Guidelines af 2011

3,623 views

Published on

Published in: Health & Medicine
  • Be the first to comment

Guidelines af 2011

  1. 1. Journal of the American College of Cardiology Vol. 57, No. 11, 2011© 2011 by the American College of Cardiology Foundation, the American Heart Association, Inc., ISSN 0735-1097/$36.00and the European Society of Cardiology doi:10.1016/j.jacc.2010.09.013Published by Elsevier Inc. PRACTICE GUIDELINES This guideline contains hyperlinks to recommendations and supporting text that have been updated by the “2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline)” (J Am Coll Cardiol 2011;57:223– 42; doi:10.1016/j.jacc.2010.10.001) and the “2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Update on Dabigatran)” (J Am Coll Cardiol 2011;57:1330 –7; doi:10.1016/j.jacc.2011.01.010). Updated sections are indicated in the Table of Contents and text. 2011 ACCF/AHA/HRS Focused Updates Incorporated Into the ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation A Report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines 2006 WRITING COMMITTEE MEMBERS Developed in partnership with the European Society of Cardiology and in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society Valentin Fuster, MD, PhD, FACC, FAHA, FESC, Co-Chair; Lars E. Rydén, MD, PhD, FACC, FAHA, FESC, Co-Chair; Davis S. Cannom, MD, FACC; Harry J. Crijns, MD, FACC, FESC*; Anne B. Curtis, MD, FACC, FAHA; Kenneth A. Ellenbogen, MD, FACC†; Jonathan L. Halperin, MD, FACC, FAHA; G. Neal Kay, MD, FACC; Jean-Yves Le Huezey, MD, FESC; James E. Lowe, MD, FACC; S. Bertil Olsson, MD, PhD, FESC; Eric N. Prystowsky, MD, FACC; Juan Luis Tamargo, MD, FESC; L. Samuel Wann, MD, MACC, FAHA, FESC 2011 WRITING GROUP MEMBERS Developed in partnership with the Heart Rhythm Society L. Samuel Wann, MD, MACC, FAHA, Chair‡; Anne B. Curtis, MD, FACC, FAHA‡§; Kenneth A. Ellenbogen, MD, FACC, FHRS†§; N.A. Mark Estes III, MD, FACC, FHRS ; Michael D. Ezekowitz, MB, ChB, FACC‡; Warren M. Jackman, MD, FACC, FHRS‡; Craig T. January, MD, PhD, FACC‡§;James E. Lowe, MD, FACC‡; Richard L. Page, MD, FACC, FHRS†; David J. Slotwiner, MD, FACC†; William G. Stevenson, MD, FACC, FAHA¶; Cynthia M. Tracy, MD, FACC‡*European Heart Rhythm Association Representative; †Heart Rhythm Society Representative; ‡ACCF/AHA Representative; §Recused from 2011 UpdateSection 8.1.8.3, Recommendations for Dronedarone; ACCF/AHA Task Force on Performance Measures Representative; ¶ACCF/AHA Task Force onPractice Guidelines Liaison; #Former Task Force member during this writing effort. The 2011 focused updates to this document were approved by the leadership of the American College of Cardiology Foundation, American HeartAssociation, and the Heart Rhythm Society, and the sections that have been updated are indicated with hyperlinks to the focused updates where applicable. The American College of Cardiology Foundation requests that this document be cited as follows: Fuster V, Rydén LE, Cannom DS, Crijns HJ, CurtisAB, Ellenbogen KA, Halperin JL, Kay GN, Le Heuzey J-Y, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann LS. 2011 ACCF/AHA/HRSfocused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the AmericanCollege of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2011;57:e101–98. This article has been copublished in Circulation. Copies: This document is available on the World Wide Web sites of the American College of Cardiology (www.cardiosource.org), the American HeartAssociation (www.my.americanheart.org). For copies of this document, please contact the Elsevier Inc. Reprint Department, fax (212) 633-3820, e-mailreprints@elsevier.com. Permissions: Modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of theAmerican College of Cardiology Foundation. Please contact Elsevier’s permission department at healthpermissions@elsevier.com.
  2. 2. e102 Fuster et al. JACC Vol. 57, No. 11, 2011 ACC/AHA/ESC Practice Guidelines March 15, 2011:e101–98 ACCF/AHA TASK FORCE MEMBERS Alice K. Jacobs, MD, FACC, FAHA, Chair; Jeffrey L. Anderson, MD, FACC, FAHA, Chair-Elect; Nancy Albert, PhD, CCNS, CCRN; Christopher E. Buller, MD, FACC#; Mark A. Creager, MD, FACC, FAHA; Steven M. Ettinger, MD, FACC; Robert A. Guyton, MD, FACC; Jonathan L. Halperin, MD, FACC, FAHA; Judith S. Hochman, MD, FACC, FAHA; Frederick G. Kushner, MD, FACC, FAHA; Erik Magnus Ohman, MD, FACC; William G. Stevenson, MD, FACC, FAHA; Lynn G. Tarkington, RN#; Clyde W. Yancy, MD, FACC, FAHA 6. Causes, Associated Conditions, Clinical TABLE OF CONTENTS Manifestations, and Quality of Life. . . . . . . . . . . .e118Preamble (UPDATED) . . . . . . . . . . . . . . . . . . . . . . . . . . . .e104 6.1. Causes and Associated Conditions . . . . . . . . . .e118 6.1.1. Reversible Causes of Atrial Fibrillation . . . .e1181. Introduction (UPDATED). . . . . . . . . . . . . . . . . . . . . . .e105 6.1.2. Atrial Fibrillation Without Associated Heart Disease . . . . . . . . . . . . . . . . . . . . . . . . .e118 1.1. Organization of Committee and 6.1.3. Medical Conditions Associated With Evidence Review (UPDATED) . . . . . . . . . . . . . . . .e105 Atrial Fibrillation . . . . . . . . . . . . . . . . . . . . . .e118 1.2. Contents of These Guidelines . . . . . . . . . . . . . . .e106 6.1.4. Atrial Fibrillation With Associated Heart Disease . . . . . . . . . . . . . . . . . . . . . . . . .e118 1.3. Changes Since the Initial Publication of 6.1.5. Familial (Genetic) Atrial Fibrillation . . . . . . . .e118 These Guidelines in 2001 . . . . . . . . . . . . . . . . . . .e107 6.1.6. Autonomic Influences in2. Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e107 Atrial Fibrillation . . . . . . . . . . . . . . . . . . . . . .e119 6.2. Clinical Manifestations . . . . . . . . . . . . . . . . . . . . .e119 2.1. Atrial Fibrillation . . . . . . . . . . . . . . . . . . . . . . . . . . .e107 6.3. Quality of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e120 2.2. Related Arrhythmias . . . . . . . . . . . . . . . . . . . . . . . .e107 7. Clinical Evaluation. . . . . . . . . . . . . . . . . . . . . . . . . . . .e1203. Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e107 7.1. Basic Evaluation of the Patient With4. Epidemiology and Prognosis . . . . . . . . . . . . . . . . . .e109 Atrial Fibrillation . . . . . . . . . . . . . . . . . . . . . . . . . . .e120 7.1.1. Clinical History and Physical Examination . . .e120 4.1. Prevalence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e109 7.1.2. Investigations . . . . . . . . . . . . . . . . . . . . . . . . .e120 4.2. Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e110 7.2. Additional Investigation of Selected Patients With Atrial Fibrillation . . . . . . . . . . . . . . . . . . . . . . .e120 4.3. Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e110 7.2.1. Electrocardiogram Monitoring and5. Pathophysiological Mechanisms. . . . . . . . . . . . . . .e111 Exercise Testing . . . . . . . . . . . . . . . . . . . . . . .e121 7.2.2. Transesophageal Echocardiography. . . . . . . .e122 5.1. Atrial Factors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e111 7.2.3. Electrophysiological Study . . . . . . . . . . . . . . .e122 5.1.1. Atrial Pathology as a Cause of 8. Management (UPDATED) . . . . . . . . . . . . . . . . . . . . . .e122 Atrial Fibrillation . . . . . . . . . . . . . . . . . . . . . .e111 5.1.1.1. PATHOLOGICAL CHANGES CAUSED BY 8.1. Pharmacological and Nonpharmacological ATRIAL FIBRILLATION .....................e112 Therapeutic Options . . . . . . . . . . . . . . . . . . . . . . . .e123 5.1.2. Mechanisms of Atrial Fibrillation . . . . . . . . .e112 5.1.2.1. AUTOMATIC FOCUS THEORY ................e112 8.1.1. Pharmacological Therapy . . . . . . . . . . . . . . . .e123 8.1.1.1. DRUGS MODULATING THE RENIN- 5.1.2.2. MULTIPLE-WAVELET HYPOTHESIS ...........e113 ANGIOTENSIN-ALDOSTERONE SYSTEM .......e123 5.1.3. Atrial Electrical Remodeling . . . . . . . . . . . . .e114 8.1.1.2. HMG COA-REDUCTASE 5.1.4. Counteracting Atrial INHIBITORS (STATINS) .....................e123 Electrical Remodeling . . . . . . . . . . . . . . . . . .e115 8.1.2. Heart Rate Control Versus 5.1.5. Other Factors Contributing to Rhythm Control . . . . . . . . . . . . . . . . . . . . . . .e123 Atrial Fibrillation . . . . . . . . . . . . . . . . . . . . . .e115 8.1.2.1. DISTINGUISHING SHORT-TERM AND 5.2. Atrioventricular Conduction . . . . . . . . . . . . . . . . .e115 LONG-TERM TREATMENT GOALS ............e123 5.2.1. General Aspects . . . . . . . . . . . . . . . . . . . . . . .e115 8.1.2.2. CLINICAL TRIALS COMPARING RATE CONTROL 5.2.2. Atrioventricular Conduction in Patients AND RHYTHM CONTROL ....................e124 With Preexcitation Syndromes . . . . . . . . . . .e116 8.1.2.3. EFFECT ON SYMPTOMS AND QUALITY OF LIFE .................................e125 5.3. Myocardial and Hemodynamic Consequences 8.1.2.4. EFFECTS ON HEART FAILURE ...............e125 of Atrial Fibrillation . . . . . . . . . . . . . . . . . . . . . . . . . .e116 8.1.2.5. EFFECTS ON 5.4. Thromboembolism . . . . . . . . . . . . . . . . . . . . . . . . . .e116 THROMBOEMBOLIC COMPLICATIONS ........e125 5.4.1. Pathophysiology of Thrombus Formation . . . .e117 8.1.2.6. EFFECTS ON MORTALITY 5.4.2. Clinical Implications . . . . . . . . . . . . . . . . . . .e118 AND HOSPITALIZATION ....................e125
  3. 3. JACC Vol. 57, No. 11, 2011 Fuster et al. e103March 15, 2011:e101–98 ACC/AHA/ESC Practice Guidelines 8.1.2.7. IMPLICATIONS OF THE RHYTHM-CONTROL 8.1.5.5.2. PROCAINAMIDE .............e147 VERSUS RATE-CONTROL STUDIES ...........e126 8.1.5.5.3. BETA BLOCKERS ............e147 8.1.3. Rate Control During Atrial 8.1.5.5.4. NONDIHYDROPYRIDINE CALCIUM Fibrillation (UPDATED) . . . . . . . . . . . . . . .e126 CHANNEL ANTAGONISTS 8.1.3.1. PHARMACOLOGICAL RATE CONTROL DURING (VERAPAMIL AND DILTIAZEM) ....e148 ATRIAL FIBRILLATION .....................e127 8.1.5.5.5. DIGOXIN....................e148 8.1.3.1.1. BETA BLOCKERS ............e127 8.1.5.5.6. DISOPYRAMIDE .............e148 8.1.3.1.2. NONDIHYDROPYRIDINE CALCIUM 8.1.5.5.7. SOTALOL ...................e148 CHANNEL ANTAGONISTS ......e129 8.1.6. Pharmacological Agents to Maintain 8.1.3.1.3. DIGOXIN....................e129 8.1.3.1.4. ANTIARRHYTHMIC AGENTS ...e129 Sinus Rhythm. . . . . . . . . . . . . . . . . . . . . . . . .e148 8.1.6.1. AGENTS WITH PROVEN EFFICACY TO 8.1.3.1.5. COMBINATION THERAPY ......e129 MAINTAIN SINUS RHYTHM .................e148 8.1.3.1.6. SPECIAL CONSIDERATIONS IN 8.1.6.1.1. AMIODARONE ...............e149 PATIENTS WITH THE WOLFF- 8.1.6.1.2. BETA BLOCKERS ............e149 PARKINSON-WHITE (WPW) 8.1.6.1.3. DOFETILIDE .................e150 SYNDROME .................e129 8.1.6.1.4. DISOPYRAMIDE .............e150 8.1.3.2. PHARMACOLOGICAL THERAPY TO CONTROL 8.1.6.1.5. FLECAINIDE .................e150 HEART RATE IN PATIENTS WITH BOTH ATRIAL 8.1.6.1.6. PROPAFENONE ..............e150 FIBRILLATION AND ATRIAL FLUTTER ..........e130 8.1.6.1.7. SOTALOL ...................e150 8.1.3.3. REGULATION OF ATRIOVENTRICULAR NODAL 8.1.6.2. DRUGS WITH UNPROVEN EFFICACY OR NO CONDUCTION BY PACING ..................e130 LONGER RECOMMENDED ..................e151 8.1.3.4. AV NODAL ABLATION ......................e130 8.1.6.2.1. DIGOXIN....................e151 8.1.4. Preventing Thromboembolism . . . . . . . . . . .e131 8.1.4.1. RISK STRATIFICATION .....................e132 8.1.6.2.2. PROCAINAMIDE .............e151 8.1.4.1.1. EPIDEMIOLOGICAL DATA......e132 8.1.6.2.3. QUINIDINE ..................e151 8.1.4.1.2. ECHOCARDIOGRAPHY AND 8.1.6.2.4. VERAPAMIL AND DILTIAZEM ....e151 RISK STRATIFICATION ........e133 8.1.7. Out-of-Hospital Initiation of Antiarrhythmic 8.1.4.1.3. THERAPEUTIC IMPLICATIONS ....e134 Drugs in Patients With Atrial Fibrillation . . . .e151 8.1.4.2. ANTITHROMBOTIC STRATEGIES FOR 8.1.8. Drugs Under Development . . . . . . . . . . . . . .e154 PREVENTION OF ISCHEMIC STROKE AND 8.1.8.1. ATRIOSELECTIVE AGENTS ..................e154 SYSTEMIC EMBOLISM .....................e135 8.1.8.2. NONSELECTIVE ION 8.1.4.2.1. ANTICOAGULATION WITH VITAMIN K CHANNEL–BLOCKING DRUGS ...............e154 ANTAGONIST AGENTS ..........e136 8.1.8.3. RECOMMENDATIONS FOR DRONEDARONE FOR 8.1.4.2.2. ASPIRIN FOR ANTITHROMBOTIC THE PREVENTION OF RECURRENT ATRIAL THERAPY IN PATIENTS WITH FIBRILLATION (NEW SECTION) ...............e154 ATRIAL FIBRILLATION..........e137 8.2. Direct-Current Cardioversion of Atrial 8.1.4.2.3. OTHER ANTIPLATELET AGENTS Fibrillation and Flutter . . . . . . . . . . . . . . . . . . . . . .e154 FOR ANTITHROMBOTIC 8.2.1. Terminology . . . . . . . . . . . . . . . . . . . . . . . . . .e155 THERAPY IN PATIENTS WITH 8.2.2. Technical Aspects . . . . . . . . . . . . . . . . . . . . .e155 ATRIAL FIBRILLATION.........e138 8.2.3. Procedural Aspects . . . . . . . . . . . . . . . . . . . . .e155 8.1.4.2.4. COMBINING ANTICOAGULANT 8.2.4. Direct-Current Cardioversion in Patients AND PLATELET-INHIBITOR THERAPY (UPDATED) .........e140 With Implanted Pacemakers 8.1.4.2.5. EMERGING AND INVESTIGATIONAL and Defibrillators . . . . . . . . . . . . . . . . . . . . . . .e156 ANTITHROMBOTIC AGENTS 8.2.5. Risks and Complications of Direct-Current (UPDATED) ..................e141 Cardioversion of Atrial Fibrillation . . . . . . . .e156 8.1.4.2.6. INTERRUPTION OF ANTICOAGULATION 8.2.6. Pharmacological Enhancement of FOR DIAGNOSTIC OR THERAPEUTIC Direct-Current Cardioversion . . . . . . . . . . . .e156 8.2.6.1. AMIODARONE ............................e157 PROCEDURES ................e141 8.2.6.2. BETA-ADRENERGIC ANTAGONISTS...........e158 8.1.4.3. NONPHARMACOLOGICAL APPROACHES TO 8.2.6.3. NONDIHYDROPYRIDINE CALCIUM PREVENTION OF THROMBOEMBOLISM CHANNEL ANTAGONISTS ...................e158 (UPDATED) ...............................e142 8.2.6.4. QUINIDINE ...............................e158 8.1.5. Cardioversion of Atrial Fibrillation . . . . . . . .e142 8.1.5.1. BASIS FOR CARDIOVERSION OF 8.2.6.5. TYPE IC ANTIARRHYTHMIC AGENTS .........e158 .....................e142 ATRIAL FIBRILLATION 8.2.6.6. TYPE III ANTIARRHYTHMIC AGENTS ..........e158 8.1.5.2. METHODS OF CARDIOVERSION .............e142 8.2.7. Prevention of Thromboembolism in 8.1.5.3. PHARMACOLOGICAL CARDIOVERSION .......e143 Patients With Atrial Fibrillation 8.1.5.4. AGENTS WITH PROVEN EFFICACY FOR Undergoing Cardioversion . . . . . . . . . . . . . . .e158 CARDIOVERSION OF ATRIAL FIBRILLATION .....e144 8.3. Maintenance of Sinus Rhythm. . . . . . . . . . . . . . .e160 8.1.5.4.1. AMIODARONE ...............e144 8.3.1. Pharmacological Therapy (UPDATED) . . .e160 8.1.5.4.2. DOFETILIDE .................e144 8.3.1.1. GOALS OF TREATMENT ....................e160 8.1.5.4.3. FLECAINIDE .................e144 8.3.1.2. ENDPOINTS IN ANTIARRHYTHMIC 8.1.5.4.4. IBUTILIDE ..................e145 DRUG STUDIES ...........................e160 8.1.5.4.5. PROPAFENONE ..............e146 8.3.1.3. PREDICTORS OF RECURRENT AF ............e161 8.1.5.5. LESS EFFECTIVE OR INCOMPLETELY STUDIED 8.3.1.4. CATHETER-BASED ABLATION THERAPY FOR AGENTS FOR CARDIOVERSION OF ATRIAL FIBRILLATION (NEW SECTION) .......e161 ATRIAL FIBRILLATION .....................e146 8.3.2. General Approach to Antiarrhythmic 8.1.5.5.1. QUINIDINE ..................e146 Drug Therapy . . . . . . . . . . . . . . . . . . . . . . . . .e161
  4. 4. e104 Fuster et al. JACC Vol. 57, No. 11, 2011 ACC/AHA/ESC Practice Guidelines March 15, 2011:e101–98 8.3.3. Selection of Antiarrhythmic Agents in expert analysis of the available data documenting absolute and Patients With Cardiac Diseases . . . . . . . . . .e162 relative benefits and risks of those procedures and therapies can 8.3.3.1. HEART FAILURE ..........................e162 8.3.3.2. CORONARY ARTERY DISEASE ..............e162 produce helpful guidelines that improve the effectiveness of care, 8.3.3.3. HYPERTENSIVE HEART DISEASE ............e162 optimize patient outcomes, and favorably affect the overall cost 8.3.4. Nonpharmacological Therapy for of care by focusing resources on the most effective strategies. Atrial Fibrillation . . . . . . . . . . . . . . . . . . . . . .e163 The American College of Cardiology Foundation (ACCF) 8.3.4.1. SURGICAL ABLATION ......................e163 and the American Heart Association (AHA) have jointly en- 8.3.4.2. CATHETER ABLATION ......................e163 8.3.4.2.1. COMPLICATIONS OF gaged in the production of such guidelines in the area of CATHETER-BASED ABLATION ...e164 cardiovascular disease since 1980. The ACC/AHA Task Force 8.3.4.2.2. FUTURE DIRECTIONS IN on Practice Guidelines, whose charge is to develop, update, or CATHETER-BASED ABLATION revise practice guidelines for important cardiovascular diseases THERAPY FOR ATRIAL and procedures, directs this effort. The Task Force is pleased to FIBRILLATION ...............e164 have this guideline developed in conjunction with the European 8.3.4.3. SUPPRESSION OF ATRIAL FIBRILLATION Society of Cardiology (ESC). Writing committees are charged THROUGH PACING ........................e165 8.3.4.4. INTERNAL ATRIAL DEFIBRILLATORS .........e165 with the task of performing an assessment of the evidence and acting as an independent group of authors to develop or update 8.4. Special Considerations . . . . . . . . . . . . . . . . . . . . .e166 written recommendations for clinical practice. 8.4.1. Postoperative AF . . . . . . . . . . . . . . . . . . . . . .e166 8.4.1.1. CLINICAL AND Experts in the subject under consideration have been selected PATHOPHYSIOLOGICAL CORRELATES ........e166 from all 3 organizations to examine subject-specific data and 8.4.1.2. PREVENTION OF POSTOPERATIVE AF ........e167 write guidelines. The process includes additional representatives 8.4.1.3. TREATMENT OF POSTOPERATIVE AF .........e167 from other medical practitioner and specialty groups when 8.4.2. Acute Myocardial Infarction . . . . . . . . . . . . .e168 appropriate. Writing committees are specifically charged to 8.4.3. Wolff-Parkinson White (WPW) Preexcitation Syndromes . . . . . . . . . . . . . . . .e168 perform a formal literature review, weigh the strength of 8.4.4. Hyperthyroidism . . . . . . . . . . . . . . . . . . . . . .e169 evidence for or against a particular treatment or procedure, and 8.4.5. Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . .e170 include estimates of expected health outcomes where data exist. 8.4.6. Hypertrophic Cardiomyopathy . . . . . . . . . . .e170 Patient-specific modifiers, comorbidities, and issues of patient 8.4.7. Pulmonary Diseases . . . . . . . . . . . . . . . . . . . .e171 preference that might influence the choice of particular tests or 8.5. Primary Prevention . . . . . . . . . . . . . . . . . . . . . . . . .e171 therapies are considered as well as frequency of follow-up and9. Proposed Management Strategies. . . . . . . . . . . . .e172 cost-effectiveness. When available, information from studies on cost will be considered; however, review of data on efficacy and 9.1. Overview of Algorithms for Management of clinical outcomes will constitute the primary basis for preparing Patients With Atrial Fibrillation . . . . . . . . . . . . .e172 recommendations in these guidelines. 9.1.1. Newly Discovered Atrial Fibrillation . . . . . .e172 The ACC/AHA Task Force on Practice Guidelines and the 9.1.2. Recurrent Paroxysmal Atrial Fibrillation . . .e172 ESC Committee for Practice Guidelines make every effort to 9.1.3. Recurrent Persistent Atrial Fibrillation . . . . .e173 9.1.4. Permanent Atrial Fibrillation . . . . . . . . . . . .e173 avoid any actual, potential, or perceived conflict of interest that might arise as a result of an outside relationship or personalAPPENDIX I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e174 interest of the writing committee. Specifically, all members of the Writing Committee and peer reviewers of the document areAPPENDIX II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e175 asked to provide disclosure statements of all such relationships that might be perceived as real or potential conflicts of interest.APPENDIX III. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e177 Writing committee members are also strongly encouraged to declare a previous relationship with industry that might beAPPENDIX IV (NEW SECTION) . . . . . . . . . . . . . . . . . . . .e178 perceived as relevant to guideline development. If a writing committee member develops a new relationship with industry during their tenure, they are required to notify guideline staff inReferences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e178 writing. The continued participation of the writing committee member will be reviewed. These statements are reviewed by thePreamble (UPDATED) For new or parent Task Force, reported orally to all members of the writing committee at each meeting, and updated and reviewed by theupdated text, view the 2011 Focused writing committee as changes occur. Please refer to the meth-Update and the 2011 Focused Update odology manuals for further description of the policies used inon Dabigatran. Text supporting guideline development, including relationships with industry,unchanged recommendations has not available online at the ACC, AHA, and ESC World Widebeen updated. Web sites (http://www.acc.org/clinical/manual/manual_ introltr.htm, http://circ.ahajournals.org/manual/, and http://It is important that the medical profession play a significant role www.escardio.org/knowledge/guidelines/Rules/). Please seein critically evaluating the use of diagnostic procedures and Appendix I for author relationships with industry and Appen-therapies as they are introduced and tested in the detection, dix II for peer reviewer relationships with industry that aremanagement, or prevention of disease states. Rigorous and pertinent to these guidelines.
  5. 5. JACC Vol. 57, No. 11, 2011 Fuster et al. e105March 15, 2011:e101–98 ACC/AHA/ESC Practice Guidelines These practice guidelines are intended to assist healthcare Association (EHRA) and the Heart Rhythm Society (HRS).providers in clinical decision making by describing a range of This document was reviewed by 2 official reviewers nomi-generally acceptable approaches for the diagnosis, manage- nated by the ACC, 2 official reviewers nominated by thement, and prevention of specific diseases and conditions. AHA, and 2 official reviewers nominated by the ESC, as wellThese guidelines attempt to define practices that meet the as by the ACCF Clinical Electrophysiology Committee, theneeds of most patients in most circumstances. These guide- AHA ECG and Arrhythmias Committee, the AHA Strokeline recommendations reflect a consensus of expert opinion Review Committee, EHRA, HRS, and numerous additionalafter a thorough review of the available, current scientific content reviewers nominated by the writing committee. Theevidence and are intended to improve patient care. If these document was approved for publication by the governingguidelines are used as the basis for regulatory/payer deci- bodies of the ACC, AHA, and ESC and officially endorsed bysions, the ultimate goal is quality of care and serving the the EHRA and the HRS.patient’s best interests. The ultimate judgment regarding care The ACC/AHA/ESC Writing Committee to Revise theof a particular patient must be made by the healthcare 2001 Guidelines for the Management of Patients With Atrialprovider and the patient in light of all of the circumstances Fibrillation conducted a comprehensive review of the rele-presented by that patient. There are circumstances in which vant literature from 2001 to 2006. Literature searches weredeviations from these guidelines are appropriate. conducted in the following databases: PubMed/MEDLINE The guidelines will be reviewed annually by the ACC/AHA and the Cochrane Library (including the Cochrane DatabaseTask Force on Practice Guidelines and the ESC Committee for of Systematic Reviews and the Cochrane Controlled TrialsPractice Guidelines and will be considered current unless they Registry). Searches focused on English-language sources andare updated, revised, or sunsetted and withdrawn from distribu- studies in human subjects. Articles related to animal experi-tion. The executive summary and recommendations are pub- mentation were cited when the information was important tolished in the August 15, 2006, issues of the Journal of the understanding pathophysiological concepts pertinent to pa-American College of Cardiology and Circulation and the August tient management and comparable data were not available16, 2006, issue of the European Heart Journal. The full-text from human studies. Major search terms included atrialguidelines are published in the August 15, 2006, issues of the fibrillation, age, atrial remodeling, atrioventricular conduc-Journal of the American College of Cardiology and Circulation tion, atrioventricular node, cardioversion, classification,and the September 2006 issue of Europace, as well as posted on clinical trial, complications, concealed conduction, cost-the ACC (www.acc.org), AHA (www.americanheart.org), andESC (www.escardio.org) World Wide Web sites. Copies of the effectiveness, defibrillator, demographics, epidemiology, ex-full-text guidelines and the executive summary are available perimental, heart failure (HF), hemodynamics, human, hy-from all 3 organizations. perthyroidism, hypothyroidism, meta-analysis, myocardial infarction, pharmacology, postoperative, pregnancy, pulmo- Sidney C. Smith Jr, MD, FACC, FAHA, FESC, Chair, nary disease, quality of life, rate control, rhythm control, ACC/AHA Task Force on Practice Guidelines risks, sinus rhythm, symptoms, and tachycardia-mediated Silvia G. Priori, MD, PhD, FESC, Chair, cardiomyopathy.The complete list of search terms is beyond ESC Committee for Practice Guidelines the scope of this section. Classification of Recommendations and Level of Evidence1. Introduction are expressed in the ACC/AHA/ESC format as follows and described in Table 1. Recommendations are evidence based and derived primarily from published data.1.1. Organization of Committee andEvidence Review (UPDATED) Classification of RecommendationsFor new or updated text, view the 2011 • Class I: Conditions for which there is evidence and/orFocused Update and the 2011 Update on general agreement that a given procedure/therapy is ben-Dabigatran. Text supporting unchanged eficial, useful, and effective.recommendations has not been updated. • Class II: Conditions for which there is conflicting evidenceAtrial fibrillation (AF) is the most common sustained cardiac and/or a divergence of opinion about the usefulness/rhythm disturbance, increasing in prevalence with age. AF is efficacy of performing the procedure/therapy.often associated with structural heart disease, although a X Class IIa: Weight of evidence/opinion is in favor ofsubstantial proportion of patients with AF have no detectable usefulness/efficacy.heart disease. Hemodynamic impairment and thromboem- X Class IIb: Usefulness/efficacy is less well established bybolic events related to AF result in significant morbidity, evidence/opinion.mortality, and cost. Accordingly, the American College of • Class III: Conditions for which there is evidence and/orCardiology (ACC), the American Heart Association (AHA), general agreement that a procedure/therapy is not useful orand the European Society of Cardiology (ESC) created a effective and in some cases may be harmful.committee to establish guidelines for optimum managementof this frequent and complex arrhythmia. Level of Evidence The committee was composed of members representing the The weight of evidence was ranked from highest (A) toACC, AHA, and ESC, as well as the European Heart Rhythm lowest (C), as follows:
  6. 6. e106 Fuster et al. JACC Vol. 57, No. 11, 2011 ACC/AHA/ESC Practice Guidelines March 15, 2011:e101–98TABLE 1. Applying Classification of Recommendations and Level of Evidence† (UPDATED) (see the 2011 Focused Update and the2011 Focused Update on Dabigatran) *Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as gender, age, history of diabetes, history of priormyocardial infarction, history of heart failure, and prior aspirin use. A recommendation with Level of Evidence B or C does not imply that the recommendation is weak.Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Even though randomized trials are not available, there maybe a very clear clinical consensus that a particular test or therapy is useful or effective. †In 2003, the ACC/AHA Task Force on Practice Guidelines developed a list of suggested phrases to use when writing recommendations. All guidelinerecommendations have been written in full sentences that express a complete thought, such that a recommendation, even if separated and presented apart fromthe rest of the document (including headings above sets of recommendations), would still convey the full intent of the recommendation. It is hoped that this willincrease readers’ comprehension of the guidelines and will allow queries at the individual recommendation level.• Level of Evidence A: Data derived from multiple random- potentially dangerous arrhythmia is then reviewed. This ized clinical trials or meta-analyses. includes prevention of AF, control of heart rate, prevention of• Level of Evidence B: Data derived from a single random- thromboembolism, and conversion to and maintenance of ized trial, or nonrandomized studies. sinus rhythm. The treatment algorithms include pharmaco-• Level of Evidence C: Only consensus opinion of experts, logical and nonpharmacological antiarrhythmic approaches, case studies, or standard-of-care. as well as antithrombotic strategies most appropriate for particular clinical conditions. Overall, this is a consensus1.2. Contents of These Guidelines document that attempts to reconcile evidence and opinionThese guidelines first present a comprehensive review of the from both sides of the Atlantic Ocean. The pharmacologicallatest information about the definition, classification, epide- and nonpharmacological antiarrhythmic approaches may in-miology, pathophysiological mechanisms, and clinical char- clude some drugs and devices that do not have the approvalacteristics of AF. The management of this complex and of all government regulatory agencies. Additional informa-
  7. 7. JACC Vol. 57, No. 11, 2011 Fuster et al. e107March 15, 2011:e101–98 ACC/AHA/ESC Practice Guidelinestion may be obtained from the package inserts when the drug P waves by rapid oscillations or fibrillatory waves that vary inor device has been approved for the stated indication. amplitude, shape, and timing, associated with an irregular, Because atrial flutter can precede or coexist with AF, frequently rapid ventricular response when atrioventricularspecial consideration is given to this arrhythmia in each (AV) conduction is intact (2) (Fig. 1). The ventricularsection. There are important differences in the mechanisms of response to AF depends on electrophysiological (EP) prop-AF and atrial flutter, and the body of evidence available to erties of the AV node and other conducting tissues, the levelsupport therapeutic recommendations is distinct for the 2 of vagal and sympathetic tone, the presence or absence ofarrhythmias. Atrial flutter is not addressed comprehensively accessory conduction pathways, and the action of drugs (3).in these guidelines but is addressed in the ACC/AHA/ESC Regular cardiac cycles (R-R intervals) are possible in theGuidelines on the Management of Patients with Supraven- presence of AV block or ventricular or AV junctionaltricular Arrhythmias (1). tachycardia. In patients with implanted pacemakers, diagno- sis of AF may require temporary inhibition of the pacemaker1.3. Changes Since the Initial Publication of to expose atrial fibrillatory activity (4). A rapid, irregular,These Guidelines in 2001 sustained, wide-QRS-complex tachycardia strongly suggestsIn developing this revision of the guidelines, the Writing AF with conduction over an accessory pathway or AF withCommittee considered evidence published since 2001 and underlying bundle-branch block. Extremely rapid rates (overdrafted revised recommendations where appropriate to incor- 200 beats per minute) suggest the presence of an accessoryporate results from major clinical trials such as those that pathway or ventricular tachycardia.compared rhythm-control and rate-control approaches tolong-term management. The text has been reorganized to 2.2. Related Arrhythmiasreflect the implications for patient care, beginning with AF may occur in isolation or in association with otherrecognition of AF and its pathogenesis and the general arrhythmias, most commonly atrial flutter or atrial tachycar-priorities of rate control, prevention of thromboembolism, dia. Atrial flutter may arise during treatment with antiarrhyth-and methods available for use in selected patients to correct mic agents prescribed to prevent recurrent AF. Atrial flutter inthe arrhythmia and maintain normal sinus rhythm. Advances the typical form is characterized by a saw-tooth pattern ofin catheter-based ablation technologies have been incorpo- regular atrial activation called flutter (ƒ) waves on the ECG,rated into expanded sections and recommendations, with the particularly visible in leads II, III, aVF, and V1 (Fig. 2). In therecognition that that such vital details as patient selection, untreated state, the atrial rate in atrial flutter typically rangesoptimum catheter positioning, absolute rates of treatment from 240 to 320 beats per minute, with ƒ waves inverted insuccess, and the frequency of complications remain incom- ECG leads II, III, and aVF and upright in lead V1. Thepletely defined. Sections on drug therapy have been con- direction of activation in the right atrium (RA) may bedensed and confined to human studies with compounds that reversed, resulting in ƒ waves that are upright in leads II, III,have been approved for clinical use in North America and/or and aVF and inverted in lead V1. Atrial flutter commonlyEurope. Accumulating evidence from clinical studies on the occurs with 2:1 AV block, resulting in a regular or irregularemerging role of angiotensin inhibition to reduce the occur- ventricular rate of 120 to 160 beats per minute (mostrence and complications of AF and information on ap- characteristically about 150 beats per minute). Atrial flutterproaches to the primary prevention of AF are addressed may degenerate into AF and AF may convert to atrial flutter.comprehensively in the text, as these may evolve further in The ECG pattern may fluctuate between atrial flutter and AF,the years ahead to form the basis for recommendations reflecting changing activation of the atria. Atrial flutter isaffecting patient care. Finally, data on specific aspects of usually readily distinguished from AF, but when atrial activ-management of patients who are prone to develop AF in ity is prominent on the ECG in more than 1 lead, AF may bespecial circumstances have become more robust, allowing misdiagnosed as atrial flutter (5).formulation of recommendations based on a higher level of Focal atrial tachycardias, AV reentrant tachycardias, andevidence than in the first edition of these guidelines. An AV nodal reentrant tachycardias may also trigger AF. In otherexample is the completion of a relatively large randomized atrial tachycardias, P waves may be readily identified and aretrial addressing prophylactic administration of antiarrhythmic separated by an isoelectric baseline in 1 or more ECG leads.medication for patients undergoing cardiac surgery. In devel- The morphology of the P waves may help localize the originoping the updated recommendations, every effort was made to of the tachycardias.maintain consistency with other ACC/AHA and ESC practiceguidelines addressing, for example, the management of pa- 3. Classificationtients undergoing myocardial revascularization procedures. Various classification systems have been proposed for AF.2. Definition One is based on the ECG presentation (2– 4). Another is based on epicardial (6) or endocavitary recordings or non-2.1. Atrial Fibrillation contact mapping of atrial electrical activity. Several clinicalAF is a supraventricular tachyarrhythmia characterized by classification schemes have also been proposed, but noneuncoordinated atrial activation with consequent deterioration fully accounts for all aspects of AF (7–10). To be clinicallyof atrial mechanical function. On the electrocardiogram useful, a classification system must be based on a sufficient(ECG), AF is characterized by the replacement of consistent number of features and carry specific therapeutic implications.
  8. 8. e108 Fuster et al. JACC Vol. 57, No. 11, 2011 ACC/AHA/ESC Practice Guidelines March 15, 2011:e101–98Figure 1. Electrocardiogram showing atrial fibrillation with a controlled rate of ventricular response. P waves are replaced by fibrillatorywaves and the ventricular response is completely irregular. Assorted labels have been used to describe the pattern of recommended in this document represents a consensus drivenAF, including acute, chronic, paroxysmal, intermittent, con- by a desire for simplicity and clinical relevance.stant, persistent, and permanent, but the vagaries of defini- The clinician should distinguish a first-detected episode oftions make it difficult to compare studies of AF or the AF, whether or not it is symptomatic or self-limited, recog-effectiveness of therapeutic strategies based on these desig- nizing that there may be uncertainty about the duration of thenations. Although the pattern of the arrhythmia can change episode and about previous undetected episodes (Fig. 3).over time, it may be of clinical value to characterize the When a patient has had 2 or more episodes, AF is consideredarrhythmia at a given moment. The classification scheme recurrent. If the arrhythmia terminates spontaneously, recur-Figure 2. Electrocardiogram showing typical atrial flutter with variable atrioventricular conduction. Note the saw-tooth pattern, F waves,particularly visible in leads II, III, and aVF, without an isoelectric baseline between deflections.
  9. 9. JACC Vol. 57, No. 11, 2011 Fuster et al. e109March 15, 2011:e101–98 ACC/AHA/ESC Practice Guidelines AF category due to aging or development of cardiac abnor- malities such as enlargement of the left atrium (LA. Then, the risks of thromboembolism and mortality rise accordingly. By convention, the term “nonvalvular AF” is restricted to cases in which the rhythm disturbance occurs in the absence of rheumatic mitral valve disease, a prosthetic heart valve, or mitral valve repair. 4. Epidemiology and Prognosis AF is the most common arrhythmia in clinical practice, accounting for approximately one-third of hospitalizations for cardiac rhythm disturbances. Most data regarding the epide- miology, prognosis, and quality of life in AF have beenFigure 3. Patterns of atrial fibrillation (AF). 1, Episodes that gen- obtained in the United States and western Europe. It has beenerally last 7 d or less (most less than 24 h); 2, episodes that estimated that 2.2 million people in America and 4.5 millionusually last longer than 7 d; 3, cardioversion failed or not at-tempted; and 4, both paroxysmal and persistent AF may be in the European Union have paroxysmal or persistent AFrecurrent. (12). During the past 20 y, there has been a 66% increase in hospital admissions for AF (13–15) due to a combination ofrent AF is designated paroxysmal; when sustained beyond factors including the aging of the population, a rising preva-7 d, AF is designated persistent. Termination with pharma- lence of chronic heart disease, and more frequent diagnosiscological therapy or direct-current cardioversion does not through use of ambulatory monitoring devices. AF is an ex-change the designation. First-detected AF may be either tremely costly public health problem (16,17), with hospitaliza-paroxysmal or persistent AF. The category of persistent AF tions as the primary cost driver (52%), followed by drugs (23%),also includes cases of long-standing AF (e.g., greater than consultations (9%), further investigations (8%), loss of work1 y), usually leading to permanent AF, in which cardioversion (6%), and paramedical procedures (2%). Globally, the annualhas failed or has not been attempted. cost per patient is close to €3000 (approximately U.S. $3600) These categories are not mutually exclusive in a particular (16). Considering the prevalence of AF, the total societal burdenpatient, who may have several episodes of paroxysmal AF is huge, for example, about €13.5 billion (approximately U.S.and occasional persistent AF, or the reverse. Regarding $15.7 billion) in the European Union.paroxysmal and persistent AF, it is practical to categorize agiven patient by the most frequent presentation. The defini- 4.1. Prevalencetion of permanent AF is often arbitrary. The duration of AF The estimated prevalence of AF is 0.4% to 1% in the generalrefers both to individual episodes and to how long the patient population, increasing with age (18,19). Cross-sectional stud-has been affected by the arrhythmia. Thus, a patient with ies have found a lower prevalence in those below the age ofparoxysmal AF may have episodes that last seconds to hours 60 y, increasing to 8% in those older than 80 y (Fig. 4)occurring repeatedly for years. (20 –22). The age-adjusted prevalence of AF is higher in men Episodes of AF briefer than 30 s may be important in (22,23), in whom the prevalence has more than doubled fromcertain clinical situations involving symptomatic patients, the 1970s to the 1990s, while the prevalence in women haspre-excitation or in assessing the effectiveness of therapeuticinterventions. This terminology applies to episodes of AF thatlast more than 30 s without a reversible cause. Secondary AFthat occurs in the setting of acute myocardial infarction (MI),cardiac surgery, pericarditis, myocarditis, hyperthyroidism,pulmonary embolism, pneumonia, or other acute pulmonarydisease is considered separately. In these settings, AF is notthe primary problem, and treatment of the underlying disorderconcurrently with management of the episode of AF usuallyterminates the arrhythmia without recurrence. Conversely,because AF is common, it may occur independently of aconcurrent disorder like well-controlled hypothyroidism, andthen the general principles for management of the arrhythmiaapply. Figure 4. Estimated age-specific prevalence of atrial fibrillation The term “lone AF” has been variously defined but (AF) based on 4 population-based surveys. Prevalence, age,generally applies to young individuals (under 60 y of age) distribution, and gender of patients with AF analysis and impli-without clinical or echocardiographic evidence of cardiopul- cations. Modified with permission from Feinberg WM, Blacks-monary disease, including hypertension (11). These patients hear JL, Laupacis A, et al. Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implica-have a favorable prognosis with respect to thromboembolism tions. Arch Intern Med 1995;155:469 –73 (19). Copyright © 1995,and mortality. Over time, patients may move out of the lone American Medical Association. All rights reserved.
  10. 10. e110 Fuster et al. JACC Vol. 57, No. 11, 2011 ACC/AHA/ESC Practice Guidelines March 15, 2011:e101–98remained unchanged (24). The median age of AF patients isabout 75 y. Approximately 70% are between 65 and 85 y old.The overall number of men and women with AF is aboutequal, but approximately 60% of AF patients over 75 y arefemale. Based on limited data, the age-adjusted risk ofdeveloping AF in blacks seems less than half that in whites(18,25,26). AF is less common among African-Americanthan Caucasian patients with heart failure (HF). In population-based studies, patients with no history ofcardiopulmonary disease account for fewer than 12% of allcases of AF (11,22,27,28). In some series, however, theobserved proportion of lone AF was over 30% (29,30). Figure 5. Incidence of atrial fibrillation in 2 American epidemio- logical studies. Framingham indicates the Framingham Heart These differences may depend on selection bias when Study. Data are from Wolf PA, Abbott RD, Kannel WB. Atrialrecruiting patients seen in clinical practice compared with fibrillation: a major contributor to stroke in the elderly. The Fra-population-based observations. In the Euro Heart Survey on mingham Study. Arch Intern Med 1987;147:1561– 4 (32). CHSAF (31), the prevalence of idiopathic AF amounted to 10%, indicates the Cardiovascular Health Study. Data are from Psaty BM, Manolio TA, Kuller LH, et al. Incidence of and risk factorswith an expected highest value of 15% in paroxysmal AF, for atrial fibrillation in older adults. Circulation 1997;96:2455– 6114% in first-detected AF, 10% in persistent AF, and only 4% (25); and Furberg CD, Psaty BM, Manolio TA, et al. Prevalencein permanent AF. Essential hypertension, ischemic heart of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). Am J Cardiol 1994;74:236 – 41 (22), and Farrell B, God-disease, HF (Table 2), valvular heart disease, and diabetes are win J, Richards S, et al. The United Kingdom transient isch-the most prominent conditions associated with AF (14). aemic attack (UK-TIA) aspirin trial: final results. J Neurol Neuro- surg Psychiatry 1991;54:1044 –54 (46).4.2. IncidenceIn prospective studies, the incidence of AF increases from associated with a reduced incidence of AF in patients withless than 0.1% per year in those under 40 y old to exceed 1.5% hypertension (41,42), although this may be confined to thoseper year in women and 2% in men older than 80 (Fig. 5) with left ventricular hypertrophy (LVH) (43– 45).(25,32,33). The age-adjusted incidence increased over a 30-yperiod in the Framingham Study (32), and this may have 4.3. Prognosisimplications for the future impact of AF (34). During 38 y of AF is associated with an increased long-term risk of strokefollow-up in the Framingham Study, 20.6% of men who devel- (47), HF, and all-cause mortality, especially in women (48).oped AF had HF at inclusion versus 3.2% of those without AF; The mortality rate of patients with AF is about double that ofthe corresponding incidences in women were 26.0% and 2.9% patients in normal sinus rhythm and linked to the severity of(35). In patients referred for treatment of HF, the 2- to 3-y underlying heart disease (20,23,33) (Fig. 6). About two-thirdsincidence of AF was 5% to 10% (25,36,37). The incidence of of the 3.7% mortality over 8.6 mo in the Etude en ActivitéAF may be lower in HF patients treated with angiotensin Libérale sur la Fibrillation Auriculaire Study (ALFA) wasinhibitors (38 – 40). Similarly, angiotensin inhibition may be attributed to cardiovascular causes (29). Table 3 shows a list of associated heart diseases in the population of the ALFATABLE 2. Prevalence of AF in Patients With Heart Failure as study (29).Reflected in Several Heart Failure TrialsPredominant Prevalence ofNYHA Class AF (%) StudyI 4 SOLVD–Prevention (1992)(14a)II-III 10 to 26 SOLVD–Treatment (1991) (14b) CHF-STAT (1995) (14c) MERIT-HF (1999) (14d) DIAMOND-CHF (1999) (501)II-IV 12 to 27 CHARM (2003) Val-HeFT (2003) (848)III-IV 20 to 29 Middlekauff (1991) (14e) Stevenson (1996) GESICA (1994) (14f)IV 50 CONSENSUS (1987) (14g) Figure 6. Relative risk of stroke and mortality in patients with AF indicates atrial fibrillation; NYHA, New York Heart Association; SOLVD, atrial fibrillation (AF) compared with patients without AF. SourceStudies Of Left Ventricular Dysfunction; CHF-STAT, Survival Trial of Antiarrhyth- data from the Framingham Heart Study (Kannel WB, Abbott RD,mic Therapy in Congestive Heart Failure; MERIT-HF, Metropolol CR/XL Ran- Savage DD, et al. Coronary heart disease and atrial fibrillation:domized Intervention Trial in Congestive Heart Failure; DIAMOND-CHF, Danish the Framingham Study. Am Heart J 1983;106:389 –96) (23), the Regional Heart Study and the Whitehall study (Flegel KM, Shi-Investigations of Arrhythmia and Mortality on Dofetilide–Congestive Heart pley MJ, Rose G. Risk of stroke in non-rheumatic atrial fibrilla-Failure; CHARM, Candesartan in Heart failure, Assessment of Reduction in tion), and the Manitoba study (Krahn AD, Manfreda J, Tate RB,Mortality and morbidity; Val-HeFT, Valsartan Heart Failure Trial; GESICA, Grupo et al. The natural history of atrial fibrillation: incidence, risk fac-Estudio de la Sobrevida en la Insufficienca Cardiaca en Argentina (V); and tors, and prognosis in the Manitoba Follow-Up Study. Am JCONSENSUS, Co-operative North Scandinavian Enalapril Survival Study. Med 1995;98:476 – 84) (33).
  11. 11. JACC Vol. 57, No. 11, 2011 Fuster et al. e111March 15, 2011:e101–98 ACC/AHA/ESC Practice GuidelinesTABLE 3. Demographics and Associated Conditions Among The rate of ischemic stroke among patients with nonval-Patients With Atrial Fibrillation in the ALFA Study vular AF averages 5% per year, 2 to 7 times that of people without AF (20,21,29,32,33,47) (Fig. 6). One of every 6 Recent- strokes occurs in a patient with AF (54). Additionally, when Total Paroxysmal Chronic Onset Population AF AF AF transient ischemic attacks (TIAs) and clinically “silent” strokes detected by brain imaging are considered, the rate ofNo. of patients 756 167 389 200 brain ischemia accompanying nonvalvular AF exceeds 7%Age, y 69 66 70 68 per year (35,55–58) In patients with rheumatic heart diseaseMale/female ratio 1 1 2 1 and AF in the Framingham Heart Study, stroke risk wasTime from first episode 47 39 66 NA increased 17-fold compared with age-matched controls (59),of AF (mo) and attributable risk was 5 times greater than that in thoseUnderlying heart disease (%) with nonrheumatic AF (21). In the Manitoba Follow-up Coronary artery disease 17 12 18 19 Study, AF doubled the risk of stroke independently of other Hypertensive heart disease 21 17 22 25 risk factors (33), and the relative risks for stroke in nonrheu- Valvular (rheumatic) 15 10 20 12 matic AF were 6.9% and 2.3% in the Whitehall and the Dilated cardiomyopathy 9 2 13 9 Regional Heart studies, respectively. Among AF patients Hypertrophic cardiomyopathy 5 3 4 9 from general practices in France, the Etude en Activité Other 9 14 9 7 Libérale sur le Fibrillation Auriculaire (ALFA) study found a None 29 46 23 28 2.4% incidence of thromboembolism over a mean of 8.6 moOther predisposing or of follow-up (29). The risk of stroke increases with age; in theassociated factors (%) Framingham Study, the annual risk of stroke attributable to Hyperthyroidism 3 4 2 5 AF was 1.5% in participants 50 to 59 y old and 23.5% in Hypertension 39 35 38 46 those aged 80 to 89 y (21). Bronchopulmonary disease 11 10 13 10 Diabetes 11 7 13 9 5. Pathophysiological Mechanisms Congestive HF 30 14 43 18 Prior embolic events 8 8 11 4Left atrial size (mm) 44 40 47 42 5.1. Atrial FactorsLeft ventricular ejection 59 63 57 58 5.1.1. Atrial Pathology as a Cause of Atrial Fibrillationfraction (%) The most frequent pathoanatomic changes in AF are atrial Persistent atrial fibrillation (AF) includes both recent-onset and chronic AF. fibrosis and loss of atrial muscle mass. Histological exami-Recent-onset AF was defined as persistent AF lasting greater than or equal to nation of atrial tissue of patients with AF has shown patchy7 and less than 30 d. Chronic AF was defined as persistent AF of more than fibrosis juxtaposed with normal atrial fibers, which may30-d duration. Patients in whom the diagnosis was definite and those in whom account for nonhomogeneity of conduction (60 – 62). Theit was probable were included. Modified with permission from Levy S, MaarekM, Coumel P, et al. Characterization of different subsets of atrial fibrillation in sinoatrial (SA) and AV nodes may also be involved, account-general practice in France: the ALFA Study, The College of French Cardiolo- ing for the sick sinus syndrome and AV block. It is difficultgists. Circulation 1999;99:3028 –35 (29). © 1999 American Heart Association. to distinguish between changes due to AF and those due to ALFA indicates Etude en Activité Libérale sur la Fibrillation Auriculaire; HF, associated heart disease, but fibrosis may precede the onset ofheart failure; and NA, not applicable or unavailable. AF (63). Biopsy of the LA posterior wall during mitral valve Mortality in the Veterans Administration Heart Failure surgery revealed mild to moderate fibrosis in specimensTrials (V-HeFT) was not increased among patients with obtained from patients with sinus rhythm or AF of relativelyconcomitant AF (49), whereas in the Studies of Left Ventric- short duration, compared with severe fibrosis and substantialular Dysfunction (SOLVD), mortality was 34% for those with loss of muscle mass in those from patients with long-standingAF versus 23% for patients in sinus rhythm (p less than AF. Patients with mild or moderate fibrosis responded more0.001) (50). The difference was attributed mainly to deaths successfully to cardioversion than did those with severedue to HF rather than to thromboembolism. AF was a strong fibrosis, which was thought to contribute to persistent AF inindependent risk factor for mortality and major morbidity in cases of valvular heart disease (64). In atrial tissue specimenslarge HF trials. In the Carvedilol Or Metoprolol European from 53 explanted hearts from transplantation recipients withTrial (COMET), there was no difference in all-cause mortality dilated cardiomyopathy, 19 of whom had permanent, 18in those with AF at entry, but mortality increased in those persistent, and 16 no documented AF, extracellular matrixwho developed AF during follow-up (51). In the Val-HeFT remodeling including selective downregulation of atrialcohort of patients with chronic HF, development of AF was insulin-like growth factor II mRNA-binding protein 2associated with significantly worse outcomes (40). HF pro- (IMP-2) and upregulation of matrix metalloproteinase 2motes AF, AF aggravates HF, and individuals with either (MMP-2) and type 1 collagen volume fraction (CVF-1) werecondition who develop the alternate condition share a poor associated with sustained AF (65).prognosis (52). Thus, managing the association is a major Atrial biopsies from patients undergoing cardiac surgerychallenge (53) and the need for randomized trials to investi- revealed apoptosis (66) that may lead to replacement of atrialgate the impact of AF on the prognosis in HF is apparent. myocytes by interstitial fibrosis, loss of myofibrils, accumu-
  12. 12. e112 Fuster et al. JACC Vol. 57, No. 11, 2011 ACC/AHA/ESC Practice Guidelines March 15, 2011:e101–98lation of glycogen granules, disruption of cell coupling at gap increase the extracellular matrix, especially during prolongedjunctions (67), and organelle aggregates (68). The concentra- periods of AF. Fibrosis is not the primary feature of AF-tion of membrane-bound glycoproteins that regulate cell-cell induced structural remodeling (95,96), although accumula-and cell-matrix interactions (disintegrin and metalloprotei- tion of extracellular matrix and fibrosis are associated withnases) in human atrial myocardium has been reported to more pronounced myocytic changes once dilation occurs duedouble during AF. Increased disintegrin and metalloprotei- to AF or associated heart disease (90,97). These changesnase activity may contribute to atrial dilation in patients with closely resemble those in ventricular myocytes in the hiber-long-standing AF. nating myocardium associated with chronic ischemia (98). Atrial fibrosis may be caused by genetic defects like lamin Among these features are an increase in cell size, perinuclearAC gene mutations (69). Other triggers of fibrosis include glycogen accumulation, loss of sarcoplasmic reticulum andinflammation (70) as seen in cardiac sarcoidosis (71) and sarcomeres (myolysis). Changes in gap junction distributionautoimmune disorders (72). In one study, histological and expression are inconsistent (61,99), and may be lesschanges consistent with myocarditis were reported in 66% of important than fibrosis or shortened refractoriness in promot-atrial biopsy specimens from patients with lone AF (62), but ing AF. Loss of sarcomeres and contractility seems to protectit is uncertain whether these inflammatory changes were a myocytes against the high metabolic stress associated withcause or consequence of AF. Autoimmune activity is sug- rapid rates. In fact, in the absence of other pathophysiologicalgested by high serum levels of antibodies against myosin factors, the high atrial rate typical of AF may cause ischemiaheavy chains in patients with paroxysmal AF who have no that affects myocytes more than the extracellular matrix andidentified heart disease (72). Apart from fibrosis, atrial interstitial tissues.pathological findings in patients with AF include amyloidosis Aside from changes in atrial dimensions that occur over(73,74), hemochromatosis (75), and endomyocardial fibrosis time, data on human atrial structural remodeling are limited(75,76). Fibrosis is also triggered by atrial dilation in any type (96,100) and difficult to distinguish from degenerativeof heart disease associated with AF, including valvular changes related to aging and associated heart disease (96).disease, hypertension, HF, or coronary atherosclerosis (77). One study that compared atrial tissue specimens from patientsStretch activates several molecular pathways, including the with paroxysmal and persistent lone AF found degenerativerenin-angiotensin-aldosterone system (RAAS). Both angio- contraction bands in patients with either pattern of AF, whiletensin II and transforming growth factor-beta1 (TGF-beta1) myolysis and mitochondria hibernation were limited to thoseare upregulated in response to stretch, and these molecules with persistent AF. The activity of calpain I, a proteolyticinduce production of connective tissue growth factor (CTGF) enzyme activated in response to cytosolic calcium overload,(70). Atrial tissue from patients with persistent AF undergo- was upregulated in both groups and correlated with ioning open-heart surgery demonstrated increased amounts of channel protein and structural and electrical remodeling.extracellular signal-regulated kinase messenger RNA (ERK- Hence, calpain activation may link calcium overload to2-mRNA), and expression of angiotensin-converting enzyme cellular adaptation in patients with AF (341).(ACE) was increased 3-fold during persistent AF (78). Astudy of 250 patients with AF and an equal number of 5.1.2. Mechanisms of Atrial Fibrillationcontrols demonstrated the association of RAAS gene poly- The onset and maintenance of a tachyarrhythmia require bothmorphisms with this type of AF (79). an initiating event and an anatomical substrate. With respect Several RAAS pathways are activated in experimental to AF, the situation is often complex, and available data(78,80 – 84) as well as human AF (78,85), and ACE inhibition support a “focal” mechanism involving automaticity or mul-and angiotensin II receptor blockade had the potential to tiple reentrant wavelets. These mechanisms are not mutuallyprevent AF by reducing fibrosis (84,86). exclusive and may at various times coexist in the same patient In experimental studies of HF, atrial dilation and interstitial (Fig. 7).fibrosis facilitates sustained AF (86 –92). The regional elec- 5.1.2.1. AUTOMATIC FOCUS THEORYtrical silence (suggesting scar), voltage reduction, and con- A focal origin of AF is supported by experimental models ofduction slowing described in patients with HF (93) are similar aconitine and pacing-induced AF (102,103) in which theto changes in the atria that occur as a consequence of aging. arrhythmia persists only in isolated regions of atrial myocar- AF is associated with delayed interatrial conduction and dium. This theory received minimal attention until the im-dispersion of the atrial refractory period (94). Thus, AF seems portant observation that a focal source for AF could beto cause a variety of alterations in the atrial architecture and identified in humans and ablation of this source couldfunction that contribute to remodeling and perpetuation of the extinguish AF (104). While PVs are the most frequent sourcearrhythmia. Despite these pathological changes in the atria, of these rapidly atrial impulses, foci have also been found inhowever, isolation of the pulmonary veins (PVs) will prevent the superior vena cava, ligament of Marshall, left posteriorAF in many such patients with paroxysmal AF. free wall, crista terminalis, and coronary sinus (79,104 –110).5.1.1.1. PATHOLOGICAL CHANGES CAUSED BY In histological studies, cardiac muscle with preservedATRIAL FIBRILLATION electrical properties extends into the PV (106,111–116), andJust as atrial stretch may cause AF, AF can cause atrial the primacy of PVs as triggers of AF has prompted substan-dilation through loss of contractility and increased compli- tial research into the anatomical and EP properties of theseance (61). Stretch-related growth mechanisms and fibrosis structures. Atrial tissue on the PV of patients with AF has
  13. 13. JACC Vol. 57, No. 11, 2011 Fuster et al. e113March 15, 2011:e101–98 ACC/AHA/ESC Practice Guidelines Figure 7. Posterior view of principal electro- physiological mechanisms of atrial fibrillation. A, Focal activation. The initiating focus (indicated by the star) often lies within the region of the pulmonary veins. The resulting wavelets repre- sent fibrillatory conduction, as in multiple-wavelet reentry. B, Multiple-wavelet reentry. Wavelets (indicated by arrows) randomly reenter tissue previously activated by the same or another wavelet. The routes the wavelets travel vary. Reproduced with permission from Konings KT, Kirchhof CJ, Smeets JR, et al. High-density mapping of electrically induced atrial fibrillation in humans. Circulation 1994;89:1665– 80 (101). LA indicates left atrium; PV, pulmonary vein; ICV, inferior vena cava; SCV, superior vena cava; and RA, right atrium.shorter refractory periods than in control patients or other For many years, the multiple-wavelet hypothesis was theparts of the atria in patients with AF (117,118). The refractory dominant theory explaining the mechanism of AF, but theperiod is shorter in atrial tissue in the distal PV than at the data presented above and from experimental (127a) andPV-LA junction. Decremental conduction in PV is more clinical (127b,127c) mapping studies challenge this notion.frequent in AF patients than in controls, and AF is more Even so, a number of other observations support the impor-readily induced during pacing in the PV than in the LA. This tance of an abnormal atrial substrate in the maintenance ofheterogeneity of conduction may promote reentry and form a AF. For over 25 y, EP studies in humans have implicatedsubstrate for sustained AF (119). Programmed electrical atrial vulnerability in the pathogenesis of AF (128 –132). Instimulation in PV isolated by catheter ablation initiated one study of 43 patients without structural heart disease, 18 ofsustained pulmonary venous tachycardia, probably as a con- whom had paroxysmal AF, the coefficient of dispersion ofsequence of reentry (120). Rapidly firing atrial automatic foci atrial refractoriness was significantly greater in the patientsmay be responsible for these PV triggers, with an anatomical with AF (128). Furthermore, in 16 of 18 patients with asubstrate for reentry vested within the PV. history of AF, the arrhythmia was induced with a single Whether the source for AF is an automatic focus or a extrastimulus, while a more aggressive pacing protocol wasmicroreentrant circuit, rapid local activation in the LA cannot required in 23 of 25 control patients without previouslyextend to the RA in an organized way. Experiments involving documented AF. In patients with idiopathic paroxysmal AF,acetylcholine-induced AF in Langendorf-perfused sheep widespread distribution of abnormal electrograms in the RAhearts demonstrated a dominant fibrillation frequency in the predicted development of persistent AF, suggesting an abnor-LA with decreasing frequency as activation progressed to the mal substrate (132). In patients with persistent AF who hadRA. A similar phenomenon has been shown in patients with undergone conversion to sinus rhythm, there was significantparoxysmal AF (121). Such variation in conduction leads to prolongation of intra-atrial conduction compared with adisorganized atrial activation, which could explain the ECG control group, especially among those who developed recur-appearance of a chaotic atrial rhythm (122). The existence of rent AF after cardioversion (130).triggers for AF does not negate the role of substrate modifi- Patients with a history of paroxysmal AF, even those withcation. In some patients with persistent AF, disruption of the lone AF, have abnormal atrial refractoriness and conductionmuscular connections between the PV and the LA may compared with patients without AF. An abnormal signal-terminate the arrhythmia. In others, AF persists following averaged P-wave ECG reflects slowed intra-atrial conductionisolation of the supposed trigger but does not recur after and shorter wavelengths of reentrant impulses. The resultingcardioversion. Thus, in some patients with abnormal triggers, increase in wavelet density promotes the onset and mainte-sustained AF may depend on an appropriate anatomical nance of AF. Among patients with HF, prolongation of the Psubstrate. wave was more frequent in those prone to paroxysmal AF5.1.2.2. MULTIPLE-WAVELET HYPOTHESIS (133). In specimens of RA appendage tissue obtained fromThe multiple-wavelet hypothesis as the mechanism of reen- patients undergoing open-heart surgery, P-wave duration wastrant AF was advanced by Moe and colleagues (123), who correlated with amyloid deposition (73). Because many ofproposed that fractionation of wavefronts propagating these observations were made prior to the onset of clinicalthrough the atria results in self-perpetuating “daughter wave- AF, the findings cannot be ascribed to atrial remodeling thatlets.” In this model, the number of wavelets at any time occurs as a consequence of AF. Atrial refractoriness increasesdepends on the refractory period, mass, and conduction with age in both men and women, but concurrent age-relatedvelocity in different parts of the atria. A large atrial mass with fibrosis lengthens effective intra-atrial conduction pathways.a short refractory period and delayed conduction increases the This, coupled with the shorter wavelengths of reentrantnumber of wavelets, favoring sustained AF. Simultaneous impulses, increases the likelihood that AF will developrecordings from multiple electrodes supported the multiple- (134,135). Nonuniform alterations of refractoriness and con-wavelet hypothesis in human subjects (127). duction throughout the atria may provide a milieu for the

×