69.993 Ataxia following unspecified cerebrovascular disease
I69.839 Monoplegia of upper limb following other cerebrovascular disease affecting unspecified side
I69.090 Apraxia following nontraumatic subarachnoid hemorrhage
I69.842 Monoplegia of lower limb following other cerebrovascular disease affecting left dominant side
I69.141 Monoplegia of lower limb following nontraumatic intracerebral hemorrhage affecting right dominant side
I69.815 Cognitive social or emotional deficit following other cerebrovascular disease
I69.053 Hemiplegia and hemiparesis following nontraumatic subarachnoid hemorrhage affecting right non-dominant side
I69.291 Dysphagia following other nontraumatic intracranial hemorrhage
I69.854 Hemiplegia and hemiparesis following other cerebrovascular disease affecting left non-dominant side
I69.911 Memory deficit following unspecified cerebrovascular disease
I69.012 Visuospatial deficit and spatial neglect following nontraumatic subarachnoid hemorrhage
I69.065 Other paralytic syndrome following nontraumatic subarachnoid hemorrhage, bilateral
I69.823 Fluency disorder following other cerebrovascular disease
I69.120 Aphasia following nontraumatic intracerebral hemorrhage
I69.931 Monoplegia of upper limb following unspecified cerebrovascular disease affecting right dominant side
I69.032 Monoplegia of upper limb following nontraumatic subarachnoid hemorrhage affecting left dominant side
I69.198 Other sequelae of nontraumatic intracerebral hemorrhage
I69.862 Other paralytic syndrome following other cerebrovascular disease affecting left dominant side
I69.161 Other paralytic syndrome following nontraumatic intracerebral hemorrhage affecting right dominant side
I69.321 Dysphagia following cerebral infarction
I69.264 Other paralytic syndrome following other nontraumatic intracranial hemorrhage affecting left non-dominant side
I69.819 Unspecified symptoms and signs involving cognitive functions following other cerebrovascular disease
I69.233 Monoplegia of upper limb following other nontraumatic intracranial hemorrhage affecting right non-dominant side
I69.049 Monoplegia of lower limb following nontraumatic subarachnoid hemorrhage affecting unspecified side
I69.853 Hemiplegia and hemiparesis following other cerebrovascular disease affecting right non-dominant side
I69.015 Cognitive social or emotional deficit following nontraumatic subarachnoid hemorrhage
I69.941 Monoplegia of lower limb following unspecified cerebrovascular disease affecting right dominant side
I69.042 Monoplegia of lower limb following nontraumatic subarachnoid hemorrhage affecting left dominant side
I69.812 Visuospatial deficit and spatial neglect following other cerebrovascular disease
I69.111 Memory deficit following nontraumatic intracerebral hemorrhage
I69.054 Hemiplegia and hemiparesis following nontraumatic subarachnoid hemorrhage affecting left non-dominant side
I69.392 Facial weakness following cerebral infarction
I69.214 Frontal lobe and executive function deficit following other nontraumatic intracranial hemorrhage
I69.351 Hemiplegia and hemiparesis following cerebral infarction affecting right dominant side
I69.869 Other paralytic syndrome following other cerebrovascular disease affecting unspecified side
I69.243 Monoplegia of lower limb following other nontraumatic intracranial hemorrhage affecting right non-dominant side
I69.890 Apraxia following other cerebrovascular disease
I69.193 Ataxia following nontraumatic intracerebral hemorrhage
I69.039 Monoplegia of upper limb following nontraumatic subarachnoid hemorrhage affecting unspecified side
I69.310 Attention and concentration deficit following cerebral infarction
I69.828 Other speech and language deficits following other cerebrovascular disease
I69.019 Unspecified symptoms and signs involving cognitive functions following nontraumatic subarachnoid hemorrhage
I69.222 Dysarthria following other nontraumatic intracranial hemorrhage
I69.234 Monoplegia of upper limb following other nontraumatic intracranial hemorrhage affecting left non-dominant side
I69.263 Other paralytic syndrome following other nontraumatic intracranial hemorrhage affecting right non-dominant side
I69.849 Monoplegia of lower limb following other cerebrovascular disease affecting unspecified side
I69.218 Other symptoms and signs involving cognitive functions following other nontraumatic intracranial hemorrhage
I69.90 Unspecified sequelae of unspecified cerebrovascular disease
I69.832 Monoplegia of upper limb following other cerebrovascular disease affecting left dominant side
I69.998 Other sequelae following unspecified cerebrovascular disease
I69.131 Monoplegia of upper limb following nontraumatic intracerebral hemorrhage affecting right dominant side
I69.920 Aphasia following unspecified cerebrovascular disease
I69.023 Fluency disorder following nontraumatic subarachnoid hemorrhage
I69.865 Other paralytic syndrome following other cerebrovascular disease, bilateral
I69.259 Hemiplegia and hemiparesis following other nontraumatic intracranial hemorrhage affecting unspecified side
I69.961 Other paralytic syndrome following unspecified cerebrovascular disease affecting right dominant side
I69.062 Other paralytic syndrome following nontraumatic subarachnoid hemorrhage affecting left dominant side
I69.063 Other paralytic syndrome following nontraumatic subarachnoid hemorrhage affecting right non-dominant side
I69.034 Monoplegia of upper limb following nontraumatic subarachnoid hemorrhage affecting left non-dominant side
I69.921 Dysphagia following unspecified cerebrovascular disease
I69.022 Dysarthria following nontraumatic subarachnoid hemorrhage
I69.864 Other paralytic syndrome following other cerebrovascular disease affecting left non-dominant side
I69.833 Monoplegia of upper limb following other cerebrovascular disease affecting right non-dominant side
I69.219 Unspecified symptoms and signs involving cognitive functions following other nontraumatic intracranial hemorrhage
I69.262 Other paralytic syndrome following other nontraumatic intracranial hemorrhage affecting left dominant side
I69.059 Hemiplegia and hemiparesis following nontraumatic subarachnoid hemorrhage affecting unspecified side
I69.223 Fluency disorder following other nontraumatic intracranial hemorrhage
I69.018 Other symptoms and signs involving cognitive functions following nontraumatic subarachnoid hemorrhage
I69.331 Monoplegia of upper limb following cerebral infarction affecting right dominant side
I69.254 Hemiplegia and hemiparesis following other nontraumatic intracranial hemorrhage affecting left non-dominant side
I69.311 Memory deficit following cerebral infarction
I69.891 Dysphagia following other cerebrovascular disease
I69.192 Facial weakness following nontraumatic intracerebral hemorrhage
I69.242 Monoplegia of lower limb following other nontraumatic intracranial hemorrhage affecting left dominant side
I69.215 Cognitive social or emotional deficit following other nontraumatic intracranial hemorrhage
I69.844 Monoplegia of lower limb following other cerebrovascular disease affecting left non-dominant side
I69.393 Ataxia following cerebral infarction
I69.239 Monoplegia of upper limb following other nontraumatic intracranial hemorrhage affecting unspecified side
I69.813 Psychomotor deficit following other cerebrovascular disease
I69.110 Attention and concentration deficit following nontraumatic intracerebral hemorrhage
I69.043 Monoplegia of lower limb following nontraumatic subarachnoid hemorrhage affecting right non-dominant side