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154Card Surgical Ablation of Atrial Fibrillation: Recommendationsr Patient Selection, Procedural Techniques, Patientanagement and Follow-up, Definitions, Endpoints, andesearch Trial Designreport of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation ofrial Fibrillation. Developed in partnership with the European Heart Rhythm Association (EHRA),registered branch of the European Society of Cardiology (ESC) and the European Cardiacrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC),erican Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and theciety of Thoracic Surgeons (STS). Endorsed by the governing bodies of the American College ofrdiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society,e European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heartythm Society, and the Heart Rhythm Society

gh Calkins, MD, FACC, FHRS, FAHA; Karl Heinz Kuck, MD, FESC; Riccardo Cappato, MD, FESC;sep Brugada, MD, FESC; A. John Camm, MD, PhD; Shih-Ann Chen, MD, FHRS;rry J.G. Crijns, MD, PhD, FESC; Ralph J. Damiano, Jr., MD; D. Wyn Davies, MD, FHRS;hn DiMarco, MD, PhD, FACC, FHRS; James Edgerton, MD, FACC, FACS, FACCP;nneth Ellenbogen, MD, FHRS; Michael D. Ezekowitz, MD; David E. Haines, MD, FHRS;chel Haissaguerre, MD; Gerhard Hindricks, MD; Yoshito Iesaka, MD; Warren Jackman, MD, FHRS;se Jalife, MD, FHRS; Pierre Jais, MD; Jonathan Kalman, MD; David Keane, MD;ung-Hoon Kim, MD, PhD; Paulus Kirchhof, MD; George Klein, MD; Hans Kottkamp, MD;ichiro Kumagai, MD, PhD; Bruce D. Lindsay, MD, FHRS; Moussa Mansour, MD;ncis E. Marchlinski, MD; Patrick M. McCarthy, MD; J. Lluis Mont, MD, FESC; Fred Morady, MD;onlawee Nademanee, MD; Hiroshi Nakagawa, MD, PhD, Andrea Natale, MD, FHRS;anley Nattel, MD; Douglas L. Packer, MD, FHRS; Carlo Pappone, MD, PhD;ic Prystowsky, MD, FHRS; Antonio Raviele, MD, FESC; Vivek Reddy, MD; Jeremy N. Ruskin, MD;chard J. Shemin, MD; Hsuan-Ming Tsao, MD; David Wilber, MDTS RepresentativePHRS RepresentativeCC RepresentativeHA Representative

SK FORCE MEMBERS:airs:gh Calkins, MD, FACC, FHRS, FAHA, Chair, Johns Hopkins Hospital, Maryland, USArl Heinz Kuck, MD, FESC, Co-Chair, Allgemeines Krankenhaus St. Georg, Hamburg, GERMANYccardo Cappato, MD, FESC, Co-Chair, Arrhythmia and EP Center, IRCCS Policlinico San Donato, Milan,ALY

ction Chairs:rial Fibrillation: Definitions, Mechanisms, and Rationale for AblationShih-Ann Chen, MD, FHRS,ipei Veterans General Hospital, TAIWAN7-5271/$ -see front matter 2012 Heart Rhythm Society, the European Heart Rhythm Association a registered branch of the European Society ofdiology, and the European Cardiac Arrhythmia Society. All rights reserved. doi:10.1016/j.hrthm.2011.12.016

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633Calkins et al HRS/EHRA/ECAS Catheter and Surgical Ablationdications for Ablation and Patient SelectionEric N. Prystowsky, MD, FHRS, The Care Group, LLC,diana, USAchniques and Endpoints for Atrial FibrillationKarl Heinz Kuck, MD, FESC, Allgemeines Krankenhaus. Georg, Hamburg, GERMANYchnologies and ToolsAndrea Natale, MD, FHRS, Texas Cardiac Arrhythmia Institute at St. Davidsdical Center, Texas, USAher Technical AspectsDavid E. Haines, MD, FHRS, Chair, William Beaumont Hospital, Michigan,Allow-up Considerations and Definitions for SuccessFrancis E. Marchlinski, MD, Hospital of theiversity of Pennsylvania, Pennsylvania, USAtcomes and Efficacy of Catheter Ablation of Atrial FibrillationHugh Calkins, MD, FACC, FHRS, FAHA,hns Hopkins Hospital, Maryland, USAmplications of Atrial Fibrillation Ablation: Definitions, Incidence, Prevention and ManagementWyn Davies, MD, FHRS, St. Marys Hospital, Imperial College Healthcare NHS Trust, London, UNITEDNGDOMining Requirements and CompetenciesBruce D. Lindsay, MD, FHRS, Cleveland Clinic Foundation,io, USArgical Ablation of Atrial FibrillationRalph Damiano, Jr., MD, Washington University School ofdicine, Missouri, USAnical Trial ConsiderationsDouglas L. Packer, MD, FHRS, Mayo Foundation, Minnesota, USA

-Authors:sep Brugada, MD, FESC, Hospital Clinic, University of Barcelona, SPAINJohn Camm, MD, PhD, St. Georges University of London, London, UNITED KINGDOMrry J.G. Crijns, MD, PhD, FESC, University Hospital Maastricht, THE NETHERLANDShn DiMarco, MD, University of Virginia Health System, Virginia, USAmes Edgerton, MD, FACC, FACS, FACCP, The Heart Hospital Baylor Plano and Cardiopulmonarysearch, Science, and Technology Institute, Texas, USAnneth Ellenbogen, MD, Virginia Commonwealth University, Virginia, USAchael D. Ezekowitz, MD, Jefferson Medical College, Pennsylvania, USAchel Haissaguerre, MD, Universit De Bordeaux, Hpital Cardiologique, FRANCErhard Hindricks, MD, University of Leipzig, Leipzig, GERMANYshito Iesaka, MD, Tsuchiura Kyodo Hospital, JAPANrren M. Jackman, MD, FHRS, University of Oklahoma Health Science Center, Oklahoma, USA

erre Jais, MD, Universit De Bordeaux, Hpital Cardiologique, FRANCEse Jalife, MD, University of Michigan, Michigan, USAnathan Kalman, MD, Royal Melbourne Hospital, Melbourne, AUSTRALIAvid Keane, MD, St. Vincents University Hospital, Dublin, IRELANDung-Hoon Kim, MD, PhD, Korea University Medical Center, Seoul, KOREAulus Kirchhof, MD, University of Birmingham Centre for Cardiovascular Sciences, Birmingham,ITED KINGDOM, and Department of Cardiology, University of Mnster, Mnster, GERMANYorge Klein, University Hospital, London, Ontario, CANADAns Kottkamp, MD, FESC, Clinic Hirslanden Zurich, SWITZERLANDichiro Kumagai, MD, PhD, Fukuoka Sanno Hospital, JAPANussa Mansour, MD, Massachusetts General Hospital, Massachusetts, USAncis Marchlinski, MD, Hospital of the University of Pennsylvania, Ohio, USAtrick McCarthy, MD, Northwestern Memorial Hospital, Illinois, USA

Lluis Mont, MD, FESC Hospital Clinic, University of Barcelona, SPAIN





























































































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634 Heart Rhythm, Vol 9, No 4, April 2012Including CFAEs, Dominant Frequency,Nests, and Rotors.............................................653

5.14. Strategies for Mapping and Ablationof Linear Ablation Lines Including LeftAtrial Flutter ....................................................653

5.15. Strategies, Tools, and Endpoints forCreation of Linear Ablation Lesionsincluding Mitral Isthmus Block ......................654

6. OTHER TECHNICAL ASPECTS...........................6566.1. Anticoagulation Strategies to Prevent

Thromboembolism During and FollowingAF Ablation .....................................................656

This article is copublished in EP Europace and Journal of Interven-al Cardiovascular Electrophysiology (JICE). The Heart Rhythm Soci-requests that this document be cited as follows: Calkins H, Brugada J,pato R, et al. 2012 HRS/EHRA/ECAS Expert Consensus Statement onheter and Surgical Ablation of Atrial Fibrillation: Recommendations forient Selection, Procedural Techniques, Patient Management and Fol--up, Definitions, Endpoints, and Research Trial Design. Copies: Thisument is available on the World Wide Web sites of the Heart Rhythmociation (www.hrsonline.org), the European Heart Rhythm Associationw.escardio.org/communities/EHRA), and the European Cardiac Ar-

thmia Society (www.ecas-cardiology.org). For copies of this document,ase contact Sonja Olson at the Heart Rhythm [email protected]. Permissions: Modification, alteration, enhancement,/or distribution of this document are not permitted without the expressmission of the Heart Rhythm Society, the European Heart Rhythmd Morady, MD, University of Michigan Health Syonlawee Nademanee, MD, Pacific Rim EP Researcroshi Nakagawa, MD, PhD, University of Oklahomanley Nattel, MD, Montreal Heart Institute, Quebrlo Pappone, MD, PhD, Maria Cecilia Hospital, Cotonio Raviele, MD, FESC, Umberto I Hospital, Ve

vek Reddy, MD, Mount Sinai School of Medicine,remy N. Ruskin, MD, Massachusetts General Hospchard J. Shemin, MD, David Geffen School of Meduan-Ming Tsao, MD, National Yang Ming Universivid Wilber, MD, FHRS, Loyola University Medical

BLE OF CONTENTS

. INTRODUCTION ....................................................635

. ATRIAL FIBRILLATION: DEFINITIONS,MECHANISMS, AND RATIONALE FORABLATION ..............................................................6362.1. Definitions........................................................6362.2. Mechanisms of Atrial Fibrillation...................6372.3. Multiple Wavelet Hypothesis..........................6382.4. Focal Triggers..................................................6392.5. Electrophysiology of the Pulmonary Veins....6402.6. Frequency Gradients in Atrial Fibrillation

Organization.....................................................6402.7. Cardiac Autonomic Nervous System and

Triggered Spontaneous Pulmonary VeinFiring......................................................................641

2.8. Electrophysiologic Basis for CatheterAblation of Atrial Fibrillation.........................642

2.9. Rationale for Eliminating Atrial Fibrillationwith Ablation ...................................................643

2.10. Mechanisms of Recurrence FollowingCatheter or Surgical AF Ablation...................644

2.11. Demographic Profile of AF Patients andRisk Factors for Development of AF .............644

2.12. Genetics of AF: Relevance to AF ..................644

WORDS Atrial fibrillation; Catheter ablation; Surgical ablation (Heartociation or the European Cardiac Arrhythmia Society., Michigan, USAtitute Center, California, USAalth Sciences Center, Oklahoma, USAANADAla, ITALYITALYYork, USAMassachusetts, USAat UCLA, California, USA

ospital, TAIWANer, Illinois, USA

. INDICATIONS FOR CATHETER ANDSURGICAL ABLATION OF ATRIALFIBRILLATION.............................................................645

. TECHNIQUES AND ENDPOINTS FORATRIAL FIBRILLATION ABLATION .................6474.1. Historical Considerations ................................6474.2. Ablation Approaches Targeting the

Pulmonary Veins .............................................6474.3. Ablation Approaches Not Targeting the

Pulmonary Veins .............................................6474.4. Task Force Consensus.....................................648

. TECHNOLOGIES AND TOOLS............................6495.1. Energy SourcesRadiofrequency Energy......6495.2. Contact Force Sensing Catheters and Systems.......6505.3. Energy SourcesCryoablation Energy ..........6505.4. Ultrasound and Laser Ablation Systems ........6505.5. Multielectrode Circumferential Ablation

Catheters ..........................................................6505.6. Electroanatomic Mapping Systems.................6515.7. Robotic and Magnetic Catheter Navigation ...6515.8. Intracardiac Echocardiography........................6515.9. Pulmonary Vein Venography..........................651

5.10. CT and/or MRI Scans and RotationalAngiography to Define the Anatomy of theAtrium, PVs, and Antrum ...............................652

5.11. Assessment of Left Atrial Volume .................6525.12. MR Imaging of Atrial Fibrosis and

Ablation Lesions..............................................6526.2. Screening Transesophageal Echocardiography.......656

















































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635Calkins et al HRS/EHRA/ECAS Catheter and Surgical Ablation6.3. Systemic Anticoagulation Prior toAF Ablation .....................................................656

6.4. Intracardiac Ultrasound and CT to Screenfor Left Atrial Thrombus ................................657

6.5. Intra-Procedural Anticoagulation ....................6576.6. Post-Procedural Anticoagulation.....................6576.7. Anesthesia/Sedation During Ablation.............6586.8. Esophageal Monitoring....................................658

. FOLLOW-UP CONSIDERATIONS .......................6597.1. ECG Monitoring Pre and Post Procedure ......6597.2. Available Methods for Arrhythmia

Monitoring .......................................................6597.3. Follow-up and Monitoring Guidelines for

Routine Clinical Care ......................................6607.4. Early Recurrence of Atrial Fibrillation...........6607.5. Atrial Tachycardias after Atrial Fibrillation

Ablation............................................................6607.6. Antiarrhythmic and Other Drug Therapy

Post Ablation ...................................................6637.7. Repeat Atrial Fibrillation Ablation

Procedures........................................................6647.8. Autonomic Alterations ....................................6647.9. Very Late Recurrence (more than one year)

after Atrial Fibrillation Ablation.....................6647.10. Anticoagulation Considerations Two or

More Months Post Ablation............................664

. OUTCOMES AND EFFICACY OF CATHETERABLATION OF ATRIAL FIBRILLATION...............6658.1. Overview..........................................................6658.2. Published Literature Review: Randomized

Clinical Trials ..................................................6668.3. Published Literature Review: Nonrandomized

Clinical Trials ...............................................................6668.4. Published Literature Review: Survey Results.........6678.5. Outcomes of AF Ablation in Patient

Populations Not Well Represented in ClinicalTrials ................................................................667

8.6. Outcomes of Cryoballoon Ablation ................6688.7. Long-Term Efficacy of Catheter Ablation

of Atrial Fibrillation ........................................6698.8. Summary of the Efficacy of Catheter

Ablation of Atrial Fibrillation.........................6698.9. Impact of Catheter Ablation of Atrial

Fibrillation on Quality of Life ........................6698.10. Impact of Catheter Ablation of Atrial

Fibrillation on LA Size and Function.............6708.11. Predictors of Success Following AF

Ablation............................................................6708.12. Cost-Effectiveness of AF Ablation.................670

. COMPLICATIONS OF CATHETER ABLATIONOF ATRIAL FIBRILLATION .....................................6719.1. Overview..........................................................6719.2. Cardiac Tamponade.........................................671

9.3. Pulmonary Vein Stenosis ................................674 Su9.4. Injury to the Esophagus and Peri-EsophagealVagal Nerves.........................................................675

9.5. Phrenic Nerve Injury .......................................6769.6. Stroke, TIA, and Silent Microemboli .............6779.7. Air Embolism ..................................................6789.8. Vascular Complications...................................6789.9. Acute Coronary Artery Occlusion ..................679

9.10. Radiation Exposure During CatheterAblation of Atrial Fibrillation.........................679

9.11. Pericarditis .......................................................6799.12. Mitral Valve Trauma and Circular Catheter

Entrapment.............................................................6799.13. Mortality Risk of AF Ablation .......................680

. TRAINING REQUIREMENTS ANDCOMPETENCIES ....................................................68010.1. Overview..........................................................68010.2. Appropriate Selection of Patients ...................68010.3. Anatomy of the Atria and Adjacent

Structures .........................................................68010.4. Conceptual Knowledge of Strategies to

Ablate Atrial Fibrillation.................................68010.5. Technical Competence ....................................68110.6. Recognition, Prevention, and Management

of Complications..............................................68110.7. Appropriate Follow-up and Long-Term

Management.....................................................682

. SURGICAL ABLATION OF ATRIALFIBRILLATION.......................................................68211.1. Development of the Cox-Maze Procedure .....68211.2. New Surgical Ablation Technology................68211.3. Surgical Atrial Fibrillation Ablation

Concomitant to Other Heart Operations.........68311.4. Stand-alone Operations for Atrial

Fibrillation........................................................68511.5. Surgical Ablation of AF: Summary and

Current Indications ..........................................686

. CLINICAL TRIAL CONSIDERATIONS...............68612.1. Overview..........................................................68612.2. Investigational Studies: Current and Future ...68712.3. Mortality Trials................................................68712.4. Multicenter Outcomes Trials...........................68712.5. Industry-Sponsored Device Approval

Studies..............................................................68712.6. Ablation Registry Studies................................68812.7. Standards for Reporting Outcomes in

Clinical Trials ..................................................689

. CONCLUSION.........................................................689

Introductionring the past decade, catheter ablation of atrial fibrillationF) has evolved rapidly from an investigational procedureits current status as a commonly performed ablationcedure in many major hospitals throughout the world.rgical ablation of AF, using either standard or minimally

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636 Heart Rhythm, Vol 9, No 4, April 2012asive techniques, is also performed in many major hos-als throughout the world.In 2007, an initial Consensus Statement on Catheter andrgical AF Ablation was developed as a joint effort of theart Rhythm Society, the European Heart Rhythm Asso-tion, and the European Cardiac Arrhythmia Society.e1e 2007 document was also developed in collaboration withSociety of Thoracic Surgeons and the American College of

rdiology. Since the publication of the 2007 document, theres been much learned about AF ablation, and the indications

these procedures have changed. Therefore the purpose ofs 2012 Consensus Statement is to provide a state-of-the-artiew of the field of catheter and surgical ablation of AF andreport the findings of a Task Force, convened by the Heartythm Society, the European Heart Rhythm Association, andEuropean Cardiac Arrhythmia Society and charged with

fining the indications, techniques, and outcomes of this pro-ure. Included within this document are recommendations

rtinent to the design of clinical trials in the field of AFlation, including definitions relevant to this topic.This statement summarizes the opinion of the Task Forcembers based on an extensive literature review as well as theirn experience. It is directed to all health care professionals whoinvolved in the care of patients with AF, particularly those whoundergoing, or are being considered for, catheter or surgical

ation procedures for AF. This statement is not intended toommend or promote catheter ablation of AF. Rather the ulti-te judgment regarding care of a particular patient must be madethe health care provider and patient in light of all the circum-nces presented by that patient.In writing a consensus document, it is recognized that con-sus does not mean that there was complete agreement amongTask Force members. Surveys of the entire Task Force wered to identify areas of consensus and also to develop recom-ndations concerning the indications for catheter and surgicalablation. The grading system for indication level of class of

dence was adapted based on that used by the American CollegeCardiology and the American Heart Association.e2 However, itimportant to state that this document is not a guideline. Theications for catheter and surgical ablation of AF are presentedth a class and grade of recommendation to be consistent withat the reader is used to seeing in guideline statements. A Classecommendation means that the benefits of the AF ablationcedure markedly exceed the risks, and that AF ablation shouldperformed. A Class IIa recommendation means that the bene-of an AF ablation procedure exceed the risks, and that it is

sonable to perform AF ablation. A Class IIb recommendationans that the benefit of AF ablation is greater or equal to thes, and that AF ablation may be considered. A Class III rec-mendation means that AF ablation is of no proven benefit andot recommended.The committee reviewed and ranked evidence supporting

rrent recommendations with the weight of evidence rankedLevel A if the data were derived from multiple randomizednical trials or meta-analyses (of selected studies) or selected

ta-analyses. The committee ranked available evidence as sidvel B when data were derived from a single randomized trialnonrandomized studies. Evidence was ranked as Level Cen the primary source of the recommendation was consen-

opinion, case studies, or standard of care. For certainnditions for which inadequate data are available, recommen-tions are based on expert consensus and clinical experienced ranked as Level C.The main objective of this document is to improve pa-nt care by providing a foundation of knowledge for thoseolved with catheter ablation of AF. It is recognized thats field continues to evolve rapidly. As this document wasing prepared, further clinical trials of catheter and surgicallation of AF were underway.The Task Force writing group was composed of expertsresenting seven organizations: the American College ofrdiology (ACC), the American Heart Association (AHA),Asia Pacific Heart Rhythm Society (APHRS), the Euro-

an Cardiac Arrhythmia Society (ECAS), the European Heartythm Association (EHRA), the Society of Thoracic Sur-ons (STS), and the Heart Rhythm Society (HRS). All mem-rs of the Task Force, as well as peer reviewers of thecument, were asked to provide disclosure statements for allationships that might be perceived as real or potential con-ts of interest. These tables are shown at the end of this

cument. Despite a large number of authors, the participationseveral societies and professional organizations, and the

empts of the group to reflect the current knowledge in theld adequately, this document is not intended as a guideline.ther, the group would like to refer to the current guidelinesAF managemente3,e4 for the purpose of guiding overall AFnagement strategies. This Consensus Document is specifi-ly focused on catheter and surgical ablation of AF, whichrecognize is relevant for only a small portion of the pop-

tion affected by AF.

Atrial fibrillation: definitions,echanisms, and rationale for ablation1. Definitions

is a common supraventricular arrhythmia that is characterizedchaotic contraction of the atrium. An electrocardiogram (ECG)ording is necessary to diagnose AF. Any arrhythmia that hasECG characteristics of AF and lasts sufficiently long for a

-lead ECG to be recorded, or at least 30 seconds on a rhythmp, should be considered an AF episode.e1,e3 The diagnosisuires an ECG or rhythm strip demonstrating: 1) absolutelygular RR intervals (in the absence of complete AV block), 2)distinct P waves on the surface ECG, and 3) an atrial cyclegth (when visible) that is usually variable and less than 200.e3 Although there are several classification systems for AF, fors consensus document, we have adopted in large part the clas-cation system that was developed by the ACC/AHA/ESC 2006idelines for the Management of Patients with Atrial Fibrillation

the ESC 2010 Guidelines for the Management of Atrialrillation.e2,e3,e5 We recommend that this classification systemused for future studies of catheter and surgical ablation of AF.Every patient who presents with AF for the first time is con-

ered to have first diagnosed AF, irrespective of the duration of

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637Calkins et al HRS/EHRA/ECAS Catheter and Surgical Ablationarrhythmia. Paroxysmal AF is defined as recurrent AF (2sodes) that terminates spontaneously within 7 days (Table 1).rsistent AF is defined as recurrent AF that is sustained for 7s. In addition, we recommend that patients with continuous AFo undergo cardioversion within 7 days be classified as havingoxysmal AF if the cardioversion is performed within 48 hoursAF onset, and persistent AF if the cardioversion is performedre than 48 hours after AF onset. A third category of AF isngstanding persistent AF that is defined as continuous AF ofater than one-years duration. The term permanent AF is de-ed as AF in which the presence of the AF is accepted by theient (and physician). Within the context of any rhythm controltegy, including catheter ablation, the term permanent AF is notaningful. The term permanent AF represents a joint decision bypatient and a physician to cease further attempts to restore/or maintain sinus rhythm at a particular point in time. It is

portant, therefore, to recognize that the term permanent AFresents a therapeutic attitude on the part of a patient and theysician rather than any inherent pathophysiological attribute ofAF. Such decisions may change as symptoms, the efficacy of

rapeutic interventions, and patient and physician preferenceslve. If after reevaluation, a rhythm control strategy is recom-nded, the AF should be redesignated as paroxysmal, persistent,longstanding persistent AF.e2 Silent AF is defined as asymp-atic AF often diagnosed by an opportune ECG or rhythm

p. Any of the above mentioned types of AF may be silent (ie,mptomatic). It is recognized that a particular patient may haveepisodes that fall into one or more of these categories.e2 It is

ommended that patients be categorized by their most frequenttern of AF during the six months prior to performance of anation procedure.It is recognized by the consensus Task Force that these

finitions of AF are very broad, and that when describing apulation of patients undergoing AF ablation, additional de-ls should be provided. This is especially important when

le 1 Types and classification of atrial fibrillation**

ial FibrillationEpisode

An atrial fibrillation episode is defined asleast 30 seconds, or if less than 30 seconThe presence of subsequent episodes of Abetween AF episodes.

oxysmal AF* Paroxysmal AF is defined as recurrent AFEpisodes of AF of 48 hours duration thshould also be classified as paroxysmal AF

sistent AF* Persistent AF is defined as continuous AFdecision is made to electrically or pharmato 7 days, should also be classified as per

gstandingPersistent AF

Longstanding persistent AF is defined as

manent AF The term permanent AF is not appropriateof AF, as it refers to a group of patientsrhythm by any means, including catheterpermanent AF is to undergo catheter or s

*It is recognized that patients may have both paroxysmal and persistent AF. A pmonths of an ablation procedure. Continuous AF is AF that is documented toe recommend that the term chronic AF not be used in the context of patinition of this term.nsidering the category of persistent AF and longstanding drirsistent AF. Pathophysiologically oriented classifications of, such as recently proposed, and reporting of concomitantdiovascular diseases will help in this regard.e6 Investigatorsurged to specify the duration of time patients have spent in

ntinuous AF prior to an ablation procedure, and also tocify whether patients undergoing AF ablation have previ-

sly failed pharmacologic therapy, electrical cardioversion,d/or catheter ablation. Shown in Table 1 are a series offinitions for types of AF that can be used for future trials of

ablation and also in the literature to help standardize re-rting of patient populations and outcomes.

2. Mechanisms of atrial fibrillationr many years, three major schools of thought competed toplain the mechanism(s) of AF: multiple random propa-ting wavelets, focal electrical discharges, and localizedntrant activity with fibrillatory conduction.e7e11 Consid-ble progress has been made in defining the mechanismsinitiation and perpetuation of AF.e12e14 Perhaps the mostiking breakthrough was the recognition that, in a subset oftients, AF was triggered by a rapidly firing focus anduld be cured with a localized catheter ablationcedure.e12,e13 This landmark observation compelled thehythmia community to refocus its attention on the pul-nary veins (PVs) and the posterior wall of the left atrium

A), as well as the autonomic innervation in that regiongure 1). It also reinforced the concept that the develop-nt of AF requires a trigger and an anatomic or func-nal substrate capable of both initiation and perpetuationAF.In this section of the document, a contemporary understand-of the mechanisms of AF is summarized. As illustrated inure 2, some authorse15e17 have proposed that, in the pres-

ce of an appropriate heterogeneous AF substrate, a focalger can result in sustained high frequency reentrant AF

at is documented by ECG monitoring and has a duration of atpresent continuously throughout the ECG monitoring tracing.ires that sinus rhythm be documented by ECG monitoring

isodes) that terminates spontaneously within 7 days.terminated with electrical or pharmacologic cardioversiondes.s sustained beyond seven days. Episodes of AF in which acally cardiovert the patient after 48 hours of AF, but priort AF episodes.uous AF of greater than 12 months duration.

e context of patients undergoing catheter or surgical ablationch a decision has been made not to restore or maintain sinusgical ablation. If a patient previously classified as havingablation, the AF should be reclassified.

AF type should be defined as the most frequent type of AF experienced withinent on all ECG monitoring performed during a defined period of time.dergoing ablation of AF as it is ambiguous, and there is no standardizedree

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638 Heart Rhythm, Vol 9, No 4, April 2012rgo spatially distributed fragmentation and give rise to fibril-ory conduction.e7,e8,e1821 Evidence suggests that when highquency atrial activation is maintained for at least 24 hours,

channel remodeling changes the electrophysiologicstrate,e8,e19,e21 promoting sustained reentry and increasingactivity of triggers, further contributing to AF permanence.

stained high rates in the atrium and/or the presence of heartease are associated with structural remodeling of the atriad alter the substrate even furthere21 and help to perpetuate. AF can also be the result of preexisting atrial disease.

though much has been learned about the mechanisms of AF,y remain incompletely understood. Because of this, it is not

t possible to precisely tailor an ablation strategy to a partic-r AF mechanism in the great majority of AF patients.3. Multiple wavelet hypothesistil the mid to late 1980s, the multiple wavelet hypothesisAF was widely accepted as the dominant AF mecha-

m.e22 This hypothesis was developed by Moe and col-

ure 1 Structure and mechanisms of atrial fibrillation. A: Schematic drascular fibers onto the PVs can be appreciated. Shown in yellow are the fiverior left GP, anterior right GP, inferior right GP, and ligament of Marshal

t have connections to the atria. Also shown in blue is the vein and ligamensuperior PV and the left atrial appendage. B: The large and small reentr

ations of PV (red) and also the common sites of origin of non-PV triggersAF. (Adapted from Circulation,e28 Am J Cardiol,e735 Tex Heart Inst J.e736gues and subsequently confirmed by experimental frark.e23 According to this hypothesis, AF results from thesence of multiple independent wavelets occurring simul-eously and propagating randomly throughout the left andht atria. This model suggests that the number of waveletsany point in time depends on the atrial conduction veloc-, refractory period, and excitable mass. Perpetuation of

requires the presence of a minimum number of co-isting wavelets and is favored by slowed conduction,rtened refractory periods, and increased atrial mass. En-

nced spatial dispersion of refractoriness promotes perpet-tion by heterogeneous conduction delay and block. It istable that the development of the surgical Maze proce-re was predicated on this model of AF and the conceptt maintenance of AF needs a critical number of circulat-

wavelets, each of which requires a critical excitabless of atrial tissue.e24 However, experimental and clinicalults suggest that, while AF maintenance by randomlypagating wavelets may occur in some cases, atrial re-

f the left and right atria as viewed from the posterior. The extension ofleft atrial autonomic ganglionic plexi (GP) and axons (superior left GP,n in blue is the coronary sinus, which is enveloped by muscular fibers

rshall, which travels from the coronary sinus to the region between theelets that play a role in initiating and sustaining AF. C: The commonin green). D: Composite of the anatomic and arrhythmic mechanismswo

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639Calkins et al HRS/EHRA/ECAS Catheter and Surgical Ablationdomly. Rather, as demonstrated in the atria of the dog,ial fibrillation cycle length (AFCL) is significantlyrter in the LA compared with the right atrium, and ana in the posterior LA is consistently found to have therter AFCL.e25

4. Focal triggersissaguerre and colleagues are credited with making thedmark observation that AF is often triggered by a focalrce, and that ablation of that focal trigger can eliminate.e12e14 This observation was reported in a series of threenuscripts. An initial series of three patients who under-nt successful catheter ablation of AF was published in94.e12 In each of these patients, AF was determined tose from a focal source. The successful treatment ofse three patients with catheter ablation suggested that ine patients, AF may result from a focal trigger and that

lation of this trigger could eliminate AF. It is notable thator research in an animal model had demonstrated that AF

ure 2 Focal triggers leading to initiation of reentry. Schematic drawingtors). Eventually, atrial remodeling leads to additional focal triggers and puld be induced by local administration of aconitine that imgered a rapid focal atrial tachycardia (AT).e26 This typefocal AF also was shown to be cured by isolation of thee of the aconitine-induced focal AT from the remainder of

atria. In a subsequent report on 45 patients with frequentg-refractory episodes of AF, Haissaguerre and col-guese27 found that a purely right-sided linear ablationproach resulted in an extremely low long-term successe. These investigators also found that linear lesions wereen arrhythmogenic due to gaps in the ablation lines, andt many patients were ultimately cured with ablation of agle rapidly firing ectopic focus. These ectopic foci werend at the orifices of the left or right superior PVs or nearsuperior vena cava (SVC). The latter observation led

se investigators to systematically attempt cure of parox-al AF by mapping and ablating individual foci of ecto-activity.e12e14 Many of these foci were found well intoPVs, outside of the cardiac silhouette, where myocardial

eves are known to extend.e14 These observations of the

ustrates the manner in which focal triggers lead to initiation of reentrytion of reentry.trigofsitthedruleaapratoftthasinfouthetheysmpicthesle

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640 Heart Rhythm, Vol 9, No 4, April 2012en confirmed by others. Thus, it is now well establishedt the PVs appear to be a crucial source of triggers thattiate AF.

5. Electrophysiology of the pulmonary veinsthan and Eliakime28 are credited with first drawing atten-n to the presence of sleeves of cardiac tissue that extendto the PVs (Figure 1). However, investigation of theatomic and electrophysiologic properties of the PVs re-ined limited, until the importance of PV triggers in the

velopment of AF was appreciated. There is now generalreement that myocardial muscle fibers extend from the

into all the PVs for 1 to 3 cm; the thickness of thescular sleeve is highest at the proximal ends (11.5 mm)

d then gradually decreases distally.e11,e29,e30PV focal firing may trigger AF or act as a rapid driver tointain the arrhythmia. The mechanisms of this focalng are incompletely understood. The location of thecursors of the conduction system is defined, during em-ological development of the heart, by the looping pro-s of the heart tube.e31,e32 Cell markers common to pre-

rsors of specialized conduction tissue derived from theart tube have been found within myocardial sleeves.e33e presence of P cells, transitional cells, and Purkinje cellss been demonstrated in human PVs.e34,e35 PV-sleeve car-myocytes have discrete ion channel and action potentialperties that predispose them to arrhythmogenesis.e34,e35ey have small background IK1, which could favor spon-eous automaticity,e34 as could their reduced coupling toial tissue, a property common to pacemaking structur-e36 Other work shows susceptibility to Ca2-dependenthythmia mechanisms,e37 possibly due to cells of melano-te origin.e38 Isolated cardiomyocytes from rabbit and ca-e PVs show abnormal automaticity and triggered activity

ring manipulations that enhance Ca2-loading.e37e39ese properties may explain the electrical activity withinPVs that is commonly observed after electrical discon-

ction of the PVs from the atrium.e40Other studies have provided evidence to suggest that thes and the posterior LA are also preferred sites for reen-nt arrhythmias.e16,e41 One important factor may be therter action potential duration of the PVs versus atriume34

e to larger delayed-rectifier K-currents and smaller in-rd Ca2-currents in PV.e39,e42 In addition, PVs demon-ate conduction abnormalities that promote reentry due torupt changes in fiber orientation as well as Na-channelctivation by reduced resting potentials due to small.

e34,e41 Yet another study examined the impact of in-asing atrial pressure on PV activation, finding that as LAssure was increased above 10 cm H2O, the LAPVction became the source of dominant rotors.e43 These

servations help explain the clinical link between AF andreased atrial pressure. Several clinical studies have re-rted shorter refractory periods inside PVs compared to the, decremental conduction inside PVs, and easy inductionPV reentry with premature stimulation from the PVs.

cordingly, rapid reentrant activity with entrainment phe- damenon have been described inside PVs after successfullmonary vein isolation (PVI).e44,e45 Electrophysiologicaluation of the PVs using a multielectrode basket catheters revealed effective refractory period heterogeneity andisotropic conduction properties within the PV and at theLA junction, which can provide a substrate for reen-.e46 The response of PV activity to adenosine administrationpatients with paroxysmal AF is more consistent with antrant than a focal ectopic type of mechanism.e47,e48 Indition, dominant-frequency analysis points to an evolu-n of mechanisms in AF patients, with PV sources becom-

less predominant as AF becomes more persistent andial remodeling progresses.e44 There is considerable evi-nce for a role of autonomic regulation in AF occurrence,d the location of autonomic ganglia close to the PVsgests a contribution of their specific innervation to PV

hythmogenesis and the beneficial effects of PV ablationcedures.e49,e50

6. Frequency gradients in atrial fibrillationganizationnumber of experimental and clinical studies have ap-

ared over the last several years demonstrating the impor-ce of the local atrial activation rate (cycle length) in theintenance of AF,e47,e49,e51e54 the role of atrial remodel-in the perpetuation of AF,e19e21 the importance of wave-

ak and reentry in the posterior LA,e53,e55 and the existencea hierarchical organization and left-to-right gradients of thectrical excitation frequency.e47,e48,e51,e52,e54 In addition, op-al mapping studies in animals have confirmed that thebulent electrical activity seen by electrogram (EGM)ordings of the atria during AF may in some cases be

plained by fibrillatory conduction from a single or a smallmber of rapidly spinning sources in the LA.e16,e56 At thecellular level, the high density of autonomic plexi and

rves on the posterior wall of the LA and its greater densityinward rectifier potassium channelse57 provide a reason-le explanation for the shorter refractory periods in thation and for the hierarchical distribution of dominantquency gradients that characterize AF. It was recentlymonstrated that in sinus rhythm there are intra-atrialterogeneities in the repolarizing currents. Chronic AFcreases ITo1 and IKur differentially in each atrium andreases IKs in both atria, an effect that further promotesntry and likely contributes to the perpetuation of thehythmia.The above studies offer mechanistic rationale for thepiric observation by clinical electrophysiologists thatLA is the region that seems to harbor the AF sources in thejority of patients. They also afford an explanation for the

ed for circumferential and linear ablation, as well as otheratomic approaches that not only include the PVs but alsoarge portion of the LA. Inclusion of the atrial myocar-m in ablation strategies is particularly important in pa-

nts with persistent AF, who in fact represent the vastjority of patients presenting with this arrhythmia. Recentta in persistent AF patients provide compelling evidence

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641Calkins et al HRS/EHRA/ECAS Catheter and Surgical Ablationt the sources are in fact reentrant and located outside ofPVs. Other studies in patients have used power spectral

alysis and mapping to localize dominant frequency sitesactivation.e48 They demonstrated that in paroxysmal AFtients, the PV ostial region does harbor the highest fre-ency sites, and AF can be terminated successfully bygeting radiofrequency (RF) ablation to those sites in up to% of patients.e48,e58 However, in longstanding persistent

patients, it is rare to find dominant frequency sites at theregion, and this agrees well with the relatively poor

cess rate of RF ablation in such patients. The data sug-st that in patients with longstanding persistent AF, atrial

odeling somehow augments the number of AF driversd shifts their location away from the PV/ostial region.

7. Cardiac autonomic nervous system andggered spontaneous pulmonary vein firingtonomic input to the atria arises from both the central

tonomic nervous system (pre-ganglionic) and the intrinsicdiac autonomic nervous system (ANS).e59,e60 The intrin-cardiac ANS includes clusters of ganglia, known as

tonomic ganglionated plexi (GP), located in specific epi-dial fat pads and within the ligament of Marshall. The GPeive input from the central (extrinsic) ANS and containerent neurons, post-ganglionic efferent parasympatheticd sympathetic neurons, and numerous interconnectingurons that provide communication within and between

GP. In animal models, stimulating the vagosympatheticnk (vagus nerve) allows AF to sustain but requirescing or other stimuli to initiate AF.e61,e62 In contrast,mulating the GP produces repetitive short bursts of rapid,egular firing in the adjacent PV, initiating sustained.e63 The focal firing in the PVs has a pause-dependent

tiation pattern and produces EGMs that are very similar topattern of firing recorded in the PVs of patients with

roxysmal AF.e64 Focal firing in the PVs by GP stimulationuires both sympathetic and parasympathetic activity.e65e67rasympathetic stimulation shortens the action potentialration (and effective refractory period) in atrial and PVocytes, and sympathetic stimulation increases calciumding and automaticity. Combined, they cause pause-in-ced early after depolarizations (EADs) and triggered ac-ity in PV and atrial myocytes. The mechanism of trig-red firing may relate to the combination of a very shortion potential duration and increased calcium release dur-systole, leading to high intracellular calcium during and

er repolarization. These observations suggest that theh calcium concentration may activate the sodium/cal-m exchanger, leading to a net inward current, EADs andgered firing.e62,e65,e68 Compared to atrial myocytes, PVocytes have a shorter action potential duration andater sensitivity to autonomic stimulation, which may

plain the predominance of focal firing in PVs in patientsth paroxysmal AF and the interruption of focal firing bylation of the autonomic GP.e69 Interruption of nervesm the GP to the PVs may explain, at least in part, the

quent elimination of focal firing within the PVs produced noPVI procedures.e70,e71 These findings suggest that inter-tion of nerves from the GP may have a role in thecess of PVI procedures and may explain the success ofly ablation studies targeting only the GP in patients with

roxysmal AF.e70,e71 Regeneration of those axons may con-ute to late recurrence of AF after PVI.e72,e73 Ablation of the

rve cell bodies, by targeting the GP, may permanently de-rvate the PVs. The addition of GP ablation to PVI appears tosynergistic, because each of these procedures is currentlyomplete: all GP tissue cannot be localized for ablation bycurrent endocardial stimulation techniques; and PVI pro-ures are frequently associated with late reconnection to the

ium.e74,e75A relationship has been observed between autonomic

activity and complex fractionated atrial EGMsFAEs). The location of the GP can be identified as sitesociated with transient AV block during high frequencyctrical stimulation (HFS, 20 Hz).e76,e77 The GP arensistently located within areas of CFAEs.e78 Stimulat-

the GP by HFS or the injection of acetylcholine intoat pad containing a GP produces CFAEs in the samea as recorded during AF.e76,e78 e80 Sequential ablationmultiple (four or more) GP in animal models and in

tients with paroxysmal or persistent AF reduces orminates all CFAEs, and decreases or eliminates theucibility of AF.e79 e81 AF persisting after GP ablationically shows more organized atrial EGMs with longer

cle lengths.e80 These changes in EGM patterns withuential ablation of GP are similar to the progressivewing and organization of EGMs during the stepwiselation technique performed in patients with longstandingrsistent AF.e81e84 The relationship between CFAE and

activity may also explain the varied success reported forAE ablation. Studies describing high success with CFAE

lation show ablation sites concentrated in areas close toGP,e82 while studies describing poor success generallyw a widespread pattern of ablation sites.e84 The latterdies may have inadvertently targeted the peripheralAE sites, leaving the GP largely intact.Several recent observations in animal models may haveinfluence on AF therapy in the future. GP activity mayy a role in the electrical remodeling produced by rapidial pacing. Shortening of the refractory period in the atriad PVs and the inducibility of AF produced in short-termdels of rapid atrial pacing are facilitated by GP stimula-n and blocked by GP ablation.e85,e86Another recent finding is the inhibition of GP activity

d PV firing by low-level stimulation of the vagosympa-tic trunk.e87 A loss of responsiveness of the GP to central

gal stimulation in older patients may help to explain theiking increase in the prevalence of AF in elderly people.erapeutic implications include the possibility that chronic-level stimulation of the vagosympathetic trunk may

lp suppress AF in patients with paroxysmal AF. Althoughse data suggest a potentially important role of the auto-

mic nervous system in the development of AF, as well as

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642 Heart Rhythm, Vol 9, No 4, April 2012ole of autonomic modulation in the treatment of AF, it isportant to recognize that definitive proof is lacking, as itnot possible to ablate autonomic ganglia without alsolating atrial myocardium.8. Electrophysiologic basis for catheterlation of atrial fibrillations well accepted that the development of AF requires bothrigger and a susceptible substrate. The goals of AF abla-n procedures are to prevent AF by either eliminating theger that initiates AF or altering the arrhythmogenic sub-

ate. The most commonly employed ablation strategy to-y, which involves the electrical isolation of the PVs byation of circumferential lesions around the right and the

ure 3 Schematic of common lesion sets employed in AF ablation. A: Tund the right and the left PVs. The primary endpoint of this ablation strategys of linear ablation lesions. These include a roof line connecting the lesiral valve and the lesion encircling the left PVs at the level of the left infor right circumferential lesion to the mitral annulus anteriorly. A linear le

ced in patients who have experienced cavotricuspid isthmus dependent atrshows additional linear ablation lesions between the superior and inferi

wing for electrical isolation of the posterior left atrial wall. An encirclingC is also shown. SVC isolation is performed if focal firing from the SVC

e of the most common sites of ablation lesions when complex fractionaapted from Circulation,e28 Am J Cardiol,e735 Tex Heart Inst J.e736)t PV ostia, probably impacts both the trigger and sub- forate of AF (Figure 3).e88e91 In particular, this approachks to electrically isolate the PVs, which are the most

mmon site of triggers for AF. Other less common triggeres for AF, including the vein and ligament of Marshalld the posterior LA wall, are also encompassed by thision set. The circumferential lesions may also alter thehythmogenic substrate by elimination of tissue locatedar the atrialPV junction that provides a substrate forntrant circuits that may generate or perpetuate AF, and/orreduction of the mass of atrial tissue needed to sustainntry. The circumferential lesion set may interrupt sym-

thetic and parasympathetic innervation from the auto-mic ganglia that have been identified as potential triggers

mferential ablation lesions that are created in a circumferential fashionelectrical isolation of the PV musculature. B: Some of the most commonircling the left and/or right PVs, a mitral isthmus line connecting the, and an anterior linear lesion connecting either the roof line or theated at the cavotricuspid isthmus is also show. This lesion is generally

er clinically or have it induced during EP testing. C: Similar to 3B butresulting in a figure of 8 lesion set as well as a posterior inferior lineof the superior vena cava (SVC) directed at electrical isolation of thedemonstrated. A subset of operators empirically isolates the SVC. D:

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643Calkins et al HRS/EHRA/ECAS Catheter and Surgical Ablationrticular challenge for the ablation of longstanding persis-t AF.e93,e94Recurrences of all types of AF following an initiallycessful AF ablation procedure result from PV reconnec-

n. It is extremely unusual to find no evidence of return ofconduction at the time of repeat AF ablation procedur-

e95 CFAEs are widely targeted in attempts to suppress the-maintaining substrate, but clinical results have varied

dely.e96 Detailed mechanistic analyses of CFAE genera-n promise to develop new methods by which they can bed to identify AF drivers.e74 There is increasing recogni-

n of the importance of atrial autonomic ganglia in AFintenance and the value of targeting them in AF ablationcedures.e97 Atrial fibrotic remodeling plays an importante in AF pathophysiology; recent work suggests that non-asive assessment of atrial fibrosis may be predictive ofoutcome of AF ablation procedures.e98

9. Rationale for eliminating atrial fibrillationth ablationere are several hypothetical reasons to perform abla-n procedures for treatment of AF. These include im-vement in quality of life (QOL), decreased stroke risk,

creased heart failure risk, and improved survival. Ins section of the document, these issues will be ex-red in more detail. However, it is important to recog-e that the primary justification for an AF ablationcedure at this time is the presence of symptomatic AF,

th a goal of improving a patients quality of life.though each of the other reasons to perform AF abla-n identified above may be correct, they have not beenstematically evaluated as part of a large randomizednical trial and are therefore unproven.Several epidemiologic studies have shown strong asso-tions between AF and increased risk of cerebral throm-embolism, development of heart failure, and increasedrtality.e99e101 It is well known that AF causes hemody-

mic abnormalities including a decrease in stroke volume,reased LA pressure and volume, shortened diastolic ven-ular filling period, AV valvular regurgitation, and an

egular and often rapid ventricular rate.e102 AF with aid ventricular response can also cause reversible left

ntricular (LV) systolic dysfunction. Persistence of AFds to anatomic and electrical remodeling of the LA thaty facilitate persistence of AF. Most importantly, many

tients, even those with good rate control, experienceptoms during AF.

There have been multiple randomized clinical trials per-med that address the question of whether rhythm controlmore beneficial than rate control for AF patients.e103e105ese studies have not demonstrated that sinus rhythmtoration is associated with better survival. In all trials,tiarrhythmic drugs were used for rhythm control. Thearmacological Intervention in AF (PIAF) trial first dem-strated that rate control was not inferior to rhythm controlthe improvement of symptoms and quality of life.e106 An

ditional study reported similar findings.e104 The Strate- ads of Treatment of AF (STAF) trial showed no significantference in the primary endpoints of death, systemic em-li, and cardiopulmonary resuscitation between the twoategies.e103 Another recent study demonstrated an im-vement in quality of life and exercise performance at 12nths follow-up in a series of patients with persistent.e107 In the AF Follow-up Investigation of Rhythm Man-

ement (AFFIRM) trial, in which 4,060 AF patients withh risk for stroke and death were randomized to eitherthm control or rate control, there were no significantferences in all-cause death between the two strat-ies.e105 However, a post-hoc on-treatment analysis of theFIRM study revealed that the presence of sinus rhythms associated with a significant reduction in mortality,ereas the use of antiarrhythmic drugs increased mortality49%,e108 suggesting that the beneficial effect of sinusthm restoration on survival might be offset by the ad-

rse effects of antiarrhythmic drugs. Previously, the Dan-Investigations of Arrhythmia and Mortality on Dofetil-(DIAMOND) study also showed the presence of sinusthm was associated with improved survival.e109 It mustnoted, however, that this was a retrospective analysis,

d the improvement in survival may have resulted fromtors other than the presence of sinus rhythm. In contrast,ecent study demonstrated that a rhythm control strategy,the presence of sinus rhythm, is not associated with bettertcomes in congestive heart failure patients with AF.e110These clinical trials clearly show that the strategy of

ing antiarrhythmic drugs to maintain sinus rhythm doest achieve the potential goals of sinus rhythm mentionedove. However, there are signals in these data to suggestt sinus rhythm may be preferred over rate control if it

uld be achieved by a method other than drug therapy.e study compared the efficacy and safety of circum-ential PV ablation with antiarrhythmic drug treatmenta large number of patients with long-term follow-upd showed that ablation therapy significantly improved

morbidity and mortality of AF patients.e90 Becauses was a single-center study, without audit of the rawta, and not a prospective randomized study, these find-s must be considered very preliminary. Several recentall randomized trials in patients with paroxysmal AFmonstrated that catheter ablation was superior to anti-hythmic therapy in the prevention of recurrent.e111 e113 A limitation of these studies is that most

tients had previously failed treatment with at least onetiarrhythmic medication. There are several publisheddies that have reported a low risk of stroke in patientso discontinue systemic anticoagulation several monthsmore following AF ablation.e114 e117 These findings

ed to be interpreted with caution, however, because AFn recur early or late after AF ablation and recurrences

more likely to be asymptomatic following, as com-red with prior to, AF ablation. In addition, patientsoke risk profile often increases as they age and pick up

ditional comorbidities such as hypertension. Thus there

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644 Heart Rhythm, Vol 9, No 4, April 2012some data to suggest that there are benefits to sinusthm obtained by ablation techniques over rate control.wever, large prospective multicenter randomized clin-l trials will be needed to definitively determineether sinus rhythm achieved with ablation techniquesers morbidity and mortality as compared with rate

ntrol alone or treatment with antiarrhythmic therapy.e ongoing Catheter Ablation vs. Antiarrhythmic Drugerapy for AF (CABANA) study will provide importantormation as it investigates whether catheter ablation isperior to medical therapy in patients with AF who areincreased stroke risk.e118

10. Mechanisms of recurrence followingtheter or surgical AF ablationis now well established that both catheter and surgicallation of AF are associated with an important risk of lateurrence of AF.e72,e73,e119e127 Although the highest riskrecurrence is during the first 6 to 12 months following

lation, there is no follow-up duration at which pointtients are no longer at risk of a new late recurrence of. Although the precise mechanisms of these late recur-ces have not been defined completely, electrical recon-

ction of one or more PVs is an almost universal findingong patients who return for a second AF ablation proce-re following an initial catheter or surgical ablation pro-ure. Because of this observation, most of the EP com-nity feels that the dominant mechanism of recurrence ofis electrical reconnection of the PVs. Additional evi-

nce supporting this mechanism is the extremely low ratelate AF following double lung transplantation in which

rmanent PVI is achieved.e128 There are several othertential mechanisms of late recurrence of AF that shouldconsidered. First, it is possible that some late recurrencesAF result from non-PV arrhythmogenic foci that were notntified and targeted during an initial ablation procedure.cond, it is possible that late recurrences of AF are ault of postablation modulation in autonomic innerva-ns of the heart and PVs.e62 e77 And finally, it is pos-le that ongoing electrical and structural remodeling ofatria as a result of aging, heart failure, inflammation,

d other comorbidities such as diabetese129 e136 leads togressive atrial electrical instability. Evidence to sup-

rt the latter hypothesis is derived in part by the studiesorting that patients with comorbid conditions such asep apnea, hypertension (HTN), and hypercholesterol-ia, as well as those with a history of persistent AF, arehighest risk of late recurrence.e135,137 e139

11. Demographic profile of AF patients and riskctors for development of AFere are multiple conditions known as risk factors for that play an etiologic role through diverse mecha-ms.e6 Some of them, like HTN,e135,e139 obesity,e140e142durance sport training,e143,e144 obstructive sleep ap-a,e140e142 and alcohol consumption,e145 are modifiable

d therefore, in theory, strictly controlling them may pre- gent arrhythmia or modify postablation evolution. On theer hand, factors such as genetic disorders,e146,e147

e,e137,e148,e149 sex,e137 or tall staturee44,e146,e150 can bentified but not prevented or treated. To individualizeatment, it is important to establish the most likely con-utors to AF in each patient. Atrial size, a relevant markerrisk for AF and for postablation recurrences of the dis-e, is a common pathway for the action of most of thentified risk factors.The well-known and more prevalent risk factors are age,le sex, HTN, diabetes mellitus, hyperthyroidism, anductural heart disease. Aging is a key risk factore136e138t probably acts through age-related fibrosis. HTN is as-iated with increased risk for AF even if apparently well

ntrolled.e138,e139,e148 Structural heart disease, regardless ofse, is also a major contributor to AF, and mitral valveease and hypertrophic cardiomyopathy produce severe atrialease. In addition, systolic or diastolic dysfunction and heartlure of any etiology predispose to AF, probably throughlume and/or pressure overload of the atrium.e151,e152 Diabe-

mellitus and hyperthyroidism are well recognized andependent risk factors for AF; even when well-controlled,may recur.e141,e153 AF risk factors have also been shown

be of value in predicting progression of paroxysmal torsistent AF. Risk factors that have been identified asependent predictors of AF recurrence include heart fail-, age, previous transient ischemic attack or stroke,

ronic obstructive pulmonary disease, and hypertension.sed on this analysis, the HATCH score was developed tolp predict those at highest risk of AF progression.e154In recent years, new risk factors have been described thaty contribute to the marked, increased prevalence of AF,ich is not fully explained by the aging of thepulation.e141,e143,e147,e150,e155e167 Obesity has proven toassociated with a higher risk of AF in several population-sed studies. Tall stature also is associated with an in-ased risk, and may explain the sex-based difference inprevalence: AF is more prevalent in men than in women.

e prevalence of AF is also increased in individuals withong history of endurance training, perhaps, as suggestedan animal model, through training-related hypertrophy,ial dilatation, fibrosis, or perhaps by training inducederations in autonomic tone. However, moderate exercisey decrease the prevalence, perhaps by controlling otherk factors such as HTN and obesity. Obstructive sleepnea also has been associated with AF. Whether this rep-ents an independent factor or acts through its associationth obesity and HTN remains to be elucidated, but it seemsincrease the risk of recurrences after AF ablation. Finally,a small percentage of patients, AF is due to hereditarynetic causes as discussed in the following paragraph.

12. Genetics of AF: relevance to AFe descendants of individuals with AF are at increasedk of developing AF, even after considering establishedk factors for AF.e157,e158,e160,e168,e169 Recent studies sug-

st that lone AF may be a traditional monogenic syndrome

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645Calkins et al HRS/EHRA/ECAS Catheter and Surgical Ablationth reduced penetrance, and multiple genetic loci have beenscribed in families with Mendelian forms of AF. However,t alle160 the responsible genes have been identified.e170,e171in-of-function mutations in KCNE2e172 and KCNJ2,e173 en-ding the inward rectifier potassium current (IK1), have beenociated with familial AF in two Chinese families. Similardies have associated familial AF with various other genes,luding those genes coding the subunit of the Kv1.5 chan-

l responsible for IKur (KCNA5); the gap junctional proteinnnexin40 (GJA5); SUR2A, the adenosine triphosphateTP) regulatory subunit of the cardiac KATP channelBCC9); and KCNE5, which co-associates with KCNQ1form the IKs channel.e174e177 Rare forms of familial AFcaused by mutations in one or more subunits of potass-, sodium, and calcium ion channel genes, as well as in a

clear poree178 anchoring protein and natriuretic peptidenee173,e179e183 and also have been associated with inheritedannelopathies such as Brugada, Long QT, Short QT syn-mes, and cardiomyopathies.e172,e175,e178e184Genetic linkage analyses have identified AF loci on

romosomes 10q22-24,e170 6q14-16,e171 5p13,e185 andp15.5.e182 In the case of 11p15.5, the genetic defect involvedterozygous missense mutations in KCNQ1, resulting inin-of function of the KCNQ1-KCNE1 and KCNQ1-NE2 ion channels conducting the slowly activating de-ed rectifier current, IKs.e186 Genetic predisposition to AF

s gained notoriety also thanks to genomic wide associa-n studies (GWAS)e187e191 that have identified at leasto genetic variants on chromosome 4q25 associated with, although the mechanism of action for these variantsains unknown. One of such variants is located near the

velopmental leftright asymmetry homeobox gene Pitx2,ich implicates this gene and its signaling pathways invention of atrial arrhythmias.e191It is reasonable to suggest that investigating in detail thederlying bases of these and other characteristics of the LAt differentiate it from the right atrium may greatly ad-

nce therapy by helping to explain the mechanisms of thenesis and perpetuation of chronic AF.

Indications for catheter and surgicallation of atrial fibrillatione 2007 HRS/EHRA/ESC Expert Consensus DocumentCatheter and Surgical Ablation of Atrial Fibrillation

ommended that the primary indication for catheter AFlation is the presence of symptomatic AF, refractory orolerant to at least one Class 1 or 3 antiarrhythmic medi-ion.e1 The 2007 Task Force also recognized that in rarenical situations, it may be appropriate to perform catheterlation of AF as first line therapy. Since publication of thiscument five years ago, a large body of literature, includ-

multiple prospective randomized clinical trials, has con-ed the safety and efficacy of catheter ablation of AF.

e substantial body of literature defining the safety andcacy of catheter ablation of AF is summarized in Sectionf this document. Similarly, the body of literature defining

safety and efficacy of surgical ablation of AF either elirformed in conjunction with another cardiac surgical pro-ure or performed as a stand-alone procedure is summa-

ed in Section 11 of this document.Shown in Table 2 of this document are the Consensusications for Catheter and Surgical Ablation of AF. As

tlined in the introduction section of this document, theseications are stratified as Class I, Class IIa, Class IIb, and

ass III indications. The evidence supporting these indica-ns is graded as Level A through C. In making theseommendations, the Task Force considered the body ofrature that has been published, which has defined theety and efficacy of catheter and surgical ablation of AF.th the number of clinical trials and the quality of thesels were considered. In considering the class of indica-

ns recommended by this Task Force, it is important toep several points in mind. First, these classes of indica-ns only define the indications for catheter and surgicallation of AF when performed by an electrophysiologist orgeon who has received appropriate training and/or has atain level of experience and is performing the procedurean experienced center (see section 10). Catheter andgical ablation of AF are highly complex procedures, andareful assessment of benefit and risk must be consideredeach patient. Second, these indications stratify patients

ly based on the type of AF and whether the procedure ising performed prior to or following a trial of one or moreass 1 or 3 antiarrhythmic medications. As detailed inction 8, there are many additional clinical and imagingsed variables that can be used to further define the effi-y and risk of ablation in a given patient. Some of the

riables that can be used to define patients in whom aer success rate or a higher complication rate can be

pected include the presence of concomitant heart disease,esity/sleep apnea, left atrial size, and the duration of timeatient has been in continuous AF. Each of these variableseds to be considered when discussing the risks and ben-ts of AF ablation with a particular patient. Third, it is keyconsider patient preference. Some patients are reluctant tonsider a major procedure or operation and have a strongference for a pharmacologic approach. In these patients,ls of additional antiarrhythmic agents and amiodaroney be preferred to catheter ablation. On the other hand,e patients prefer a nonpharmacologic approach. Fourth,

s also important to recognize that in some patients, AF islowly progressive condition and that patients early in theurse of their AF disease may do well with only infrequentisodes for many years to come and/or may be responsivewell-tolerated antiarrhythmic drug therapy. And finally, itimportant to bear in mind that a decision to performheter or surgical AF ablation should only be performeder a patient carefully considers the risks, benefits, andernatives to the procedure.As demonstrated in a large number of published stud-, the primary clinical benefit from catheter ablation of

is an improvement in quality of life resulting from

mination of arrhythmia-related symptoms such as pal-

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646 Heart Rhythm, Vol 9, No 4, April 2012ations, fatigue, or effort intolerance (see section 8).us, the primary selection criterion for catheter ablationould be the presence of symptomatic AF. As notedove, there are many other considerations in patientection other than type of AF alone. In clinical practice,ny patients with AF may be asymptomatic but seek

theter ablation as an alternative to long-term anticoag-tion with warfarin or other drugs with similar efficacy.though retrospective studies have demonstrated thatcontinuation of warfarin therapy after catheter abla-n may be safe over medium-term follow-up in somebsets of patients, this has never been confirmed by age prospective randomized clinical trial and thereforeains unproven.e116,e117,e191,e192 Furthermore, it is well

ognized that symptomatic and/or asymptomatic AFy recur during long-term follow-up after an AF abla-

le 2 Consensus indications for catheter and surgical ablation

ications for catheter ablation of AF

ptomatic AF refractory or intolerant to at least one Class 1 or 3Paroxysmal: Catheter ablation is recommended*Persistent: Catheter ablation is reasonableLongstanding Persistent: Catheter ablation may be considered

ptomatic AF prior to initiation of antiarrhythmic drug therapy wParoxysmal: Catheter ablation is reasonablePersistent: Catheter ablation may be consideredLongstanding Persistent: Catheter ablation may be considered

ications for concomitant surgical ablation of AF

ptomatic AF refractory or intolerant to at least one Class 1 or 3Paroxysmal: Surgical ablation is reasonable for patients undergoiPersistent: Surgical ablation is reasonable for patients undergoinLongstanding Persistent: Surgical ablation is reasonable for patie

ptomatic AF prior to initiation of antiarrhythmic drug therapy wParoxysmal: Surgical ablation is reasonable for patients undergoiPersistent: Surgical ablation is reasonable for patients undergoinLongstanding Persistent: Surgical ablation may be considered for

indications

ications for stand alone surgical ablation of AF

ptomatic AF refractory or intolerant to at least one Class 1 or 3Paroxysmal: Stand alone surgical ablation may be considered for

ablation but prefer a surgical approachParoxysmal: Stand alone surgical ablation may be considered for

attempts at catheter ablationPersistent: Stand alone surgical ablation may be considered for p

ablation but prefer a surgical approachPersistent: Stand alone surgical ablation may be considered for p

attempts at catheter ablationLongstanding Persistent: Stand alone surgical ablation may be co

catheter ablation but prefer a surgical approachLongstanding Persistent: Stand alone surgical ablation may be co

or more attempts at catheter ablationptomatic AF prior to initiation of antiarrhythmic drug therapy w

Paroxysmal: Stand alone surgical ablation is not recommendedPersistent: Stand alone surgical ablation is not recommendedLongstanding Persistent: Stand alone surgical ablation is not rec

*Catheter ablation of symptomatic paroxysmal AF is considered a Classropriate training and is performing the procedure in an experienced center.n procedure.e72,e73,e119,e122,e124,e126,e127 It is for these latsons that this Task Force recommends that discontin-tion of warfarin or equivalent therapies postablation ist recommended in patients who have a high stroke risk

determined by the CHADS2 or CHA2DS2VAScre.e193 Either aspirin or warfarin is appropriate for

tients who do not have a high stroke risk. If anticoag-tion withdrawal is being considered, additional ECGnitoring may be required, and a detailed discussion of

k versus benefit should be entertained. A patientssire to eliminate the need for long-term anticoagulationitself should not be considered an appropriate selec-

n criterion. In arriving at this recommendation, thesk Force recognizes that patients who have undergonetheter ablation of AF represent a new and previouslystudied population of patients. Clinical trials therefore

needed to define the stroke risk of this patient popu-

Class Level

rhythmic medicationI AIIa BIIb B

Class 1 or 3 antiarrhythmic agentIIa BIIb CIIb C

rhythmic medicationery for other indications IIa Cry for other indications IIa Cdergoing surgery for other indications IIa CClass 1 or 3 antiarrhythmic agentery for other indications IIa Cry for other indications IIa Cts undergoing surgery for other IIb C

rhythmic medicationts who have not failed catheter IIb C

ts who have failed one or more IIb C

who have not failed catheter IIb C

who have failed one or more IIb C

ed for patients who have not failed IIb C

ed for patients who have failed one IIb C

Class 1 or 3 antiarrhythmic agentIII CIII C

ded III C

tion only when performed by an electrophysiologist who has receivedrea

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647Calkins et al HRS/EHRA/ECAS Catheter and Surgical Ablationthe CHADS2 or CHA2DS2VASc or other scoring sys-s apply to these patients.

Techniques and endpoints for atrialrillation ablation1. Historical considerationsx and colleagues are credited with developing and dem-strating the efficacy of surgical ablation of AF.e24,e194bsequent surgeons evaluated the efficacy of surgical ap-aches that limit the lesion set to PVI.e195,e196 The final

ration of the procedure developed by Cox, which is re-red to as the Maze-III procedure, was based on a modelAF in which maintenance of the arrhythmia was shown touire maintenance of a critical number of circulatingvelets of reentry. The Maze-III procedure was designedabort or block all possible anatomical reentrant circuits inth atria. The success of the Maze-III procedure in thely 1990s led some interventional cardiac electrophysi-gists to attempt to reproduce the procedure with RFheter lesions using a transvenous approach. Swartz andlleaguese197 reported recreation of the Maze-I lesion set inmall series of patients using specially designed sheaths

d standard RF catheters. Although the efficacy was mod-, the complication rate was high, and the procedure andoroscop

2012 hrs ehra ecas af ablation

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