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CPG management of atrial fibrillation

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Malaysia CPG 2012

Malaysia CPG 2012

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    CPG management of atrial fibrillation CPG management of atrial fibrillation Document Transcript

    • MOH/P/PAK/259.12(GU)
    • STATEMENT OF INTENTThis guideline is meant to be a guide for clinical practice, based on the bestavailable evidence at the time of development. Adherence to this guideline maynot necessarily guarantee the best outcome in every case. Every health careprovider is responsible for the management of his/her unique patient based onthe clinical picture presented by the patient and the management optionsavailable locally.This guideline was issued in 2011 and will be reviewed in 2016 or sooner ifnew evidence becomes availableCPG Secretariatc/o Health Technology Assessment UnitMedical Development DivisionMinistry of Health Malaysia4th floor, Block E1, Parcel E62590, Putrajaya.Electronic version available on the following website:http://www.malaysianheart.orghttp:// www.moh.gov.myhttp://www.acadmed.org.my i
    • ii
    • FOREWORD BY PRESIDENT OF NATIONAL HEART ASSOCIATIONOF MALAYSIA (NHAM)THE PUBLICATION of the Clinical Practice Guidelines for Atrial Fibrillationmarked a milestone in the evolution of clinical practice guidelines and the deliveryof care in cardiology. Specifically, these guidelines assist physicians in clinicaldecision making by describing a range of generally acceptable approachesfor the diagnosis, management, and prevention of AF. Clinical Issues eg: AFassessment, best treatment strategy for acute AF & reduce risk of adverseoutcomes from AF, best long term treatment strategy, management of AF inspecific special groups have been addressed in the CPG.In a broader sense, these guidelines emphasized that AF is a worldwide publichealth problem with increasing incidence and prevalence, high cost, and pooroutcomes. Importantly, this AF CPG has provided the framework for a publichealth approach to improve the quality of care and outcomes of all individuals withAF. This is a major paradigm shift from the focus on AF treatment and care thathas dominated the practice to IMPORTANT STRATEGIES eg: risk stratification,appropriate antithrombotic therapy, safety consideration of antiarrhythmic agentsemphasized in rhythm strategy.This latest version has undergone extensive revision in response to commentsduring the public review. While considerable effort has gone into their preparationover the past 2 years, and every attention has been paid to their detail and scientificrigor, no set of guidelines, no matter how well developed, achieves its purposeunless it is implemented and translated into clinical practice. Implementation is anintegral component of the process and accounts for the success of the guidelines.The Work Group is now developing implementation tools essential to the successof this AFCPG.In a voluntary and multidisciplinary undertaking of this magnitude, many individualsmake contributions to the final product now in your hands. It is impossible toacknowledge them individually here, but to each and every one of them we extendour sincerest appreciation, especially to the members of the Writing Panel, aneffort subsequently reinforced by the review of these final guidelines by theexternal reviewers. Thank you one and all for Making Lives Better for patients withAF throughout Malaysia. A special debt of gratitude is due to the members of theWork Group, their chair, Dr Ahmad Nizar. It is their commitment and dedicationthat has made it all possible.Professor Dr. Sim Kui Hian FNHAMNHAM President iii
    • ABOUT THE GUIDELINEGUIDELINE DEVELOPMENT PROCESSThis is the first Clinical Practice Guideline (CPG) for Atrial Fibrillation (AF). Acommittee was appointed by the National Heart Association of Malaysia (NHAM),Ministry of Health (MOH) and the Academy of Medicine Malaysia (AMM) to draw upthis CPG. It comprises of sixteen members including cardiologists, a neurologist,a haematologist, a cardiac surgeon, an obstetrician, a gynaecologist, generalphysicians, an intensivist, a family medicine specialist and an emergency medicinespecialist from the government, private sector and the public universities.ObjectivesThis CPG is intended to assist health care providers in clinical decision makingby describing a range of generally acceptable approaches for the diagnosis,management, and prevention of AF.Rigour of DevelopmentEvidence was obtained by systematic review of current medical literature on AtrialFibrillation using the usual search engines – Guidelines International Network(G-I-N), Pubmed/Medline, Cochrane Database of Systemic Reviews (CDSR),Database of Abstracts of Reviews of Effectiveness (DARE), Journal full text viaOVID search engine, International Health Technology Assessment websites (referto Appendix A for Search Terms). In addition, the reference lists of all retrievedarticles were searched to identify relevant studies. Search was limited to literaturepublished in English. All searches were officially conducted between 15 January2010 and 10 December 2011. We suggest that future CPG updates will considerevidence published after this cut-off date. The details of the search strategy canbe obtained upon request from the CPG secretariat.Reference was also made to other guidelines on Atrial Fibrillation, Guidelinesfor the Management of Atrial Fibrillation published by The Task Force for theManagement of Atrial Fibrillation of the European Society of Cardiology (ESC)2010, The National Institute for Health and Clinical Excellence Atrial FibrillationGuideline 2006, Evidence-based Best Practice Guideline of New Zealand onAtrial Fibrillation 2005 and the ACC/AHA/ESC Guidelines for the Managementof Patients With Atrial Fibrillation 2006 were also studied. These CPGs wereevaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE)prior being used as references.Forty-three clinical questions were developed and divided into eight major sectionsand members of the development panel were assigned individual questions withinthese subtopics (refer to Appendix B for Clinical Questions). The group membersmet a total 18 times throughout the development of the guideline. All retrievedliterature were appraised by at least two members and subsequently presentedfor discussion during development group meetings. iv
    • All statements and recommendations formulated were agreed collectively bymembers of the Development Panel. Where the evidence was insufficient therecommendations were derived by consensus of the Panel. These CPG arebased largely on the findings of systematic reviews, meta-analyses and clinicaltrials, with local practices taken into consideration.On completion, the draft guidelines was sent for review by external reviewers. Itwas posted on the Ministry of Health of Malaysia official website for comment andfeedback from any interested parties. These guidelines had also been presentedto the Technical Advisory Committee for CPG, and the HTA and CPG Council,Ministry of Health of Malaysia for review and approval.The level of recommendation and the grading of evidence used in this guidelinewere adapted from the American Heart Association and the European Society ofCardiology (AHA/ESC) and outlined on page xi. In the text, this is written in blackand boxed on the left hand margin.Sources of FundingSanofi Aventis (M) Sdn. Bhd. supported the development of the CPG onManagement of Atrial Fibrillation financially. However, the views of the fundingbody have not influenced the content of the guideline.Disclosure statementThe development panel members had completed disclosure forms. None heldshares in pharmaceutical firms or acted as consultants to such firms. (Details areavailable upon request from the CPG Secretariat)Clinical Issues Addressed1. How do you assess a patient suspected of having atrial fibrillation?2. What is the best strategy to treat patients with atrial fibrillation in the acute setting?3. What is the best strategy to reduce the risk of adverse outcomes from atrial fibrillation?4. What is the best long-term management strategy?5. How to manage atrial fibrillation in specific special groups? 
Target GroupThis CPG is directed at all healthcare providers treating patients with AF –allied professionals, family and general physicians, medical officers, emergencyphysicians, intensivists and cardiologists.Target PopulationIt is developed to assist clinical decision making for all adults and pregnantwomen with AF. v
    • Period of Validity of the GuidelinesThis guideline needs to be revised at least every 5 years to keep abreast withrecent developments and knowledge.Implementation of the GuidelinesTo ensure successful implementation of this CPG we suggest:1. Constant checks and feedback on whether the guideline is relevant.2. Identify implementation leaders Identification of multiple leaders to share the implementation work and ensure seamless care. These leaders are likely to be prominent figures who will champion the guideline and inspire others.3. Identify an implementation group Support from medical associations such as the Private Medical Practitioners Society (PMPS), Society of Pacing and Electrophysiology (SOPACE) and Malaysian Medical Association (MMA) will help dissemination of the guidelines.4. Carrying out a baseline assessment This involves comparing current practice with the recommendations. The audit criteria will help this baseline assessment.5. Developing an action plan The baseline assessment will have identified which recommendations are not currently being carried out. These recommendations could be put into an action plan.6. Key areas for implementation We have identified several goals for implementation based on the key priorities for implementation identified in the guideline vi
    • GUIDELINE WORKING GROUPChairpersonDr Ahmad Nizar b JamaluddinConsultant Cardiologist & ElectrophysiologistSime Darby Medical CentreSelangorDr Anita bt AliasIntensivistHospital MelakaMelakaDatuk Dr Hj Azhari b Rosman,Consultant Cardiologist & ElectrophysiologistNational Heart InstituteKuala LumpurDato’ Dr Chang Kian MengConsultant Heamatologist & Head of DepartmentDepartment of HaematologyHospital AmpangKuala LumpurDr Ernest Ng Wee OonConsultant Cardiologist and ElectrophysiologistPantai Hospital KLKuala LumpurDr Hashim b TahirConsultant Obstetrician & GynaecologistUniversiti Technologi MARASelangorAssociate Professor Dr Imran b Zainal AbidinAssociate Professor of Medicine & Consultant CardiologistUniversity Malaya Medical CentreKuala LumpurDr Jeswant DillonConsultant Cardiothoracic SurgeonNational Heart InstituteKuala Lumpur vii
    • Professor Dato’ Dr Khalid b Haji Yusoff,Professor of Medicine and Senior Consultant CardiologistUniversiti Teknologi MARASelangorDr Lai Voon MingConsultant Cardiologist and ElectrophysiologistSri Kota Medical CentreSelangorDr Ngau Yen YewConsultant PhysicianHospital Kuala LumpurKuala LumpurDato’ Dr Omar b Ismail,Consultant Cardiologist & Head of DepartmentDepartment of CardiologyHospital Pulau PinangProf. Madya Dr Oteh b MaskonConsultant Cardiologist & Head of DepartmentDepartment of CardiologyHospital Universiti Kebangsaan MalaysiaKuala LumpurDatuk Dr Raihanah bt Abdul KhalidConsultant NeurologistPantai Hospital KLKuala LumpurDr Ridzuan b Dato Mohd IsaEmergency Medicine Specialist & Head of DepartmentDepartment of Accident & EmergencyHospital AmpangKuala LumpurDr V ParanthamanFamily Medicine Specialist & Head of DepartmentKlinik Kesihatan JelapangPerak viii
    • EXTERNAL REVIEWERS1) Dato’ Dr Ravindran Jegasothy Senior Consultant & Head of Department Obstetrics & Gynaecology Hospital Kuala Lumpur2) Datuk Dr Razali b Omar Deputy Head, Consultant Cardiologist & Electrophysiologist Director of Clinical Electrophysiology & Pacemaker Service Department of Cardiology3) Professor Dr Sim Kui Hian Visiting Senior Consultant Cardiologist Department of Cardiology Sarawak General Hospital Heart Centre Adjunct Professor Faculty of Medicine & Health Sciences University Malaysia Sarawak (UNIMAS)4) Dato’ Dr. Sree Raman Senior Consultant Physician Hospital Tuanku Jaafar Seremban5) Dr Tai Li Ling Consultant Intensivist Department of Anaesthesia and Intensive Care Hospital Kuala Lumpur. ix
    • SUMMARYKEY MESSAGES1 An electrocardiogram (ECG) should be performed in all patients, whether symptomatic or not, in whom AF is suspected because an irregular pulse has been detected.2 The stroke risk stratification algorithms, CHADS2 and CHA2DS2VASc, should be used in patients with AF to assess their risk of stroke and thrombo-embolism, while the HAS-BLED score should be used to assess their risk of bleeding.3 Antithrombotic therapy should be based upon the absolute risks of stroke/ thrombo-embolism and bleeding, and the relative risk and benet for a given patient.4 When choosing either an initial rate-control or rhythm-control strategy, the indications for each option should not be regarded as mutually exclusive and the potential advantages and disadvantages of each strategy should be explained to patients before agreeing which to adopt. Any comorbidities that might indicate one approach rather than the other should be taken into account . Irrespective of whether a rate-control or a rhythm-control strategy is adopted in patients with persistent or paroxysmal AF, appropriate antithrombotic therapy should be used.5 When choosing an antiarrhythmic agent for rhythm control strategy, safety rather than efficacy considerations should primarily guide the choice of antiarrhythmic agent.6 In patients with permanent AF, who need treatment for rate control, beta- blockers or rate-limiting calcium antagonists should be the preferred initial monotherapy in all patients while digoxin should only be considered as monotherapy in predominantly sedentary patients. x
    • The management cascade for patients with AF. ACEI = angiotensin-converting enzyme inhibitor; AF = atrialfibrillation; ARB = angiotensin receptor blocker; PUFA = polyunsaturated fatty acid; TE = thrombo-embolism.Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heartJournal 2010; doi:10.1093/eurheartj/ehq278) xi
    • <<ATRIAL FIBRILLATION MANAGEMENT CASCADE>> <<ATRIAL FIBRILLATION MANAGEMENT CASCADE>>Grading System Grading SystemThe format used forfor Classification of Recommendations and Level of Evidence The format used Classification of Recommendations and Level of Evidencewas adapted from thethe American Heart Association and the European Society of was adapted from American Heart Association and the European Society ofCardiology. Cardiology. GRADES OFOF RECOMMENDATIONS AND LEVELS OF EVIDENCE GRADES RECOMMENDATIONS AND LEVELS OF EVIDENCE GRADES OFOF RECOMMENDATION GRADES RECOMMENDATION Conditions forfor which there evidence and/or general agreement Conditions which there is is evidence and/or general agreement I I that a given procedure/therapy is beneficial, useful and/or that a given procedure/therapy is beneficial, useful and/or effective. effective. Conditions forfor which there conflicting evidence and/or Conditions which there is is conflicting evidence and/or II II divergence of opinion about thethe usefulness/efficacy a a divergence of opinion about usefulness/efficacy of of procedure/therapy. procedure/therapy. II-aII-a Weight of evidence/opinion is in favor of its its usefulness/efficacy. Weight of evidence/opinion is in favor of usefulness/efficacy. II-bII-b Usefulness/efficacy is less well established by by evidence/opinion Usefulness/efficacy is less well established evidence/opinion Conditions forfor which there evidence and/or general agreement Conditions which there is is evidence and/or general agreement III III that a procedure/therapy is not useful/effective and in some that a procedure/therapy is not useful/effective and in some cases may be be harmful. cases may harmful. LEVELS OFOF EVIDENCE LEVELS EVIDENCE Data derived from multiple randomised clinical trials or meta Data derived from multiple randomised clinical trials or meta A A analyses analyses Data derived from a single randomised clinical trial or large non Data derived from a single randomised clinical trial or large non B B randomised studies randomised studies Only consensus of opinions of experts, case studies or standard Only consensus of opinions of experts, case studies or standard C C of care of care Adapted from the American Heart Association/American College of Cardiology (AHA/ ACC) and the European Society of Cardiology (ESC) xii
    • TABLE OF CONTENTSStatement of IntentForewordAbout the Guideline Guideline Development Process Guideline Working Group External ReviewerSummary Key Messages Atrial Fibrillation Management Cascade Grading SystemTable of ContentI. Introduction 1.1 Definition 1.2 Types of Atrial Fibrillation 1.3 AF Natural Time Course 1.4 Epidemiology and Prognosis2. Pathophysiology 2.1. Clinical Aspects 2.1.1. Causes and Associated Conditions3. Initial Management 3.1. Clinical History and Physical Examination and Investigations 3.1.1. Detection 3.1.1.1. Electrocardiogram 3.1 Diagnostic Evaluation 3.2 Echocardiogram 3.3 Clinical Follow-up4 Management Principles 4.1 General Principles 4.2 Thromboembolic Prophylaxis 4.3 Heart Rate vs Rhythm Control5 Management – Acute-onset AF 5.1 Acute AF In Hemodynamically Unstable Patients 5.1.1 Acute Rate Control 5.1.2 Pharmacological Cardioversion 5.1.2.1 Pill-in-the-pocket Approach 5.1.3 Direct Current Cardioversion 5.1.3.1 Procedure 5.1.3.2 Complications 5.1.3.3 Cardioversion In Patients With Implanted Pacemakers And Defibrillators 5.1.3.4 Recurrence After Cardioversion 5.1.4 Antithrombotic Therapy For Acute-onset AF6 Management - Prevention of Thromboembolism xiii
    • 6.1 Risk Stratification For Stroke 6.2 Strategies for Thromboembolic Prophylaxis 6.3 Antithrombotic Therapy 6.3.1 Anticoagulation With Vitamin K Antagonists 6.3.2 Optimal International Normalized Ratio 6.3.2.1 Point-of-care testing and self-monitoring of anticoagulation 6.3.3 Anticoagulation With Direct Thrombin Inhibitors 6.3.4 Investigational Agents 6.3.5 Antiplatelet Agent Aspirin 6.3.6 Aspirin And Clopidogrel Combination 6.4 Anticoagulation In Special Circumstances 6.4.1 Peri-operative Anticoagulation 6.4.2 Acute Stroke 6.4.3 Anticoagulant and Antiplatelet Therapy Use in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention 6.4.4 Non-ST Elevation Myocardial Infarction 6.4.5 Cardioversion 6.5 Non-pharmacological Methods To Prevent Strokes 6.6 Risk of Long-term Anticoagulation 6.6.1 Assessment Of Risk Of Bleeding 6.6.2 Risk Score For Bleeding7 Management – Long-term Rate Control 7.1 Pharmacological Rate Control 7.1.1 Combination Therapy 7.2 Non-Pharmacological Rate Control 7.2.1 AV Nodal Ablation And Pacing8 Management – Long-term Rhythm Control 8.1 Efficacy Of Antiarrhythmic Drugs In Preventing Recurrent AF 8.2 Choice Of Antiarrhythmic drugs 8.2.1 Patients With Lone AF 8.2.2 Patients With Underlying Heart Disease 8.2.2.1 Patients With Left Ventricular Hypertrophy 8.2.2.2 Patients With Coronary Artery Disease 8.2.2.3 Patients With Heart Failure 8.3 Non-Pharmacological Therapy 8.3.1 Left Atrial Catheter Ablation 8.3.2 Surgical Ablation 8.3.3 Suppression of AF Through Pacing 8.4 Upstream Therapy 8.4.1 Angiotensin-converting Enzyme Inhibitors and Angiotensin Receptor Blockers 8.4.2 Statins 8.4.3 Polyunsaturated Fatty Acids and Aldosterone Antagonist9 Management – Special Populations xiv
    • 9.1 Post-Operative AF 9.1.1 Prevention Of Post-operative AF 9.1.2 Treatment of Post-operative AF 9.2 Acute Coronary Syndrome 9.3 Wolff-Parkinson-White (WPW) Pre-excitation Syndromes 9.3.1 Sudden Death And Risk Stratification 9.4 Hyperthyroidism 9.5 Pregnancy 9.6 Hypertrophic Cardiomyopathy 9.7 Pulmonary Diseases 9.8 Heart Failure 9.9 Athletes 9.10 Valvular Heart Disease10 Referrals11 Audit and EvaluationAppendixesGlossaryReferences xv
    • 1 INTRODUCTION1.1 DEFINITIONAtrial fibrillation (AF) is an atrial tachyarrhythmia characterized by uncoordinatedatrial activation with consequent deterioration of atrial mechanical function. Thesurface ECG is characterized by ‘absolutely’ irregular RR intervals and theabsence of any distinct P waves. The P waves are replaced by fibrillary (F)waves.Atrial Flutter (AFl) in the typical form is characterized by a saw-tooth pattern ofregular atrial activation called flutter (F) waves on the ECG. AFl commonlyoccurs with 2:1 AV block, resulting in a regular or irregular ventricular rate of 120to 160 beats per minute (most characteristically about 150 beats per minute).1.2 TYPES OF ATRIAL FIBRILLATIONClinically, five types of AF are recognized based on the presentation and theduration of the episode. These categories are set out below. (See Table 1 andFigure 2)<<Table 1 >>Table 1. Classification of AF subtypesThe term ‘lone AF’ applies to young individuals (under 60 years of age) without Terminology Clinical Features Patternclinical or(first Initial event echocardiographic evidence of cardiopulmonary disease, including Symptomatic May or may not recurhypertension. These Asymptomatichave a favourable prognosis with respect to detected episode) patientsthromboembolism andOnset unknown Paroxysmal mortality. Spontaneous termination <7 days and most often < Recurrent 48 hours‘Silent AF’ being asymptomatic is detected by an opportunistic ECG or may Persistent Not self terminating Recurrentpresent as an AF-related complication such cardioversion for stroke. Lasting >7 days or requiring termination as ischemic Long standing persistent AF that has lasted for RecurrentThis classication is useful for clinical management of AF patients (Figure 1), 1 year when it is decided to adopt a rhythm control strategyespecially when AF-related symptoms are also considered. Permanent Not terminated Established<<Figure 1>> Terminated but relapsed No cardioversion attempt1.3 AF NATURAL TIME COURSEAdapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010Version)naturally progressive disease except for a small proportion of patients (2-AF is a (European heart Journal 2010; doi:10.1093/eurheartj/ehq278)3%), who are free of AF-promoting conditions (see section 2.1.1, page 5), mayremain in paroxysmal AF over several decades.1 AF progresses from short rareepisodes, to longer and more frequent attacks (See Figure 2). With time, oftenyears, many patients will develop sustained forms of AF. Paroxysm of AFepisodes also occurs in cluster and ”AF burden” can vary markedly over monthsor years.2 1
    • 1.2 TYPES OF ATRIAL FIBRILLATION Clinically, five types of AF are recognized based on the presentation and the duration of the episode. These categories are set out below. (See Table 1 and Figure 2) <<Table 1 >> The term ‘lone AF’ applies to young individuals (under 60 years of age) without clinical or echocardiographic evidence of cardiopulmonary disease, including hypertension. These patients have a favourable prognosis with respect to thromboembolism and mortality.‘Silent AF’ being asymptomatic is detected by an opportunistic ECG or maypresent as an AF-related complication such as ischemic stroke.1 INTRODUCTION1 INTRODUCTION1.1 DEFINITION is useful for clinical management of AF patients (Figure 1),This classication1.1 DEFINITION AF-related symptoms are also considered.especially whenAtrial fibrillation (AF) is an atrial tachyarrhythmia characterized by uncoordinatedAtrial activation (AF) consequenttachyarrhythmia characterized by uncoordinatedatrial fibrillation with is an atrial deterioration of atrial mechanical function. The<<Figure 1>>atrial activation characterized deterioration of atrial mechanical function. thesurface ECG iswith consequentby ‘absolutely’ irregular RR intervals and Thesurface NATURAL TIME COURSE The P waves are replaced by fibrillary theabsence ECG is distinct P waves. ‘absolutely’ irregular RR intervals and (F)1.3 AF of any characterized byabsence of any distinct P waves. The P waves are replaced by fibrillary (F)waves.waves. naturally progressive disease except for a small proportion of patients (2-AF is aAtrial who are free in the typical form is characterized by a saw-tooth pattern of3%), Flutter (AFl) of AF-promoting conditions (see section 2.1.1, page 5), mayAtrial Flutter (AFl) in the called several (F) waves AF progresses AFl commonlyregular in paroxysmal AFtypical flutter isdecades.1 on the aECG. from pattern ofremain atrial activation over form characterized by saw-tooth short rareregular with 2:1 AV block,called frequent(F) waves irregular ventricular rate ofoftenoccurs atrial longer and more fluttera regular or on Figure 2). With time, 120episodes, to activation resulting in attacks (See the ECG. AFl commonlyoccurs beats2:1 AV block, resulting in sustained or irregular beatsParoxysm of 120to 160 with per minute will develop a regular about 150 AF. per minute). AFyears, many patients (most characteristically forms of ventricular rate ofto 160 beats per minute (most characteristically about vary beats per minute).episodes also occurs in cluster and ”AF burden” can 150 markedly over months 21.2years. OF ATRIAL FIBRILLATIONor TYPES1.2 TYPES OF ATRIAL FIBRILLATIONClinically, five types of AF are recognized based on the presentation and theClinically, five episode. These categories are set out below. (See Table theduration of thetypes of AF are recognized based on the presentation and1 anddurationFigure 2)of the episode. These categories are set out below. (See Table 1 andFigure 2)<<Table 1 >><<Table 1 >>The term ‘lone AF’ applies to young individuals (under 60 years of age) withoutclinical or‘lone AF’ applies to young individuals (under 60 years of age) withoutThe term echocardiographic evidence of cardiopulmonary disease, includingclinical or echocardiographic evidence of cardiopulmonary disease, includinghypertension. These patients have a favourable prognosis with respect tohypertension. These patients have a favourable prognosis with respect tothromboembolism and mortality.thromboembolism and mortality.‘Silent AF’ being asymptomatic is detected by an opportunistic ECG or may‘Silent as being asymptomatic is detected ischemic stroke.presentAF’ an AF-related complication such asby an opportunistic ECG or maypresent as an AF-related complication such as ischemic stroke.Figure 1: Different types is AF. AF = atrial fibrillation; CV = cardioversion. The arrhythmia tends to progress This classication of useful for clinical management of AF patients (Figure 1),from paroxysmal (self-terminating, usually ,48 h) to persistent AF patients (Figure 1), This classication is useful for clinical management of [non-self-terminating or requiringcardioversion when long-standing persistent (lasting longer considered. and eventually to permanent especially (CV)], AF-related symptoms are also than 1 year) especially when AF-related symptoms are also considered.(accepted) AF. First-onset AF may be the first of recurrent attacks or already be deemed permanent.Adapted from 1>> <<Figure the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart <<Figure 1>>Journal 2010; doi:10.1093/eurheartj/ehq278)1.3 AF NATURAL TIME COURSE1.3 AF NATURAL TIME COURSE AF is a naturally progressive disease except for a small proportion of patients (2- AF is who are free of AF-promoting conditions (see section 2.1.1, of patients (2- 3%), a naturally progressive disease except for a small proportion page 5), may 3%), who paroxysmal AF-promoting conditions (see section 2.1.1, page 5), may remain in are free of AF over several decades.1 AF progresses from short rare 1 remain in paroxysmal AFmore frequentdecades.(See progressesWith time, often episodes, to longer and over several attacks AF Figure 2). from short rare episodes, to patients will develop sustained forms of AF. With time, often years, many longer and more frequent attacks (See Figure 2).Paroxysm of AF years, many occurs cluster and sustained can of markedly over of AF episodes also patientsinwill develop ”AF burden”formsvary AF. Paroxysm months episodes or years.2 also occurs in cluster and ”AF burden” can vary markedly over months or years.2Asymptomatic AF is common even in symptomatic patients, irrespective ofwhether the initial presentation was persistent or paroxysmal. This has importantimplications for strategies aimed at preventing AF-related complications.<<Figure 2>> 2
    • Figure 22: :‘Natural’ time course of AF. AF = atrial fibrillation. The dark blue boxes show a typical sequence of Figure ‘Natural’ time course of AF. AF = atrial fibrillation. a typical sequence ofperiods in AF against a background of sinus rhythm, and illustrate the progression of AF from silent and periods in AF against a background of sinus rhythm, and of AF from silent andundiagnosed to paroxysmal and chronic forms, at times symptomatic. The upper bars indicate therapeutic undiagnosed to paroxysmal and chronic forms, at times bars indicate therapeuticmeasures that could be pursued. Light blue boxes indicate therapies that have proven effects on ‘hard measures that could be pursued. Light blue boxes indicate proven effects on ‘hardoutcomes’ in AF, such as stroke or acute heart failure. Red boxes indicatepatients,that are currently used Asymptomatic AF is common heart failure. Red outcomes’ in AF, such as stroke or acute even in symptomatic therapies that are currently used irrespective offor symptom relief, but may in the future was persistent or paroxysmal. This has important whether the initial may in the future contribute to reduction of AF-related complications. Rate control for symptom relief, but presentation contribute to reduction complications. Rate control implications for for symptom relief and may improve cardiovascular outcomes. (grey box) is valuable for symptom relief and may improve(grey box) is valuablestrategies aimed at preventing AF-related complications.Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart<<Figure 2>>Journal 2010; doi:10.1093/eurheartj/ehq278)1.4 EPIDEMIOLOGY AND PROGNOSISAF is the commonest sustained cardiac arrhythmia. Information on AF inMalaysia is scarce. Hospital practice data may give a biased view of the clinicalepidemiology of AF, since only one-third of patients with AF may actually havebeen admitted to hospital.Data from predominantly western populations suggest the estimated prevalenceof AF is 0.4% to 1% in the general population. The prevalence of AF doubles witheach decade of age, from 0.5% at age 50-59 years to almost 9% at age 80-89years.3-4The mortality rate of patients with AF is about double that of patients in sinusrhythm.2,5AF is associated with a prothrombotic state, intra-atrial stasis, structural heartdisease or blood vessel abnormalities and abnormal platelets haemostasis,leading to a predisposition to thrombus formation. This prothrombotic state leadsto stroke and thromboembolism in AF (See Table 1, Page 1). Only antithrombotictherapy has been shown to reduce AF-related deaths.6<<Table 2 >> 3Stroke in AF is often severe and results in long-term disability or death.Approximately 20% of stroke is due to AF and undiagnosed ‘silent AF’ is a likely
    • Table 2: Clinical events (outcomes) affected by AF Relative change in AF Outcome parameter patientsAsymptomatic AF is common even in symptomatic patients, irrespective of 1. Deathwhether the initial presentation was persistent or rate doubled. has important Death paroxysmal. Thisimplications for strategies aimed at preventing AF-related complications. 2. Stroke (includes Stroke risk increased; AF is haemorrhagic stroke and<<Figure 2>> associated with more severe cerebral bleeds) stroke. Hospitalizations are frequent in1.4 EPIDEMIOLOGY AND PROGNOSIS AF patients and may contribute 3. Hospitalizations to reduced quality of life.AF is the commonest sustained cardiac arrhythmia. Information on AF inMalaysia is scarce. Hospital practice data may give a biased view of the clinicalepidemiology of AF, since only one-thirdWide variation, from no effect of patients with AF may actually havebeen admitted to hospital. to major reduction. 4. Quality of life and exercise AF can cause marked distressData capacity from predominantly western populations suggest the estimated prevalence through palpitations and otherof AF is 0.4% to 1% in the general population. The prevalence of AF doubles with AF-related symptoms.each decade of age, from 0.5% at age 50-59 years to almost 9% at age 80-89years.3-4 5. Left ventricular function Wide variation, from no changeThe mortality rate of patients with AF isto tachycardiomyopathy with about double that of patients in sinusrhythm.2,5 acute heart failure.AF is associated with a prothrombotic state, intra-atrial stasis, structural heartdisease or fibrillation. AF = atrial blood vessel abnormalities and abnormal platelets haemostasis,leading to a are listed in hierarchical order modified prothrombotic state leads Outcomes predisposition to thrombus formation. This from a suggestion put forward and thromboembolism in AF (See The 1, Page 1). Only antithromboticto stroke in a recent consensus document.2Table prevention of these outcomestherapy has been shown to reduce AF-related deaths.6 is the main therapeutic goal in AF patients.<<Table 2 >>Stroke in AF is often severe and results in long-term disability or death.Approximately 20% of stroke is due to AF and undiagnosed ‘silent AF’ is a likelycause of some ‘cryptogenic’ strokes.2,7 Paroxysmal AF carries the same strokerisk as permanent or persistent AF.8AF also account for one-third of all admissions for cardiac arrhythmias. AcuteCoronary Syndrome (ACS), aggravation of heart failure, thrombo-emboliccomplications, and acute arrhythmia management are the main causes.Quality of life and exercise capacity are degraded in patients with AF.9 This maybe related to impaired left ventricular (LV) function that accompanies theirregular, fast ventricular rate, loss of atrial contractile function and increasedend-diastolic LV lling pressure. 4
    • 2. PATHOPHYSIOLOGYUnderstanding the pathophysiology of atrial brillation (AF) requires integrationof information from clinical, histological, electrophysiological andechocardiographic sources. There is no single cause or mechanism that resultsin AF, and it may present in a multitude of ways.2.1 CLINICAL ASPECTSThere are many risk factors for developing AF. In the Framingham study thedevelopment of AF was associated with increasing age, diabetes, hypertensionand valve disease. It is also commonly associated with, and complicated by HFand strokes.2.1.1 CAUSES AND ASSOCIATED CONDITIONSAF is often associated with co-existing medical conditions. The underlyingconditions and factors predisposing patients to AF are listed in Table 3.<<Table 3 >> Table 3: Common cardiac and non-cardiac risk factors of AF.Some of the conditions predisposing to AF may be reversible such as acute Elevated Atrial Pressureinfections, alcohol excess, surgery, pericarditis, myocarditis, pulmonary Systemic HypertensionpathologyHypertension Pulmonary and thyrotoxicosis. Therefore, long-term therapy of AF may not beindicated disease (cardiomyopathy with systolic and/or diastolicbeen addressed. When AF is Myocardial once the reversible causes have dysfunction) Mitral or tricuspid valve disease Aortic or pulmonary other supraventricular arrhythmias, treatment of the primaryassociated withvalve diseasearrhythmiatumours Intracardiac reduces or eliminates the recurrence of AF. Sleep apnoea Atrial ischemia Coronary artery diseaseApproximately 30 – 40%disease Inflammatory or infiltrative atrial of cases of paroxysmal AF and 20 – 25% of persistentAF occur or pericarditis patients without demonstrable Myocarditis in young underlying disease. These Amyloidosiscases are oftenfibrosis Age-induced atrial referred to as ‘lone AF’. Primary or metastatic cancer in/or adjacent to the atrial wall Drugs Alcohol Caffeine Endocrine disorders Hyperthyroidism Phaeochromocytoma Changes in autonomic tone Increased sympathetic tone Increased parasympathetic tone Postoperative Cardiothoracic surgery Oesophageal surgery Neurogenic Subarchnoid haemorrhage Haemorrhagic stroke Ischemic stroke Idiopathic Lone AF Familial AF Other Congenital heart disease Chronic renal disease Obesity 5
    • 2.1.1 CAUSES AND ASSOCIATED CONDITIONSAF is often associated with co-existing medical conditions. The underlyingconditions and factors predisposing patients to AF are listed in Table 3.<<Table 3 >>Some of the conditions predisposing to AF may be reversible such as acuteinfections, alcohol excess, surgery, pericarditis, myocarditis, pulmonarypathology and thyrotoxicosis. Therefore, long-term therapy of AF may not beindicated once the reversible causes have been addressed. When AF isassociated with other supraventricular arrhythmias, treatment of the primaryarrhythmia reduces or eliminates the recurrence of AF.Approximately 30 – 40% of cases of paroxysmal AF and 20 – 25% of persistentAF occur in young patients without demonstrable underlying disease. Thesecases are often referred to as ‘lone AF’.3 INITIAL MANAGEMENT3.1 CLINICAL HISTORY, PHYSICAL EXAMINATION AND INVESTIGATIONSThe acute management of AF patients should concentrate on Relief of symptoms Assessment of AF-associated risk Determination of the European Heart Rhythm Association (EHRA) score (Table 5, page 7) Estimation of stroke risk (see Section 6.1, page 26) Search for conditions that predispose to AF (see Section 2.1.1, page 5) and Search for complications of the arrhythmia (see Section 1.4, page 3)With the above in mind, a thorough medical history should be obtained from thepatient with suspected or known AF (see Table 4).<<Table 4>> questions to be put to a patient with suspected or known AFTable 4: Relevant questions to be put to a patient with suspected or known AFTable 4: Relevant Does the heart rhythm during the episode feel regular or irregular?The there any precipitating factor such as exercise, emotion,tool for Is EHRA symptom score (see Table 5) provides a simple clinical orassessing symptoms during AF. The score only considers symptoms that are alcohol intake?attributable to AF and reverse or reduce upon restoration of sinus rhythm or witheffective rate control. Are symptoms during the episodes moderate or severe—the severity<<Table 5 expressed using the EHRA score, which is similar to the may be >> 3 CCS-SAF score.41 Are the episodes frequent or infrequent, and are they long or short3.1.1 DETECTION lasting?Those with undiagnosed AF can receive treatment sooner if an opportunistic Is there a history of concomitant disease such as hypertension,case finding is undertaken. Routine palpation of the radial pulse (not less than 20 coronary heart disease, heart failure, peripheral vascular disease,seconds) during screening of blood pressure will be a good opportunity to pick upundiagnosed atrial fibrillation. stroke, diabetes, or chronic pulmonary cerebrovascular disease, disease?In patients presenting with any of the following: breathlessness/dyspnoea, Is there an alcohol abuse habit? palpitations, syncope/dizziness, Is there a family history of AF? chest discomfort or stroke/TIA,manual fibrillation; CCS-SAF =should be performed to assess in Atrial Fibrillation; EHRA = anAF = atrial pulse palpation Canadian Cardiovascular Society Severity for the presence ofAF = atrial fibrillation; CCS-SAF = Canadian Cardiovascular Society Severity in Atrial Fibrillation; EHRA =irregular pulse thatAssociation.European Heart Rhythm may indicate AF.European Heart Rhythm Association. 6
    • With the above in mind, a thorough medical history should be obtained from thepatient with suspected or known AF (see Table 4).<<Table 4>>3 INITIAL MANAGEMENTThe EHRA symptom score (see Table 5) provides a simple clinical tool for3.1 CLINICAL HISTORY, PHYSICAL EXAMINATION AND INVESTIGATIONSassessing symptoms during AF. The score only considers symptoms that areattributable to AF and reverse or reduce upon restoration of sinus rhythm or withThe acute management of AF patients should concentrate oneffective rate control. Relief of symptoms Assessment of AF-associated risk<<Table 5 >> Determination of the European Heart Rhythm Association (EHRA) scoreTable 5 : EHRA score of AF-related symptoms (Table 5, page 7) Estimation of stroke risk (see Section 6.1, page 26) Search for conditions of AF-related symptoms (EHRA score) 5) and Classification that predispose to AF (see Section 2.1.1, page3.1.1 DETECTION Search for complications of the arrhythmia (see Section 1.4, page 3) EHRA class ExplanationThose with undiagnosed AF can receive treatment sooner if an opportunisticWith the above in mind, a thorough medical history should be obtained from thecase finding is undertaken. Routine palpation of the radial pulse (not less than 20patient with suspected or known AF (see Table 4). ‘No symptoms’seconds)Iduring screening of blood pressure will be a good opportunity to pick up EHRAundiagnosed atrial fibrillation.<<Table 4>> EHRA II ‘Mild symptoms’; normal daily activity not affectedIn patients presenting with any of the following: EHRA III ‘Severe symptoms’; normal daily activity affected breathlessness/dyspnoea, palpitations,The EHRA symptom score (see Table 5) provides a simple clinical tool for EHRA IV syncope/dizziness, ‘Disabling symptoms’; normal daily activityassessing symptoms during AF. The score only considers symptoms that areattributable discontinued chestto AF and reverse or reduce upon restoration of sinus rhythm or with discomfort or stroke/TIA,manual pulsecontrol.effective rate palpation should be performed to assess for the presence of anirregular pulse that may indicate AF.AF = atrial fibrillation; EHRA = European Heart Rhythm Association.<<Table 5 >>3.1.1 DETECTIONThose with undiagnosed AF can receive treatment sooner if an opportunisticcase finding is undertaken. Routine palpation of the radial pulse (not less than 20seconds) during screening of blood pressure will be a good opportunity to pick upundiagnosed atrial fibrillation.In patients presenting with any of the following: breathlessness/dyspnoea, palpitations, syncope/dizziness, chest discomfort or stroke/TIA,manual pulse palpation should be performed to assess for the presence of anirregular pulse that may indicate AF.3.1.1.1 ELECTROCARDIOGRAMThe diagnosis of AF requires confirmation by ECG, sometimes in the formof bedside telemetry, ambulatory Holter recordings and event looprecordings. 2, 10If AF is present at the time of recording, a standard 12-lead ECG is sufficient toconfirm the diagnosis. In paroxysmal AF, 7-days Holter ECG recording or dailyand symptom-activated event recordings may document the arrhythmia in 70% ofAF patients.2The search for AF should be intensified; including prolonged monitoring, when 7patients
    • of bedside telemetry, ambulatory Holter recordings and event looprecordings. 2, 10If AF is present at the time of recording, a standard 12-lead ECG is sufficient toconfirm the diagnosis. In paroxysmal AF, 7-days Holter ECG recording or dailyand symptom-activated event recordings may document the arrhythmia in 70% ofAF patients.2The search for AF should be intensified; including prolonged monitoring, whenpatients Are highly symptomatic (EHRA III & IV) Present with recurrent syncope and After a cryptogenic stroke.11, 12In stroke survivors, a step-wise addition of ve daily short-term ECGs, one 24 hHolter ECG, and another 7-day Holter ECG will each increase the detection rateof AF by a similar extent.113.2 DIAGNOSTIC EVALUATIONThe initial diagnostic work-up is driven by the initial presentation.The time of onset of AF should be established to dene the type of AF (Figure 2).Patients with AF and signs of acute heart failure require urgent rate control andoften cardioversion. An urgent transthoracic echocardiogram (TTE) should beperformed in haemodynamically-compromised patients to assess LV and valvularfunction and right ventricular pressure. If AF duration is >48 h or there is doubtabout its duration, transesophageal echocardiogram (TOE) should be used torule out intracardiac thrombus prior to cardioversion.13Patients with stroke or TIA require immediate stroke diagnosis, usually viaemergency computed tomography (CT).Patients should be assessed for risk of stroke. Most patients with acute AF willrequire anticoagulation unless they are at low risk of thromboemboliccomplications (no stroke risk factors) and no cardioversion is necessary (e.g. AFterminates within 24 – 48 h).After the initial management of symptoms and complications, underlying causesof AF should be sought. A TTE is useful to detect ventricular, valvular, and atrialdisease as well as rare congenital heart disease. Thyroid function tests, a fullblood count, a serum creatinine measurement and analysis for proteinuria,measurement of blood pressure, and a test for diabetes mellitus are useful. Aserum test for hepatic function may be considered in selected patients. A stresstest is reasonable in patients with signs or risk factors for coronary arterydisease. Patients with persistent signs of LV dysfunction and/or signs ofmyocardial ischemia are candidates for coronary angiographyTable 6 lists the clinical evaluation that may be necessary in patients with AF.<<Table 6 >>3.3 ECHOCARDIOGRAPHYTTE should be performed in patients with AF: o For whom a baseline echocardiogram is important for long-term management. o For whom a rhythm-control strategy that includes cardioversion (electrical or pharmacological) is being considered. o In whom there is a high risk or a suspicion of underlying structural/functional heart disease (such as heart failure or heart 8 murmur) that influences their subsequent management (for
    • Table 6 : Clinical Evaluation in Patients With AFMinimum evaluation1. Electrocardiogram, to identify Rhythm (verify AF) LV hypertrophy P-wave duration and morphology or fibrillatory waves Preexcitation Bundle-branch block Prior MI Other atrial arrhythmias To measure and follow the R-R, QRS, and QT intervals in conjunction with antiarrhythmic drug therapy2. Transthoracic echocardiogram, to identify Valvular heart disease LA and RA size LV size and function Peak RV pressure (pulmonary hypertension) LV hypertrophy LA thrombus (low sensitivity) Pericardial disease3. Blood tests of thyroid, renal, and hepatic function For a first episode of AF, when the ventricular rate is difficult to controlAdditional testingOne or several tests may be necessary.1. Six-minute walk test If the adequacy of rate control is in question2. Exercise testing If the adequacy of rate control is in question (permanent AF) To reproduce exercise-induced AF To exclude ischemia before treatment of selected patients with a type IC antiarrhythmic drug3. Holter monitoring or event recording If diagnosis of the type of arrhythmia is in question As a means of evaluating rate control4. Transesophageal echocardiography To identify LA thrombus (in the LA appendage) To guide cardioversion5. Electrophysiological study To clarify the mechanism of wide-QRS-complex tachycardia To identify a predisposing arrhythmia such as atrial flutter or paroxysmal supraventricular tachycardia To seek sites for curative ablation or AV conduction block/modification6. Chest radiograph, to evaluate Lung parenchyma, when clinical findings suggest an abnormality Pulmonary vasculature, when clinical findings suggest an abnormalityType IC refers to the Vaughan Williams classification of antiarrhythmic drugs (see Appendix D). AF = atrialfibrillation; AV = atrioventricular; LA = left atrial; LV = left ventricular; MI = myocardial infarction; RA = rightatrial; RV = right ventricular. 9
    • disease. Patients with persistent signs of LV dysfunction and/or signs ofmyocardial ischemia are candidates for coronary angiographyTable 6 lists the clinical evaluation that may be necessary in patients with AF.<<Table 6 >>3.3 ECHOCARDIOGRAPHYTTE should be performed in patients with AF: o For whom a baseline echocardiogram is important for long-term management. o For whom a rhythm-control strategy that includes cardioversion (electrical or pharmacological) is being considered. o In whom there is a high risk or a suspicion of underlying structural/functional heart disease (such as heart failure or heart murmur) that influences their subsequent management (for example, choice of antiarrhythmic drug) o In whom refinement of clinical risk stratification for antithrombotic therapy is needed.In patients with AF who require anticoagulation therapy based on relevant clinicalcriteria, TTE need not be routinely performed.TOE should be performed in patients with AF: o Where TTE is technically difficult and/or of questionable quality and where there is a need to exclude cardiac abnormalities o For whom TOE-guided cardioversion is being considered. (See section 6.4.5, page 38)3.4 CLINICAL FOLLOW-UPThe specialist caring for the AF patient should not only perform the baselineassessment and institute the appropriate treatment, but also suggest a structuredplan for follow-up.Important considerations during follow-up of the AF patient are listed below: Has the risk prole changed (e.g. new diabetes or hypertension), especially with regard to the indication for anticoagulation? Is anticoagulation now necessary—have new risk factors developed, or has the need for anticoagulation passed, e.g. postcardioversion in a patient with low thrombo-embolic risk? Have the patient’s symptoms improved on therapy; if not, should other therapy be considered? Are there signs of proarrhythmia or risk of proarrhythmia; if so, should the dose of an antiarrhythmic drug be reduced or a change made to another therapy? Has paroxysmal AF progressed to a persistent/permanent form, in spite of antiarrhythmic drugs; in such a case, should another therapy be considered? Is the rate control approach working properly; has the target for heart rate at rest and during exercise been reached?The diagnosis of AF requires documentation by ECG.2,10 10In patients with suspected AF, an attempt to record an ECG should be made
    • dose of an antiarrhythmic drug be reduced or a change made to another therapy? Has paroxysmal AF progressed to a persistent/permanent form, in spite of antiarrhythmic drugs; in such a case, should another therapy be considered? Is the rate control approach working properly; has the target for heart rateKeypoints at rest and during exercise been reached? IBIB The diagnosis of AF requires documentation by ECG.2,10IB IB In patients with suspected AF, an attempt to record an ECG should be made when symptoms suggestive of AF occur.2,14 A simple symptom score (EHRA class) is recommended to quantify AF-related IBIB symptoms.2,15 IC All patients with AF should undergo a thorough physical examination, and aIC cardiac- and arrhythmia-related history should be taken.IB In patients with severe symptoms, documented or suspected heart disease, or IB risk factors, an echocardiogram is recommended.2,16,17 IC In patients treated with antiarrhythmic drugs, a 12-lead ECG should be recordedIC at regular intervals during follow-up. IIaB In patients with suspected symptomatic AF, additional ECG monitoring should beIIa B considered in order to document the arrhythmia.2,18 IIaB Additional ECG monitoring should be considered for detection of ‘silent’ AF inIIa B patients who may have sustained an AF-related complication. 2,19 In patients with AF treated with rate control, Holter ECG monitoring should be IIaCIIa C considered for assessment of rate control or bradycardia.IIa C IIaC In young active patients with AF treated with rate control, exercise testing should be considered in order to assess ventricular rate control. In patients with documented or suspected AF, an echocardiogram should be IIaCIIa C considered. IIaC Patients with symptomatic AF or AF-related complications should be consideredIIa C for referral to a cardiologist. IIaC A structured follow-up plan prepared by a specialist is useful for follow-up by aIIa C general or primary care physician. IIbB In patients treated with rhythm control, repeated ECG monitoring may beIIb B considered to assess the efficacy of treatment.2,20,21 IIbC Most patients with AF may benet from specialist follow-up at regular intervals.IIb C <<Figure 3>> 11
    • 12 Figure 3: Choice of rate and rhythm control strategies. Rate control is needed for most patients with AF unless the heart rate during AF is naturally slow. Rhythm control may be added to rate control if the patient is symptomatic despite adequate rate control, or if a rhythm control strategy is selected because of factors such as the degree of symptoms, younger age, or higher activity levels. Permanent AF is managed by rate control unless it is deemed possible to restore sinus rhythm when the AF category is re-designated as ‘long-standing persistent’. Paroxysmal AF is more often managed with a rhythm control strategy, especially if it is symptomatic and there is little or no associated underlying heart disease. Solid lines indicate the first-line management strategy. Dashed lines represent fall-back objectives and dotted lines indicate alternative approaches which may be used in selected patients. Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal 2010; doi:10.1093/eurheartj/ehq278)
    • 4. MANAGEMENT PRINCIPLES4.1 GENERAL PRINCIPLESIn patients with AF or AFI, the aims of treatment involve the following fiveobjectives. I Relief of symptoms, such as palpitations, dizziness, fatigue and dyspnoea, is paramount to the patient. II. The prevention of serious complications, such as thromboembolism (particularly ischaemic stroke) and heart failure, is equally important. III. Optimal management of concomitant cardiovascular disease. IV. Rate control. V. Correction of rhythm disturbance.These goals are not mutually exclusive and may be pursued simultaneously. Theinitial strategy may differ from the long-term therapeutic goal.A fundamental question to be answered for every patient with AF or AFI iswhether to obtain and maintain sinus rhythm by pharmacological ornonpharmacological means (a rhythm-control strategy), or whether to aimprimarily to control heart rate rather than the rhythm (a rate-control strategy).For patients with symptomatic AF lasting many weeks, initial therapy may beanticoagulation and rate control while the long-term goal is to restore sinusrhythm.If rate control offers inadequate symptomatic relief, restoration of sinus rhythmbecomes a clear long-term goal. When cardioversion is contemplated and theduration of AF is unknown or exceeds 48 h, anticoagulation will be necessary.Early cardioversion may be necessary if AF causes hypotension or worseningheart failure. In contrast, amelioration of symptoms by rate control in olderpatients may steer the clinician away from attempts to restore sinus rhythm. Insome circumstances, when the initiating pathophysiology of AF is reversible, asfor instance in the setting of thyrotoxicosis or after cardiac surgery, no long-termtherapy may be necessary.Regardless of the approach, the need for anticoagulation is based on stroke riskand not on whether sinus rhythm is maintained.For rate and rhythm control, drugs remain the first choice. Radiofrequencyablation may be considered in symptomatic AF and in lone AF to avoid long-termdrug therapy. In selected individuals undergoing cardiac surgery, surgical mazeprocedure may be a therapeutic option.4.2 THROMBOEMBOLIC PROPHYLAXISAntithrombotic therapy must be considered in all patients with AF. Strategies thatmay reduce thromboembolic risk include the following treatments: 13• Anticoagulants such as Vitamin K Antagonist,
    • For rate and rhythm control, drugs remain the first choice. Radiofrequencyablation may be considered in symptomatic AF and in lone AF to avoid long-termdrug therapy. In selected individuals undergoing cardiac surgery, surgical mazeprocedure may be a therapeutic option.4.2 THROMBOEMBOLIC PROPHYLAXISAntithrombotic therapy must be considered in all patients with AF. Strategies thatmay reduce thromboembolic risk include the following treatments:• Anticoagulants such as Vitamin K Antagonist,• Antiplatelet agents, such as aspirin and clopidogrel• Intravenous (IV) heparin or low molecular weight heparin (LMWH)• Left atrial appendage (LAA) occlusion, either surgically or percutaneously.The decision regarding the method of reduction in the risk of stroke, should takeinto account both the person’s risk of thromboembolism and their risk of bleeding.It is important to remember that vitamin K antagonist such as Warfarin is veryeffective and reduces the risk of stroke overall by two thirds. (For details seeSection 6, page 26)4.3. HEART RATE CONTROL VERSUS RHYTHM CONTROLRate control involves the use of chronotropic drugs or electrophysiological orsurgical interventions to reduce the rapid heart rate (ventricular rate) often foundin patients with AF. Although the atria continue to fibrillate with this strategy, it isnonetheless thought to be an effective treatment as it improves symptoms andreduces the risk of associated morbidity. However, the persistence of thearrhythmia continues the risk of stroke and thromboembolic events occurring.Administering antithrombotic drugs reduces this risk. (See Figure 3, page 12)Rhythm control involves the use of electrical or pharmacological cardioversion orelectrophysiological or surgical interventions to convert the arrhythmia associatedwith AF to normal sinus rhythm. Patients who have been successfullycardioverted are generally administered antiarrhythmic drugs for the long term tohelp prevent the recurrence of AF. The rhythm control strategies also require theappropriate administration of antithrombotic therapy to reduce the risk of strokeand thromboembolic events occurring.Randomized trials comparing outcomes of rhythm versus rate control strategiesin patients with AF are summarized in Table 7 and 8.22-28<<Table 7>><<Table 8>> 14
    • Table 7: General characteristic s of rhythm control and rate control trials in patients with AF Trial Ref Patients Mean Mean Inclusion criteria Primary outcome parameter Patients reaching primary (n) age follow-up outcome (n) (years) (years) Rate Rhythm P control control Persistent AF 76/125 70/127 PIAF (2000) 22 252 61.0 1.0 Symptomatic improvement 0.32 (7–360 days) (60.8%) (55.1%) Paroxysmal AF or persistent AF, age >65 310/2027 356/2033 AFFIRM (2002) 23 4060 69.7 3.5 All-cause mortality 0.08 years, or risk of stroke or (25.9%) (26.7%) death Composite: cardiovascular Persistent AF or flutter for death, CHF, severe bleeding, <1 years and 1–2 pacemaker implantation, 44/256 60/266 RACE (2002) 24 522 68.0 2.3 cardioversions over 2 0.11 thrombo-embolic events, (17.2%) (22.6%) years and oral severe adverse effects of anticoagulation antiarrhythmic drugs Persistent AF Composite: overall (>4 weeks and mortality, cerebrovascular 10/100 9/100 STAF (2003) 25 200 66.0 1.6 <2 years), LA size 0.99 complications, CPR, embolic (10.0%) (9.0%) >45 mm, CHF NYHA15 events II–IV, LVEF <45% First clinically overt Composite: death, persistent AF (>–7 days thrombo-embolic events; 1/101 4/104 HOTCAFE (2004) 26 205 60.8 1.7 > 0.71 and <2 years), intracranial/major (1.0%) (3.9%) age 50–75 years haemorrhage LVEF <–35%, symptoms of CHF, history of AF 175/1376 182/1376 AF-CHF (2008) 27 1376 66 3.1 Cardiovascular death 0.59 (>–6 h or (25%) (27%) DCC <last 6 months) Composite of total mortality, symptomatic cerebral infarction, 89/405 64/418 J-RHYTHM (2009) 28 823 64.7 1.6 Paroxysmal AF systemic embolism, major 0.012 (22.0%) (15.3%) bleeding, hospitalization for heart failure, or physical/ psychological disability AF = atrial fibrillation; AFFIRM = Atrial Fibrillation Follow-up Investigation of Rhythm Management; CHF = congestive heart failure; CPR = cardiopulmonary resuscitation; DCC = direct current cardioversion; HOT CAFE´ = How to Treat Chronic Atrial Fibrillation; J-RHYTHM = Japanese Rhythm Management Trial for Atrial Fibrillation; LVEF = left ventricular ejection fraction; NYHA = New York Heart Association; PIAF = Pharmacological Intervention in Atrial Fibrillation; RACE = RAte Control versus Electrical cardioversion for persistent atrial fibrillation; STAF = Strategies of Treatment of Atrial Fibrillation.
    • Table 8: Comparison of adverse outcomes in rhythm control and rate control trials in patients with AF Trial Ref Death from all causes Deaths from Deaths from non- Stroke Thrombo-embolic Bleeding (in rate/rhythm) cardiovascular cardiovascular causes events causes a PIAF (2000) 22 4 1/1 1 ND ND ND AFFIRM (2002) 23 666 (310/356) 167/164 113/165 77/80 ND 107/96 RACE (2002) 24 36 18/18 ND ND 14/21 12/916 STAF (2003) 25 12 (8/4) 8/3 0/1 1/5 ND 8/1 HOT CAFÉ (2004) 26 4 (1/3) 0/2 1/1 0/3 ND 5/8 AF-CHF (2008) 27 228/217 175/182 53/35 11/9 ND ND a Total number of patients not reported. AF = atrial fibrillation; AFFIRM = Atrial Fibrillation Follow-up Investigation of Rhythm Management; HOT CAFE´ = HOw to Treat Chronic Atrial Fibrillation; ND = not determined; PIAF = Pharmacological Intervention in Atrial Fibrillation; RACE = RAte Control versus Electrical cardioversion for persistent atrial fibrillation; STAF = Strategies of Treatment of Atrial Fibrillation.
    • The consistent nding in all ve studies was that rhythm control offered nosurvival advantage and, in most cases, had little effect on morbidity and quality oflife. However, it should be emphasised that these conclusions are not necessarilyapplicable to all groups of patients. The ve recent studies enrolled mostly olderpatients with additional risk factors for stroke, many of whom also had heartfailure. Younger patients with normal hearts and primarily paroxysmal atrialbrillation (PAF) were not well represented. Importantly, in a predened subgroupof AFFIRM participants aged less than 65 years, hazard ratios for death showeda paradoxical trend towards superiority of the rhythm-control strategy.The initial therapy after onset of AF should always include adequateantithrombotic treatment and control of the ventricular rate. If the ultimate goal isrestoration and maintenance of sinus rhythm, rate control medication should becontinued throughout follow-up, unless continuous sinus rhythm is present. Thegoal is to control the ventricular rate adequately whenever recurrent AF occurs.The decision to add rhythm control therapy to the management of AF requires anindividual decision and should therefore be discussed at the beginning of AFmanagement. Before choosing rate control alone as a long-term strategy, theclinician should consider how permanent AF is likely to affect the individualpatient in the future and how successful rhythm control is expected to be (Figure3, page 12). Symptoms related to AF are an important determinant in making thedecision to opt for rate or rhythm control (e.g. globally assessed by the EHRAscore, Table 5, page 7), in addition to factors that may inuence the success ofrhythm control. The latter include a long history of AF, older age, more severeassociated cardiovascular diseases, other associated medical conditions, andenlarged LA size.A rate-control strategy should be the preferred initial option in the followingpatients with persistent AF: Over 65 years old With coronary artery disease and/or left ventricular dysfunction With contraindications to antiarrhythmic drugs Unsuitable for cardioversion*A rhythm-control strategy should be the preferred initial option in the followingpatients with persistent AF: Those who are symptomatic Younger patients Those presenting for the first time with lone AF Those with AF secondary to a treated/corrected precipitantKeypoints Rate control should be the initial approach in elderly patients with AF and minor IA IA symptoms (EHRA class 1).23,24,27 Rhythm control is recommended in patients with symptomatic (EHRA class 2) IB IB AF despite adequate rate control.2,21,29,30,31 Rate control should be continued throughout a rhythm control approach to IA IA ensure adequate control of the ventricular rate during recurrences of AF. 23 Rhythm control as an initial approach should be considered in young IIaC IIaC symptomatic patients in whom catheter ablation treatment has not been ruled out. 17 Rhythm control should be considered in patients with AF secondary to a trigger IIaC or substrate that has been corrected (e.g. ischaemia, hyperthyroidism).
    • AF despite adequate rate control. Rate control should be continued throughout a rhythm control approach to IA ensure adequate control of the ventricular rate during recurrences of AF. 23 Rhythm control as an initial approach should be considered in young IIaC symptomatic patients in whom catheter ablation treatment has not been ruled out. Rhythm control should be considered in patients with AF secondary to a trigger IIac IIaC or substrate that has been corrected (e.g. ischaemia, hyperthyroidism). IIaB Rhythm control in patients with AF and AF-related heart failure should be IIaB considered for improvement of symptoms.29,30,325. MANAGEMENT – ACUTE-ONSET AF 5. MANAGEMENT – ACUTE-ONSET AF5.1 ACUTE AF IN HEMODYNAMICALLY UNSTABLE PATIENTS 5.1 ACUTE AF IN HEMODYNAMICALLY UNSTABLE PATIENTSThe majority of patients who present with AF are hemodynamically stable butthere is a small group of patientswho present with AF are hemodynamically stable but The majority of patients who are significantly compromised by the onsetof AF. These patients requireof patients who are significantly compromised by the onset there is a small group immediate hospitalization and urgent interventionto preventof AF. These patients require immediate hospitalization and urgent intervention further deterioration. to prevent further deterioration.Those considered in this group are; 33 Those considered in this group are; 33 Those with a ventricular rate greater than 150 bpm With ongoing chest pains, or rate greater than 150 bpm Those with a ventricular With ongoing chest pains, or Critical perfusion. Critical perfusion.In these circumstances, the concerns regarding intervention in the absence ofanticoagulation and echocardiography are regarding intervention inthe need forof In these circumstances, the concerns counterbalanced by the absence anticoagulation and echocardiography are counterbalanced by the need forurgent treatment. urgent treatment.5.1.1 ACUTE RATE CONTROL 5.1.1 ACUTE RATE CONTROLIt is important important to understandinthat in these circumstances the slow onsetofof It is to understand that these circumstances the slow onsetdigoxin makes it makes it inappropriate forinuse in situation. Patients whose AF isis digoxin inappropriate for use this this situation. Patients whose AFassociated with thyrotoxicosis will not respond to any any measures untilthe associated with thyrotoxicosis will not respond to measures until theunderlyingunderlying thyroid disease treated. Patients with with accessory pathway such thyroid disease is first is first treated. Patients accessory pathway suchas the Wolff-Parkinson-White (WPW) syndrome are particularly at risk following as the Wolff-Parkinson-White (WPW) syndrome are particularly at risk followingthe onset the onset of AF becausecan present with with very rapid ventricular rates of AF because they they can present very rapid ventricular rates(greater than 200 than 200 bpm) and mayspecific management. (greater bpm) and may need need specific management.When patients present with unacceptably high ventricular raterate the primary aim is When patients present with unacceptably high ventricular the primary aim isone of rate control. control. one of rateAF with slow with slow ventricular rates may respond to atropine (0.5 – 2 mg i.v.), but many AF ventricular rates may respond to atropine (0.5 – 2 mg i.v.), but many patients with symptomatic bradyarrhythmia may require either urgent placementpatients with symptomatic bradyarrhythmia may require either urgent placement of a temporary pacemaker lead in the right ventricle and/or cardioversion.of a temporary pacemaker lead in the right ventricle and/or cardioversion. Acute initiation of rate control therapy should usually be followed by a long-termAcute initiation of rate control therapy should usually be followed by a on page 66. rate control strategy; details of drugs and doses are given in Section 7 long-termrate control strategy; details of drugs and doses are given in Section 7 on page 66.Keypoints In the acute setting in the absence of pre-excitation, i.v. administration of - IAIn the acute setting in the absence of pre-excitation, i.v. administration of - blockers or non-dihydropyridine calcium channel antagonists is recommended to slow the ventricular response to AF, exercising caution in patients withblockers or non-dihydropyridine calcium channel antagonists is recommended toslow the ventricular responsefailure.34 exercising caution in patients with hypotension or heart to AF, IB In the acute setting, i.v. administration of amiodarone is recommended to control IB the heart rate in patients with AF and concomitant heart failure, or in the setting of hypotension.35 IC In pre-excitation, preferred drugs 18 class I antiarrhythmic drugs (See Appendix are D) or amiodarone.
    • hypotension or heart failure.34 In the acute setting, i.v. administration of amiodarone is recommended to control IB the heart rate in patients with AF and concomitant heart failure, or in the setting of hypotension.35 IC In pre-excitation, preferred drugs are class I antiarrhythmic drugs (See Appendix IC D) or amiodarone. When pre-excited AF is present, ß-blockers, non-dihydropyridine calcium IIIC IIIC channel antagonists, digoxin, and adenosine are contraindicated. <<Table 9>> 5.1.2 PHARMACOLOGICAL CARDIOVERSION Table 9 : Intravenous pharmacological agents for acute control of ventricular rate in AF/AFL Drug In the presence of other cardiacCommonly-used Commonly Onset of abnormalities (e.g. hypertensive heart disease, Adverse Limitations Commonly- valvulardose (IV) disease), onset of maintenance acceptable ventricular ratesused oralstill heart used loading action AF with dose (IV) effects may maintenance compromised cardiac function. While rate control is unlikely to bring aboutfor long- dose clinical improvement in these circumstances, there is a need for the restorationcontrol of sinus term rate Beta-blockers rhythm. Esmolol 0.5 mg/kg 5 min 0.05 to 0.2 mg/ Hypotension, Negative Oral (very short- over 1 min acting) Pharmacological AF may heart block, cardioversion ofkg/min infusion be initiated by a inotropic administration bradycardia, bolus effect preparation not available of an antiarrhythmic drug. Although the conversion rate with antiarrhythmic drugs asthma, heart failure is lower than with direct current cardioversion (DCCV), it does not require Metoprolol conscious sedation or anesthesia, and may facilitate the choice of antiarrhythmic In people 23.75 to 200 with heart mg/day drug therapy to prevent recurrent AF. failure, lower (divided doses) doses may be advisable. Most patients who undergo pharmacological cardioversion require continuous Negative inotropic medical supervision and ECG monitoring during the drug effect infusion and for a Propanolol 0.15mg/kg over 5 5 min N/A 80 to 240 period afterwards (usually about half the drug elimination half-life) to (divided min mg/day detect proarrhythmic events such as ventricular proarrhythmia, sinus node arrest, or doses) atrioventricular block. Several Calcium channel blockers agents are available for pharmacological cardioversion (see Table 10 on Diltiazem Hypotension, In people 120 to 360 page 20). heart block, with heart mg/day heart failure failure, lower (once daily doses may long- <<Table 10>> be advisable. acting) Negative inotropic In clinicalto 0.15 Verapamil0.075 practice, 3 amiodarone isN/A mg/kg over 2 min to 5 min the most usedto(divided 120 360 mg/ day common agent in the effect management of patients presenting in AF with haemodynamic compromise,once it doses or as daily long- appears to have a hybrid effect of rapid reduction in ventricular rateacting)most in hypotension or heart failure.34 of these reverting to sinus rhythm over a longer period. Other patients with a proportion Digoxin 0.25 to 1.0 2 hr 0.125 to 0.25 Digoxin N/A 0.0625 to 0.375 In the acute setting, i.v. administration of mg/day mg <<Figure 4>> amiodaroneblock,recommended tomg/day toxicity, heart is controlIB (individualise the heart rate in patients with AF and concomitant heart failure, or in thedosage) bradycardia setting 35 of hypotension. 5 mg/kg Amiodarone Variable 50 mg/hour Hypotension, N/A 100 to 200 over 20 min (10 min to infusion back pain, mg/day 4 hours) heart block,IC In pre-excitation, preferred drugs are class I antiarrhythmic drugs (See Appendix phlebitis D) or amiodarone. Note: Administration of beta-blockers together with IV verapamil is contraindicated. N/A = not pre-excited AF is present, ß-blockers, non-dihydropyridine calcium When availableIIIC Adapted from: Fuster V, Ryden LE, Asinger RW, et al.134 channel antagonists, digoxin, and adenosine are contraindicated. <<Table 9>> 5.1.2 PHARMACOLOGICAL CARDIOVERSION In the presence of other cardiac abnormalities (e.g. hypertensive heart disease, valvular heart disease), onset of AF with acceptable ventricular rates may still compromised cardiac function. While rate control is unlikely to bring about clinical improvement in these circumstances, there is a need for the restoration of sinus rhythm. Pharmacological cardioversion of AF may be initiated by a bolus administration of an antiarrhythmic drug. Although the 19 conversion rate with antiarrhythmic drugs is lower than with direct current cardioversion (DCCV), it does not require
    • 5.1.2 PHARMACOLOGICAL CARDIOVERSION In the presence of other cardiac abnormalities (e.g. hypertensive heart disease, valvular heart disease), onset of AF with acceptable ventricular rates may still compromised cardiac function. While rate control is unlikely to bring about clinical improvement in these circumstances, there is a need for the restoration of sinus rhythm.hypotension or heart failure.34 of AF may be initiated by a bolus administrationPharmacological cardioversionof an antiarrhythmic drug. Although the conversion rate with antiarrhythmic drugsIn the acute setting, i.v. administration of amiodarone is recommended to controlis lower than with direct current cardioversion (DCCV), it does not requirethe heart rate in patients with AF and concomitant heart choice of antiarrhythmicconscious sedation or anesthesia, and may facilitate the failure, or in the settingof hypotension.35drug therapy to prevent recurrent AF.In pre-excitation, preferred drugs are class I antiarrhythmic drugs (See AppendixMost patients who undergo pharmacological cardioversion require continuousD) or amiodarone.medical supervision and ECG monitoring during the drug infusion and for aperiod afterwards (usually about half the drug elimination half-life) to detectWhen pre-excited AF is as ventricular proarrhythmia, sinus node arrest, orproarrhythmic events such present, ß-blockers, non-dihydropyridine calciumchannel antagonists, digoxin, and adenosine are contraindicated.atrioventricular block. <<Tableagents are available for pharmacological cardioversion (see Table 10 on Several 9>> page 20). 5.1.2 PHARMACOLOGICAL CARDIOVERSION <<Table 10>>Table 10: presence of for pharmacologicalabnormalities (e.g. hypertensive heart disease, In the Drug and doses other cardiac conversion of (recent-onset) AF In clinical practice, amiodarone is the most common agent used in the valvular heart disease), onset of AF with acceptable ventricular rates may still compromised of patients Dose WhileinFollow-up dose unlikely to bring about clinical management cardiac function. Drug presenting rate control is AF with haemodynamic compromise, as it Risk improvement in thesemg/kg i.veffect of 50mg/kg reduction Phlebitis, hypotension. Will in sinus appears to have a 5hybrid over 1h Amiodarone circumstances, rapid is a need in ventricular rate of most there for the restoration slow patients with a proportion of these reverting to sinus rhythm over rate. Delayed AF rhythm. the ventricular a longer period. conversion to sinus rhythm. Flecainide 200-300 mg p.o N/A Not suitable for patients with<<Figure 4>>Pharmacological cardioversion of AF may be initiated by astructural administration marked bolus heart disease,of an antiarrhythmic drug. Although the conversion rate with antiarrhythmicand may prolong QRS duration, drugsis lower than with direct current cardioversion (DCCV), itQT interval; and may hence the does not require inadvertently increase theconscious sedation or anesthesia, and may facilitate the choice of antiarrhythmic ventricular rate due to conversiondrug therapy to prevent recurrent AF. to atrial flutter and 1:1 conduction to the ventricles.Most patients who 450-600 mg p.o Propafenone Not suitable for patients with undergo pharmacological cardioversion require continuous marked structural heartmedical supervision and ECG monitoring during the drugmay prolong QRS for a disease; infusion andperiod afterwards (usually about half the drug elimination half-life) to detect duration; will slightly slowproarrhythmic events such as ventricular proarrhythmia, sinus rate, but may the ventricular node arrest, or inadvertently increase theatrioventricular block. ventricular rate due to conversion to atrial flutter and 1:1 conductionSeveral agents are available for pharmacological cardioversion (see Table 10 on to the ventricles.page 20).<<Table 10>>In clinical practice, amiodarone is the most common agent used in themanagement of patients presenting in AF with haemodynamic compromise, as itappears to have a hybrid effect of rapid reduction in ventricular rate in mostpatients with a proportion of these reverting to sinus rhythm over a longer period.Adapted with modification from the ESC Guidelines for the Management of Atrial<<Figure 4>>Fibrillation (2010 Version) (European heart Journal 2010; doi:10.1093/eurheartj/ehq278) 20
    • Recent Onset AF (<48 h) Haemodynamic instability Yes No Electrical cardioversion Structural heart disease21 Yes No i.v amiodarone oral flecainide oral propefenone Figure 4 Direct current conversion and pharmacological cardioversion of recent-onset AF in patients considered for pharmacological cardioversion. AF= atrial fibrillation Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal 2010; doi:10.1093/eurheartj/ehq278)
    • In suitable patients with recent-onset AF (generally <48 hours duration), a trial ofIn suitable patients with recent-onset AFrhythm can <48 offeredduration), a trial orpharmacological cardioversion to sinus (generally be hours with ecainide ofpharmacological cardioversion to or no underlying structural heart disease) or i.vpropafenone (when there is little sinus rhythm can be offered with ecainide or In suitable patients with recent-onset AF (generally <48 hours duration), a trial ofpropafenonepharmacologicalis is structural sinus rhythm(Figure offered disease) or i.vamiodarone (when there cardioversion to disease)structural heart with ecainide or there little or no underlying can be 4, page 21). Theamiodaroneconversion rate is there iswithin disease) (Figure 4, heart disease) Theanticipated propafenone (when 50% little or~15underlying structural page 21). or i.v (when there is structural no – 120 min.anticipated conversion rate is there within ~15 – disease) (Figure 4, page 21). The amiodarone (when 50% is structural 120 min. suitable patients with rate is 50% AF (generally <48 hours duration), a trial of Inanticipated conversion recent-onset within ~15 – 120 min. pharmacological cardioversion to sinus rhythm can be offered with ecainide or Keypoints When pharmacological(when there is little or no underlying there is no structural heart propafenone cardioversion is preferred and structural heart disease) or i.v When pharmacological(when propafenone is recommended is no structural heart disease, oral ecainidecardioversion is preferred and there for is no structural heart amiodarone or there is structural disease) (Figure cardioversion of When pharmacological cardioversion is preferred and there 4, page 21). The disease, oralAF.36-38 oral ecainide or propafenone ~15recommended for cardioversion of IA recent-onsetdisease, conversion rate is 50% within is – 120 min.for cardioversion of ecainide or propafenone is recommended anticipated AF.36-38 recent-onsetrecent-onset AF.36-38 In patients with recent-onset AF and structural heart disease, i.v. amiodarone is recommended.patients with39-41 AF and AF andis preferreddisease, i.v.no structural heart In IA IA patients When recent-onset cardioversion structural heart disease, i.v. amiodaroneis In pharmacological with39-41 recent-onset structural heart and there is amiodarone is disease, oral ecainide or propafenone is recommended for cardioversion of recommended. 36-38 recommended.39-41 recent-onset AF. Digoxin (Level of Evidence Evidence A), verapamil, sotalol, metoprolol (Level of Evidence Digoxin (Level of A), verapamil, sotalol, metoprolol (Level of Evidence Digoxin (Level of Evidence A),agentsof Evidence C) heartineffective in inEvidence B), other InB), other with recent-onset AF andsotalol, metoprolol (Level amiodarone is IIIABC IIIABC -blocking agents (Level (Level of Evidence C) are ineffectiveofconverting patients -blocking verapamil, structural are disease, i.v. converting IA B), other recommended. AF to (Level ofareand are not recommended. recent- onset AF toonset rhythm and Evidence C) are ineffective in converting -blocking agents sinus rhythm not recommended. recent- sinus 39-41 recent- onset AF to sinus rhythm and are not recommended. In ICIC Digoxin (Level with a life-threatening deterioration haemodynamic stability patients In patientslife-threatening verapamil, sotalol, metoprolol (Level of Evidence with a of Evidence A), deterioration in in haemodynamic stabilityIIIABC In patients following -blocking agentsAF, emergency electrical cardioversion should be B), other the onset of (Level of Evidence C) are ineffective in converting following thewith onsetlife-threatening deterioration in cardioversion should be a AF, emergency electrical haemodynamic stability onset of to sinus rhythm and are recent- performed, irrespective of the duration ofnot recommended. AF the AF. following the onset of the duration of the electrical cardioversion should be performed, irrespective of AF, emergency AF. performed,In5.1.2.1 Pill-in-the-pocket approach deterioration in haemodynamic stability irrespective of the duration of the AF. patients with a life-threatening IC 5.1.2.1 Pill-in-the-pocket approach emergency electrical cardioversion should be following the onset of AF, The pill-in-the-pocket approach42 refers AF. 5.1.2.1 Pill-in-the-pocket approach duration of theto outpatient administration of oral performed, irrespective of the The pill-in-the-pocket approach42 or propafenone (450 to 600 mg) to carefully selected ecainide (200 to 300 mg) refers to outpatient administration of oral ecainide (200 to Pill-in-the-pocket approach (450 to was effective carefully selected The pill-in-the-pocket mg) or propafenonehospital 600 mg) to and well tolerated. patients whose initial therapy in to outpatient administration of oral 5.1.2.1 42 300 approach refers This 300 mg) or propafenone in appropriately selected patientsselected in hospital was effective to carefully who ecainidewhose approach could be considered(450 to 600 mg)and well tolerated.oral patients (200 toinitial therapyapproach42 refers to outpatient administration of have IIaB The pill-in-the-pocket patients whose initial therapy insymptoms of paroxysmal600 (PAF). carefully selected infrequent but prolonged hospital was effective and well tolerated. ecainide (200 to 300 mg) or propafenone (450 to AF mg) to This approach could be considered in in hospital was selected and well tolerated. Keypoints patients whose initial therapy appropriately effective patients who have This approachprolonged consideredof paroxysmal AFselected with this approach and infrequent but could be symptoms in appropriately (PAF). patients who have There is an uncommon probability of AF reverting to AFL before antiarrhythmic medication is initiated, a beta-blocker, diltiazem or infrequent but prolongedcould be considered in appropriately selected patients who have This approach symptoms of paroxysmal AF (PAF). IIaB IIaB infrequent but probability of prevent paroxysmal AF with this approach and verapamil should be given to rapid AV conduction. There is an uncommon prolonged symptomsreverting to AFL (PAF). AF of There isantiarrhythmic the conditions belowreverting a AFL with this approach and before an uncommon probability ofis initiated, to beta-blocker, diltiazem and medication AF of AF reverting to AFL such thisapproach: or There is an uncommon probability are contraindicated for with an approach Patients with before antiarrhythmic agedto prevent75 years, initiated, beta-blocker, diltiazem or verapamil shouldThose medication is initiated, a a beta-blocker, diltiazem or before be given moremedication is conduction. antiarrhythmic than rapid AV verapamil shouldThose withbe given to prevent AV conduction. verapamil should to prevent greater rapid 7 days, be given AF duration rapid than AV conduction. Patients with the NYHA Class below are contraindicated for such an approach: conditions III to IV or signs of heart failure on examination, Patients with the AF with thanbelow are contraindicated for such an an approach: Those agedconditions 75ventricular rate less than 70 bpm, such approach: Patientsmorethe mean years, with a conditions below are contraindicated for Those with AF duration 75 thaninfarction or angina, agedPrevious myocardial 75 years,days, Those aged more years, more than greater than 7 Valvular heart disease, Those Class III to IVAF duration greater than 7 days, Those with NYHA with AF duration signs of than 7failure on examination, or greater heart days, Cardiomyopathy, NYHA Class III to IV or signs of heart failure on examination, NYHA Class III to IV or signs of less than 70 on examination, AF with a mean ventricular rate heart failure bpm, AF with abranch ventricular rate less than 70 bpm, Bundle mean block, AF with amyocardial infarction or angina, 70 bpm, Previous mean ventricular syndrome, than Previous sick sinus rate less or angina, Known myocardial infarction Previousheart disease,disease, or angina, Valvular myocardial infarction Valvular heart Valvular heart disease, Cardiomyopathy, Cardiomyopathy, Cardiomyopathy,branch Bundle branch block, block, Bundle Known branch block,sinus syndrome, Known sick Bundle sick sinus syndrome, Low serum potassium, Known sick sinus syndrome, Or renal or hepatic insufficiency. With such an approach emergency room visits and hospitalization could markedly be reduced. In selected patients with recent-onset AF and no signicant structural heart IIaB IIaB disease, a single high oral dose of ecainide or propafenone (the ‘pill-in-the- pocket’ approach) should be considered, provided this treatment has proven safe during previous testing in a medically secure environment.42 5.1.3 DIRECT CURRENT CARDIOVERSION 22 DCCV is an effective method of converting AF to sinus rhythm. Successful DCCV is usually dened as termination of AF, documented as the presence of two or
    • With such an approach emergency room visits and hospitalization could markedly be reduced. In selected patients with recent-onset AF and no signicant structural heartIaB disease, a single high oral dose of ecainide or propafenone (the ‘pill-in-the- pocket’ approach) should be considered, provided this treatment has proven safe during previous testing in a medically secure environment.42 5.1.3 DIRECT CURRENT CARDIOVERSION DCCV is an effective method of converting AF to sinus rhythm. Successful DCCV is usually dened as termination of AF, documented as the presence of two or more consecutive P waves after shock delivery. 5.1.3.1 Procedure Low serum potassium, Unless adequatehepatic insufficiency. been documented for 4 weeks or AF is 48 Or renal or anticoagulation has h from a denite onset, a TOE should be performed to rule out atrial thrombi (see Figuresuch an39). With 9, page approach emergency room visits and hospitalization could markedly be reduced. A pacing catheter or external pacing pads may be needed if asystole or bradycardia occurs. with recent-onset AF and no signicant structural heart In selected patientsIaB disease, a single high oral dose of ecainide or propafenone (the ‘pill-in-the- Evidence favours the use be biphasic external debrillators because of their lower pocket’ approach) should of considered, provided this treatment has proven safe energyprevious testing inand greatersecure environment.42 with monophasic during requirements a medically efficacy compared debrillators. Trials have demonstrated a signicant increase in the rst shock 5.1.3 DIRECT CURRENT CARDIOVERSION success rate of DCCV for AF when biphasic waveforms were used. Currently, two conventionalof positions are to sinus rhythm. Successful DCCV DCCV is an effective method converting AF commonly used for electrode placementdenedFigure 5). SeveralAF, documented as thethat anteroposterior is usually (see as termination of studies have shown presence of two or more consecutive P is more effective than anterolateral placement.43 If initial electrode placementwaves after shock delivery. shocks are unsuccessful for terminating the arrhythmia, the electrodes should be repositioned and cardioversion repeated. 5.1.3.1 Procedure << Figure 5>> anticoagulation has been documented for 4 weeks or AF is 48 Unless adequate h Figure 5: Patch/paddle placement for DCCV from a denite onset, a TOE should be performed to rule out atrial thrombi (see Figure 9, page 39). The recommended initial energy for synchronised cardioversion (see figure 6) is: A pacing catheter or external pacing pads may be needed if asystole or Sternal patch/paddle bradycardia occurs. 200J or greater with monophasic waveform Sternal patch Evidence favours the use of biphasic external debrillators because of their lower 100J or greater with biphasic waveform Apex patch/paddle energy requirements and greater efficacy compared with monophasic 10-50J biphasic waveform for AFL debrillators. Trials have demonstrated a signicant increase in the rst shock success rate of DCCV for AF when biphasic waveforms were used. Currently, two conventional positions are commonly used for electrode placement (see Figure 5). Several studies have shown that anteroposterior electrode placement is more effective than anterolateral placement.43 If initial Apex patch shocks are unsuccessful for terminating the arrhythmia, the electrodes should be repositioned and cardioversion repeated. << Figure 5>> The recommended initial energy for synchronised cardioversion (see figure 6) is: 200J or greater with monophasic waveform 100J or greater with biphasic waveform 10-50J biphasic waveform for AFL 23
    • Figure 6 : ECG strip showing synchronized cardioversion<< Figure 6>>Outpatient/day care DCCV can be undertaken in patients who arehaemodynamically stable and do not have severe underlying heart disease. Atleast 3 h of ECG and haemodynamic monitoring are needed after the procedure,before the patient is allowed to leave the hospital.Internal cardioversion may be helpful in special situations, e.g. when a patientundergoes invasive procedures and cardioversion catheters can be placedwithout further vascular access and when implanted debrillation devices arepresent.5.1.3.2 ComplicationsThe risks and complications of cardioversion are associated primarily with Thrombo-embolic events, Post-cardioversion arrhythmias, and The risks of general anesthesia.The procedure is associated with 1 – 2% risk of thromboembolism, which can bereduced by adequate anticoagulation in the weeks prior to cardioversion or byexclusion of left atrium thrombi before the procedure. Skin burns are a commoncomplication. In patients with sinus node dysfunction, especially in elderlypatients with structural heart disease, prolonged sinus arrest without an adequateescape rhythm may occur. Dangerous arrhythmias, such as ventriculartachycardia and brillation, may arise in the presence of hypokalaemia, digitalisintoxication, or improper synchronization. The patient may become hypoxic orhypoventilate from sedation, but hypotension and pulmonary oedema are rare.5.1.3.3 Cardioversion in patients with implanted pacemakers anddebrillatorsThe electrode paddle should be at least 8 cm from the pacemaker battery, andthe antero-posterior paddle positioning is recommended. Biphasic shocks arepreferred because they require less energy for AF termination. In pacemaker-dependent patients, an increase in pacing threshold should be anticipated. In theabsence of a pacemaker programmer, a pacing magnet may be placed over thepacemaker generator pocket to provide temporary pacing support. Thesepatients should be monitored carefully. After cardioversion, the device should beinterrogated and evaluated to ensure normal function.5.1.3.4 Recurrence after cardioversionRecurrences after DCCV can be divided into three phases:(1) Immediate recurrences, which occur within the rst few minutes after DCCV.(2) Early recurrences, which occur during the rst 5 days after DCCV. 24
    • (3) Late recurrence, which occur thereafter. Factors that predispose to AF recurrence are age, AF duration before (3) Late recurrence, which occur thereafter. cardioversion, number of previous recurrences, an increased LA size or reduced LA function, and the presence of coronary heart diseaseage,pulmonary or mitral Factors that predispose to AF recurrence are or AF duration before valve disease. Atrial ectopic beats with recurrences, an increased LA size or reduced cardioversion, number of previous a long – short sequence, faster heart rates, and variations inand theconduction increase heart disease orrecurrence. mitral LA function, atrial presence of coronary the risk of AF pulmonary or Pre-treatment with antiarrhythmic drugs such as long – short sequence, ecainide, valve disease. Atrial ectopic beats with a amiodarone, sotalol, faster heart rates, increases the likelihood of restoration of sinus rhythm.44-46 and propafenoneand variations in atrial conduction increase the risk of AF recurrence. Some highly symptomatic patients in whom AF occurs infrequently (e.g.ecainide, Pre-treatment with antiarrhythmic drugs such as amiodarone, sotalol, once or and propafenone increases the likelihood of restoration of sinus rhythm.44-46 twice a year) strongly prefer to undergo repeated cardioversions as a long-term rhythm control strategy, rather than opting for rate control or other rhythm once or Some highly symptomatic patients in whom AF occurs infrequently (e.g. control modalities whicha year) strongly prefer to undergo repeated cardioversions as a long-term twice they may nd uncomfortable. rhythm control strategy, rather than opting for rate control or other rhythm control modalities which they may nd uncomfortable. Keypoints Immediate DCCV is recommended when a rapid ventricular rate does notC respond promptly to pharmacological measures inapatients with AF rate does not Immediate DCCV is recommended when rapid ventricular and ongoing IC myocardial respond promptly to pharmacological measures in patients with AF and ongoing IC ischaemia, symptomatic hypotension, angina, or heart failure. myocardial ischaemia, symptomatic hypotension, angina, or heart failure. Immediate DCCV is recommended for patients with AF involving pre-excitationB tachycardia or is recommended for patients present.47 47 when rapid Immediate DCCVhaemodynamic instability iswith AF involving pre-excitation IB IB when rapid tachycardia or haemodynamic instability is present. Elective DCCV should be considered in order to initiate a long-term rhythmIaB control management strategy for be considered AF. 41,43,48 initiate a long-term rhythm IIaB IIaB Elective DCCV should patients with in order to 41,43,48 control management strategy for patients with AF. Pre-treatment with amiodarone, ecainide, propafenone or or sotalolshould be Pre-treatment with amiodarone, ecainide, propafenone sotalol should beIaB IIaB to enhance enhance of DCCV and prevent recurrent AF.44-46 considered considered to successsuccess of DCCV and prevent recurrent AF.44-46 IIaBIbC Repeated DCCV may be considered in highlyhighly symptomatic patients refractory to IIbC IIbC Repeated DCCV may be considered in symptomatic patients refractory to other therapy. therapy. other Pre-treatment with -blockers, diltiazem or verapamil maymay be consideredfor rate IIbC IIbC Pre-treatment with -blockers, diltiazem or verapamil be considered for rateIbC control, although the efficacy of these agents in enhancing success of of DCCVor control, although the efficacy of these agents in enhancing success DCCV or preventing early recurrence of AF isof AF is uncertain. preventing early recurrence uncertain. IIIC IIIC DCCV is contraindicated in patients with digitalis toxicity.IIC DCCV is contraindicated in patients with digitalis toxicity. 5.1.3 Antithrombotic therapy for acute-onset AF Please go to section 6, page 26. 25
    • 6. MANAGEMENT - PREVENTION OF THROMBOEMBOLISM6.1 RISK STRATIFICATION FOR STROKEAssessment of thromboembolic risk or risk stratification allows the clinician toconsider anticoagulant treatment for those people who are at an increased risk ofstroke.Two recent systematic reviews have addressed the evidence base for stroke riskfactors in AF,49,50 and concluded that prior stroke/TIA/thrombo-embolism, age,hypertension, diabetes, and structural heart disease are important risk factors.The presence of moderate to severe LV systolic dysfunction TTE is the onlyindependent echocardiographic risk factor for stroke on multivariable analysis.On TOE, the presence of LA thrombus, complex aortic plaques, spontaneousecho-contrast and low LAA velocities are independent predictors of stroke andthrombo-embolism.Patients with paroxysmal AF should be regarded as having a stroke risk similarto those with persistent or permanent AF, in the presence of risk factors.Patients aged less than 60 years, with ‘lone AF’, i.e. no clinical history or physicalevidence of cardiovascular disease, carry a very low cumulative stroke risk,estimated to be 1.3% over 15 years.The various stroke clinical risk factors has led to publication of various strokeschemes.51,52 The simplest risk assessment scheme is the CHADS2 score and asshown in Table 11, has good stroke correlation. The CHADS2 [cardiac failure,hypertension, age, diabetes, stroke (doubled)] risk index evolved from the AFInvestigators and Stroke Prevention in Atrial Fibrillation (SPAF) Investigatorscriteria, and is based on a point system in which 2 points are assigned for ahistory of stroke or TIA and 1 point each is assigned for age >75 years, a historyof hypertension, diabetes, or recent cardiac failure.51The CHADS2 stroke risk stratication scheme should be used as an initial, rapid,and easy-to-remember means of assessing stroke risk. In patients with aCHADS2 score 2, chronic OAC therapy with a VKA is recommended in a dose-adjusted approach to achieve an international normalized ratio (INR) target of 2.5(range, 2.0 – 3.0), unless contraindicated.6,52<<Table 11>>A comparison of the 12 published risk-stratication49 schemes to predict stroke inpatients with non-valvular AF found that most had very modest predictive valuefor stroke and the proportion of patients assigned to individual risk categoriesvaried widely across the schemes. The CHADS2 score categorized most subjectsas ‘moderate risk’. The choice of antithrombotic (anticoagulants or antiplatelets) 26
    • 6.1 RISK STRATIFICATION FOR STROKEAssessment of thromboembolic risk or risk stratification allows the clinician toconsider anticoagulant treatment for those people who are at an increased risk ofstroke.Two recent systematic reviews have addressed the evidence base for stroke risk 49,50Table 11: CHADS2 score andstroke ratefactors in AF, and concluded that prior stroke/TIA/thrombo-embolism, age,hypertension, diabetes, and structural heart disease are important risk factors.The presence of moderate to severe LV systolic dysfunction TTE is the only Adjusted stroke rateindependent echocardiographic risk factor for stroke on multivariable analysis. PatientsOn TOE, the presence of LA thrombus, complex aortic plaques, spontaneous (%/year)aecho-contrast Score LAA velocities are independent predictors of stroke and CHADS2 and low (n=1733)thrombo-embolism. (95% confidence interval)Patients with paroxysmal AF should be regarded as having a stroke risk similar 0 120 1.9 (1.2-3.0)to those with persistent or permanent AF, in the presence of risk factors.Patients aged less than 60 years, with ‘lone AF’, i.e. no clinical history or physical 1 463 2.8 (2.0-3.8)evidence of cardiovascular disease, carry a very low cumulative stroke risk,estimated to be 1.3% over 15 years. 2 523 4.0 (3.1-5.1)The various stroke clinical risk factors has led to publication of various strokeschemes.51,52 The simplest risk assessment scheme is the 5.9 (4.6-7.3) and as 3 CHADS2 score 337shown in Table 11, has good stroke correlation. The CHADS2 [cardiac failure,hypertension, age, diabetes, stroke (doubled)] risk index evolved from the AF 4 220 8.5 (6.3-11.1)Investigators and Stroke Prevention in Atrial Fibrillation (SPAF) Investigatorscriteria, and is based on a point system in which 2 points are assigned for ahistory of stroke or TIA and 1 point each is assigned for age >75 years, a history 5 65 12.5 (8.2-17.5)of hypertension, diabetes, or recent cardiac failure.51 6 The CHADS2 stroke risk stratication 5 scheme should be 18.2 (10.5-27.4) rapid, used as an initial, and easy-to-remember means of assessing stroke risk. In patients with a CHADS2 score 2, chronic OAC therapy with a VKA is recommended in a dose-a adjusted approach to achieve frominternational normalized rationo aspirin usage;of 2.5 The adjusted stroke rate was derived an the multivariable analysis assuming (INR) target thesestroke rates are based on data from a cohort of hospitalized AF patients, published in 2001, with low (range,in those 3.0),aunless 2contraindicated.6,52 an accurate judgement of the risk in thesenumbers 2.0 – with CHADS score of 5 and 6 to allowpatients. Given that stroke rates are declining overall, actual stroke rates in contemporary non- 51hospitalized cohorts may also vary from these estimates. Adapted from Gage F et al. AF = atrial <<Table 11>>fibrillation; CHADS2 = cardiac failure, hypertension, age, diabetes, stroke (doubled).A comparison of the 12 published risk-stratication49 schemes to predict stroke inpatients with non-valvular AF found that most had very modest predictive valuefor stroke and the proportion of patients assigned to individual risk categoriesvaried widely across the schemes. The CHADS2 score categorized most subjectsas ‘moderate risk’. The choice of antithrombotic (anticoagulants or antiplatelets)for the ‘moderate risk’ group was at best uncertain.Several published analyses 49,50,53-55 have found even patients at ‘moderate risk’(currently dened as CHADS2 score =1, i.e. one risk factor) still derive signicantbenet from OAC over aspirin use, often with low rates of major haemorrhage.Importantly, prescription of an antiplatelet agent was not associated with a lowerrisk of adverse events.Also, the CHADS2 score does not include many stroke risk factors, and other‘stroke risk modiers’ need to be considered in a comprehensive stroke riskassessment (see Table 11, page 27).Rather than the use of the ‘low’, ‘moderate’, and ‘high’ risk characterization thatonly showed a modest predictive value, this guideline has adopted and recognizethat risk is a continuum. A risk factor-based approach for a more detailed strokerisk assessment is encouraged for recommending the use of antithrombotictherapy. 27The risk factor-based approached for patients with non-valvular AF have beengiven an acronym, CHA2DS2VASc and the schema is based on two groups of
    • assessment (see Table 11, page 27).Rather than the use of the ‘low’, ‘moderate’, and ‘high’ risk characterization thatonly showed a modest predictive value, this guideline has adopted and recognizethat risk is a continuum. A risk factor-based approach for a more detailed strokerisk assessment is encouraged for recommending the use of antithrombotictherapy.The risk factor-based approached for patients with non-valvular AF have beengiven an acronym, CHA2DS2VASc and the schema is based on two groups ofrisk factors: Major risk factors - prior history of stroke, TIA or thromboembolism and/or age 75 or older Clinically relevant ‘non-major’ risk factors - hypertension, heart failure (EF 40%), diabetes, age 65–74 years, female gender, and vascular disease (myocardial infarction, complex aortic plaques and PAD).The risk may be calculated based on a point system in which 2 points areallocated for each ‘Major risk factors’; and 1 point each is assigned for‘Clinically relevant ‘non major’ risk factors’ (see Table 11 on page 27).6.2 STRATEGIES FOR THROMBOEMBOLIC PROPHYLAXISThe CHADS2 stroke risk stratication scheme should be used as a simple initial(and easily remembered) means of assessing stroke risk, particularly suited toprimary care doctors and non-specialists.In patients with a CHADS2 score of 2, chronic OAC therapy, e.g. with a VKA, isrecommended in a dose adjusted to achieve an INR value in the range of 2.0 –3.0, unless contraindicated.In patients with a CHADS2 score of 0 – 1, or where a more detailed stroke riskassessment is indicated, it is recommended to use a more comprehensive riskfactor-based approach incorporating other risk factors for thrombo-embolism (seeTable 12 and Figure 7).56-58In all cases where OAC is considered, a discussion of the pros and cons with thepatient, and an evaluation of the risk of bleeding complications, ability to safelysustain adjusted chronic anticoagulation, and patient preferences are necessary.In some patients, for example, women aged less than 65 years with no other riskfactors (i.e. a CHA2DS2VASC score of 1) aspirin rather than OAC therapy may beconsidered.<<Table 12>><<Figure 7>> 28
    • Table 12. CHA2DS2VASC Score, stroke rate and approach to thromboprophylaxis in patients with AF a) Risk Factors for Stroke and thrombo embolism in non-valvular AF Major risk factors Clinically relevant non-major risk factors Heart failure or moderate to severe LV systolic dysfunction Previous stroke, TIA (e.g, LV EF 40%) or systemic embolism Hypertension - Diabetes mellitus Age 75 years Female sex - Age 65-74 years Vascular diseasea b) Risk factor-based approach expressed as a point based scoring system, with the acronym CHA2DS2-VASc (Note: maximum score is 9 since age may contribute 0,1 or 2 points) Risk factor Score Congestive heart failure/LV dysfunction 1 Hypertension 1 Age 75 2 Diabetes mellitus 1 Stroke/TIA/thrombo-embolism 2 Vascular disease 1 Age 65-74 1 Sex category (i.e, female sex) 1 Maximum score 9 c) Adjusted stroke rate according to CHA2DS2-VASc score Adjusted stroke rate CHA2DS2-VASC score Patients (n=7329) b (%/year) 0 1 0% 1 422 1.30% 2 1230 2.20% 3 1730 3.20% 4 1718 4.00% 5 1159 6.70% 6 679 9.80% 7 294 9.60% 8 82 6.70% 9 14 15.20% Approach to thromboprophylaxis in patients with AF CHA2DS2-VASC Recommended Risk category score antithrombotic therapy One major risk factor or 2 c clinically relevant non-major risk 2 OAC factors Either OAC or aspirin 75- One clinically relevant non-major 1 325 mg daily. Preferred: risk factor OAC rather than aspirin Either aspirin 75-325mg daily or no antithrombotic No risk factors 0 therapy. Preferred: no antithrombotic therapy rather than aspirin 29
    • See text for definitions. a Prior myocardial infarction, peripheral artery disease, aortic plaque. Actual rates of stroke in contemporary cohorts may vary from these estimates. b Based on Lip et al.54 AF=atrial fibrillation; EF =ejection fraction (as documented by echocardiography, radionuclide ventriculography, cardiac catheterization, cardiac magnetic resonance imaging, etc.); LV=left ventricular; TIA=transient ischaemic attack. CHA2DS2-VASC=cardiac failure, hypertension, age 75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65–74 and sex category (female); INR=international normalized ratio; OAC=oral anticoagulation, such as a vitamin K antagonist (VKA) adjusted to an intensity range of INR 2.0–3.0 (target 2.5). c OAC, such as a VKA, adjusted to an intensity range of INR 2.0–3.0 (target 2.5). New OAC drugs, which may be viable alternatives to a VKA, may ultimately be considered. For example, should both doses of dabigatran etexilate receive regulatory approval for stroke prevention in AF, the recommendations for thromboprophylaxis could evolve as follows considering stroke and bleeding risk stratification: (a) Where oral anticoagulation is appropriate therapy, dabigatran may be considered, as an alternative to adjusted dose VKA therapy. (i) If a patient is at low risk of bleeding (e.g. HAS-BLED score of 0–2; see Table 14 for HAS-BLED score definition), dabigatran 150 mg b.i.d. may be considered, in view of the improved efficacy in the prevention of stroke and systemic embolism (but lower rates of intracranial haemorrhage and similar rates of major bleeding events, when compared with warfarin); and (ii) If a patient has a measurable risk of bleeding (e.g. HAS-BLED score of 3), dabigatran etexilate 110 mg b.i.d. may be considered, in view of a similar efficacy in the prevention of stroke and systemic embolism (but lower rates of intracranial haemorrhage and of major bleeding compared with VKA). (b) In patients with one ‘clinically relevant non- major’ stroke risk factor, dabigatran 110 mg b.i.d. may be considered, in view of a similar efficacy with VKA in the prevention of stroke and systemic embolism but lower rates of intracranial haemorrhage and major bleeding compared with the VKA and (probably) aspirin. (c) Patients with no stroke risk factors (e.g. CHA2DS2-VASC = 0) are clearly at so low risk, either aspirin 75–325 mg daily or no antithrombotic therapy is recommended. Where possible, no antithrombotic therapy should be considered for such patients, rather than aspirin, given the limited data on the benefits of aspirin in this patient group (i.e., lone AF) and the potential for adverse effects, especially bleeding. + CHADS2 score 2 + CHADS2 Score Risk Factors Score No Yes Congestive heart failure 1 Hypertension 1 Consider other risk factors* Age 75 1 Age 75 years Diabetes 1 Stroke/TIA 2 *Other clinically relevant non- No Yes major risk factor: Age 65-74, female sex, vascular disease 2 other risk factors* No Yes OAC 1 other risk factor* Yes OAC (or aspirin) No Nothing (or aspirin) Figure 7 Clinical flowchart for the use of oral anticoagulant for stroke prevention in AF. AF = atrial fibrillation; OAC = oral anticoagulant; TIA = transient ischaemic attack.7 Clinical flowchart for the use of oral anticoagulant for stroke prevention in AF. AF = atrial fibrillation; OAC = oral anticoagulant; TIA = transient ischaemic attack. A fullption of the CHADS2 from the ESCpage ? Adapted can be found on Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal 2010; doi:10.1093/eurheartj/ehq278) 30
    • 6.3 ANTITHROMBOTIC THERAPY 6.3.1 ANTICOAGULATION WITH VITAMIN K ANTAGONISTS 6.3 ANTITHROMBOTIC THERAPY There were 6 large randomized trials, both primary and secondary prevention, that provided an extensive and robust evidence base for VKA therapy in AF. 6.3.1 ANTICOAGULATION WITH VITAMIN K ANTAGONISTS In a meta-analysis55 adjusted-dose VKA (international normalized ratio prevention, There were 6 large randomized trials, both primary and secondary [INR] 2-3) showed athat provided 64% risk reduction ofevidence and 26% risk reduction of all significant an extensive and robust stroke base for VKA therapy in AF. cause mortality in patients with non valvular AF.53,59-63 In a meta-analysis55 adjusted-dose VKA (international normalized ratio [INR] 2-3) Risk of intracranial significant 64%was reduction of stroke 53,59-63 When reductiongiven showed a hemorrhage risk small (0.3-1.8%). and 26% risk VKA is of all 53,59-63 to elderly patients withpatients with non valvular AF. cause mortality in atrial fibrillation, hypertension must be managed aggressively. 53,59-63 Risk of intracranial hemorrhage was small (0.3-1.8%). When VKA is given to elderly patients with atrial fibrillation, hypertension must be managed Antithrombotic therapy is recommended for patients with atrial utter as for those Keypointsaggressively. IC with AF. Antithrombotic therapy is recommended for patients with atrial utter as for those IC IC The selection AF. antithrombotic therapy should be considered using the same with ofIIaA criteria irrespective of the pattern of AF (i.e. paroxysmal, persistent, or The selection of antithrombotic therapy should be considered using the same permanent).49,50 IIaA IIaA criteria irrespective of the pattern of AF (i.e. paroxysmal, persistent, or permanent).49,50 Antithrombotic therapy to prevent thrombo-embolism is recommended for all IA patients with AF, except in those prevent risk (lone AF, aged recommendedor with Antithrombotic therapy to at low thrombo-embolism is <65 years, for all IA contraindications).49,50,64 except in those at low risk (lone AF, aged <65 years, or with IA patients with AF, contraindications).49,50,64 It is recommended that the selection of the antithrombotic therapy should be IA It is recommended that the selection of the antithrombotic therapy should be based upon theupon the absoluteof stroke/ thrombo-embolism and bleeding, and IA absolute risks risks of stroke/ thrombo-embolism and bleeding, and IA based 49,50,51 the relative risk and risk and benet for a given patient.49,50,51 the relative benet for a given patient. The CHADS2 CHADS2 [cardiac failure, hypertension, age, diabetes, stroke(doubled)] IA The [cardiac failure, hypertension, age, diabetes, stroke (doubled)] IA IA score is score is recommended as a simple 51 (easily remembered) means of recommended as a simple initialinitial (easily remembered) means assessing stroke risk in non-valvular AF. assessing stroke risk in non-valvular AF.51 IA For the patients with a CHADS score of 2, chronic OAC therapy with a VKA is 2 For IA patients with a in a dose-adjusted regimen to achieve an INR range of VKA is the recommended CHADS2 score of 2, chronic OAC therapy with a 2.0–3.0 IA recommended in a dose-adjusted regimen to achieve an INR range of 2.0–3.0 (target 2.5), unless contraindicated.49,50,55 (target 2.5), unless contraindicated.49,50,55 IA IA For a more detailed or comprehensive stroke risk assessment in AF (e.g. with IA CHADS2 scores 0–1), a risk factor-based risk assessment in AF (e.g. with For a more detailed or comprehensive strokeapproach is recommended, considering ‘major’ 0–1), a risk factor-based approach risk factors.53 CHADS2 scores and ‘clinically relevant non-major’ stroke is recommended, considering ‘major’ and ‘clinically relevant non-major’ stroke risk factors.53 IA IA Patients with 1 ‘major’ or > 2 ‘clinically relevant non-major’ risk factors are high risk, and OAC therapy is recommended, unless contraindicated.53 IA Patients with 1 ‘major’ or > 2 ‘clinically relevant non-major’ risk factors are high risk, and OAC therapy is recommended, unless contraindicated.53 intermediate risk Patients with one ‘clinically relevant non-major’ risk factor are at and antithrombotic therapy is recommended, either as: IA IA i. VKA therapy53 or IB IB ii. aspirin 75–325 mg daily50 IB Patients with no risk factors are at low risk (essentially patients aged <65 years IB with lone AF, with none of the risk factors) and the use of either aspirin 75–325 mg daily or no antithrombotic therapy is recommended.53 Most patients with one ‘clinically relevant non-major’ risk factor should be 31 IIaA considered for OAC therapy (e.g. with a VKA) rather than aspirin, based upon an assessment of the risk of bleeding complications, the ability to safely sustain
    • IA VKA therapy or andi.antithrombotic therapy is recommended, either as: IB ii. aspirin 75–325 mg daily50 IA i. VKA therapy53 or IB Patients with75–325 mg dailyare at low risk (essentially patients aged <65 years ii. aspirin no risk factors 50 IB with lone AF, with none of the risk factors) and the use of either aspirin 75–325 mg daily or no antithrombotic therapy is recommended.53 Patients with no risk factors are at low risk (essentially patients aged <65 years IB Mostlone AF, with none of‘clinically factors) and the use of either aspirin 75–325 with patients with one the risk relevant non-major’ risk factor should be IIaA IIaA considered no antithrombotic(e.g. withis recommended.53 aspirin, based upon an mg daily or for OAC therapy therapy a VKA) rather than assessment of the risk of bleeding complications, the ability to safely sustain adjusted chronic anticoagulation, and patient non-major’ 49,50 Most patients with one ‘clinically relevant preferences. risk factor should be IIaA considered for OAC therapy (e.g. with a VKA) rather than aspirin, based upon an IA IA Anticoagulation with VKA bleeding complications, patients to more than 1 assessment of the risk of is also recommended forthe ability withsafely sustain adjusted chronic anticoagulation, and age between 65-74, 49,50 moderate risk factor (female gender, patient preferences. hypertension, diabetes mellitus, vascular disease, HF, or impaired LV systolic function [ejection fraction 3,4,65 35% or less or fractional shorteningrecommended for patients with more than 1 Anticoagulation with VKA is also less than 25%]). IA moderate risk factor (female gender, age between 65-74, hypertension, diabetes 6.3.2 OPTIMAL INTERNATIONAL NORMALIZED RATIO systolic function [ejection fraction mellitus, vascular disease, HF, or impaired LV 35% or less or fractional shortening less than 25%]).3,4,65 The level of anticoagulation is expressed as the INR and is derived from the ratio between the actual prothrombin time and that of a standardized control serum. 6.3.2 OPTIMAL INTERNATIONAL NORMALIZED RATIO level of anticoagulation is expressed AF, theisINR and is derived from target intensity of TheIA For patients with non-valvular as it recommended that the the ratio between Keypoints 49,50,64 timewith a VKA a standardized control serum. anticoagulation and that of should to maintain an INR range of 2.0-3.0 (target the actual prothrombin Patients with one ‘clinically relevant non-major’ risk factor are at intermediate risk 2.5) and antithrombotic non-valvular AF, it is recommended that the target intensity of For patients with therapy is recommended, either as: IA IA For patients with AF who have mechanical heart valves, it is recommended that anticoagulation with a VKA should to maintain an INR range of 2.0-3.0 (target IB 2.5) target intensity of anticoagulation with a VKA should be based on the type the 49,50,64 IA and VKA therapy or 53 i. position of the prosthesis, maintaining an INR of at least 2.5 in the mitral position and at least 2.0 for an aortic valve.64,66 For patients with AF who have mechanical heart valves, it is recommended that IB IBIB ii. aspirin 75–325 mg daily50 the target intensity of anticoagulation with a VKA should be based on the type <<Figure 8>> and position of the prosthesis, maintaining an INR of at least 2.5 in the mitral position and at least 2.0 for an aortic valve.64,66 Patients with no risk factors are at low risk (essentially patients aged <65 years IB 8: Adjusted odds ratios for ischaemic stroke and intracranial bleeding in relation to intensity of Figure 8: Adjusted odds ratios2.5 ischaemic stroke and intracranial safe for primary prevention in Figure withtarget AF, withfor (targetthe riskof 2.0 to and thebleeding either aspirin 75–325 <<Figure 8>>of none of range factors) 3.0) is use of in relation to intensity of A lone INR IA anticoagulationdaily or no antithromboticyears, unless contraindicated.67 atrial fibrillation. anticoagulation in patients more than antithromboticis recommended. with atrial fibrillation. mg in randomised trials of antithrombotic therapy for people53 older randomised trials of 75 therapy therapy for people with Figure 8: Adjusted odds ratios for ischaemic stroke and intracranial bleeding in relation to intensity of anticoagulation inmajor bleeding one antithrombotic therapy for is trialswith primary per shouldInbe The randomised trials of for 5 randomized clinical safe forrisk factor year. A target INR with rate ‘clinically 2.0 to 3.0) people atrial fibrillation. Most patients of 2.5 (target range ofrelevant non-major’was 1.2% prevention in 2 IIaA IA considered for OAC therapy years, of a VKA) rather than 67elderlybased upon an time-dependent INR analyses with anticoagulation in aspirin, AF cohorts, older patients more than 75 (e.g. unless contraindicated. assessment bleed increased with INR values over 3.5 toability and safely was no intracranial of the risk of bleeding complications, the 4.0, to there sustain adjusted chronic anticoagulation, and patient preferences.49,501.2% per year. In 2 The major bleeding rate for 5 randomized clinical trials was time-dependent INR analyses of anticoagulation in elderly AF cohorts, Anticoagulation with VKA is also INR values overfor patients and there was no intracranial bleed increased with recommended 3.5 to 4.0, with more than 1 IA moderate risk factor (female gender, age between 65-74, hypertension, diabetes mellitus, vascular disease, HF, or impaired LV systolic function [ejection fraction 35% or less or fractional shortening less than 25%]).3,4,656.3.2 OPTIMAL INTERNATIONAL NORMALIZED RATIOThe level of anticoagulation is expressed as the INR and is derived from the ratio betweenthe actual prothrombin time and that of a standardized control serum. For patients with non-valvular AF, it is recommended that the target intensity of IA anticoagulation with a VKA should to maintain an INR range of 2.0-3.0 (target 2.5) 49,50,64 For patients with AF who have mechanical heart valves, it is recommended that IB the target intensity of anticoagulation with a VKA should be based on the type and position of the prosthesis, maintaining an INR of at least 2.5 in the mitral position and at least 2.0 for an aortic valve.64,66 Reproduced with permission from Ann Intern Med. Hylek E, Singer D. Risk factors for intracranial Reproduced with permission from Ann Intern Med. Hylek E, Singer D. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994;120:897-902. <<Figure 8>> hemorrhage in outpatients taking warfarin. Ann Intern Med 1994;120:897-902. Reproduced with permission from Ann Intern Med. Hylek E, Singer D. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994;120:897-902. IA A target INR of 2.5 (target range of 2.0 to 3.0) is safe for primary prevention in IA older patients more than 75 years, unless contraindicated.67 The major bleeding rate for 5 randomized clinical trials was 1.2% per year. In 2 time-dependent INR analyses of anticoagulation in elderly AF cohorts, 32 intracranial bleed increased with INR values over 3.5 to 4.0, and there was no
    • position and at least 2.0 for an aortic valve.64,66 <<Figure 8>> A target INR of 2.5 (target range of 2.0 to 3.0) is safe for primary prevention in IA older patients more than 75 years, unless contraindicated.67 The major bleeding rate for 5 randomized clinical trials was 1.2% per year. In 2 time-dependent INR analyses of anticoagulation in elderly AF cohorts, intracranial bleed increased with INR values over 3.5 to 4.0, and there was no increment with values between 2.0 and 3.0 compared with lower INR levels. (See Figure 6, page 24) For guide of using VKA in daily practice please refer to Appendix C, page 74. 6.3.2.1 Point-of-care values between 2.0 and 3.0 compared with lower INR levels. (See increment with testing and self-monitoring of anticoagulation incrementpage 24) Figure 6, with values between 2.0 and 3.0 compared with lower INR levels. (See Figure 6, page 24) Self-monitoring may be considered if preferred by a patient who is both physically and cognitively able to perform daily self-monitoring test, and, if not, a designated For guide of using VKA in the practice please refer to Appendix C, page 74. For guide of using VKA in daily practice please refer to Appendix C, page 74. carer could help. Appropriate training by a competent healthcare professional is 6.3.2.1 Point-of-care testing and self-monitoring of anticoagulation important, and Point-of-care testing and self-monitoring ofa named clinician. 6.3.2.1 the patient should remain in contact with anticoagulation These point-of-care devices considered if be useful in patient who is both and allow Self-monitoring may be may also preferred by a remote places physically patients Self-monitoring may testing. Point-of-care devices also if not, a designated and cognitively able be perform the if preferred by a test, and, require physically easy access to to considered self-monitoring patient who is both adequate quality assurance and able to perform the self-monitoring test, and, if not, a designated and cognitively calibration. training by a competent healthcare professional is carer could help. Appropriate carer could help. Appropriate training byin contact withhealthcare professional is important, and the patient should remain a competent a named clinician. important, and the patient should remain in contact withremote places These point-of-care devices may also be useful in a named clinician. 6.3.3 ANTICOAGULATION WITH DIRECT THROMBIN INHIBITORS and allow These point-of-care devices may Point-of-care devices also places and allow patients easy access to testing. also be useful in remote require adequate patients easy access calibration. Point-of-care devices also require adequate quality assurance and to testing. Dabigatran etexilate is and calibration. quality assurance an oral prodrug that is rapidly converted by a serum esterase6.3.3 ANTICOAGULATION WITH DIRECT THROMBIN INHIBITORS . It does to dabigatran, a potent, direct, competitive inhibitor of thrombin not require regular monitoring and has a serumTHROMBIN 12 to 17 hours. 6.3.3 ANTICOAGULATION WITH DIRECT half-life of INHIBITORS Dabigatran etexilate is an oral prodrug that is rapidly converted by a serum The Randomized dabigatran, a of oral prodrugcompetitive inhibitor of thrombin(RE-LY) Dabigatran etexilate is an esterase to Evaluation potent, direct, that is rapidly converted by a It does Long-term Anticoagulation Therapy . serum esterase to regular not require dabigatran, a potent,two a competitive inhibitor of thrombin. It doesa direct, was a randomized trial monitoring and hasfixed doses of of 12 to 17 hours. comparing has a serum half-life of 12 to 17 hours. not require regular monitoring and serum half-life dabigatran, given in blinded manner, with open-label use of VKA in patients with atrial fibrillation.58 The Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) Dabigatran 110 mg b.i.d. was non-inferior to VKA for the prevention of stroke The a randomizedEvaluation of Long-term Anticoagulation Therapy (RE-LY) was Randomized trial comparing two fixed doses of dabigatran, given in a and systemic embolism with comparing two VKA in patients dabigatran, dabigatran was a randomized trial lower ratesof fixed doses of with whilstfibrillation.58 blinded manner, with open-label use of major bleeding, atrial given in a 58 150 mgDabigatran 110 associated with lower to in patientsstroke and of stroke blinded manner, mg b.i.d. was non-inferior rates for the prevention systemic b.i.d. was with open-label use of VKA VKA of with atrial fibrillation. Dabigatran 110 rates of with lower rates of major for the prevention of stroke embolism with similar mg b.i.d. major haemorrhage, compared with VKA. and systemic embolism was non-inferior to VKA bleeding, whilst dabigatran and systemic embolism with lower rates of major bleeding, whilst dabigatran 150 mg b.i.d. was associated with lower rates of stroke and systemic 150 mg b.i.d. similar associated with lower rates of stroke and systemic embolism with was rates of major haemorrhage, compared with VKA. embolism with similar rates of major haemorrhage, compared with VKA.IB Keypoints anticoagulation is appropriate therapy for patients with non-valvular Where oral AF, dabigatran may be considered, as an alternative to adjusted dose VKA therapy. Where oral anticoagulation is appropriate therapy for patients with non-valvular Where oral anticoagulation is appropriate an alternative to adjusted dose VKA IB IBIB AF, dabigatran may be considered, as therapy for patients with non-valvular AF, dabigatran may be considered, as an alternative to adjusted dose VKA therapy. There is therapy. no evidence to support the use of dabigatran for AF associated currently with valve disease, prosthetic valve,to support the use of chronic renal AF associated There is currently no evidence in pregnancy and dabigatran for failure. with valve disease, prosthetic valve, in pregnancy of dabigatran for AF associated There is currently no evidence to support the use and chronic renal failure. with valve disease, prosthetic valve, in pregnancy and chronic renal failure. Patients with AF who are indicated for OAC but are unwilling to go on VKAIB becausePatients inconvenience, chronic oral anticoagulant therapy withgo on VKA IB Patients with AF who are indicated for OAC but are unwilling to dabigatran of the with AF who are indicated IBIB because of the inconvenience, chronicfor OAC but are unwilling with dabigatran oral anticoagulant therapy to go on VKA 150 mg twice daily the inconvenience, chronic oral contraindicated. because of may be considered, unless anticoagulant therapy with dabigatran 150 mg twice daily may be considered, unless contraindicated. 150 mg twice daily may be considered, unless contraindicated. Where patients are at are at a higher of bleeding (HAS-BLED 3), dabigatran 110 Where patients a higher risk risk of bleeding (HAS-BLED 3), dabigatran 110IC IC mg twice daily may be are be considered, unless contraindicated. ICIC mg twice daily may at a higher risk of contraindicated. Where patients considered, unless bleeding (HAS-BLED 3), dabigatran 110 mg twice daily may be considered, unless contraindicated. There was however an increase in the rate of gastrointestinal bleeding with the There was however an increase in the raterate gastrointestinal bleeding with the of of gastrointestinal bleeding with the There was however an increase in the higher dose of dabigatran, despite an overall lower rates of bleeding at other sites. IA IA Antithrombotic agent should be chosen based upon the absolute risks of stroke and bleeding and the relative risk and benefit for a given patient. 33 6.3.4 INVESTIGATIONAL AGENTS
    • higher dose of dabigatran, despite an overall lower rates of bleeding at other sites. Antithrombotic agent should be chosen based upon the absolute risks of stroke and bleeding and the relative risk and benefit for a given patient. 6.3.4 INVESTIGATIONAL AGENTS Several new anticoagulant drugs-broadly in two classes, another oral direct thrombin inhibitors (e.g. AZD0837) and the oral factor Xa inhibitors (rivaroxaban, apixaban, edoxaban, betrixaban, YM150, etc.)-are being developed for stroke prevention in AF. 6.3.5 ANTIPLATELET AGENT ASPIRIN Aspirin has been perceived to be safer than VKA in AF patients, but recent trials have shown that VKA are substantially more effective than aspirin for stroke prevention, with no difference in major bleeding event rates between VKA and aspirin treated patients.55,68 In seven primary prevention trials, treatment with aspirin was associated with a non-signicant 19% reduction in the incidence of stroke. There was an absolute risk reduction of 0.8% per year for primary prevention trials and 2.5% per year for secondary prevention by using aspirin. When data from all comparisons of antiplatelet agents and placebo or control groups were included in the meta- analysis, antiplatelet therapy reduced stroke by 22%.55 The magnitude of stroke reduction from aspirin vs. placebo in the meta-analysis is broadly similar to that seen when aspirin is given to vascular disease subjects. Given that AF commonly co-exists with vascular disease, the modest benet seen for aspirin in AF is likely to be related to its effects on vascular disease. In the Japan Atrial Fibrillation Stroke Trial,69 patients with lone AF were randomized to an aspirin group (aspirin at 150 – 200 mg/day) or a placebo control group. The primary outcomes of cardiovascular death and non fatal stroke or TIA was 3.1% per year in the aspirin group and was worse than those in the control group, 2.4% per year, and treatment with aspirin caused a non- signicant increased risk of major bleeding (1.6%) compared with control (0.4%). The Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study also showed that VKA (target INR 2 – 3) was superior to aspirin 75 mg daily in reducing the primary endpoint of fatal or disabling stroke, intracranial hemorrhage, or thromboembolism by 52%, with no difference in the risk of major hemorrhage between VKA and aspirin.68 6.3.6 ASPIRIN AND CLOPIDOGREL COMBINATION In patients with non valvular AF, adjusted dose VKA was found to be superior to the combination of clopidogrel (75mg daily) plus aspirin (75-100 mg daily) for the prevention of first occurrence of stroke, non-CNS systemic embolism, myocardial infarction and vascular death.56 However, clopidogrel (75mg daily) plus aspirin (75-100 mg daily) conferred a relative risk reduction of 11% compared to aspirin.57 There was an increased risk of major bleeding in patients receiving clopidogrel plus aspirin compared to patients receiving aspirin alone and was broadly similar to that seen with VKA.57 Combination therapy with aspirin 75–100 mg plus clopidogrel 75 mg daily, shouldB be considered for stroke prevention in patients for whom there is patient refusal 34 to take OAC therapy or a clear contraindication to OAC therapy (e.g. inability to cope or continue with anticoagulation monitoring), where there is a low risk of
    • However, infarction and vascular death.56 clopidogrel (75mg daily) plus aspirin (75-100 mg daily) conferred a relative risk reduction of 11% compared to aspirin.57 However, clopidogrel (75mg daily) plus aspirin (75-100 mg daily) conferred a 57 There was an increased riskof 11% compared to aspirin. relative risk reduction of major bleeding in patients receiving clopidogrel plus aspirin compared to patients receiving aspirin alone and was broadly similar There was an increased risk of major bleeding in patients receiving clopidogrel to that seen with VKA.57 plus aspirin compared to patients receiving aspirin alone and was broadly similar to that seen with VKA.57 Keypoints therapy with aspirin 75–100 mg plus clopidogrel 75 mg daily, should CombinationIIaB be considered for stroke prevention in 75–100 mg plus clopidogrel 75 patient refusal Combination therapy with aspirin patients for whom there is mg daily, should IIaB toIIaB OACconsidered for stroke prevention in patients OAC therapy (e.g. inability to take be therapy or a clear contraindication to for whom there is patient refusal cope or continue with anticoagulationcontraindication where there is (e.g. inability of to take OAC therapy or a clear monitoring), to OAC therapy a low risk to cope or continue with anticoagulation monitoring), where there is a low risk of bleeding.57 57 bleeding. In some patients patients with one ‘clinically relevant non-major’ risk factor, e.g.,female In some with one ‘clinically relevant non-major’ risk factor, e.g., femaleIIbC IIbC patients aged <65 years with no other other factors, aspirin may be considered IIbC patients aged <65 years with no risk risk factors, aspirin may be considered rather than OAC therapy. rather than OAC therapy. 6.4 ANTICOAGULATION IN SPECIAL CIRCUMSTANCES 6.4 ANTICOAGULATION IN SPECIAL CIRCUMSTANCES 6.4.1 PERIOPERATIVE ANTICOAGULATION 6.4.1 PERIOPERATIVE ANTICOAGULATION Patients with AF who are anticoagulated will require temporary interruption of Patients with AF who are anticoagulatedinvasive procedure. Many surgeons require VKA treatment before surgery or an will require temporary interruption of VKA treatment before surgery or anINR normalization before undertaking surgery. The an INR less than 1.5 or even invasive procedure. Many surgeons require an INR less than 1.5 or signicant bleeding, even among outpatients undergoing minor risk of clinically even INR normalization before undertaking surgery. The risk of clinically signicant be weighed even among outpatients undergoing minor procedures, should bleeding, against the risk of stroke and thrombo-embolism procedures, an individual patient against the administration of bridging anticoagulant in should be weighed before the risk of stroke and thrombo-embolism therapy. (see Appendix C.1.9, page 80) in an individual patient before the administration of bridging anticoagulant therapy. (see Appendix C.1.9, pagewhich has a half-life of 36 – 42 h, treatment should If the VKA used is warfarin, 80) be interrupted for about 5 days before surgery (corresponding approximately to If the VKA used is warfarin, which has a half-life of 36 – 42 h, treatment should ve half-lives of warfarin), be interrupted for about 5 days before surgery (corresponding approximately to Examples of procedures with a low risk of bleeding, ve half-lives of warfarin), Examples of procedures with– Restorative Surgery and Extractions Dental Surgery a low risk of bleeding, o Anticoagulation can be continued with an INR of less than 3.0 and Dental Surgery appropriate topical haemostatic measures should be used. There is – Restorative Surgery and Extractions no need to discontinue warfarin. o Anticoagulation can be continued with an INR of less than 3.0 and appropriate topical haemostatic measures should be used. There is no need to discontinue warfarin. Minor Non-Invasive Surgery (e.g., dilation and curettage [D & C]) o Transient adjustment of the INR to below 1.5 for the perioperative Minor Non-Invasive Surgery (e.g., dilation and curettage [D & C]) period is required. In cases o SurgeryNon-Invasive Surgery (e.g., should and curettage [DtheC]) of Transient adjustment of Anticoagulation Required) perioperative major (Interruption of the INR to below 1.5 for the Major period is required.consideration dilation be given to & risk of Minor surgery, thromboembolism. (see CHA2DS2Vasc scoring on page 29) o Transient adjustment of the INR to below 1.5 for the perioperative o In most people without mechanical prosthetic heart valves, period is required. Major Surgery (Interruption of Anticoagulation Required) anticoagulation can be safely discontinued temporarily, without the need for heparin cover. The Anticoagulation Required) basis of the Major Surgery (Interruption of decision is made on the o In most people without mechanical prosthetic heart valves, risk of thrombosis. anticoagulation can be safely discontinued temporarily, without the o In most people without mechanical prosthetic heart valves, need foranticoagulation can be safely discontinued temporarily, without the heparin cover. The decision is made on the basis of the In patients with AF who dofor heparin cover. The decision is made onvalves or those not have mechanical prosthetic heart the basis of the risk of thrombosis. needIIaC who are not at high risk of thrombosis. risk for thrombo-embolism who are undergoing surgical or Keypoints procedures that carry a risk of bleeding, the interruption of OAC (with sub diagnostic In patients with AF who do not have mechanical prosthetic heart valves or thoseIIaC therapeutic anticoagulation for up tonot have mechanical prosthetic heart valves or those In patients with AF who do 48 h) should be considered, without substituting who are not at high risk for risk for thrombo-embolism who are undergoingsurgical or IIaC IIaC thrombo-embolism who are undergoing heparin aswho are not at high ‘bridging’ anticoagulation therapy. (see Appendix C.1.9 on pagesurgical or 80). diagnostic diagnostic procedures that carry ofrisk of bleeding, interruption of of OAC (with sub procedures that carry a risk a bleeding, the the interruption OAC (with sub therapeutic anticoagulation for up to 48 h) 48 h) should be considered, without substituting therapeutic anticoagulation for up to should be considered, without substituting In patients with a mechanical prosthetic heart valve or AF at high risk forIIaC heparin asheparin as ‘bridging’ anticoagulation therapy. (see Appendix C.1.9 on page 80). ‘bridging’ anticoagulation therapy. (see Appendix C.1.9 on page 80). thrombo-embolism who are undergoing surgical or diagnostic procedures, ‘bridging’ Inanticoagulation mechanical prosthetic heart valve oreither high risk for patients with a with therapeutic doses of LMWH or patients with a mechanical prosthetic heart valve or AFAF athigh risk for InIIaC IIaC atIIaC unfractionated heparin during the temporary interruptionor diagnostic procedures, thrombo-embolism who are undergoing surgical of OAC therapy should thrombo-embolism anticoagulation with therapeutic doses of either procedures, ‘bridging’ who are undergoing surgical or diagnostic LMWH or be considered. ‘bridging’ unfractionated heparin during the35 anticoagulation with therapeutic doses of ofeither therapy should temporary interruption OAC LMWH or unfractionated heparin during the temporary interruption of OAC therapy should be considered. Following surgical procedures, resumption of OAC therapy should be considered
    • need for heparin cover. The decision is made on the basis of the risk of thrombosis. In patients with AF who do not have mechanical prosthetic heart valves or those IIaC who are not at high risk for thrombo-embolism who are undergoing surgical or In patients with AF who do not have mechanical prosthetic heart valves or those diagnostic procedures that carry a risk of bleeding, the interruption of OAC (with sub IIaC who are not at high risk for thrombo-embolism who are undergoing surgical or therapeutic anticoagulation for up to 48 h) should be considered, without substituting diagnostic procedures that carry a risk of bleeding,Appendix C.1.9 on OAC (with sub heparin as ‘bridging’ anticoagulation therapy. (see the interruption of page 80). therapeutic anticoagulation for up to 48 h) should be considered, without substituting heparin as ‘bridging’ anticoagulation therapy. (see Appendixor AF on page 80). for In patients with a mechanical prosthetic heart valve C.1.9 at high risk IIaC thrombo-embolism who are undergoing surgical or diagnostic procedures, In patients with a mechanical ‘bridging’ anticoagulation with prosthetic heartdoses or AF at high risk for therapeutic valve of either LMWH or IIaC thrombo-embolism who are the temporary interruption diagnostic procedures, unfractionated heparin during undergoing surgical or of OAC therapy should ‘bridging’ anticoagulation with therapeutic doses of either LMWH or be considered. unfractionated heparin during the temporary interruption of OAC therapy should be considered. Following surgical procedures, resumption of OAC therapy should be considered IIaB IIaB at the ‘usual’ maintenance dose (without a loading dose) on the evening of (or Following surgical procedures, resumptionthere is adequateshould be considered the next morning after) surgery, assuming of OAC therapy haemostasis. IIaB at the ‘usual’ maintenance dose (without a loading dose) on the evening of (or When surgical procedures require interruption is adequate haemostasis. than the next morning after) surgery, assuming there of OAC therapy for longer IIbC IIbC 48h in high-risk patients, unfractionated heparin or subcutaneous LMWH may be When surgical procedures require interruption of OAC therapy for longer than considered. IIbC 48h in high-risk patients, unfractionated heparin or subcutaneous LMWH may be considered. STROKE 6.4.2 ACUTE Keypoints allACUTE STROKE who have had an acute stroke, any uncontrolled IIaC 6.4.2 patients with AF In hypertension should be appropriately managed before antithrombotic therapy is IIaC IIaC In all .patients with AF who have had an acute stroke, any uncontrolled started hypertension should be appropriately managed before antithrombotic therapy is IIaC started. with AF and an acute stroke should have imaging done to exclude Patients cerebral haemorrhage. In the presence of cerebral infarction, the decision on the IIaC IIaC Patients with AF and anshould be weighed between imaging done to exclude timing of anticoagulation acute stroke should have the risk of haemorrhagic cerebral haemorrhage. risk of recurrent thromboembolism. transformation and the In the presence of cerebral infarction, the decision on the timing of anticoagulation should be weighed between the risk of haemorrhagic transformation and the risk of recurrent thromboembolism. In the absence of haemorrhage, anticoagulation may start 2 weeks after stroke. In the presence of a largehaemorrhage, anticoagulation may delayed after In the absence of infarct, anticoagulation may be start 2 weeks after stroke. 2 weeks. In the presence of haemorrhage, anticoagulation should be withheld In the presence of a large infarct, anticoagulation may be delayed after 2 weeks. until an appropriate time. In the presence of haemorrhage, anticoagulation should be withheld until an appropriate time. Patients with AF and therecent TIA should infarct,imaging done to exclude cerebral In a presence of a large have anticoagulation may be delayed afterC 2 weeks. haemorrhage. Patients with AF and a recent TIA should have imaging done to exclude cerebral IIaC IIaC In the presence of haemorrhage, anticoagulation should be withheld haemorrhage. until an appropriate time. In the absence of a haemorrhage, anticoagulation should be started as soon as possible. In the absence of a haemorrhage, anticoagulation should be started as Patients with AF and a recent TIA should have imaging done to exclude cerebral IIaC soon as possible. haemorrhage. In patients with AF who sustain ischaemic stroke or systemic embolism duringC treatment In patients with absence sustain ischaemic stroke or systemic embolism during IIbC IIb C In the AF who with usual intensity anticoagulation with VKA (INR 2.0–3.0),be startedthe of a haemorrhage, anticoagulation should raising as treatment with usual intensity anticoagulation with VKA (INR 2.0–3.0), raising the intensity of the anticoagulation to a maximum target INR of of 3.0–3.5 may be intensity of the anticoagulation to a maximum target INR 3.0–3.5 may be soon as possible. considered, rather than adding adding an antiplatelet agent. considered, rather than an antiplatelet agent. In patients with AF who sustain ischaemic stroke or systemic embolism during IIb C 6.4.3 Anticoagulant and Antiplatelet Therapy UseUsePatients With Atrial the treatment with usual intensity anticoagulation with VKA (INR 2.0–3.0), raising 6.4.3 Anticoagulant and Antiplatelet Therapy in in Patients With Atrial intensity of the anticoagulation to a maximum target INR of 3.0–3.5 may be Fibrillation Undergoing Percutaneous Coronary Intervention Fibrillation Undergoing Percutaneousantiplatelet agent. considered, rather than adding an Coronary Intervention There is 6.4.3 Anticoagulant published evidence what is thethe optimalmanagement There is of lack of a lack a published evidence on on what is Patients With Atrial and Antiplatelet Therapy Use in optimal management strategy in anticoagulated patients with nonvalvular atrial fibrillation (AF) who strategy in anticoagulated patients with nonvalvular atrial hence, need (AF) who fibrillation antiplatelet Fibrillation Undergoing Percutaneous Coronary Intervention undergo percutaneous coronary intervention (PCI) and, undergo percutaneous coronary intervention (PCI) and, hence, need antiplatelet therapy. therapy. There is a lack of published evidence on what is the optimal management Based on consensus, the post-PCI strategy should be tailored to the (AF) who strategy in anticoagulated patients with nonvalvular atrial fibrillation individual Based on patient and their risk of coronary intervention (PCI) and, hence, need antiplatelet undergo percutaneous thromboembolism and stent thrombosis weighed against consensus, the post-PCI strategy should be tailored to the individual therapy. patient and their risk of thromboembolismtriple therapythrombosis13) their risk of bleeding while receiving and stent (see Table weighed against their risk of bleeding while receiving triple therapy (see Table 13) to the individual Based on consensus, the post-PCI strategy should be tailored Following elective PCI in patients with AF with stable coronary artery disease, IIaC patient and their risk of thromboembolism and stent thrombosis weighed against BMS should be considered, and drug-eluting stents avoided or strictly limited toC Keypointselectiveof bleeding while receiving triple therapy (see Table 13)artery disease, Following their risk PCI and/or anatomical AF with stablelong lesions, small vessels, those clinical in patients with situations (e.g. coronary BMS should be considered, and drug-eluting stents avoided or strictly limited to diabetes, etc.), where a signicant benet is expected when compared with BMS. those clinical and/or anatomicalpatients with AF with stable coronary artery vessels, IIaC IIaC Following elective PCI in situations (e.g. long lesions, small disease, BMS should be considered, and drug-eluting stents avoided or strictly limited to diabetes, etc.), where aand/or anatomical situations (e.g.when compared with BMS. signicant benet is expected long lesions, small vessels, Following elective PCI, triple therapy (VKA, aspirin, clopidogrel) should be those clinical IIaC considered in the short term, followed by more long-term therapy (up to 1 year) diabetes, etc.), where a signicant benet is expected when compared with BMS. Following with VKA plus clopidogrel therapy (VKA,alternatively, aspirin 75–100 mg daily). elective PCI, triple 75 mg daily (or, aspirin, clopidogrel) should beC 36 considered in the short term, followedtherapy (VKA, aspirin,therapy (up to 1 year) Following elective PCI, triple by more long-term clopidogrel) should be IIaC Following elective PCI, clopidogrel should be considered in combination with with VKA plus clopidogrel short term, followed by moreafter aspirin 75–100 a to daily). considered in the 75 mg daily (or, alternatively, VKA plus aspirin for a minimum of 1 month implantation of mg long-term therapy (up 1 year) BMS, but
    • patient and their risk of thromboembolism and stent thrombosis weighed against Following their risk ofPCI in patients with AF with stable coronary artery disease, elective bleeding while receiving triple therapy (see Table 13)IIaC BMS should be considered, and drug-eluting stents avoided or strictly limited to those clinical and/or anatomical situations AF withlong lesions, small vessels, IIaC Following elective PCI in patients with (e.g. stable coronary artery disease, diabetes, BMS should be signicant benet is expected when compared with BMS. etc.), where a considered, and drug-eluting stents avoided or strictly limited to those clinical and/or anatomical situations (e.g. long lesions, small vessels, Following diabetes, etc.), where a signicant benet is expected when compared with BMS. elective PCI, triple therapy (VKA, aspirin, clopidogrel) should beIIaC considered in the short term, followed by more long-term therapy (up to 1 year) Following elective PCI, triple therapy (VKA, aspirin, clopidogrel) should be IIaC with VKA considered in the short term, followed by more long-term therapy (up to 1 year) IIaC plus clopidogrel 75 mg daily (or, alternatively, aspirin 75–100 mg daily). with VKA plus clopidogrel 75 mg daily (or, alternatively, aspirin 75–100 mg daily).IIaC Following elective PCI, clopidogrel should be considered in combination with VKA plusFollowing for a minimum of 1 month after considered in combination with IIaC IIaC aspirin elective PCI, clopidogrel should be implantation of a BMS, but longer with a drug-eluting stent (at least 3 months for implantation of a BMS, but VKA plus aspirin for a minimum of 1 month after a sirolimus-eluting stent longer with a drug-eluting stent (at least 3 months for a sirolimus-eluting stent and at least 6 months for a paclitaxel-eluting stent); following which VKA and and at least 6 months for a paclitaxel-eluting stent); following which VKA and clopidogrel 75 mg daily (or, alternatively, aspirin 75–100 mgmg daily). clopidogrel 75 mg daily (or, alternatively, aspirin 75–100 daily). 6.4.4 NON-ST NON-ST ELEVATION MYOCARDIAL INFARCTION 6.4.4 ELEVATION MYOCARDIAL INFARCTION In patients with non-ST non-ST elevation myocardial infarction, dual antiplatelet therapy In patients with elevation myocardial infarction, dual antiplatelet therapy with aspirin plus clopidogrel is recommended, but in AF patients at moderate to high risk of stroke, OAC should also be given. In the acute setting, patients are often given aspirin, clopidogrel, UFH, or LMWH (e.g. enoxaparin) or bivalirudin and/or a glycoprotein IIb/IIIa inhibitor (GPI). Drug- eluting stents should be limited to clinical situations, as described above (see Table 13). An uninterrupted strategy of OAC is preferred, and radial access should be used as the rst choice. For medium to long-term management, triple therapy (VKA, aspirin, and clopidogrel) should be used in the initial period (3 – 6 months), or for longer in selected patients at low bleeding risk. In patients with a high risk of cardiovascular thrombotic complications [e.g. high Global Registry of Acute Coronary Events (GRACE) or TIMI risk score], long-term therapy with VKA may be combined with clopidogrel 75 mg daily (or, alternatively, aspirin 75 – 100 mg daily). <<Table Antithrombotic strategies following coronary artery stenting in patients with AF at moderate to high Table 13: 13>> thrombo-embolic risk (in whom oral anticoagulation therapy is required) Following an ACS with or without PCI inimplanted with AF, triple therapy (VKA, Haemorrhagic risk Clinical setting Stent patients Anticoagulation regimenIIaC aspirin, clopidogrel) should be considered in the short term (3–6 months), or Low or intermediate (e.g Elective Bare-metal 1 month: triple therapy of VKA (INR longer in score 0-2) patients at low bleeding risk, followed + aspirin 75-100mg/day HAS-BLED selected 2.0-2.5) by long-term therapy +clopidogrel 75 mg/day with VKA plus clopidogrel 75 mg daily (or, alternatively, aspirin 75–100 mgalone Lifelong: VKA (INR 2.0-3.0) daily). Elective Drug-eluting 3 (-olimusa group) to 6 (paclitaxel) In anticoagulated patients at very high risk of thrombo-embolism, uninterrupted months: triple therapy of VKA (INRIIaC 2.0-2.5) + aspirin 75-100mg/day therapy with VKA as the preferred strategy and radial access used as the rst +clopidogrel 75 mg/day choice even during therapeutic anticoagulation (INR 2–3). 12th month: combination of Up to VKA (INR 2.0-2.5) + clopidogrel 75/dayb When VKA is given in combination with clopidogrel or aspirin 100m/day) (or low-dose aspirin, carefulIIbC regulation of the anticoagulation dose intensity may be considered, with alone Lifelong: VKA (INR 2.0-3.0) an INR range of 2.0–2.5. ACS Bare-metal/drug- 6 months: triple therapy of VKA (INR eluting 2.0-2.5) + aspirin 75-100mg/day +clopidogrel 75 mg/dayIIbC Following revascularization surgery in patients with to 12th VKA combinationsingle Up AF, month: plus a of antiplatelet drug may be considered in the initial 12 months, but this clopidogrel has VKA (INR 2.0-2.5) + strategy 75/dayb not been evaluated thoroughly and is associated with (or aspirin 100m/day) of an increased risk bleeding. Lifelong: VKA (INR 2.0-3.0) alone High Elective Bare-metalc 2-4 weeks: triple therapy of VKA (e.g, HAS-BLED score (INR 2.0-2.5) + aspirin 75- In patients with stable vascular disease (e.g. >1 year, 100mg/day acute events), VKA >3) with no +clopidogrel 75 mg/dayIIbC monotherapy may be considered, and concomitant Lifelong: VKA (INR 2.0-3.0) alone antiplatelet therapy should not be prescribed in the absence of Bare-metalc ACS a subsequent cardiovasculartherapy of VKA (INR 4 weeks: triple event. 2.0-2.5) + aspirin 75-100mg/day +clopidogrel 75 mg/day (or aspirin 100m/day) Lifelong: VKA (INR 2.0-3.0) alone 37 ACS = acute coronary syndrome; AF = atrial fibrillation; INR = international normalized ratio; VKA = vitamin K antagonist. Gastric protection with a proton pump inhibitor (PPI) should be considered where necessary.
    • with aspirin plus clopidogrel is recommended, but in AFVKA (INR 2.0-3.0) alone to Lifelong: patients at moderateHigh high risk of stroke, OAC should also be given. Elective Bare-metalc 2-4 weeks: triple therapy of VKA(e.g, HAS-BLED score (INR 2.0-2.5) + aspirin 75->3) 100mg/day +clopidogrel 75 mg/day In the acute setting, patients are often given aspirin, clopidogrel, 2.0-3.0)or LMWH Lifelong: VKA (INR UFH, alone (e.g. enoxaparin) or bivalirudin and/or a glycoprotein IIb/IIIa inhibitorof VKA (INR ACS Bare-metalc 4 weeks: triple therapy (GPI). Drug- eluting stents should be limited to clinical situations, asaspirin 75-100mg/day (see 2.0-2.5) + described above Table 13). An uninterrupted strategy of OAC is preferred, mg/day +clopidogrel 75 and radial access should be used as the rst choice. (or aspirin 100m/day) Lifelong: VKA (INR 2.0-3.0) alone For medium to long-term management, triple therapy (VKA, aspirin, andACS = acute coronary syndrome; AF = atrial fibrillation; INR = international normalized ratio; VKA = vitaminK antagonist. clopidogrel) should be used in the initial period (3 – 6 months), or for longer inGastric protection with a proton pump inhibitor (PPI) should be considered where necessary. high risk of selected patients at low bleeding risk. In patients with aa cardiovascular thrombotic complications [e.g. high Global Registry of Acute Sirolimus, everolimus, and tacrolimus.b Combination of VKA (INR 2.0–3.0)+aspirin or TIMI risk(with PPI, long-term therapy considered as an Coronary Events (GRACE) 100 mg/day score], if indicated) may be with VKA mayalternative. be combined with clopidogrel 75 mg daily (or, alternatively, aspirin 75 – 100 mgc Drug-eluting stents should be avoided as far as possible, but, if used, consideration of more prolonged (3–6 daily).months) triple antithrombotic therapy is necessary. 54Adapted from Lip et al. <<Table 13>>Keypoints Following an ACS with or without PCI in patients with AF, triple therapy (VKA, IIaC IIaC aspirin, clopidogrel) should be considered in the short term (3–6 months), or longer in selected patients at low bleeding risk, followed by long-term therapy with VKA plus clopidogrel 75 mg daily (or, alternatively, aspirin 75–100 mg daily). In anticoagulated patients at very high risk of thrombo-embolism, uninterrupted IIaC IIaC therapy with VKA as the preferred strategy and radial access used as the rst choice even during therapeutic anticoagulation (INR 2–3). IIbC When VKA is given in combination with clopidogrel or low-dose aspirin, careful IIbC regulation of the anticoagulation dose intensity may be considered, with an INR range of 2.0–2.5. IIbC IIbC Following revascularization surgery in patients with AF, VKA plus a single antiplatelet drug may be considered in the initial 12 months, but this strategy has not been evaluated thoroughly and is associated with an increased risk of bleeding. In patients with stable vascular disease (e.g. >1 year, with no acute events), VKA IIbC IIbC monotherapy may be considered, and concomitant antiplatelet therapy should not be prescribed in the absence of a subsequent cardiovascular event.6.4.5 CARDIOVERSION6.4.5 CARDIOVERSIONConversion of AF to sinus rhythm results in transient mechanical dysfunction ofConversion of AF to 70 sinus rhythm results in transient mechanical dysfunction ofthe LA 6.4.5 CARDIOVERSIONthe LA and LAA70 ("stunning"), which can occur after spontaneous, and LAA ("stunning"), which can occur after spontaneous,pharmacological,48,71 or electrical71-73 conversion of AF. Thrombus may formpharmacological, 48,71 71-73 Conversion or electricalrhythm results in transient return of mechanical conversion of AF. Thrombus may formduring the period ofofstunning and is expelled after themechanical dysfunction of AF to sinusduring the period andstunning ("stunning"), which after the return of spontaneous, the LA of LAA70 and is expelled can occur after mechanicalfunction, explaining the clustering of thromboembolic events during the first 10 dfunction, explaining the clustering of thromboembolic events during the first 10 d 48,71 pharmacological, or electrical71-73 conversion of AF. Thrombus may formafter cardioversion.74,75 Recovery ofand is expelled function return be mechanicalafter cardioversion.74,75 Recovery of mechanical function may be delayed, during the period of stunning mechanical after the may of delayed, 76,46,87depending partially on the duration of AFof thromboembolic events during the first 10 ddepending partially on the duration of AF before conversion.76,46,87 function, explaining the clustering before conversion. after cardioversion.74,75 Recovery of mechanical function may be delayed, 77,78The risk of thromboembolism the duration of AF before conversion.76,46,87 5%77,78 andThe risk of thromboembolism after cardioversion is between 1% and 5% depending partially on after cardioversion is between 1% and andis reduced when anticoagulation (INR 2.0 to 3.0) is given for 4 wk before and anticoagulation (INR 2.0 to 3.0) is given for 4is reduced when of thromboembolism after cardioversion is between 1%wk before and The riskafter conversion 79,80 (see Figure 9). and 5%77,78 andafter conversion79,80 (see Figure 9). is reduced when anticoagulation (INR 2.0 to 3.0) is given for 4 wk before and 79,80 after conversion (see Figure 9).KeypointsFor patients with AF or AFL of 48-h duration or longer, or when the duration ofFor patients with AF or AFL of 48-h duration or longer, or when the duration ofAF or AFL is patients withanticoagulation (INR 2.0 to 3.0) is or when the duration at For unknown, anticoagulation (INR 2.0 to 3.0) is recommended for atAFIB AFL is unknown, AF or AFL of 48-h duration or longer, recommended for of IB orleast 4 weeks prior to and 4 weeks after cardioversion, regardless of the method AF or AFL is unknown, anticoagulation (INR 2.0 to 3.0) is recommended for atleast 4 weeks prior to and 4 weeks after cardioversion, regardless of the methodused to restore4sinus rhythm.64 4 weeks after cardioversion, regardless of the method least weeks prior to andused to restore sinus rhythm.64 used to restore sinus rhythm.64For patients with AF requiring immediate/emergency cardioversion because ofFor patients with AF with For patients requiring immediate/emergency cardioversion because ofhaemodynamic instability, AF requiring immediate/emergency cardioversion because ofhaemodynamic instability, heparin (i.v. UFH UFH bolus followed by infusion, orweight- IC heparin (i.v. UFH bolus followed by infusion, or weight- IC haemodynamic instability, heparin (i.v. bolus followed by infusion, or weight-adjusted therapeutic dose LMWH) is recommended.adjusted therapeutic dose LMWH) is recommended. adjusted therapeutic dose LMWH) is recommended.After immediate/emergency cardioversion in patients with AFAF of 48 hourdurationAfter immediate/emergency cardioversion in patients with AF of 48 hour duration After immediate/emergency cardioversion in patients with of 48 hour durationor Blonger, or when the duration of AF is unknown, OAC therapy is recommended or when the duration of AF is unknown, OAC therapy is recommended I longer, or longer, or when the duration of AF is unknown, OAC therapy is recommendedor IB for weeks, weeks, similar to patients undergoing elective cardioversion. 64for at least 4 at least 4similar to patients undergoing elective cardioversion. 64for at least 4 weeks, similar to patients undergoing elective cardioversion. 64 38For patients with AF with AF duration that is clearly <48 h and no thrombo-embolic risk For patients duration that is clearly <48 h and no thrombo-embolic risk AFFor patients with i.v. durationor weight- adjusted therapeutic thrombo-embolic risk IIbC factors, heparin that is clearly <48 h and no dose LMWH may befactors, i.v. heparin or weight- adjusted therapeutic dose LMWH may be
    • For patients with AF requiring immediate/emergency cardioversion because of IC haemodynamic instability, heparin (i.v. UFH bolus followed by infusion, or weight- adjusted therapeutic dose LMWH) is recommended. After immediate/emergency cardioversion in patients with AF of 48 hour duration IB or longer, or when the duration of AF is unknown, OAC therapy is recommended for at least 4 weeks, similar to patients undergoing elective cardioversion. 64 For patients with AF duration that is clearly <48 h and no thrombo-embolic risk IIbC IIbC factors, i.v. heparin or weight- adjusted therapeutic dose LMWH may be considered peri-cardioversion, without the need for post-cardioversion oral anticoagulation. It is important to stress that in following cardioversion of all patients at high risk of AF recurrence or with stroke risk factors, consideration should be given towards long-term anticoagulation, as thromboembolism may occur during asymptomatic recurrence of AF. IB For patients with AF <48 h and at high risk of stroke, i.v. heparin or weight- IB adjusted therapeutic dose LMWH is recommended peri-cardioversion, followed by OAC therapy with a VKA (INR 2.0–3.0) long term.49,55,64 In patients at high risk of stroke, OAC therapy with a VKA (INR 2.0–3.0) is IIB B recommended to be continued long-term.49,55,64 <<Figure 9>>Figure 9: Cardioversion of haemodynamically stable AF, the role of TOE-guided cardioversion, andsubsequent anticoagulation strategy. AF = atrial fibrillation; DCC = direct current cardioversion; LA = leftatrium; LAA = left atrial appendage; OAC = oral anticoagulant; SR = sinus rhythm; TOE = transoesophagealechocardiography.Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heartJournal 2010; doi:10.1093/eurheartj/ehq278) 39
    • As an alternative to anticoagulation prior to cardioversion of AF or AFL, it isreasonable to perform TOE in search of thrombus.13 For As an alternative to identifiable thrombus, cardioversion of AF or AFL, it is patients with no anticoagulation prior to cardioversion is reasonable IB IB immediately after anticoagulation. of thrombus.13 reasonable to perform TOE in search IIaB Thereafter, continuation of oral anticoagulation (INR 2.0 to 3.0) is IIaB For patients with no identifiable thrombus, cardioversion is reasonable reasonable for at least 4 anticoagulation. elective cardioversion. immediately after weeks, as for IIaB Thereafter, continuation of oral anticoagulation (INR 2.0 to 3.0) is IIaB For patients in whomfor at least 4is identified, oral anticoagulation (INR 2.0 to reasonable thrombus weeks, as for elective cardioversion. 3.0) is reasonable for at least 4 weeks before and 4 weeks after IIaB restoration of sinusin whom thrombus is identified, oral anticoagulation (INR 2.0 to For patients rhythm, and longer anticoagulation may be appropriate IIaB after apparently successful atcardioversion, before and theweeks after 3.0) is reasonable for least 4 weeks because 4 risk of thromboembolism often remains elevated inanticoagulation may be appropriate restoration of sinus rhythm, and longer such cases. after apparently successful cardioversion, because the risk of thromboembolism often remains elevated in such cases.For patients undergoing a TOE-guided strategy in whom thrombus is identied,VKA (INR 2.0–3.0) is recommended for at least 4 weeks, followed by a repeat IC IC For patients undergoing a TOE-guided strategy in whom thrombus is identied,TOE to ensure (INR 2.0–3.0) is recommended for at least 4 weeks, followed by a repeat VKA thrombus resolution. TOE to ensure thrombus resolution.If thrombus resolution is evident on repeat TOE, cardioversion should beperformed, and OAC should be is evident onfor 4 weeks orcardioversionrisk factors If thrombus resolution considered repeat TOE, lifelong (if should be IIaC IIaCare present). performed, and OAC should be considered for 4 weeks or lifelong (if risk factors are present).If thrombus remains on repeat TOE, an alternative strategy (e.g. rate control) If thrombus remains on repeat TOE, an alternative strategy (e.g. rate control) IIbCmay be considered. IIbC may be considered.This strategy may be useful to allow early early cardioversion patients with AF 48 This strategy may be useful to allow cardioversion of of patients with AF 48hours or where or minimal minimal period of anticoagulation is preferred. hours a where a period of anticoagulation is preferred. 6.5 NON-PHARMACOLOGICAL METHODS TO PREVENT STROKE6.5 NON-PHARMACOLOGICAL METHODS TO PREVENT STROKE The left atrial appendage (LAA) is considered the main site of atrialThe left thrombogenesis and thus, occlusion of the LAA orice may reduce the atrial appendage (LAA) is considered the main site of atrialthrombogenesis and ofthus, thrombi and stroke in patients with AF may reduce the development atrial occlusion of the LAA oricedevelopment of atrial thrombi and stroke in patients with AF The PROTECT AF trial81 randomized 707 eligible patients to percutaneousThe PROTECT of thetrial81 using a WATCHMAN eligibleand subsequent percutaneous closure AF LAA randomized 707 device patients to discontinuationclosure ofof warfarin using a WATCHMAN device and subsequent discontinuation the LAA (intervention, n = 463), or to VKA treatment (INR range 2 – 3; control, n = 244). The primary efficacy event rate (a composite endpoint of stroke,of warfarin (intervention, n = 463), or to VKA treatment (INR range 2 – 3; control, cardiovascular death, and systemic embolism) of the WATCHMAN device wasn = 244).considered non-inferior to that of VKA. There composite endpoint of stroke, The primary efficacy event rate (a was a higher rate of adverse safetycardiovascular death, and systemic embolism) of the WATCHMAN device was events in the intervention group than in the control group, due mainly toconsidered non-inferior complications. periprocedural to that of VKA. There was a higher rate of adverse safetyevents in the intervention group than in the control group, due mainly toperiprocedural complications.6.6 RISK OF LONG-TERM ANTICOACULATION6.6.1. ASSESSMENT OF RISK OF BLEEDINGAn assessment of bleeding risk should be part of the clinical assessment ofpatients before starting anticoagulation therapy.In order to provide adequate thromboprophylaxis with minimal risk of bleeding,current clinical practice aims for a target INR of between 2.0 and 3.0; INRs ofmore than 3.0 are associated with increases in bleeding and INRs of less than2.0 are associated with increases in stroke risk.The annual risks of intracranial haemorrhage increased from 0.1% in control to0.3% in VKA groups, which represents 40 excess of two intracranial bleeds per anannum per 1,000 patients treated.
    • 6.6 RISK OF LONG-TERM ANTICOACULATION6.6.1. ASSESSMENT OF RISK OF BLEEDINGAn assessment of bleeding risk should be part of the clinical assessment ofpatients before starting anticoagulation therapy.In order to provide adequate thromboprophylaxis with minimal risk of bleeding,current clinical practice aims for a target INR of between 2.0 and 3.0; INRs ofmore than 3.0 are associated with increases in bleeding and INRs of less than2.0 are associated with increases in stroke risk.The annual risks of intracranial haemorrhage increased from 0.1% in control to0.3% in VKA groups, which represents an excess of two intracranial bleeds perannum per 1,000 patients treated.Even low-dose aspirin increases the risk of major haemorrhage by two-fold,especially in the setting of uncontrolled hypertension.Controlling and monitoring of hypertension and other associated co morbidities isextremely important in minimizing the risk of bleeding in patients on prophylacticOAC.The fear of falls may be overstated, as a patient may need to fall 300 times peryear for the risk of intracranial haemorrhage to outweigh the benet of OAC instroke prevention.While these factors are often cited as reasons for non-prescription of VKA in theelderly, the absolute benefit is likely to be greatest in this same group in view oftheir high risk.686.6.2 RISK SCORE FOR BLEEDINGThe bleeding risk score HAS-BLED was formulated by incorporating risk factorsfrom a derivation cohort of a large population database of the prospective EuroHeart Survey on AF.82 The clinical characteristic comprising the HAS-BLEDbleeding risk score is shown in Table 14.It is reasonable to use the HAS-BLED score to assess bleeding risk in AFpatients, whereby a score of 3 indicates ‘high risk’, and some caution andregular review of the patient is needed following the initiation of antithrombotictherapy, whether with VKA or aspirin.A schema such as HAS-BLED is a user-friendly method of predicting bleedingrisk and is easy to remember. 41
    • Table 14 : Clinical characteristics comprising the HAS-BLED bleeding risk score Table 14 : Clinical characteristics comprising the HAS-BLED bleeding risk score Letter Clinical characteristica Points awarded H Hypertension 1 Abnormal renal and liver A 1 or 2 function (1 point each) S Stroke 1 B Bleeding 1 L Labile INRS 1 E Elderly (e.g. age >65 years) 1 D Drugs or alcohol (1 point each) 1 or 2 Maximum 9 pointsa’ Hypertension’ is defined as systolic blood pressure .160 mmHg. ‘Abnormal kidney function’ is definedas the presence of chronic dialysis or renal transplantation or serum creatinine 200 mmol/L. ‘Abnormalliver function’ is defined as chronic hepatic disease (e.g. cirrhosis) or biochemical evidence of significanthepatic derangement (e.g. bilirubin .2 x upper limit of normal, in association with aspartateaminotransferase/alanine aminotransferase/alkaline a’phosphatase .3 is defined as systolic blood pressure .160 refers to previous kidney function’ is defined Hypertension’ x upper limit normal, etc.). ‘Bleeding’ mmHg. ‘Abnormal bleeding history and/or as the presence bleeding, dialysis or renal transplantation or serum creatinine 200 mmol/L. ‘Abnormalpredisposition to of chronic e.g. bleeding diathesis, anaemia, etc. ‘Labile INRs’ refers to unstable/highINRs function’ is defined as chronic range (e.g.<60%). Drugs/alcohol use refers to concomitant use of liver or poor time in therapeutic hepatic disease (e.g. cirrhosis) or biochemical evidence of significant hepatic derangement (e.g. bilirubin .2 x upper limit of normal, in association with aspartatedrugs, such as antiplatelet agents, non-steroidal anti-inflammatory drugs, or alcohol abuse, etc. INR = aminotransferase/alanine aminotransferase/alkalineinternational normalized ratio.Adapted from Pistersupper limit normal, etc.). ‘Bleeding’ refers to previous bleeding history and/or phosphatase .3 x et al.82 predisposition to bleeding, e.g. bleeding diathesis, anaemia, etc. ‘Labile INRs’ refers to unstable/high INRs or poor time in therapeutic range (e.g.<60%). Drugs/alcohol use refers to concomitant use of drugs, such<<Table 14>>agents, non-steroidal anti-inflammatory drugs, or alcohol abuse, etc. INR = as antiplateletKeypoints normalized ratio. international 82 Adapted from Pisters et al. IIaA IIaA Assessment of the risk of bleeding should be considered when prescribing antithrombotic therapy (whether with VKA or aspirin), and the bleeding risk with aspirin should be considered as being similar to VKA, especially in the elderly.68,82,83 IIaB The HAS-BLED score [hypertension, abnormal renal/liver function, stroke, IIaB bleeding history or predisposition, labile INR, elderly (>65), drugs/alcohol concomitantly] should be considered as a calculation to assess bleeding risk, whereby a score of 3 indicates ‘high risk’ and some caution and regular review is needed, following the initiation of antithrombotic therapy, whether with OAC or aspirin.827 MANAGEMENT – LONGTERM RATE CONTROL7.1 PHARMACOLOGICAL RATE CONTROLCriteria for rate control vary with patient age but usually involve achievingventricular rates 60 - 80 beats per minute at rest and 90 – 115 beats per minute during moderate exercise.23However, maintaining lenient control of heart rate (a resting rate of less than 100beats per minute) is easier to achieve and is comparable to strict control (aresting heart rate of 80 beats per minute and a heart rate during moderate 42exercise of less than 110 beats per minute) on long-term composite outcomes.84
    • 7.1 PHARMACOLOGICAL RATE CONTROLCriteria for rate control vary with patient age but usually involve achievingventricular rates 60 - 80 beats per minute at rest and 90 – 115 beats per minute during moderate exercise.23However, maintaining lenient control of heart rate (a resting rate of less than 100beats per minute) is easier to achieve and is comparable to strict control (aresting heart rate of 80 beats per minute and a heart rate during moderateexercise of less than 110 beats per minute) on long-term composite outcomes.84For patients without severe symptoms due to high ventricular rate, a lenient ratecontrol therapy approach is reasonable (See Figure 10).<<Figure 10>>Drugs commonly used are ß-blockers, non-dihydropyridine calcium channelantagonists, and digitalis. Acute treatment is described in Section 5.1.1.7 MANAGEMENTdrugs may be necessary. Dronedarone may also effectivelyCombinations of – LONGTERM RATE CONTROLreduce heart rate during AF recurrences. Amiodarone may be suitable for some7.1 PHARMACOLOGICAL RATErate control. The combination of apatients with otherwise refractory CONTROLß-blocker and digitalis may be benecial in patients with heart failure.Criteria for rate control vary with patient age but usually involve achievingventricular rates control policy is adopted (resting heart rate < 80 bpm and aWhen a strict ratetarget heart rate of <110 bpm duringrest and exercise) a 24 h Holter monitor 60 - 80 beats per minute at moderate 23should be 90 – 115 beats per minute during bradycardia. performed to assess pauses and moderate exercise.However, of the most effectivecontrol of heart rate (a restingagent, or combinationSelection maintaining lenient and appropriate rate-control rate of less than 100beats per minute) Table 15 listsachieve and treatments in order of preference,of agents, is vital. is easier to rate-control is comparable to strict control (aresting into accountof 80 beats per minute and a present. Figure 11, moderatetaking heart rate other conditions that may be heart rate during page 47exercise of less than 110 beats to make theon long-term composite outcomes.84provides an algorithm on how per minute) drug choice and Table 16 list theFor patients without severe symptoms due to high ventricular rate, a lenient ratedrugs and their doses for rate control.control therapy approach is reasonable (See Figure 10).<<Table 15>> level of heart rate control. Figure 10:Optimal<<Figure 10>>Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European<<Table 16>>heart Journal 2010; doi:10.1093/eurheartj/ehq278)Drugs commonly used are ß-blockers, non-dihydropyridine calcium channelantagonists, and digitalis. Acute treatment is described in Section 5.1.1.Combinations of drugs may be necessary. Dronedarone may also effectivelyreduce heart rate during AF recurrences. Amiodarone may be suitable for somepatients with otherwise refractory rate control. The combination of aß-blocker and digitalis may be benecial in patients with heart failure.When a strict rate control policy is adopted (resting heart rate < 80 bpm and atarget heart rate of <110 bpm during moderate exercise) a 24 h Holter monitorshould be performed to assess pauses and bradycardia.Selection of the most effective and appropriate rate-control agent, or combinationof agents, is vital. Table 15 lists rate-control treatments in order of preference,taking into account other conditions that may be present. Figure 11, page 47provides an algorithm on how to make the drug choice and Table 16 list thedrugs and their doses for rate control.<<Table 15>><<Table 16>> 43
    • Table 15: Choice of a rate-control agent Co morbidity First-line Second-line Less effective or desirable No heart disease Beta-blockers* Digoxin‡ OR (can be rst-line in Non-dihydropyridine people unlikely to be Calcium channel active) blockers† Hypertension Beta-blockers* Digoxin‡ OR Non-dihydropyridine Calcium channel blockers† Ischaemic heart Beta-blockers* First line agent plus Ablation + pacing disease Non-dihydropyridine Calcium-channel blockers† OR Digoxin‡ Congestive heart Digoxin in overt heart Beta-blockers* Amiodarone failure failure (excluding carvedilol, bisoprolol Carvedilol or bisoprolol and metoprolol) Ablation and pacing or metoprolol OR should be considered in stable heart failure Diltiazem Chronic obstructive Non-dihydropyridine First line agent plus Digoxin‡ pulmonary disease Calcium channel beta-blockers blockers† (if there is no reversible bronchospasm. * excluding sotalol † diltiazem or verapamil ‡ as monotherapy (can be used in combination with other rate-control agents)Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal2010; doi:10.1093/eurheartj/ehq278) 44
    • Table 16: Oral pharmacological agents for rate control in people with atrial fibrillation/atrial flutter Drug Oral Onset Commonly used Adverse effects Comments loading of action oral maintenance dose dosesBeta-blockersAtenolol N/A 2 to 3 hr 25 to 50 mg Hypotension, In people with heart block, heart failure,Carvedilol N/A 60 to 90 min 6.25 to 25 mg bd bradycardia, lower doses may asthma, heart failure be advisableMetoprolol N/A 4 to 6 hr 23.75 to 200 mg/day * (negative inotropicNadolol N/A 3 to 4 hr 20 to 80 mg/day effect)Propanolol N/A 60 to 90 min 80 to 240 mg/dayCalcium channel blockersDiltiazem N/A 1 to 4 hr 120 to 360 mg/day Hypotension, In people with heart block, heart failure, heart failure lower doses may be advisableVerapamil N/A 1 to 2 hr 120 to 360 mg/day Hypotension, In people with heart block, heart failure, heart failure, lower doses may digoxin be advisable interaction (negative inotropic effect)OtherDigoxin 0.5 to 1.0 2 hr 0.0625 to 0.375 Digoxin toxicity, First-line therapy mg mg/day heart block, only for people bradycardia unlikely to be active (eg, older people or infirm) and for people with heart failure. Less effective in hyperadrenergic statesAmiodarone 400 to 800 1 to 3 wk 200 mg/day Photosensitivity Although there mg/day and other skin is fairly good for 1 week reactions, evidence of pulmonary efficacy, this is toxicity, an agent of last polyneuropathy, resort in this gastrointestinal indication, due upset, to its long-term bradycardia, toxicity hepatic toxicity, thyroid dysfunction, torsades de pointes (rare)N/A = Not applicableAdapted from: Fuster V, Ryden LE, Asinger RW, et al.134Keypoints Rate control using pharmacological agents ( -blockers, non-dihydropyridine IB IB calcium channel antagonists, digitalis, or a combination thereof) is recommended in patients with paroxysmal, persistent, or permanent AF. The choice of medication should be individualized and the dose modulated to avoid bradycardia.34 In patients who experience symptoms related to AF during activity, the adequacy IC IC of heart rate control should be assessed during exercise, adjusting pharmacological treatment as necessary to keep the rate in the physiological range. In pre-excitation AF, or in patients with a history of AF, preferred drugs for rate IC IC control are propafenone or amiodarone It is reasonable to initiate treatment with a lenient rate control protocol aimed at a 45 IIbB resting heart rate <110 bpm.84
    • In patients who experience symptoms related to AF during activity, the adequacy IC of heart rate control should be assessed during exercise, adjusting pharmacological treatment as necessary to keep the rate in the physiological range. In pre-excitation AF, or in patients with a history of AF, preferred drugs for rate IC control are propafenone or amiodarone It is reasonable to initiate treatment with a lenient rate control protocol aimed at a IIbB IIbB resting heart rate <110 bpm.84 It is reasonable to adopt a stricter rate control strategy when symptoms persist or IIbB IIbB tachycardiomyopathy occurs, despite lenient rate control: resting heart rate <80 bpm and heart rate during moderate exercise <110 bpm. After achieving the strict heart rate target, a 24 h Holter monitor is recommended to assess safety.84 IIa C Digoxin is indicated in patients with heart failure and LV dysfunction, and in IIaC sedentary (inactive) patients. Rate control may be achieved by administration of oral amiodarone when other IIbC IIb C measures are unsuccessful or contraindicated. Digitalis should not be used as the sole agent to control the rate of ventricular IIIB III B response in patients with paroxysmal AF.88 Intravenous administration of amiodarone is recommended to control the heart IB IB rate in patients with AF and HF who do not have an accessory pathway. IIaC Intravenous amiodarone can be useful to control the heart rate in patients with IIaC AF when other measures are unsuccessful or contraindicated. 357.1.2 Combination therapyCombination of drugs may be required to control heart rate. Care should betaken to avoid Combination therapy The combination of digoxin and ß-blocker 7.1.2 severe bradycardia.appears more effective than the combination of digoxin with a CCB.89 Combination of drugs may be required to control heart rate. Care should beA combination of avoid severe bradycardia. ß-blocker, diltiazem, or verapamil is taken to digoxin and either a The combination of digoxin and ß-blockerKeypoint appears more effective than the combinationand during exercise89in patientsreasonable to control the heart rate both at rest of digoxin with a CCB.with AF. A combination of digoxin and either a ß-blocker, diltiazem, or verapamil is IIaB IIaB reasonable to control the heart rate both at rest and during exercise in patients<<Figure 11>>AF. with <<Figure 11>> 46
    • Figure 11 : Rate control. COPD = chronic obstructive pulmonary disease. *Small doses of b1-electiveFigure 11may be used in COPD if=rate control is not adequate with disease. *Small doses of b1-electiveblockers : Rate control. COPD chronic obstructive pulmonary non-dihydropyridine calcium channelblockers may be digoxin. COPD if rateiscontrolused for rate control in patients who do not respond toantagonists and used in Amiodarone also is not adequate with non-dihydropyridine calcium channelantagonists b-blockers or non-dihydropyridine calcium for rate control in patients who do not respond toglycosides, and digoxin. Amiodarone is also used antagonists. Dronedarone may also be used for rateglycosides, b-blockersrecurrent episodes of atrial fibrillation.control in patient with or non-dihydropyridine calcium antagonists. Dronedarone may also be used for ratecontrol in patient with recurrent episodes of atrial fibrillation. Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal 2010; doi:10.1093/eurheartj/ehq278)7.2 NON-PHARMACOLOGICAL RATE CONTROL7.2.1 AV NODAL ABLATION AND PACINGAV nodal ablation in conjunction with permanent pacemaker implantationprovides highly effective control of the heart rate and improves symptoms, qualityof life, exercise capacity, ventricular function and healthcare utilization in selectedpatients with AF.90,100Ablation of the atrioventricular node is a palliative but irreversible procedure andis therefore reasonable in patients in whom pharmacological rate control,including combination of drugs, has failed or rhythm control with drugs and/or LAablation has failed.When the rate of ventricular response to AF cannot be controlled withpharmacological agents or tachycardia-mediated cardiomyopathy is suspected,catheter-directed ablation of the AV node may be considered in conjunction withpermanent pacemaker implantation.It is suggested that programming the pacemaker initially for the 1 st month post- 47ablation to a higher nominal rate (90 beat per minutes) will reduce the risk of
    • including combination of drugs, has failed or rhythm control with drugs and/or LAablation has failed.of the atrioventricular node is a palliative but irreversible procedure and Ablation is therefore reasonable in patients in whom pharmacological rate control,When the including combination of drugs, has failed or rhythm control with drugs and/or LA rate of ventricular response to AF cannot be controlled with ablation has failed.pharmacological agents or tachycardia-mediated cardiomyopathy is suspected,catheter-directed the rate of the AV node may beto AF cannotinbe controlled with When ablation of ventricular response considered conjunction withpermanent pharmacological agents or tachycardia-mediated cardiomyopathy is suspected, pacemaker implantation. catheter-directed ablation of the AV node may be considered in conjunction withIt is suggested that programming the pacemaker initially for the 1 st month post- permanent pacemaker implantation.ablation to a higher nominal rate (90 beat per minutes) will reduce the risk of It is suggested that programming the pacemaker initially for the 1 st month post-sudden cardiac death. higher nominal rate (90 beat per minutes) will reduce the risk of ablation to a sudden cardiac death.KeypointsAblation of the AV node to control heart rate should be considered when the ratecannot be Ablation of the AV node to control heart rate should be considered when the rate IIaB IIa B controlled with pharmacological agents and when AF cannot beprevented by antiarrhythmic therapy or is associated with and when AF cannot be cannot be controlled with pharmacological agents intolerable side effects, prevented by antiarrhythmic therapy or is associated with intolerable side effects,and direct catheter-based or surgical ablation of AF is not not indicated, has failed, or and direct catheter-based or surgical ablation of AF is indicated, has failed, oris rejected.90,100 is rejected.90,100Ablation of Ablation of the AV node should be considered patients with permanent AF the AV node should be considered for for patients with permanent AF IIaBand B indication indication for CRT (NYHA functional class or ambulatory class IV IIa an and an for CRT (NYHA functional class III III or ambulatory class IVsymptoms despite despite medical therapy, LVEF <35%, QRS width >130 symptoms optimal optimal medical therapy, LVEF <35%, QRSwidth >130 101-104ms).101-104 ms). Ablation of the AV node should be considered for CRT non-responders in whom IIaCAblation of AF prevents effective biventricular stimulation and non-responders in whom the AV node should be considered for CRT amiodarone is ineffective or IIa CAF prevents effective biventricular stimulation and amiodarone is ineffective or contraindicated.contraindicated. In patients with any type of AF and severely depressed LV function (LVEF <35%) IIaCIn patients and severe heart AF and severely(NYHA III or LV function (LVEF <35%) IIa C with any type of failure symptoms depressed IV), biventricular stimulation should be considered after AV node ablation.and severe heart failure symptoms (NYHA III or IV), biventricular stimulationshould be considered afterAV node to control heart rate may be considered when Ablation of the AV node ablation. IIbC IIb C tachycardia-mediated cardiomyopathy is suspected and the rate cannot beAblation of the AV node to controlagents, and direct ablation of AF is not indicated, controlled with pharmacological heart rate may be considered whentachycardia-mediated is rejected. has failed, or cardiomyopathy is suspected and the rate cannot be Ablation of the AV node with consecutive implantation of a CRT device may be IIbC considered in patients with permanent AF, LVEF <35%, and NYHA functional IIb C class I or II symptoms on optimal medical therapy to control heart rate when pharmacological therapy is insufficient or associated with side effects. In patients with any type of AF, moderately depressed LV function (LVEF <45%) IIbC IIb C and mild heart failure symptoms (NYHA II), implantation of a CRT pacemaker may be considered after AV node ablation. In patients with paroxysmal AF and normal LV function, implantation of a dual- IIbC IIb C chamber (DDDR) pacemaker with mode-switch function may be considered after AV node ablation. In patients with persistent or permanent AF and normal LV function, implantation IIbC IIb C of a single- chamber (VVIR) pacemaker may be considered after AV node ablation. Catheter ablation of the AV node should not be attempted without a prior trial of IIIC III C medication, or catheter ablation for AF, to control the AF and/or ventricular rate in patients with AF.8 MANAGEMENT – LONGTERM RHYTHM CONTROLThe term ‘rhythm control’ encompasses the processes of conversion of atrialbrillation (AF) or atrial utter (AFI) to normal sinus rhythm, as well as themaintenance of sinus rhythm.Maintenance of sinus rhythm may also be referred to as prevention of AF/AFIrelapse or recurrence, and may be achieved by pharmacological ornonpharmacological means, or both (hybrid therapy).In the absence of spontaneous reversion, cardioversion is chosen as part of the 48rhythm-control strategy.
    • The term ‘rhythm control’ encompasses the processes of conversion of atrialThe term ‘rhythm control’ encompasses the processes of conversion of atrialbrillation (AF) or atrial utter (AFI) to normal sinus rhythm, as well as thebrillation (AF) or atrial utter (AFI) to normal sinus rhythm, as well as themaintenance of sinus rhythm.maintenance of sinus rhythm.Maintenance of sinus rhythm may also be referred to asMaintenance of sinus rhythm may also be referred to as prevention of AF/AFI prevention of AF/AFIrelapse or recurrence, and may be achieved byrelapse or recurrence, and may be achieved by pharmacological or pharmacological ornonpharmacological means, or both (hybrid therapy).nonpharmacological means, or both (hybrid therapy).In the absence of spontaneous reversion, cardioversion is chosen as part of theIn the absence of spontaneous reversion, cardioversion is chosen as part of therhythm-control strategy.rhythm-control strategy.The following are the guiding principles of antiarrhythmic drug therapy toThe following are the guiding principles of antiarrhythmic drug therapy tomaintain sinus rhythm in AF:maintain sinus rhythm in AF:(1) Treatment is motivated by attempts to reduce AF-related symptoms.(1) Treatment is motivated by attempts to reduce AF-related symptoms.(2) Efficacy of antiarrhythmic drugs to maintain sinus rhythm is modest.(2) Efficacy of antiarrhythmic drugs to maintain sinus rhythm is modest.(3) Clinically successful antiarrhythmic drug therapy may reduce rather than(3) Clinically successful antiarrhythmic drug therapy may reduce rather than eliminate recurrence of AF. eliminate recurrence of AF.(4) If one antiarrhythmic drug ‘fails’, a clinically acceptable response may be(4) If one antiarrhythmic drug ‘fails’, a clinically acceptable response may be achieved with another agent. achieved with another agent.(5) Drug-induced proarrhythmia or extra-cardiac side effects are frequent.(5) Drug-induced proarrhythmia or extra-cardiac side effects are frequent.(6) Safety rather than efficacy considerations should primarily guide the choice(6) Safety rather than efficacy considerations should primarily guide the choice of antiarrhythmic agent of antiarrhythmic agent8.1 EFFICACY OF ANTIARRHYTHMIC DRUGS IN PREVENTING8.1 EFFICACY OF ANTIARRHYTHMIC DRUGS IN PREVENTINGRECURRENT ATRIAL BRILLATIONRECURRENT ATRIAL BRILLATIONIn a recent meta-analysis of 44 randomized controlled trials comparingIn a recent meta-analysis of 44 randomized controlled trials comparingantiarrhythmic drugs against control,105 the antiarrhymic drugs signicantlyantiarrhythmic drugs against control,105 the antiarrhymic drugs signicantlyreduced the rate of recurrent AF. Overall, the likelihood of maintaining sinusreduced the rate of recurrent AF. Overall, the likelihood of maintaining sinusrhythm is approximately doubled by the use of antiarrhythmic drugs.106rhythm is approximately doubled by the use of antiarrhythmic drugs.106Amiodarone was superior to class I agents and sotalol.Amiodarone was superior to class I agents and sotalol.The number of patients needed to treat for 1 year was 2 – 9. Withdrawal due toThe number of patients needed to treat for 1 year was 2 – 9. Withdrawal due toside effects was frequent (1 in 9 – 27 patients), and all drugs except amiodaroneside effects was frequent (1 in 9 – 27 patients), and all drugs except amiodaroneand propafenone increased the incidence of proarrhythmia.105 The number ofand propafenone increased the incidence of proarrhythmia.105 The number ofpatients needed to harm was 17 – 119. Most of the trials included in the analysispatients needed to harm was 17 – 119. Most of the trials included in the analysisenrolled relatively healthy patients without severe concomitant cardiac disease.Although mortality was low in all studies (0 – 4.4%), rapidly dissociating sodiumchannel blockers (disopyramide phosphate, quinidine sulfate) were associatedwith increased mortality.8.2 CHOICE OF ANTIARRHYTHMIC DRUGSAntiarrhythmic therapy for recurrent AF is recommended on the basis ofchoosing safer, although possibly less efficacious, medication before resorting tomore effective but less safe therapy. Upon initiation of antiarrhythmic therapy,regular ECG monitoring is recommended (see Table 16. page 45).8.2.1 PATIENTS WITH LONE ATRIAL FIBRILLATIONIn patients with no or minimal heart disease, ß-blockers represent a logical rstattempt to prevent recurrent AF when the arrhythmia is clearly related to mental orphysical stress (adrenergic AF). Flecainide, propafenone, sotalol, or dronedaroneis usually prescribed as second line agents (Figure 12, page 50).107,108<<Figure 12>> 49
    • enrolled relatively healthy patients without severe concomitant cardiac disease. No or minimal structural heart diseaseenrolled relatively healthy patients without severe concomitant cardiac disease.Although mortality was low in all studies (0 – 4.4%), rapidly dissociating sodiumAlthoughblockers (disopyramide phosphate,– quinidine sulfate) were associatedchannel mortality was low in all studies (0 4.4%), rapidly dissociating sodiumchannel blockers (disopyramide phosphate, quinidine sulfate) were associatedwith increased mortality.with increased mortality. Adrenergically mediated Undetermined8.2 CHOICE OF ANTIARRHYTHMIC DRUGS8.2 CHOICE OF ANTIARRHYTHMIC DRUGSAntiarrhythmic therapy for recurrent AF is recommended on the basis of B-Blocker DronedaroneAntiarrhythmic therapy for recurrent efficacious, medication before resorting tochoosing safer, although possibly less AF is recommended on the basis of Flecainide Propafenonechoosing safer, but less safe therapy. efficacious, medication before resorting tomore effective although possibly less Upon initiation of Sotalol antiarrhythmic therapy,more effective but less is recommended (seeinitiation ofpage 45).regular ECG monitoring safe therapy. Upon Table 16. antiarrhythmic therapy,regular ECG monitoring Sotalol is recommended (see Table 16. page 45).8.2.1 PATIENTS WITH LONE ATRIAL FIBRILLATION8.2.1 PATIENTS WITH LONE ATRIAL FIBRILLATIONIn patients withDronedarone no or minimal heart disease, ß-blockers represent a logical rst AmiodaroneIn patientsprevent recurrent AF heart disease, ß-blockers represent ato mental orattempt to with no or minimal when the arrhythmia is clearly related logical rstattempt to prevent recurrentAF).when the arrhythmia is clearly relateddronedaronephysical stress (adrenergic AF Flecainide, propafenone, sotalol, or to mental orphysical stress (adrenergic AF).line agents (Figure 12, page 50).107,108dronedaroneis usually prescribed as second Flecainide, propafenone, sotalol, oris usually prescribed as second line agents (Figure 12, page 50).107,108Figure 12. Choice of antiarrhythmic medication for the patient with AF and no or minimal structural heart<<Figure 12>> may be initially based on the pattern of arrhythmia onset. Antiarrhythmic agents aredisease. Medication<<Figure 12>> order within each treatment box.listed in alphabeticalAdapted with modification from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (Europeanheart Journal 2010; doi:10.1093/eurheartj/ehq278)8.2.2 PATIENTS WITH UNDERLYING HEART DISEASE8.2.2 PATIENTS WITH UNDERLYING HEART DISEASECardiovascular disease has conventionally been divided into a variety ofCardiovascular disease has conventionally ischaemia, and into a variety ofpathophysiological substrates: hypertrophy, been divided congestive heartpathophysiological substrates:ofhypertrophy, ischaemia, and congestive heartfailure (Figure 13). For each these it has been recommended that specicfailure be avoided. For each of these it has been recommended that specicdrugs (Figure 13).drugs be avoided.<<Figure 13>><<Figure 13>>Individual drugs and their main disadvantages are listed in Table 17.Individual drugs and their main disadvantages are listed in Table 17.Amiodarone is the most efficacious antiarrhythmic drug for the prevention ofAmiodarone is the most efficacious antiarrhythmic drug for failed to identify ofrecurrent AF. However, several meta-analyses105,109-111 have the prevention arecurrent effect of amiodarone meta-analyses105,109-111 have view to identify abenecial AF. However, severalon cardiovascular outcomes. Infailed of the betterbenecial effect of amiodarone on cardiovascular outcomes. In view ofas the rstsafety and potential outcome benet, dronedarone may be preferable the bettersafety and potential outcome benet, dronedarone may be preferable as the rstantiarrhythmic option, at least in patients with symptomatic AF and underlyingantiarrhythmic option, at least in patients with symptomatic control symptoms,cardiovascular disease. Should dronedarone fail to AF and underlyingcardiovascular disease. necessary.amiodarone might then be Should dronedarone fail to control symptoms,amiodarone might then be necessary.Dronedarone can be used safely in patients with ACS, chronic stable angina,Dronedarone heartbe used safely in patients with only be used in maintaininghypertensive can disease. Dronedarone should ACS, chronic stable angina,hypertensive and in disease. Dronedarone should only be used in maintainingsinus rhythm heart whose normal heart rhythm has been restored. Dronedaronesinus rhythm and inin patients with heart rhythm112 been restored. Dronedaroneshould not be used whose normal failure. hasshould not be used in patients with heart failure.112Figure 13. Choice of antiarrhythmic drug according to underlying pathology. ACEI=angiotensin-converting enzyme inhibitor; ARB=angiotensin receptor blocker; CAD = coronary artery disease; CHF=congestive heart failure; HT=hypertension; LVH =left ventricularhypertrophy; NYHA=New York Heart Association; unstable=cardiac decompensation within the prior 4 weeks. Antiarrhythmic agentsare listed in alphabetical order within each treatment box. ? = evidence for ‘upstream’ therapy for prevention of atrial remodelling stillremains controversial.Adapted with modification from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal2010; doi:10.1093/eurheartj/ehq278) 50
    • Cardiovascular disease has conventionally been divided into a variety of pathophysiological substrates: hypertrophy, ischaemia, and congestive heart failure (Figure 13). For each of these it has been recommended that specic drugs be avoided. <<Figure 13>> Individual drugs and their main disadvantages are listed in Table 17. Amiodarone is the most efficacious antiarrhythmic drug for the prevention of recurrent AF. However, several meta-analyses105,109-111 have failed to identify a benecial effect of amiodarone on cardiovascular outcomes. In view of the better safety and potential outcome benet, dronedarone may be preferable as the rst antiarrhythmic option, at least in patients with symptomatic AF and underlying cardiovascular disease. Should dronedarone fail to control symptoms, amiodarone might then be necessary. Dronedarone can be used safely in patients with ACS, chronic stable angina, hypertensive heart disease. Dronedarone should only be used in maintaining sinus rhythm and in whose normal heart rhythm has been restored. Dronedarone should not be used in patients with heart failure.112 8.2.2.1 Patients with left ventricular hypertrophy In patients with LV hypertrophy, sotalol is thought to be associated with an increased incidence of proarrhythmia. Flecainide and propafenone may be used, but there is some concern about proarrhythmic risk, especially in patients with marked hypertrophy (LV wall thickness >1.4 cm according to previous guidelines), and associated coronary artery disease. Since dronedarone was demonstrated to be safe and well tolerated in a large study including patients with hypertension and possible LV hypertrophy, it is an option for this population, although denitive data do not exist. Amiodarone should be considered when symptomatic AF recurrences continue to impact on the quality of life of these patients. 8.2.2.2 Patients with coronary artery disease Patients who have coronary artery disease should not receive ecainide163 or propafenone. Sotalol or dronedarone should be administered as rst-line therapy. Dronedarone may be preferred based on its safety prole. Amiodarone is considered as the drug of last resort in this population due to its extra-cardiac side effect prole. 8.2.2.3 Patients with heart failure Amiodarone is the only agents available in Malaysia that can be safely administered in patients with heart failure. Dronedarone is contraindicated in patients with all classes of heart failure.112 In such patients, amiodarone should be used. The following antiarrhythmic drugs are recommended for rhythm control in patients with AF, depending on underlying heart disease:IA amiodarone21,105,113IA dronedarone85,86IA ecainide105,114 51IA propafenone105,113
    • side effect prole. side effect prole.Amiodarone is the only agents available in Malaysia that can be safelyadministered in Patients with heart failure 8.2.2.3 patients with heart failure. 8.2.2.3 Patients with heart failureDronedarone is contraindicated agents available in in Malaysia heartcan be 112 In Amiodarone is is the only agents available Malaysia of that failure.safely Amiodarone the only in patients with all classes that can be safelysuch patients, amiodarone should heart failure. administered in patients with administered in patients with heart failure. be used. Dronedarone is contraindicated in patients with all all classes heart failure.112 112 In Dronedarone is contraindicated in patients with classes of of heart failure. In such patients, amiodarone should be be used. such patients, amiodarone should used.The following antiarrhythmic drugs are recommended for rhythm control inpatients with AF, depending on underlying heart disease: The following antiarrhythmic drugs areare recommended for rhythm control in The following antiarrhythmic drugs recommended for rhythm control inKeypoints patients with AF, depending on underlying heart disease: patients with AF, depending on underlying heart disease: amiodarone21,105,113I AIA IA amiodarone21,105,113 amiodarone21,105,113 dronedarone85,86I AIA IA dronedarone85,86 dronedarone85,86 ecainide105,114I AIA IA ecainide105,114 ecainide105,114 105,113I AIA propafenone IA propafenone105,113 propafenone105,113I AIA d,I-sotalol21,48,105 21,48,105 IA d,I-sotalol 21,48,105 d,I-sotalol IA/C I A/C Amiodarone is more effective in maintaining sinus rhythm than sotalol, propafenone, ecainide (by analogy), or dronedarone (Level of Evidence A), but because of its toxicity prole should generally be used when other agents have failed or are contraindicated (Level of Evidence C).21,105,110,113 In patients with severe heart failure, NYHA class III and IV or recently unstable IB IB (decompensation within the prior month) NYHA class II, amiodarone should be the drug of choice.115 In patients without signicant structural heart disease, initial antiarrhythmic IA IA therapy should be chosen from dronedarone, ecainide, propafenone, and sotalol.85,86,105,113-115 IC IC -Blockers are recommended for prevention of adrenergic AF. If one antiarrhythmic drug fails to reduce the recurrence of AF to a clinically IIaC IIa C acceptable level, the use of another antiarrhythmic drug should be considered. Dronedarone should be considered in order to reduce cardiovascular IIaB IIa B hospitalizations in patients with non-permanent AF and cardiovascular risk factors.85,86 IIaC IIa C -blockers should be considered for rhythm (plus rate) control in patients with a rst episode of AF. Dronedarone is not recommended for treatment of permanent AF and all classes IIIB III B of heart failure. Antiarrhythmic drug therapy is not recommended for maintenance of sinus IIIC III C rhythm in patients with advanced sinus node disease or AV node dysfunction unless they have a functioning permanent pacemaker.8.3 NONPHARMACOLOGICAL THERAPYThere is a variety of alternative non-pharmacological therapies for the preventionand control of AF.8.3.1 LEFT ATRIAL CATHETER ABLATIONCatheter ablation of AF particularly circumferential pulmonary vein ablation(isolation) in the left atrium represents a promising and evolving therapy forselected patients resistant to pharmacological therapy.Ablation is indicated in highly symptomatic, paroxysmal or persistent AF, despiteoptimal medical therapy and in patients with minimal or moderate structural heartdisease. 52A recent meta-analysis found a 77% success rate for catheter ablation strategiesvs. 52% for antiarrhythmic medication.117 Similar results have been reported in
    • Catheter ablation of AF particularly circumferential pulmonary vein ablation (isolation) in the left atrium represents a promising and evolving therapy for selected patients resistant to pharmacological therapy. Ablation is indicated in highly symptomatic, paroxysmal or persistent AF, despite optimal medical therapy and in patients with minimal or moderate structural heart disease. A recent meta-analysis found a 77% success rate for catheter ablation strategies vs. 52% for antiarrhythmic medication.117 Similar results have been reported in other meta-analyses,118,-120 one of which showed that PV isolation for paroxysmal or persistent AF was associated with markedly increased odds of freedom from AF at 1 year.119 Ablation may particularly benefit younger patients with lone AF who are frequently symptomatic and for whom long-term antiarrhythmic poses higher risk and lifestyle cost. For patients with either persistent AF or long-standing persistent AF, and no or minimal organic heart disease, the treatment strategies and the benet – risk ratio of catheter ablation are less well established. Extensive and frequently repeated ablation procedures may be necessary in these patients, and it seems reasonable to recommend that they should be refractory to antiarrhythmic drug treatment before ablation is considered (See Figure 14). <<Figure 14>> Adapted with modification from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal 2010; Figure 14. Choice between ablation and antiarrhythmic drug therapy for patients with and without structural heart disease. Proposed integration each treatment box. Please note that left atrium (LA) ablation as first-line therapy (dashed line) is a Class IIb recommendation for patients with disease, including hypertension (HT) without left ventricular hypertrophy (LVH). †More extensive LA ablation may be needed; *usually PVI is hypertrophy; NYHA=New York Heart Association; PVI=pulmonary vein isolation. Antiarrhythmic agents are listed in alphabetical order within of antiarrhythmic drug and catheter ablation for AF in patients with relevant underlying heart disease and for those with no or minimal heart paroxysmal AF and no or minimal heart disease, who remain highly symptomatic, despite rate control, and who reject antiarrhythmic drug For symptomatic paroxysmal and persistent AF in patients with relevant organic appropriate. AF= atrial fibrillation; CAD = coronary artery disease; CHF = congestive heart failure; HT=hypertension; LVH=left ventricular heart disease, antiarrhythmic drug treatment is recommended before catheter ablation. In such patients, successful ablation is more difficult to achieve. Major symptoms should be associated with the arrhythmia to justify the procedure. Ablation of persistent and long-standing persistent AF is associated with variable but encouraging success rates, but very often requires several attempts. Ablation of common atrial utter is recommended as part of an AF ablationIB procedure if documented prior to the ablation procedure or occurring during the AF ablation.18 Catheter ablation for paroxysmal AF should be considered in symptomaticIIa A doi:10.1093/eurheartj/ehq278) therapy. 53
    • minimal organic heart disease, the treatment strategies and the benet – are Ablation may particularly benefit younger patients with lone AF who risk frequently symptomatic and for whom long-term antiarrhythmic poses higher riskratio of catheter ablation are less well established. Extensive and frequently and lifestyle cost.repeated ablation procedures may be necessary in these patients, and it seemsreasonable to patients with either persistent AF or long-standing to antiarrhythmicno or For recommend that they should be refractory persistent AF, and drugtreatment before ablation heart disease, the treatment strategies and the benet – risk minimal organic is considered (See Figure 14). ratio of catheter ablation are less well established. Extensive and frequently repeated ablation procedures may be necessary in these patients, and it seems<<Figure 14>> reasonable to recommend that they should be refractory to antiarrhythmic drug treatment before ablation is considered (See Figure 14).For symptomatic paroxysmal and persistent AF in patients with relevant organicheart disease, antiarrhythmic drug treatment is recommended before catheter <<Figure 14>>ablation. In such patients, successful ablation is more difficult to achieve. Majorsymptoms For symptomatic paroxysmal and the arrhythmiapatients with the procedure. should be associated with persistent AF in to justify relevant organicAblation ofheart disease, antiarrhythmic drug treatment AF is associated with catheter persistent and long-standing persistent is recommended before variable ablation. In such patients, successful ablation is more difficult to achieve. Majorbut encouraging success rates, but very often requires several attempts. symptoms should be associated with the arrhythmia to justify the procedure. Ablation of persistent and long-standing persistent AF is associated with variableKeypoints but encouraging success rates, but very often requires part of attempts. ablationAblation of common atrial utter is recommended as several an AFprocedure if documented prior to the ablation procedure or occurring during theAF ablation.18 Ablation of common atrial utter is recommended as part of an AF ablation IIB B procedure if documented prior to the ablation procedure or occurring during the AF ablation.18Catheter ablation for paroxysmal AF should be considered in symptomatic Catheter ablation for paroxysmal AF should be considered in symptomatic IIaA IIa A patients who have previously failed a trial of antiarrhythmic medication.31,117,122-125 Ablation of persistent symptomatic AF that is refractory to antiarrhythmic therapy IIaB IIa B should be considered a treatment option.18 In patients post-ablation, LMWH or i.v. UFH should be considered as ‘bridging therapy’ prior to resumption of systemic OAC, which should be continued for a IIaC IIa C minimum of 3 months. Thereafter, the individual stroke risk factors of the patient should be considered when determining if OAC therapy should be continued. Continuation of OAC therapy post- ablation is recommended in patients with 1 IIaB IIa B ‘major’ (‘denitive’) or >2 ‘clinically relevant non-major’ risk factors (i.e. CHA 126 2DS2-VASc score >2). IIbC IIb C Catheter ablation of AF may be considered in patients with symptomatic long- standing persistent AF refractory to antiarrhythmic drugs. IIbB Catheter ablation of AF in patients with heart failure may be considered when IIb B antiarrhythmic medication, including amiodarone, fails to control symptoms.29,30 Catheter ablation of AF may be considered prior to antiarrhythmic drug therapy in IIbB IIb B symptomatic patients despite adequate rate control with paroxysmal symptomatic AF and no signicant underlying heart disease.1178.3.2 SURGICAL ABLATIONThe major 8.3.2 SURGICAL ABLATION indication for surgical ablation of AF is the presence of both AF andthe requirement for cardiac surgery for structural heart disease.120,127,128 Stand-alone surgery major indication for surgical ablationfor AF is the presence of both AF who The for AF should be considered of symptomatic AF patients and 120,127,128prefer a surgical approach, have failed one for structural heart disease. the requirement for cardiac surgery or more attempts at catheter ablation, Stand-or who are alone surgery for for catheter ablation. not candidates AF should be considered for symptomatic AF patients who prefer a surgical approach, have failed one or more attempts at catheter ablation, or who are not candidates for catheter ablation.KeypointsSurgical ablation of AF should be considered in patients with symptomatic AFundergoingSurgical ablation of 120,127,128 be considered in patients with symptomatic AF cardiac surgery. AF should IIaA IIa A 120,127,128 undergoing cardiac surgery.Surgical ablation of AF may be performed in patients with asymptomatic AFundergoingSurgical ablation of AF may be performed in patients with asymptomatic AF IIbC IIb C cardiac surgery if feasible with minimal risk. undergoing cardiac surgery if feasible with minimal risk.Minimally invasive surgical surgical ablation of AF without concomitant cardiacsurgery is Minimally invasive ablation of AF without concomitant cardiac surgery isfeasible and may be performed in patients with with symptomatic AF afterfailure of IIbC IIb C feasible and may be performed in patients symptomatic AF after failure ofcatheter ablation. ablation. catheter 8.3.3 SUPPRESSION OF AF THROUGH PACING8.3.3 SUPPRESSION OF AF THROUGH PACING 54 Several studies have examined the role of atrial pacing to prevent recurrent
    • Surgical ablation of AF may be performed in patients with with symptomatic AF Surgical ablation of AF should be considered in patients asymptomatic AFIIb C IIa A undergoing cardiac surgery surgery. 120,127,128 minimal risk. undergoing cardiac if feasible with Minimally invasive ablation of AF mayof AF without concomitant cardiac surgeryAF Surgical surgical ablation be performed in patients with asymptomatic is IIb CIIb C feasible and may becardiac surgery ifpatientswith minimal risk. undergoing performed in feasible with symptomatic AF after failure of catheter ablation. invasive surgical ablation of AF without concomitant cardiac surgery is Minimally IIb C feasible and may be performed in patients with symptomatic AF after failure of 8.3.3 SUPPRESSION OF AF THROUGH PACING catheter ablation. Several studiesSUPPRESSION OF AF THROUGH atrial pacing to prevent recurrent 8.3.3 have examined the role of PACING paroxysmal AF. In patients with symptomatic bradycardia, the risk of AF is lower with atrial than with ventricularexamined the role of atrial pacing to prevent recurrent Several studies have pacing.129 In patients with sinus node dysfunction paroxysmal AF. In patients with symptomatic bradycardia, the risk of AF is lower and normal AV conduction, data frompacing.129 In patients with sinussupport atrial or with atrial than with ventricular several randomized trials node dysfunction dual-chamber rather than ventricular pacingseveral randomized trials 130-133 Patients and normal AV conduction, data from for prevention of AF. support atrial or with paroxysmal AF rather symptomatic bradycardia shouldof be 130-133 Patients dual-chamber and than ventricular pacing for prevention AF. referred for electrophysiological review AF consideration of atrial based pacing.be referred for with paroxysmal for and symptomatic bradycardia should electrophysiological review for consideration of atrial based pacing. Keypoint When ventricular pacing with dual-chamber devices is unavoidable because of When ventricular pacing with dual-chamber devices is unavoidable because ofIIaB IIaB concomitant disease of the AV conduction system, the the evidence is lessclear that IIaB concomitant disease of the AV conduction system, evidence is less clear that atrial-based pacing ispacing is superior. Although atrial-based pacing associated with a atrial-based superior. Although atrial-based pacing is is associated with a lower burden ofburden of AF and strokecompared to ventricular-based pacing in lower AF and stroke risk risk compared to ventricular-based pacing in patients requiring requiring pacemakers for bradyarrhythmias, the value of pacing as a patients pacemakers for bradyarrhythmias, the value of pacing as a primary therapy for prevention of recurrent AF has not been proven. primary therapy for prevention of recurrent AF has not been proven. 8.4 UPSTREAM THERAPY Upstream therapy is a term used that relates to prevention or delaying of myocardial remodelling associated with hypertension, heart failure, or inammation (e.g. after cardiac surgery) and therefore may deter the development of new AF THERAPY prevention) or, once established, its rate of 8.4 UPSTREAM (primary recurrence or progression to permanent AF (secondary prevention).135 Upstream therapy is a term used that relates to prevention or delaying of Treatmentsmyocardial remodelling associated with inhibitors (ACEIs), angiotensin with angiotensin-converting enzyme hypertension, heart failure, or receptor blockers (ARBs), after cardiac surgery) and therefore and omega-3 inammation (e.g. aldosterone antagonists, statins, may deter the development of new AF (primary prevention) or, once established, its rate of polyunsaturated fatty progression to permanentusually referred to as 135 recurrence or acids (PUFAs) are AF (secondary prevention). ‘upstream’ therapies for AF. Treatments with angiotensin-converting enzyme inhibitors (ACEIs), angiotensin 8.4.1 ANGIOTENSIN-CONVERTINGaldosterone INHIBITORS statins, and omega-3 receptor blockers (ARBs), ENZYME antagonists, AND polyunsaturated fatty acids (PUFAs) are usually referred to as ‘upstream’ ANGIOTENSIN RECEPTOR BLOCKERS therapies for AF. Primary prevention 8.4.1 ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS In patients with congestive cardiac failure, several meta-analyses have shown a signicant 30 – prevention Primary 48% reduction in risk of AF associated with ACEI and ARB therapies.136-140 In patients with congestive cardiac failure, several meta-analyses have shown While in patients with 30 – 48% reduction meta-analyses, the overallACEI and ARB a signicant hypertension, in in risk of AF associated with trend was in therapies.136-140 favour of ACEI- or ARB-based therapy, but only one meta-analysis has shown a statistically While in patients with hypertension,of incident AF.138the overall trend was in signicant 25% reduction in RR in meta-analyses, favour of ACEI- or ARB-based therapy, but only one meta-analysis has shown a ACEIs and ARBs should be considered for of incident AF.138 Keypoints statistically signicant 25% reduction in RR prevention of new-onset AF inIIa A patients with heart failure and reduced ejection fraction.136-140 IIaA ACEIs and ARBs should be considered for prevention of new-onset AF in IIa A patients with heart failure and reduced ejection fraction.136-140IIa B ACEIs and ARBs should be considered for prevention of new-onset AF in 138,141,142 patients with hypertension, particularly considered for prevention of new-onset AF in ACEIs and ARBs should be with left ventricular hypertrophy. IIaB IIa B 138,141,142 patients with hypertension, particularly with left ventricular hypertrophy. Upstream therapies with ACEIs, ARBs, and statins are not recommended forIII C primary prevention of AF in patients without cardiovascularare not recommended for Upstream therapies with ACEIs, ARBs, and statins disease. IIIC III C primary prevention of AF in patients without cardiovascular disease. Secondary prevention Secondary prevention 55 Several relatively relatively prospective randomized controlled trials have Several small small prospective randomized controlled trials have demonstrated that therapy with ACEI/ARB conferred an additional benet on risk demonstrated that therapy with ACEI/ARB conferred an additional benet on risk
    • patients with heart failure and reduced ejection fraction.136-140ACEIs and ARBs should be considered for prevention of new-onset AF inpatients with hypertension, particularly with left ventricular hypertrophy.138,141,142Upstream therapies with ACEIs, ARBs, and statins are not recommended forprimary prevention of AF in patients without cardiovascular disease.Secondary preventionSeveral relatively small prospective randomized controlled trials havedemonstrated that therapy with ACEI/ARB conferred an additional benet on riskof recurrent AF after cardioversion when co-administered with antiarrhythmicdrug therapy, usually amiodarone, compared with an antiarrhythmic drugalone.143,144 Meta-analyses driven by these studies have reported a signicant 45– 50% reduction in RR of recurrent AF.136-139 Conversely, a double-blind,placebo-controlled study failed to demonstrate any benet of therapy withcandesartan for promotion of sinus rhythm after cardioversion in patients who didnot receive antiarrhythmic drug therapy. 145Evidence to support the use of ACEI/ARB in patients with paroxysmal orpersistent AF who are not undergoing electrical cardioversion remainscontroversial.Evidence to support the use of ACEI/ARB in patients with paroxysmal orpersistent Evidence ACEIs and ARBs may be considered in patients with recurrent AF who are not use of ACEI/ARB in patients with paroxysmal or to support thePre-treatment with AF who areundergoing electrical cardioversion remains persistent not undergoing electrical cardioversion remainscontroversial.AF and receiving antiarrhythmic drug therapy.136-138,143,144Keypoints controversial.Pre-treatment support be useful for prevention be consideredpatients with recurrentEvidence ACEIs may theand ARBsACEI/ARB of recurrentinwith paroxysmal orARBs or to with ACEIs ACEIsof may be considered in paroxysmal recurrent Pre-treatment with use and ARBs may in patients patients with AF or in IIbB 136-138,143,144AF and receivingwho areantiarrhythmic drug therapy.136-138,143,144patients with and antiarrhythmic drug therapy. electrical cardioversion remains IIb Bpersistent AF persistent AF undergoing electrical cardioversion in the absence of AF receiving not undergoing Evidence to support the use of ACEI/ARB in patients with paroxysmal orcontroversial.signicant structural heart disease if these agents are indicated for other reasons persistent AF who are not for prevention electrical cardioversion AF or ARBs may useful undergoing of recurrent paroxysmal remainsARBs or ACEIs or ACEIs may be for prevention of recurrent paroxysmal AF or in IIbB IIb B controversial.be useful(e.g. hypertension).136,146,147 in patients with persistent AF undergoing electrical cardioversion in the absence ofpatients with persistent AF undergoing electrical cardioversion in for other reasons the absence ofPre-treatment with ACEIs and ARBs mayifbe considered in patients with recurrent signicant structural heart disease these agents are indicatedsignicant structural heart disease if these may be considered in patients with recurrentAF and receiving antiarrhythmic drug ARBs agents are indicated for other reasons (e.g. hypertension).ACEIs and therapy. Pre-treatment with 136,146,147 136-138,143,144 IIb AF and 136,146,147(e.g.B STATINS receiving antiarrhythmic drug therapy.136-138,143,1448.4.3hypertension).ARBs or ACEIs may be useful for prevention of recurrent paroxysmal AF or in ARBs or ACEIs 8.4.3 STATINS may be useful for prevention of recurrent paroxysmal AF or inpatients with persistent AF undergoing electrical cardioversion inin theabsence ofFor B IIb post-operative AF, a recent undergoing electrical cardioversion the absence of patients with persistent AF systematic review, 148 have reported a lower8.4.3 STATINSsignicant structuralonset disease if thesestatins. are are indicated reported reasonsincidence signicant structural hearta recent if these agents indicated for particularly in heart AF favouring agents review, studies, other a lower For new 136,146,147136,146,147 of post-operative AF, disease systematicSome 148 have for other reasons(e.g. hypertension). of new onset heart failure, statins.shown a 20 – 50% reductionpatients with LV dysfunction and AF favouring have Some studies, particularly in (e.g. hypertension). incidence 148For post-operative AF, dysfunction and heart failure, have shown a 20 – 50% reductionin the incidence ofwith LV a recent systematic review, patients new-onset AF. 149 have reported a lowerincidence of the incidence of AF favouring statins. Some studies, particularly in in new onset new-onset AF.149patients should STATINS 8.4.3Statins with LV dysfunction and heart failure, of new-onset AF after coronary8.4.3 STATINS be considered for prevention have shown a 20 – 50% reduction the of new-onset AF.149inIIa B incidencegrafting, be consideredin combinationof with148artery bypass post-operative AF, aor for systematic review, valvular interventions. Statins should isolated recent prevention new-onset AF after coronary For artery bypass grafting, isolated or in combination with have reported a lower 148 valvular interventions.For post-operative of new onset AF favouring statins. Some studies, particularly in148,150 incidence AF, a recent systematic review, 148,150 have reported a lowerStatins shouldnewwith LV dysfunction and heart failure,Someshown a 20 – 50% coronaryincidence patients considered favouring statins. new-onset AF after reduction of be onset AF for prevention of have studies, particularly inartery bypassbeincidence isolated heart failure, have shown a 20 inininterventions.Keypoints in thegrafting, of new-onset AF.149Statins may LV dysfunction and or for preventionnew-onset AF – 50% reductionpatients with may be considered in combination with valvular patients with Statins considered for prevention of of new-onset AF patients with IIb B148,150 149in the incidence of new-onset AF.particularly heart failure.151,152 heart disease, particularly heart failure.151,152underlying underlying heart disease, Statins should be considered for prevention of new-onset AF after coronary IIaB IIa BStatins may bebe considered for FATTY in combinationANDAF ALDOSTERONE artery bypass grafting, isolated or 8.4.4 POLYUNSATURATED FATTY of ACIDS with valvularpatients with8.4.4 should considered for prevention ACIDS POLYUNSATURATED 148,150 of interventions. prevention new-onset AF ALDOSTERONE AND in after coronary new-onsetunderlying ANTAGONIST isolated or in combination with valvular interventions.artery bypass grafting, particularly heart failure.ANTAGONIST disease, heart 151,152148,150 Statins may be is no robust for prevention of any recommendation for the with At present, there considered evidence to make new-onset AF in patients use IIbB IIb B8.4.4 POLYUNSATURATED antagonist for primary or 151,152 there is heart disease, FATTY ACIDS AND ALDOSTERONEAt present,of PUFAs or aldosterone particularlymakefailure. secondary prevention of AF. underlying no robust evidence to heart any recommendation for the useANTAGONIST considered for prevention of or secondaryAF in patients withStatins may aldosterone antagonist for primary new-onset prevention of AF.of PUFAs or beunderlying 8.4.4 disease, particularly heart failure.ACIDS AND ALDOSTERONE heart POLYUNSATURATED FATTY 151,152At present,ANTAGONIST there is no robust evidence to make any recommendation for the useof PUFAs or aldosterone antagonist for primary make any AND prevention ofthe use8.4.4 POLYUNSATURATED FATTY to or secondary ALDOSTERONE At present, there is no robust evidence ACIDS recommendation for AF.ANTAGONIST of PUFAs or aldosterone antagonist for primary or secondary prevention of AF.At present, there is no robust evidence to make any recommendation for the useof PUFAs or aldosterone antagonist for primary or secondary prevention of AF. 56
    • 9 MANAGEMENT – SPECIAL POPULATIONS9.1 POST-OPERATIVE AFAlthough AF may occur after noncardiac surgery, the incidence of atrialarrhythmias including AF after open-heart surgery is between 20% and 50%.Post-operative AF usually occurs within 5 d of open-heart surgery, with a peakincidence on the second day. The arrhythmia is usually self-correcting, and sinusrhythm resumes in more than 90% of patients by 6 to 8 wk after surgery.A systematic review of 58 studies in 8565 patients has shown that interventionsto prevent and/or treat post-operative AF with ß-blockers, sotalol, or amiodaroneand, less convincingly, atrial pacing, are favoured with respect to outcome. 1539.1.1 PREVENTION OF POST-OPERATIVE ATRIAL FIBRILLATIONß-Blocker therapy is most effective when provided both before and after cardiacsurgery compared with only before or after surgery.153-155 Withdrawal of ß-blockers is a signicant risk factor for the development of post-operative AF andshould be avoided. Treatment should be started at least 1 week before surgerywith a ß-blocker without intrinsic sympathomimetic activity.Prophylactic amiodarone decreased the incidence of post- operative AF156. Thebenecial effect of amiodarone has been consistently demonstrated in asystematic review.153The adverse effects of perioperative prophylactic i.v.amiodarone include an increased probability of post-operative bradycardia andhypotension.153Sotalol has been reported to reduce the incidence of post-operative AF by 64%compared with placebo.153 However, the use of sotalol places patients at risk ofbradycardia and torsade de pointes, especially those with electrolytedisturbances, and its use in post-operative AF is limited.Meta-analyses demonstrated that corticosteroid therapy was associated with a26 – 45% reduction in post-operative AF and shorter hospital stay. 157 However,the potential adverse effects on glucose metabolism, wound healing, andinfection, make their use for prevention of AF as controversial.One meta-analysis of eight trials has shown that prophylactic atrial pacingreduced the incidence of post-operative AF regardless of the atrial pacing site orpacing algorithm used. 1539.1.2 TREATMENT OF POST-OPERATIVE ATRIAL FIBRILLATIONIn haemodynamically stable patients, the majority will convert spontaneously tosinus rhythm within 24 h. Initial management includes correction of predisposingfactors (such as pain management, haemodynamic optimization, weaning of i.v.inotropes, correcting electrolytes and metabolic abnormalities, and addressinganaemia or hypoxia) where possible.158In the highly symptomatic patient or when rate control is difficult to achieve,cardioversion may be performed. DCCV is 95% successful but pharmacologicalcardioversion is more commonly used. Amiodarone was shown to be moreeffective than placebo in converting post-operative AF to sinus rhythm. 57Short-acting ß-blockers (e.g. esmolol) are particularly useful when
    • factors (such as pain management, haemodynamic optimization, weaning of i.v.inotropes, correcting electrolytes and metabolic abnormalities, and addressinganaemia or hypoxia) where possible.158In the highly symptomatic patient or when rate control is difficult to achieve,cardioversion may be performed. DCCV ishaemodynamic optimization, weaning of i.v. factors (such as pain management, 95% successful but pharmacological inotropes, correcting electrolytes and metabolic abnormalities, and addressingcardioversion is more commonly possible.Amiodarone was shown to be more anaemia or hypoxia) where used. 158effective than placebo in converting post-operative AF to sinus rhythm. In the highly symptomatic patient or when rate control is difficult to achieve,Short-acting ß-blockers be performed. DCCV are particularlybut useful when cardioversion may (e.g. esmolol) is 95% successful pharmacologicalhaemodynamic instability more commonly used. Amiodarone was shown to blocking cardioversion is is a concern. Other atrioventricular nodal be more effective than placebo in converting post-operative AF to sinus rhythm. be usedagents, such as non-dihydropyridine calcium channel antagonists, canas alternatives, but digoxin is less (e.g. esmolol) are particularly is high. when Short-acting ß-blockers effective when adrenergic tone useful Theagents used for rate control of AF following cardiac surgery are listed in Table 15. haemodynamic instability is a concern. Other atrioventricular nodal blocking agents, such as non-dihydropyridine calcium channel antagonists, can be usedA number as alternatives, but shown anless effective risk of stroke in patients after of studies have digoxin is increased when adrenergic tone is high. Thecardiac surgery. used for rate control of AF followingor VKAsurgery are listed in Table AF agents Anticoagulation with heparin cardiac is appropriate when 15.persists longer than 48 h.159 Standard precautions regarding anticoagulationpericardioversion should be used (see Section 4.3). risk of stroke in patients after A number of studies have shown an increased cardiac surgery. Anticoagulation with heparin or VKA is appropriate when AF persists longer than 48 h.159 Standard precautions regarding anticoagulation pericardioversion should be used (see Section 4.3).KeypointsOral -blockers are recommended to prevent post-operative AF for patientsundergoing cardiac surgery in the absence of contraindications.153,154 Oral -blockers are recommended to prevent post-operative AF for patients IA IA 153,154If used, -blockers (or othersurgery in the absence of contraindications. undergoing cardiac oral antiarrhythmic drugs for AF management) arerecommended to be-blockers (or until the day of surgery. 154,155 AF management) are If used, continued other oral antiarrhythmic drugs for IB IB recommended to be continued until the day of surgery. 154,155Restoration of sinus rhythm by DCCV is recommended in patients who developpost-operative AF andof sinus rhythm by DCCV is recommended in patients who develop IC IC Restoration are haemodynamically unstable. post-operative AF and are haemodynamically unstable.Ventricular rate control is recommended in patients with AF without Ventricular rate control is recommended in patients with AF withouthaemodynamic instability.155 IB IB haemodynamic instability.155Pre-operative administration of amiodarone should be considered asas prophylactic Pre-operative administration of amiodarone should be considered prophylactic IIaAtherapy for therapy for patients at high post-operative AF.153,154,160 IIa A patients at high risk for risk for post-operative AF.153,154,160 IIaA IIa A Unless contraindicated, antithrombotic/anticoagulation medication for post-Unless contraindicated, antithrombotic/anticoagulation medication for159post-operative AF shouldAF should be considered the duration of AF AF>48 hours.159 operative be considered when when the duration of is is >48 hours. If sinus rhythm is restored successfully, duration of anticoagulation should be for IIaBIf IIa B rhythm is restored successfully, duration of anticoagulation should be risk sinus a minimum of 4 weeks but more prolonged in the presence of stroke fora minimum of 4159 factors. weeks but more prolonged in the presence of stroke risk 159factors. Antiarrhythmic medications should be considered for recurrent or refractory IIaC IIa CAntiarrhythmic medications an attemptbe maintain sinus rhythm. postoperative AF in should to considered for recurrent or refractorypostoperative be considered for prevention of AF after cardiac surgery, but isSotalol may AF in an be considered for prevention rhythm. Sotalol may attempt to maintain sinus of AF after cardiac surgery, but is IIbA IIb A 153associated associatedof proarrhythmia.153 with risk with risk of proarrhythmia. Biatrial pacing may be considered for prevention of AF after cardiac surgery.153 IIbABiatrial pacing may be considered for prevention of AF after cardiac surgery.153 IIb A Corticosteroids may be considered in order to reduce the incidence of AF after IIbB IIb B 157Corticosteroids may be considered in order to reduce the incidence of AF after cardiac surgery, but are associated with risk.cardiac surgery, but are associated with risk.157 161 Atrial flutter is less common than AF after cardiac surgery, but pharmacological therapy is similar. Prevention of postoperative atrial flutter is as AF after cardiac surgery,161 forAtrial flutter is as prevention of AF, thanatrial overdrive pacing is generally useful but difficult less common butpharmacological therapy is similar. Prevention electrodes are in place. flutter is as termination of atrial flutter when epicardial of postoperative atrialdifficult as prevention of AF, but atrial overdrive pacing is generally useful fortermination of atrial flutter when epicardial electrodes are in place. 9.2 ACUTE CORONARY SYNDROME9.2 ACUTE CORONARYan incidence between 2 to 21% in patients with ACS162 and is AF occurs with SYNDROME 58 more commonly associated with ACS in older patients and those with higher 162
    • Ib B cardiac surgery, but are associated with risk.157 Sotalol may be considered for prevention of AF after cardiac surgery, but is IIb A associated with risk of proarrhythmia.153 Atrial flutter is less common than AF after cardiac surgery,161 but pharmacological therapymaysimilar. Prevention of postoperativecardiac flutter is as Biatrial pacing is be considered for prevention of AF after atrial surgery.153 IIb A difficult as prevention of AF, but atrial overdrive pacing is generally useful for termination Corticosteroids may be epicardial electrodes reduce place. IIb B of atrial flutter when considered in order to are in the incidence of AF after cardiac surgery, but are associated with risk.157 Atrial flutter is less common than AF after cardiac surgery,161 but 9.2 ACUTEpharmacological SYNDROME CORONARY therapy is similar. Prevention of postoperative atrial flutter is as difficult as prevention of AF, but atrial overdrive pacing is generally useful for termination of atrial flutter when epicardial electrodes are in place. AF occurs with an incidence between 2 to 21% in patients with ACS162 and is more commonly associated with ACS in older patients and those with higher heart rate and LV dysfunction.162 SYNDROME 9.2 ACUTE CORONARY AF is associated with increased in-hospital mortality in the setting of ACS. Stroke AF occurs with an incidence between 2 to 21% in patients with ACS162 and is rates are also increased in associated withACS andolder patients and those with higher more commonly patients with ACS in AF. heart rate and LV dysfunction.162 Specific recommendations for management of patients with AF in the setting of ACS are based primarily on consensus, becausemortality in the setting of ACS. Stroke AF is associated with increased in-hospital no adequate trials have tested alternative strategies. increased in patients with ACS and AF. rates are also Specific recommendations for management of patients with AF in the setting of Direct-current cardioversion is onrecommended forno patients trials have tested ACS are based primarily consensus, because adequate with severeC hemodynamic compromise or intractable ischemia, or when adequate rate Keypoints alternative strategies. control cannot be achieved with pharmacological agents in patients with ACS and AF. Direct-current cardioversion is recommended for patients with severe ICIC hemodynamic compromise or intractable ischemia, or when adequate rate Intravenouscontrol cannot be achieved with pharmacologicalcalcium inantagonists ACS beta blockers and nondihydropyridine agents patients with areC and AF. recommended to slow a rapid ventricular response to AF in patients with ACS who do not Intravenous beta blockers and nondihydropyridine calcium antagonists are have LV dysfunction, bronchospasm, or AV block. IC IC recommended to slow a rapid ventricular response to AF in patients with ACSC Intravenouswho do not have LV dysfunction, bronchospasm, or AV block. amiodarone is recommended to slow a rapid ventricular response to AF and improve LV function in patients with ACS. IC IC Intravenous amiodarone is recommended to slow a rapid ventricular response to AF and improve LV function in patients with ACS. Intravenous administration of non-dihydropyridine calcium antagonistsIa C (verapamil, Intravenous should be considered to slow a rapid ventricular antagonists diltiazem) administration of non-dihydropyridine calcium response toIIa C in patients with ACS and should be considered heart failure. ventricular response AF IIaC (verapamil, diltiazem) no clinical signs of to slow a rapid to AF in patients with ACS and no clinical signs of heart failure. Intravenous administration of digoxin may be considered to slow a rapidIb C ventricular response in administration ACS and AF associated with heart failure. IIbC IIb C Intravenous patients with of digoxin may be considered to slow a rapid ventricular response in patients with ACS and AF associated with heart failure.III B Administration of ecainide or propafenone is notis not recommended in patientswith IIIB III B Administration of ecainide or propafenone recommended in patients with AF in the settingthe setting163 ACS. 163 AF in of ACS. of 9.3 WOLFF-PARKINSON-WHITE (WPW) PRE-EXCITATION SYNDROMES 9.3 WOLFF-PARKINSON-WHITE (WPW) PRE-EXCITATION SYNDROMES Since accessory pathways (AP) lack the decremental conduction properties of Since accessory pathways (AP)with overt pre-excitation and AF are at risk of rapid the AV node, patients lack the decremental conduction properties of the AV node, patients with overt pre-excitation and AF are at possible sudden conduction across the AP, resulting in fast ventricular rates and risk of rapid conductioncardiac deathAP, resulting in of degeneration into ventricular brillation. This across the (SCD) because fast ventricular rates and possible sudden makes AF in this patient cohort a potentially life-threatening arrhythmia. For cardiac death (SCD) relating to of degeneration into ventricular brillation. This information because acute and long-term pharmacological rate control in makes AF patients with an AP, see Section 5.1.1, pagelife-threatening arrhythmia. For in this patient cohort a potentially 18. information relating to acute and long-term pharmacological rate control in patients with an SUDDEN DEATH AND RISK STRATIFICATION 9.3.1 AP, see Section 5.1.1, page 18. 9.3.1 SUDDENincidence of SCD in patients with the Wolff – Parkinson – White syndrome The DEATH AND RISK STRATIFICATION has ranged from 0.15 to 0.39% over 3- to 22-year follow-up. The incidence markers of increased risk are: Wolff – Parkinson – White syndrome The of SCD in patients with the has ranged from 0.15 topre-excited RR3- to 22-year follow-up. spontaneous or induced Shortest 0.39% over interval <250 ms during AF. The markers of A history of symptomatic tachycardia. increased risk are: Shortest pre-excited RR multiple APs. The presence of interval <250 ms during spontaneous or induced AF. Ebstein’s anomaly. 59 A history of symptomatic tachycardia.
    • Since accessory pathways (AP) lack the decremental conduction properties ofthe AV node, patients with overt pre-excitation and AF are at risk of rapidconduction across the AP, resulting in fast ventricular rates and possible suddencardiac death (SCD) because of degeneration into ventricular brillation. Thismakes AF in this patient cohort a potentially life-threatening arrhythmia. Forinformation relating to acute and long-term pharmacological rate control inpatients with an AP, see Section 5.1.1, page 18.9.3.1 SUDDEN DEATH AND RISK STRATIFICATIONThe incidence of SCD in patients with the Wolff – Parkinson – White syndromehas ranged from 0.15 to 0.39% over 3- to 22-year follow-up.The markers of increased risk are: Shortest pre-excited RR interval <250 ms during spontaneous or induced AF. A history of symptomatic tachycardia. The presence of multiple APs. Ebstein’s anomaly.Since the efficacy of catheter ablation of APs is 95%, this is the management ofchoice for patients with evidence pre-excitation and AF.16 Patients who havesurvived SCD in the presence of an overt AP should have urgent AP ablation.Successful catheter ablation in those patients eliminates the risk for SCD.Patients with overt pre-excitation and high risk of AF, or patients with high-riskprofessions such as public transport vehicle drivers, pilots, or competitiveathletes should be considered for ablation.The indication for catheter ablation of an overt AP in an asymptomatic patient isstill controversial (especially in children).165 Most patients with asymptomatic pre-excitation have a good prognosis; SCD is rarely the rst manifestation of thedisease.The positive predictive value of invasive electrophysiological testing isconsidered to be too low to justify routine use in asymptomatic patients. Catheterablation of an asymptomatic overt AP should remain a case-by-case decisionwith detailed counseling of the patient (and family) about the natural course andthe risk of SCD versus the risk of an ablation procedure.Catheter ablation of an overt AP in patients with AF is recommended to preventKeypointsSCD.164 Catheter ablation of an overt AP in patients with AF is recommended to prevent IA IA 164Immediate SCD. referral to an experienced ablation centre for catheter ablation isrecommended for patients who survived SCD and have evidence of ablation is Immediate referral to an experienced ablation centre for catheter overt AP ICconduction.recommended for patients who survived SCD and have evidence of overt AP IC conduction.Catheter ablation is recommended for patients with high-risk professions (e.g.pilots, public transport drivers) and overt but asymptomatic AP conduction on(e.g. IB IB Catheter ablation is recommended for patients with high-risk professions thesurface ECG.164 public transport drivers) and overt but asymptomatic AP conduction on the pilots, 164 surface ECG.Catheter ablation isablation is recommended in patients at high riskdeveloping AF in the Catheter recommended in patients at high risk of of developing AF in the IBIB 166presence of an overt but overt but asymptomatic AP on the surface ECG.166 presence of an asymptomatic AP on the surface ECG. IIaB IIa B Asymptomatic patients with evidence overt AP AP should considered forAsymptomatic patients with evidence of an of an overt should be be considered 166 forcatheter ablation ofablation of the AP only afterexplanation andand careful counseling. catheter the AP only after a full a full explanation careful counseling.166 9.4 HYPERTHYROIDISM9.4 HYPERTHYROIDISM AF occurs in 10% to 25% of patients with hyperthyroidism, more commonly inAF occurs men and elderly patients. in 10% to 25% of patients with hyperthyroidism, more commonly inmen and elderly patients. Treatment is directed primarily toward restoring a euthyroid state, which is usuallyTreatment is directedwith a spontaneous restoringto sinus rhythm. associated primarily toward reversion a euthyroid state, which is usually 60associated Antiarrhythmic drugs and direct-current cardioversion are generally unsuccessful with a spontaneous reversion to sinus rhythm.
    • 164 surface ECG. Asymptomatic patients with evidence of an overt AP should be considered forIa B catheter ablation of the AP only after a full explanation and careful counseling.166 Catheter ablation is recommended in patients at high risk of developing AF in the IB presence of an overt but asymptomatic AP on the surface ECG.166 9.4 HYPERTHYROIDISM IIa B Asymptomatic patients with evidence of an overt AP should be considered for AF occurs catheter ablation of the patients with full explanation and careful counseling.166in in 10% to 25% of AP only after a hyperthyroidism, more commonly men and elderly patients. 9.4 HYPERTHYROIDISM Treatment is directed primarily toward restoring a euthyroid state, which is usually AF occurs in 10% to 25% of patients with hyperthyroidism, more commonly in associated men and elderly patients. with a spontaneous reversion to sinus rhythm. Antiarrhythmic drugs and direct-current cardioversioneuthyroid state, which is usually Treatment is directed primarily toward restoring a are generally unsuccessful while the thyrotoxicosis persists. associated with a spontaneous reversion to sinus rhythm. Antiarrhythmic drugs and direct-current treatment with amiodarone is often The occurrence of hyperthyroidism following cardioversion are generally unsuccessful encountered in the thyrotoxicosis persists. are two types of amiodarone-induced while clinical practice. There hyperthyroidism: The occurrence of hyperthyroidism following treatment with amiodarone is often Type I, where there clinicalexcess iodide-induced production of T4 and T3 encountered in is an practice. There are two types of amiodarone-induced Type hyperthyroidism: is a destructive thyroiditis with a transient excess II, where there release of Type I, whereand, later,excess iodide-induced production of T4 and T3 T4 and T3, there is an reduced thyroid function. Type II, where there is a destructive thyroiditis with a transient excess release of T4 and T3, and, later, reduced thyroid function. Although amiodarone may be continued when hypothyroidism has been successfully treatedamiodarone may be therapy, itwhennecessary to discontinue Although with replacement continued is hypothyroidism has been amiodarone if hyperthyroidism develops. Thyrotoxicosis necessary to occur after successfully treated with replacement therapy, it is may also discontinue amiodarone if hyperthyroidism develops. Thyrotoxicosis may also occur after cessation of amiodarone therapy. cessation of amiodarone therapy. Keypoints In patients In patients with active thyroid disease, antithrombotic therapy is recommended with active thyroid disease, antithrombotic therapy is recommended IC IC IC based on the presencepresence of other stroke risk factors. based on the of other stroke risk factors. When a Administration of a be used, recommendedcontrol a non-dihydropyridine Administration of a cannot -blocker is administration control the rateof ventricular IC IC -blocker -blocker is recommended to to of the rate of ventricularICIC response in patients with AF with AF complicating thyrotoxicosis, unless contraindicated. response in patients complicating thyrotoxicosis, unless contraindicated. calcium channel antagonist (diltiazem or verapamil) is recommended to control the ventricular rate in-blocker cannotAF and thyrotoxicosis. of a non-dihydropyridine When a patients with be used, administration IC IC calcium channel antagonist (diltiazem or verapamil) is recommended to control If a rhythmthe ventricular rate in patients with AF it is thyrotoxicosis. to normalize thyroid control strategy is desirable, and necessaryIC function prior to cardioversion, as otherwise the risk of relapsea non-dihydropyridine When a -blocker cannot be used, administration of remains high. IC If a rhythm control strategy (diltiazem or verapamil) is recommended to thyroid calcium channel antagonist is desirable, it is necessary to normalize control IC IC function prior torate the ventricular cardioversion, as otherwise the risk of relapse remains high.IC Once a euthyroid state in patients with AF and thyrotoxicosis. for antithrombotic is restored, recommendations prophylaxisOncerhythm control for patientsdesirable,recommendations tofor antithrombotic IC IC If a the same as strategy isrestored, hyperthyroidism. normalize thyroid are a euthyroid state is without it is necessary IC prophylaxis are the same as foras otherwise the risk of relapse remains high. function prior to cardioversion, patients without hyperthyroidism. I PREGNANCY euthyroid state is restored, recommendations for antithrombotic 9.5. C Once a 9.5. PREGNANCY same as for patients without hyperthyroidism. prophylaxis are the AF is rare AF is rare during pregnancy and usually an identifiable underlying cause, during pregnancy and usually has has an identifiable underlying cause, such as: suchPREGNANCY 9.5. as: 167 167 AF o Mitral stenosis, o Mitral stenosis,during pregnancy and usually has an identifiable underlying cause, is rare such as: o congenital heart disease,168 or 168 o congenital heart disease, or o hyperthyroidism.169 o Mitral stenosis, 167 o hyperthyroidism.169 A o congenital heart disease,168 or AF rapid ventricular response to can have serious hemodynamic A rapid ventricular response to AF and the have In a pregnant woman who consequences for both169 mother can foetus. serious hemodynamic the consequencesofor both diagnosis and and the foetus.underlying condition causingwho hyperthyroidism. develops AF, the mother treatment of the In a pregnant woman the develops AF, diagnosis the first priorities. of the underlying condition hemodynamic arrhythmia are and treatment to AF can have serious causing the A rapid ventricular response arrhythmia are the first priorities. the mother and the foetus. In a channel antagonist is consequences for both Digoxin, a beta blocker, or non-dihydropyridine calcium pregnant woman who IC develops AF, diagnosis and treatment of the underlying condition causing the recommended to control the ventricular rate in pregnant patients.170-172 arrhythmia are the first priorities.C Keypoints Digoxin, a beta blocker, or non-dihydropyridine calcium channel antagonist is recommended to control the ventricular rate thepregnant patients.170-172antagonist is Propranolol beta metoprolol would be in beta-blockers of channel while atenolol Digoxin, a and blocker, or non-dihydropyridine calcium choice, IC IC is contraindicated. Atenolol given in the rst trimester, but not 170-172 has been later, recommended to control the ventricular rate in pregnant patients. Propranololassociated with foetal growththe beta-blockers ofbeta-blockers in atenolol and metoprolol would be retardation. Use of choice, while the first is contraindicated. is to be metoprolol in the be thetrimester, butofnot later, has been trimester Propranolol and preferably avoided. Atenolol given would rst beta-blockers choice, while atenolol associated All contraindicated. Atenolol given in the rst of beta-blockers to crossbeen iswith foetal available antiarrhythmic drugs trimester, but not later, the first growth retardation. Use have has currentlywith foetal growth retardation. Use ofthe potential inin the first the associated beta-blockers trimester is placenta and enter breast milk and should therefore be avoided if possible. to be preferably avoided. trimester is to be preferably avoided. 171 173 173 All currently available sotalol, antiarrhythmic drugs have been potential tocross the All currently available and flecainide have the the used successfully the Quinidine, antiarrhythmic 61drugs have all potential to cross for placenta and enter breast milk and shouldshould therefore however,if inif possible. small pharmacological cardioversionand therefore be avoided possible. placenta and enter breast milk during pregnancy, be avoided relatively numbers of cases.
    • IC Digoxin, a beta blocker, or non-dihydropyridine calcium channel antagonist is recommended to control the ventricular rate in pregnant patients.170-172 Propranolol and metoprolol would be the beta-blockers of choice, while atenolol is contraindicated. Atenolol given in the rst trimester, but not later, has been associated with foetal growth retardation. Use of beta-blockers in the first trimester is to be preferably avoided. All currently available antiarrhythmic drugs have the potential to cross the placenta and enter breast milk and should therefore be avoided if possible. Quinidine,171 sotalol,173 and flecainide173 have all been used successfully for pharmacological cardioversion during pregnancy, however, in relatively small numbers of cases.DCCV can be performed safely at all stages of pregnancy, and is recommended IIbC Quinidine (has the longest record of safety in pregnancy) or procainamide mayinIIbC patients who are haemodynamically unstable due to AF, and whenever the risk be considered for pharmacological cardioversion in hemodynamically stableof ongoingpatients who develop AFhigh, for the mother or for the foetus. Foetal AF is considered during pregnancy.171,174monitoring should be done during and following the DCCV. DCCV can be performed safely at all stages of pregnancy, and is recommended IC IC in patients who are haemodynamically unstable due to AF, and whenever the risk of ongoing AF is considered high, for the mother or for the foetus. FoetalThe role ofmonitoring should be done duringsystemic arterial embolism has not been anticoagulation to prevent and following the DCCV.systematically studied in pregnant patients with AF, but the arrhythmia isfrequently associated with conditions that carry a high risk of thromboembolism,including congenital or valvular heart disease. The role of anticoagulation to prevent systemic arterial embolism has not been systematically studied in pregnant patients with AF, but the arrhythmia isProtection against thromboembolism is recommendedhigh risk of thromboembolism, frequently associated with conditions that carry a throughout pregnancy for including congenital or valvular heart disease.patients with AF except those at low thromboembolic risk. The choice ofanticoagulant or aspirin should be chosen according to the throughoutpregnancy.for Protection against thromboembolism is recommended stage of pregnancy ICIC patients with AF except those at low thromboembolic risk. The choice ofConsideration should or aspirin shouldavoiding warfarin to the stageit crosses the anticoagulant be given to be chosen according because of pregnancy.placental barrier and is associated with teratogenic embryopathy in the first Consideration haemorrhagetrimester and with foetal should be giveninto avoidingstages of because it crosses the the later warfarin pregnancy. 172-179 placental barrier and is associated with teratogenic embryopathy in the first trimester and with foetal haemorrhage in the later stages of pregnancy. 172-179Heparin is the preferred anticoagulant because it does not cross the placenta. Heparin is the preferred anticoagulant because it does not cross the placenta.Subcutaneous administration of LMWH in weight-adjusted therapeutic doses isrecommended during the rst trimester and the last month of pregnancy. doses is Subcutaneous administration of LMWH in weight-adjusted therapeuticAlternatively, UFH may during the rst trimester and the last month of pregnancy. IB IB recommended be given, to prolong the activated partial thromboplastin Alternatively, UFH may be given, to prolong the activated partial thromboplastintime to 1.5 time to the times the180 times 1.5 control. control.180During the second trimester, consider oral anticoagulation for for pregnantwomen IIbC IIbC During the second trimester, consider oral anticoagulation pregnant women 180 with thromboembolic risk.180with AF at high AF at high thromboembolic risk. The following are guiding principles for the use of drugs in pregnancy:The following areFrequent monitoring with ECGuse of drugs in pregnancy: to reduce o guiding principles for the and drug levels is recommended o Frequent monitoring with ECG and drug levels is recommended to reduce the risk of toxicity. the risko If possible, start after 8 weeks of pregnancy or as late as possible. of toxicity. o If possible, start after 8 weeks of pregnancy or as late as possible. o Use lowest effective dose. o Low dose combination therapy preferable to higher dose single drug o Use lowest effective dose. o Low dose therapy. combination therapy preferable to higher dose single drug o Use older agents with longest tract record. therapy. o Use older agents with longest tract record. 9.6 HYPERTROPHIC CARDIOMYOPATHY Patients with hypertrophic cardiomyopathy (HCM) are at greater risk of9.6 HYPERTROPHIC CARDIOMYOPATHY population, and around 20 – 25% developing AF compared with the general develop AF with an annual incidence of 2%.Patients with hypertrophic cardiomyopathy (HCM) are at greater risk ofdeveloping AF compared with the general population, and around 20 – 25%develop AF with an annual incidence of 2%. 62
    • AF is the major determinant of hemodynamic deterioration in patients with HCM and is the major determinant of hemodynamic deterioration in patients with HCM AF symptoms can be ameliorated by restoration of sinus rhythm. and symptoms can be ameliorated by restoration of sinus rhythm. Amiodarone may be the most effective agent for reducing the occurrence of paroxysmal AF andbe the most effective agent for reducing the occurrence of Amiodarone may for preventing recurrence. paroxysmal AF and for preventing recurrence. AF is the major determinant of hemodynamic deterioration in patients with HCM In chronic and symptoms can be ameliorated by restoration of sinus rhythm. AF, rate control can usually be achieved with ß-blockers and verapamil. AF, rate control can usually ventricular pacing ß-blockers and In chronicAV nodal ablation with permanentbe achieved with (to promote late septal activation) may may be the permanent agent verapamil. Amiodaroneablation withmost effective ventricular pacing the occurrencelate AV nodal be helpful in selected patients. for reducing (to promote of septal activation) may be helpful in selected patients. paroxysmal AF and for preventing recurrence. Unless contraindicated, OAC therapy should be administered to patients with Unless contraindicated, OAC control can usually be achieved withtoß-blockers and In chronic AF, rate therapy should HCM and paroxysmal, persistent, or permanent be ventricular pacing (to promote with AF. administered patients verapamil. AV nodal ablation with permanent late HCM and paroxysmal, persistent, or permanent AF. septal activation) may be helpful in selected patients. Outcomes after AF ablation in patients with HCM are favourable, but not as successful Unless AF ablation populations.with ablationadministered to patients with Outcomes as in contraindicated, OAC therapy should beare favourable, but not as after unselected in patients LA HCM is signicantly better in paroxysmalHCMin unselected populations.permanent AF. is signicantly better in successful as and paroxysmal, persistent, or addition, patients with marked atrial AF than in persistent AF. In LA ablation enlargement AF than in diastolic dysfunction are at high risk ofwith marked atrial paroxysmal and severe persistent AF. In addition, patients recurrence. enlargement and severe diastolic dysfunction are atHCM are favourable, but not as Outcomes after AF ablation in patients with high risk of recurrence. successful as in unselected populations. LA ablation is signicantly better in The small series of surgical ablation (Maze-III addition, patientscombination atrial paroxysmal AF than in persistent AF. In procedure) in with marked with myomectomy when LV outflow tract obstruction was at high risk forrecurrence. with The small enlargementsurgical ablation (Maze-III procedure) in of AF in patients series of and severe diastolic dysfunction are present, combination with HCM showed no increase tract obstruction was present,high AF in patients myomectomy when LV outflow in operative mortality and a for proportion of patients remained in sinus surgicaloperative mean follow-up high proportion181 with HCM The small no increase in ablationa(Maze-III procedure) of combination with showed series of rhythm over mortality and a in 15 months. of mean was present, 15 effect 181 Despite conicting in sinus LV outflow over obstruction overall benecial months. of patients remained data, there seems to abe an follow-up offor AF in patients myomectomy when rhythm tract Despite conicting showedthere seems operativean overall benecial effect 181 with HCM data, no increase in to be mortality and a high proportion of myomectomy in reducing thein sinus rhythm in HCM mean follow-up of 15 months. of patients remained burden of AF over a patients. myomectomy in reducing thedata, there AF in HCM patients. Despite conicting burden of seems to be an overall benecial effect of Restorationmyomectomy rhythm by DCCV of AF in HCM patients. cardioversion is of sinus in reducing the burden or pharmacological Keypoints of B recommended insinus rhythm HCM DCCV or pharmacological cardioversion is Restoration patients with by presenting with recent-onset AF.182IB recommended in patientssinus HCM presenting with recent-onset AF.182 Restoration of with rhythm by DCCV or pharmacological cardioversion is 182 OAC therapy (INR 2.0–3.0) is recommended in patients with HCMAF. develop IBIB recommended in patients with HCM presenting with recent-onset who B OAC therapy (INR 2.0–3.0) AF unless contraindicated.182is recommended in patients with HCM who develop OAC therapy (INR 2.0–3.0) is recommended in patients with HCM who developIB AF unless contraindicated.182 IBIB AF unless contraindicated.182Ia C Amiodarone should be considered in order to achieve rhythm control and toIIa C maintain sinus rhythmbe patientsconsidered in orderachieve rhythm control and to Amiodarone should in considered in order to to achieve rhythm control and to IIaC IIa C Amiodarone should be with HCM. maintain sinus rhythm in patients with HCM.HCM. maintain sinus rhythm in patients with Catheter ablation of AF should be considered in patients with symptomatic AFIa C Catheter to pharmacological AF should be considered in patients with symptomatic AF IIaC IIa C Catheter ablation of refractory ablation of AF should be considered in patients with symptomatic AF control.IIa C refractory to pharmacological control. refractory to pharmacological control.Ia C Ablation procedures (with concomitant septalseptal myomectomy indicated) may be IIaC IIa C Ablation procedures (with concomitant myomectomy if if indicated) may beIIa C considered considered inwith HCM and refractory myomectomy if indicated) may be Ablation procedures (with concomitant and refractory AF. in patients patients with HCM septal AF. considered in patients with HCM and refractory AF. 9.7 PULMONARY DISEASES 9.7 PULMONARY DISEASES 9.7 PULMONARY DISEASES Supraventricular arrhythmias, including AF, are common in patients with COPD Supraventricular arrhythmias, including AF, areincommonwith patients with COPD and have adverse prognostic implications patients in acute exacerbations of Supraventricular prognostic including AF, are common in patients with COPD and have adversearrhythmias,implications in patients with acute exacerbations of COPD. and have adverse prognostic implications in patients with acute exacerbations of COPD. COPD. Keypoints For patients who develop AF during an acute pulmonary illness or exacerbation IC IC of chronic pulmonary disease, treatment of the underlying lung disease and correction of hypoxemia and acidosis are the primary therapeutic measures. IIIC IIIC Theophylline and beta-adrenergic agonist agents are not recommended in patients with bronchospastic lung disease who develop AF. Beta-blockers, sotalol, propafenone, and adenosine are contraindicated in IIIC IIIC patients with bronchospasm. Diltiazem or verapamil is recommended to control the ventricular rate in patients 63 IC with obstructive pulmonary disease who develop AF with or without digoxin.
    • IC of chronic pulmonary disease, treatment of the underlying lung disease andpatients with bronchospastic lung disease who the primary therapeutic measures. correction of hypoxemia and acidosis are develop AF.Beta-blockers, sotalol,and beta-adrenergic agonist agents are not recommended in IIIC Theophylline propafenone, and adenosine are contraindicated inpatients with bronchospasm. patients with bronchospastic lung disease who develop AF.Diltiazem or verapamil issotalol, propafenone,controladenosine are contraindicated in IIIC Beta-blockers, recommended to and the ventricular rate in patients patients with bronchospasm.with obstructive pulmonary disease who develop AF with or without digoxin. IC Diltiazem or verapamil is recommended to control the ventricular rate in patients IC selective blockers (e.g. bisoprolol) in small doses should be considered as an -1 with obstructive pulmonary disease who develop AF with or without digoxin.alternative for ventricular rate control. -1 selective blockers (e.g. bisoprolol) in small doses should be considered as an IIaC IIa C alternative for ventricular rate control.Cardioversion may be ineffective against AF unless respiratory decompensationhas been corrected. Cardioversion may be ineffective against AF unless respiratory decompensation has been corrected.Direct-current cardioversion should be attempted in patients with pulmonarydisease who become hemodynamically unstable as a consequencewithAF. Direct-current cardioversion should be attempted in patients of pulmonary ICIC disease who become hemodynamically unstable as a consequence of AF.In patients refractory to drug therapy, AV nodal ablation and ventricular pacingmay be necessary to refractory to drug therapy, AV nodal ablation and ventricular pacing In patients control the ventricular rate. may be necessary to control the ventricular rate.In patientsIn patients and AF and pulmonary disease, general recommendations for with AF with pulmonary disease, the the general recommendations forantithrombotic therapy apply. apply. antithrombotic therapy 9.8 HEART FAILURE9.8 HEART FAILURE AF is a strong and independent risk factor for the development of heart failure,AF is a strong both conditions frequentlyfactor for theThe onset of AFof heart failure, and and independent risk co-exist.17,183 development in a patient with 17,183and both conditions frequently to symptomatic deterioration, of AF in a to episodes of heart failure often leads co-exist. The onset predisposes patient withheart failure often leads tofailure, increases the risk of thrombo-embolic episodes, and worsening heart symptomatic deterioration, predisposes to episodes ofworsening worsensfailure, increases the risk of thrombo-embolic episodes, and heart long-term outcome.worsens long-term outcome. In the initial approach to heart failure patients with AF, the following issues need to be considered:17In the initial approach to heart failure patients with AF, the following issues needto be considered:17 Potential precipitating factors and secondary causes should be identied and if possible corrected. Potential precipitating factors and secondary causes should be identied Background heart failure treatment should be optimized. and if possible corrected. When ventricular rate control is required in patients with heart failure and AF, ß- Background heart failure treatment should be optimized.When ventricular rate control is required in patients with heart failure and AF, ß-blockers are preferred over digitalis glycosides due to their rate-controlling effectduring exertion rather than only at rest. A combination of digoxin and a ß-blockermay be more effective than a single drug for heart-rate control at rest. Therapywith ß-blockers alone or in combination with digoxin was associated with lowermortality rates compared with treatment with digoxin alone.184ß-Blockers have favourable effects on mortality and morbidity in patients withsystolic heart failure. A recent meta-analysis also showed a 27% reduction in theincidence of new-onset AF in patients with systolic heart failure treated with ß-blockers.185Although diltiazem effectively controls excessive heart rate during exercise, itadversely suppresses myocardial contraction and increases the risk of heartfailure. For patients with heart failure and preserved ejection fraction, these drugsused in combination with digoxin appear to be more effective in controlling heartrate over 24 h and during exercise than digoxin or non-dihydropyridine calciumchannel antagonist monotherapy.The rhythm control strategy has not been shown to be superior to rate control inheart failure patients with AF.27 Catheter-based LA ablation procedures in heartfailure patients may lead to improvement in LV function, exercise tolerance, andquality of life in selected patients (see Section 8.3.1).29,30 64The prevention of thrombo-embolism is covered in Section 6, but the presence ofheart failure due to systolic dysfunction is itself a risk factor for stroke and
    • rate over 24 h anddiltiazem exercise than digoxin or non-dihydropyridine calcium Although during effectively controls excessive heart rate during exercise, it adversely suppresses myocardial contraction and increases the risk of heart channel antagonist monotherapy. failure. For patients with heart failure and preserved ejection fraction, these drugs used in combination with digoxin appear to be more effective in controlling heart The rhythm control 24 h and during exercise than digoxinbe superior to rate control in rate over strategy has not been shown to or non-dihydropyridine calcium heart failure patients with AF.27 Catheter-based LA ablation procedures in heart channel antagonist monotherapy. failure patients may lead to improvement in LV function, exercise tolerance, and quality of life inrhythm control strategy hasSection 8.3.1).29,30 superior to rate control in The selected patients (see not been shown to be 27 heart failure patients with AF. Catheter-based LA ablation procedures in heart failure patients may lead to improvement in LV function, exercise tolerance, and The prevention of thrombo-embolism is(see Section 8.3.1).29,30 6, but the presence of quality of life in selected patients covered in Section heart failure due to systolic dysfunction is itself a risk factor for stroke and thrombo-embolism, and of thrombo-embolism is covered in Section 6, but the presence of The prevention OAC therapy is generally indicated when AF is present. heart failure due to systolic dysfunction is itself a risk factor for stroke and The use ofthrombo-embolism, and OAC therapy is generally indicated when AF is present. in aspirin is not recommended due to the increased risk of bleeding combination with OAC therapy and some evidence that aspirin may increase the The use of aspirin is not recommended due to the increased risk of bleeding in risk of hospitalizationswith OAC therapy and some evidence that aspirin may increase the combination for heart failure. risk of hospitalizations for heart failure. KeypointsIC DCCV is recommended when a rapid ventricular rate does not respond to pharmacological ismeasures in when a rapid ventricular rate ongoing myocardial ICIC DCCV recommended patients with AF and does not respond to ischaemia,pharmacologicalhypotension, orpatients withofAF and ongoing myocardial symptomatic measures in symptoms pulmonary congestion. ischaemia, symptomatic hypotension, or symptoms of pulmonary congestion. In patientsInwith AF with AF and severe (NYHA class or IV)IV) or recent (<4 weeks) patients and severe (NYHA class III III or or recent (<4 weeks)IC unstable heart failure, the use the antiarrhythmic therapy to maintain sinus rhythm ICIC unstable heart failure, of use of antiarrhythmic therapy to maintain sinus rhythm should be restrictedrestricted to amiodarone. should be to amiodarone. Administration of amiodarone is a is a reasonable option forpharmacological Administration of amiodarone reasonable option for pharmacological IIaB IIa B 21,39,45,186IIa B cardioversion of AF, or of AF, or to facilitate electrical cardioversion of AF. cardioversion to facilitate electrical cardioversion of AF.21,39,45,186 In patients with AF and stable heart failure (NYHA class I, II) dronedarone should InIIaC IIa C patients be considered stable heart failure (NYHA class I, II) dronedarone should with AF andIIa C For patients with heart to reduce cardiovascular hospitalizations. AF despite adequate failure and symptomatic persistentIIb B be considered to reduce cardiovascular hospitalizations. rate control, patients with heart failure and symptomaticrhythm control may be For electrical cardioversion and persistent AF despite adequate IIbB IIb B considered. 27,29,30,32,187 rate control, electrical cardioversion and rhythm control may be 27,29,30,32,187 considered. Catheter ablation (pulmonary vein isolation) may be considered in heart failureIIb B Catheter ablation (pulmonary vein isolation) may be considered in heart failure 29,30 patients with refractoryrefractory symptomatic AF.29,30 IIbB IIb B patients with symptomatic AF. 9.9 ATHLETES 9.9 ATHLETES In population-based studies, studies, the intensity of physical activity showed aU-shaped In population-based the intensity of physical activity showed a U-shaped relationship with incident AF, which may indicate that the positive antiarrhythmic relationship with incident AF, which may indicate that the positiveexercise is too effects of physical activity are partially negated when antiarrhythmic effects of strenuous.188,189 AF is 2 are times more prevalent in when orexercise is too physical activity – 10 partially negated active former competitive 188,189 strenuous. athletes and 2 – 10 times more prevalent in active or former competitive AF is those performing intense recreational endurance sports. 190,191 The reasons performing intense recreational endurance sports. 190,191 The athletes and thosefor this association are probably both functional (increased sympathetic reasons foractivity, volume load during exercise, vagotonia at rest) and structural (atrial this association are probably both functional (increased sympathetic activity, volume load and dilatation). hypertrophy during exercise, vagotonia at rest) and structural (atrial hypertrophy andcontrol is difficult to achieve in athletes. ß-blockers are not well tolerated Rate dilatation). and may even be prohibited in some competitive sports, and digoxin or non- Rate control is difficult to achieve in athletes. ß-blockersenough to slow heart rate dihydropyridine calcium antagonists will not be potent are not well tolerated and may even be prohibited in some competitive sports, and digoxin or non- during exertional AF. dihydropyridine calcium antagonists will not be potent enough to slow heart rate during exertionalthe heart rate during AF is acceptable at maximal physical performance for When AF. a given athlete without signs of haemodynamic impairment (dizziness, syncope, sudden fatigue), competitive sports activity can be resumed. When the heart rate during AF is acceptable at maximal physical performance for a given athlete without signs when using flecainide impairment (dizziness, syncope, Caution is necessary of haemodynamic and propafenone as monotherapy in athletes with AF.192 sports activity lead to atrial utter, sudden fatigue), competitive These drugs maycan be resumed. with 1 to 1 conduction to the ventricles during high sympathetic tone. Therefore, ablation of the utter Caution is necessarybe needed in athletes with and propafenoneutter. Continuation of circuit may when using flecainide documented atrial as monotherapy in drug therapy for AF will often be required despite successful ablation (‘hybrid athletes with AF.192 These drugs may lead to atrial utter, with 1 to 1 conduction therapy’). to the ventricles during high sympathetic tone. Therefore, ablation of the utter circuit mayIn some athletes with paroxysmaldocumented atrial utter. Continuationfor be needed in athletes with AF, ecainide or propafenone can be used of drug therapy forconversion often be required despite successful ablation 42 These acute AF will (the ‘pill-in-the-pocket’ approach; see Section 5.1.2.1). (‘hybrid therapy’). patients should refrain from sports as long as the atrial arrhythmia persists and until one to two half-lives of the antiarrhythmic drug have elapsed. 65 In some athletes with paroxysmal AF, ecainide or ablation can be can be used for Non- pharmacological options such as catheter propafenone considered. 193 acute conversion (the ‘pill-in-the-pocket’ approach; see Section 5.1.2.1).42 These
    • Caution is necessary when using flecainide and propafenone as monotherapy inathletes with AF.192 These drugs may lead to atrial utter, with 1 to 1 conductionto the ventricles during high sympathetic tone. Therefore, ablation of the uttercircuit may be needed in athletes with documented atrial utter. Continuation ofdrug therapy for AF will often be required despite successful ablation (‘hybridtherapy’).In some athletes with paroxysmal AF, ecainide or propafenone can be used foracute conversion (the ‘pill-in-the-pocket’ approach; see Section 5.1.2.1).42 Thesepatients should refrain from sports as long as the atrial arrhythmia persists anduntil one to two half-lives of the antiarrhythmic drug have elapsed.Non- pharmacological options such as catheter ablation can be considered. 193Anticoagulation may be necessary depending on the presence of risk factors forthrombo-embolic events (see Section 6.1). However, anticoagulation cannot beused in individuals participating in sporting activities with a risk of bodily collision.When a ‘pill-in-the-pocket’ approach with sodium channel blockers is used, sportcessation should be considered for as long as the arrhythmia persists, and untilKeypoints1–2 half-lives of the antiarrhythmic drug used have elapsed. When a ‘pill-in-the-pocket’ approach with sodium channel blockers is used, sport IIaC IIa CIsthmus ablation should bebe consideredin competitivethe arrhythmia persists, andwith cessation should considered for as long as or leisure-time athletes until 1–2 half-lives of the antiarrhythmic drug used have elapsed.documented atrial utter, especially when therapy with ecainide or propafenoneis intended.Isthmus ablation should be considered in competitive or leisure-time athletes with IIaC IIa C documented atrial utter, especially when sodium channel blockers is used, sport When a ‘pill-in-the-pocket’ approach with therapy with ecainide or propafenone IIa CWhere appropriate, AF ablation should be considered toarrhythmia recurrent AF in iscessation should be considered for as long as the prevent persists, and until intended.athletes. 1–2 half-lives of the antiarrhythmic drug used have elapsed. IIaC IIa C Where appropriate, AF ablation should be considered to prevent recurrent AF in athletes.When a specic ablation should be considered in competitive an leisure-time propafenone IIa C Isthmus cause for AF is identied in or athlete athletes with documented atrial utter, especially when therapy with ecainide or (such ashyperthyroidism), it is not recommendedAF continue participation in competitive is intended. When a specic cause for to is identied in an athlete (such asor IIIC III C leisure time sports until correction of the cause. continue participation in competitive hyperthyroidism), it is not recommended to IIa C or leisure time sportsAF ablation shouldthe cause. Where appropriate, until correction of be considered to prevent recurrent AF in athletes.It is not recommended to allow physical sports activity when symptoms due tohaemodynamic not recommended toas dizziness) are present. when symptoms due to IIIC III C It is impairment (such allow physical sports activity III C haemodynamic impairment (such as dizziness) are present. athlete (such as When a specic cause for AF is identied in an hyperthyroidism), it is not recommended to continue participation in competitive or leisure time sports until correction of the cause.9.10 VALVULAR HEART DISEASE 9.10 VALVULAR HEART DISEASE III C It is not recommended to allow physical sports activity when symptoms due toAF frequently frequently accompanies(such as dizziness) are present. haemodynamic impairment AF accompanies valvularvalvular heart disease. distension is is anearly heart disease. LA LA distension an earlymanifestation of progressive mitral mitral valve disease, and the presence of manifestation of progressive valve disease, and the presence ofparoxysmal or permanent AF is anDISEASE indication for for early percutaneous or paroxysmal or permanent AF is an accepted indicationearly percutaneous or 9.10 VALVULAR HEART accepted surgical mitral intervention.66 AFsurgical mitral intervention.66 AF is also is also frequently seenlater stages ofof aortic frequently seen in in later stages aortic valve disease when LV dilatation and elevated end-diastolic pressure exertvalve disease wheneffectsdilatation and elevateddisease. LA distension is anexert AF frequently accompanies valvular heart end-diastolic pressure early secondary LV on LA function. manifestation of progressive mitral valve disease, and the presence ofsecondary effects on LA function. Managementor permanent AF conventional recommendations in the setting or paroxysmal of AF follows is an accepted indication for early percutaneous of surgical mitral intervention.66 AF also frequently seen in is stages adopted valvular heart disease, althoughisa recommendations laterusually of aorticManagement of AF follows conventional and elevated strategy in the setting of rate control because of the although dilatation valve disease when LV end-diastolic pressure exertvalvular heart disease, low on LA function. control strategy in the long term. likelihood ofrate a maintaining sinus rhythm is usually adopted secondary effectsbecause of the low likelihood of maintaining sinus rhythm in the long term. Principal concerns surround the high risk of thrombo-embolism in subjects with Management of AF follows conventional recommendations in the setting of valvular heart disease, and a low threshold for anticoagulation is recommendedPrincipal concerns surround the high risk a rate control strategy is usually adopted valvular heart disease, although of thrombo-embolism in subjects with (See Section 6.1).valvular heart disease,the low likelihood of maintaining sinus rhythm inis recommended because of and a low threshold for anticoagulation the long term.(See SectionPrincipal concerns surround the high risk of thrombo-embolism in subjects with 6.1). OAC therapy (INR 2.0–3.0) is indicated in patients with mitral stenosis and AFIC (paroxysmal, persistent,andpermanent). valvular heart disease, or a low threshold for anticoagulation is recommended (See Section 6.1).KeypointsOAC therapy (INR 2.0–3.0) is indicated in patients with mitral stenosis and AF OAC therapy (INR 2.0–3.0) is recommended in patients with AF and clinically(paroxysmal, persistent, or permanent).IC signicant mitral regurgitation. OAC therapy (INR 2.0–3.0) is indicated in patients with mitral stenosis and AF ICIC (paroxysmal, persistent, or permanent).OAC therapy (INR 2.0–3.0) is recommended should be considered for asymptomatic Percutaneous mitral balloon valvotomy in patients with AF and clinicallyIIa Csignicant mitral regurgitation.2.0–3.0) is recommended inand suitable valve anatomy who patients with moderate or severe mitral stenosis patients with AF and clinically OAC therapy (INR ICIC have new-onset AF in the absence of LA thrombus. signicant mitral regurgitation.Percutaneous mitral balloon valvotomy should be considered for asymptomaticpatients withPercutaneous mitral balloon valvotomy should suitable valve anatomy who IIa C moderate or severe mitral 66 stenosis and be considered for asymptomatic patients with moderate or severe mitral stenosis and suitable valve anatomy whohave new-onset AF in the absenceabsence of LA thrombus. have new-onset AF in the of LA thrombus.
    • valvular heart disease, and a low threshold for anticoagulation is recommended (See Section 6.1). OAC therapy (INR 2.0–3.0) is indicated in patients with mitral stenosis and AF IC (paroxysmal, persistent, or permanent). IC OAC therapy (INR 2.0–3.0) is recommended in patients with AF and clinically signicant mitral regurgitation. Percutaneous mitral balloon valvotomy should be considered for asymptomatic IIaC IIa C patients with moderate or severe mitral stenosis and suitable valve anatomy who have new-onset AF in the absence of LA thrombus. Early mitral valve surgery should be considered in severe mitral regurgitation, IIaCIIa C preserved LV function, and new-onset AF, even in the absence of symptoms, particularly when valve repair is feasible.10. REFERRALS 10.1 Acute hospitalisation/referral This is required for patients with: AF/AFL with haemodynamic compromise, acute dyspnoea, acute heart failure, chest pain, ischaemia, near syncope, hypotension AF/AFL with rapid uncontrolled heart rate, e.g., over 140 bpm at rest AF/AFL with acute systemic illness requiring acute management rst/new onset of AF/AFL symptoms, no contraindications to cardioversion, with the possibility of cardioversion within 48 hours of onset. 10.2 Outpatient specialist physician/cardiologist Outpatient specialist referral is recommended for those who: Need further investigation/echocardiography Have suspected structural heart disease (e.g., hypertensive, valvular, ischaemic) Are to be considered for cardioversion Are highly symptomatic, requiring ‘maintenance of sinus rhythm’ antiarrhythmic therapy Are having difficulty with pharmacological rate control Require a second opinion of the risk/benet ratio of anticoagulation Are having syncopal attacks. 10.3 Cardiac electrophysiologist (heart-rhythm specialist) Tertiary referral is recommended for patients who have: AF with WPW syndrome (pre-excited AF) Highly-symptomatic AF unresponsive to rst-line antiarrhythmic treatment Uncontrolled ventricular rate with maximally tolerated atrioventricular- blocking therapy Recurrent AFL (including mixed AFL and AF where AFL is the dominant arrhythmia) Tachycardia-bradycardia syndrome (sinus node dysfunction) Suspicion or documentation of a regular tachycardia triggering AF (e.g., SVT). 10.4 No referral Referral is not needed for patients who have rate-controlled AF with mild or occasional symptoms, for whom echocardiography is not required (e.g., previously obtained), and for whom the decision regarding stroke prevention management is clear cut. 67
    • 11. AUDIT & EVALUATIONThe Table below lists the audit criteria identified to evaluate the impact of theimplementation of the six key priority areas detailed above on clinical practiceand health outcomes.Criterion Exception Definition of termsAll people presenting to None. Percentage of patientprimary or secondary records with a newcare with a history of diagnosis of AF madehypertension, heart following an ECG madefailure, diabetes or stroke on the basis of detectionand noted to have an of an irregular pulse.irregular pulse to beoffered an ECG and anynew diagnosis of AFrecorded.All patients should be Haemodynamically Percentage of patientassessed for risk of unstable patients or records with astroke/ thromboembolism those in whom documentation of riskand given assessment is impossible assessment andthromboprophylaxis or inappropriate. thromboprophylaxisaccording to the stroke consistent with the strokerisk stratification risk stratificationalgorithms and have this algorithm.assessment and anyantithrombotic therapyrecorded.All patients should be Haemodynamically Percentage of patientassessed for risk of unstable patients or records with ableeding and according those in whom documentation of riskto the bleeding risk assessment is impossible assessment for bleedingstratification algorithms or inappropriate. consistent with theand have this bleeding risk stratificationassessment recorded. algorithm.All AF patients in whom a Postoperative or Percentage of patientrate-control or rhythm- haemodynamically records with acontrol strategy is unstable patients, or documentation ofinitiated to have their those otherwise not able involvement of the patientinvolvement in choosing to engage in a decision- in the decision- makinga treatment strategy making process. process.recorded.All patients who are None. Percentage of patientprescribed digoxin as records with ainitial monotherapy for prescription of digoxin for 68
    • rate control to have the initial rate-controlreason for this monotherapy where theprescription recorded reason for digoxinwhere it is not obvious prescription is:(e.g. sedentary patient, • Sedentary patientpresence of • Presence of contra-contraindication to indications to beta-alternative agents). blockers or rate-limiting calcium Antagonists • Other reasons.All patients who are None. Percentage of patientprescribed amiodarone records with aas long-term therapy for prescription ofrhythm control to have amiodarone for long-termthe reason for this rhythm-control therapyprescription recorded where the reason forwhere it is not obvious amiodarone prescription(e.g. failure of other is:agents to control rhythm, • Presence of contra-presence of indications to beta-contraindication to blockers, dronedarone,alternative agents). flecainide or propafenone • Other reasons. 69
    • APPENDIX ASearch TermsScope of searchA literature search was conducted for guidelines, systematic reviews andrandomized controlled trials on the primary care management of Atrialfibrillation, with additional searches in the following areas: • Outpatient therapy • Rhythm versus rate control • Anti-arrhythmics for cardioversion • Drugs for rate control • Anticoagulation versus antiplatelet drugs to prevent thromboembolism • Stroke risk versus bleeding risk • Invasive or emerging therapies • Referral criteriaSearch datesJanuary 2010 –December 2011Key search termsVarious combinations of searches were carried out. The terms listed below arethe core search terms that were used for Medline and these were adapted forother databases. • exp Atrial Fibrillation/, atrial fibrillation.tw • exp Diagnosis/, exp Diagnosis, Differential/, exp Electrocardiography/, exp Echocardiography/, exp Radiography, Thoracic/, exp Thyroid Function Tests/, exp Hematologic Tests/, blood test$.tw • exp atrial flutter.tw • Outpatients/ • Ambulatory Care/ • (outpatient or out-patient).tw. • exp Platelet Aggregation Inhibitors/, exp Aspirin/, exp Warfarin/ • exp thromboembolism/ • exp anticoagulants/ • $thromb$.ti,ab. • anticoagul$.tw. • exp Blood Coagulation/de, dt, pc [Drug Effects, Drug Therapy, Prevention & Contro • exp Platelet Aggregation Inhibitors/ • Aspirin/ • aspirin.tw. • exp Anti-Arrhythmia Agents/, exp Calcium Channel Blockers/, exp Verapamil/, exp Diltiazem/, exp Nifedipine/ • exp Adrenergic beta-Antagonists/, exp Atenolol/, exp Bisoprolol/, exp Metoprolol/, exp Acebutolol/, exp Nadolol/, exp Oxprenolol/, exp Propranolol/ 70
    • • exp Digoxin/, exp Amiodarone/• cardioversion/• defibrillation/• (countershock$ or (counter adj shock$)).tw. cardioconver$.tw.• (electr$ adj3 (cardiover$ or conver$ or countershock)).tw. rhythm control.tw.• (electrover$ or (electric$ adj3 defibrillat$)).tw• (antiarrhythm$ or anti-arrhythm$).tw.• (pharmacol$ adj3 (cardiover$ or conver$ or cardioconver$)).tw.• exp heart rate/• (heart or cardiac or ventricular) adj3 rate).tw.• (rate adj3 (control$ or reduc$ or normal$)).tw.• (chronotrop$ adj3 therapy).tw.• Digoxin/• Verapamil/• Diltiazem/• (beta$ adj block$).tw.• exp Beta Adrenergic Receptor Blocking Agent/• Amiodarone/• Clonidine/• (ventricular adj5 pac$).• exp thromboembolism/• exp anticoagulants/• $thromb$.ti,ab.• anticoagul$.tw.• exp Blood Coagulation/de, dt, pc [Drug Effects, Drug Therapy, Prevention & Control• exp Platelet Aggregation Inhibitors/• Aspirin/• aspirin.tw.• exp Stroke/• exp Hemorrhage/• (heart or ventricular) adj3 rate).tw.• *Heart Rate/de [Drug Effects]• rate control.tw.• (Cox or Maze).tw.• (internal adj3 (defibrill$ or cardiover$)).tw.• (radio$ or microwave$).tw.• (cryotherm$ or cryoablat$).tw.• laser$.tw.• (atrial adj3 pac$).tw.• (dual adj3 pac$).tw.• (implant$ adj3 pacemaker$).tw.• (AV nod$ adj3 ablat$).tw.• (implant$ adj3 defibrill$).tw.• (surg$ or catheter$) adj3 ablat$).tw.• surgery/ or thoracic surgery/• defibrillators, implantable/ or implants, experimental/• exp Pulmonary Veins/ pulmonary vein$.tw• exp Catheter Ablation/ or radiofrequency ablation.tw• exp Catheter Ablation or radiofrequency catheter ablation.tw 71
    • APPENDIX BClinical questionsA. Introduction 1. What is the best way to classify atrial fibrillation? 2. What is the epidemiological characteristic of atrial fibrillation?B. Initial management 1. What are the frequencies of the presenting symptoms? 2. In patients with suspected AF based on an irregular pulse, how accurate is an ECG in diagnosing AF? 3. Should echocardiography be performed to identify underlying structural heart disease? 4. In patients with suspected intermittent AF, how effective is ambulatory ECG compared to an event ECG in diagnosing AF? 5. Which patients with AF would benefit from referral to specialist?C. Management principles 1. In which patients with persistent AF does rate control result in improved mortality/morbidity/quality of life over rhythm control? 2. In which patients with persistent AF does rhythm control result in improved mortality/morbidity/quality of life over rate control?D. Acute-onset AF 1. In haemodynamically unstable patients presenting with acute AF, what is the best treatment strategy? 2. In which patients should pill-in-the-pocket therapy be recommended? 3. Does electrical cardioversion versus pharmacological cardioversion affect rates of thromboembolism, quality of life, success rates? 4. In patients with persistent AF, is amiodarone better than a) flecainide or b) propafenone for use in cardioversion? 5. In patients with persistent AF is amiodarone better than sotalol for use in cardioversion? 6. What is the safety and efficacy of the adjunctive administration of antiarrhythmic drugs for use in electrical cardioversion in comparison to electrical cardioversion without adjunctive antiarrhythmic drugs? 7. Is a conventional anticoagulation strategy for elective cardioversion as effective as a transoesophageal echocardiogram plus anticoagulation?E. Prevention of thromboembolism 1. In patients with AF, what are the risk factors associated with stroke/TIA and thromboembolism? 2. What is the efficacy of anticoagulation therapy versus placebo for stroke prevention in: a) paroxysmal AF b) permanent AF c) peri/post cardioversion to sinus rhythm d) acute/post-op AF e) peri/post stroke f) 72
    • asymptomatic AF? 3. What is the efficacy of anticoagulation therapy versus antiplatelet therapy for stroke prevention in: a) paroxysmal AF b) permanent AF c) peri/post cardioversion to sinus rhythm d) acute/post-op AF e) peri/post stroke f) asymptomatic AF? 4. What is the efficacy of antiplatelet therapy versus placebo for stroke prevention in: a) paroxysmal AF b) permanent AF c) peri/post cardioversion to sinus rhythm d) acute/post-op AF e) peri/post stroke f) asymptomatic AF? 5. What is the efficacy of vitamin K antagonist versus novel anticoagulant for stroke prevention in: a) paroxysmal AF b) permanent AF c) peri/post cardioversion to sinus rhythm d) acute/post-op AF e) peri/post stroke f) asymptomatic AF? 6. What is the role of point-of-care testing and self-monitoring of anticoagulation. 7. How best to institute anticoagulant and antiplatelet therapy in patients with AF undergoing percutaneous coronary intervention and non-ST elevation myocardial infarction 8. In patients with AF what are the risks of long-term oral anticoagulation therapy? 9. In patients with AF and vitamin K antagonist, what are the risk factors associated with bleeding?F. Long-term rate control 1. In patients with permanent AF, what is the efficacy of rate-limiting calcium antagonists compared with digoxin in rate control? 2. In patients with permanent AF, what is the efficacy of beta-blockers compared with digoxin in rate control? 3. In patients with permanent AF, what is the efficacy of beta-blockers compared with rate-limiting calcium antagonists in rate control? 4. In patients with permanent AF, what is the efficacy of rate-limiting calcium antagonists in combination with digoxin compared with rate- limiting calcium antagonists monotherapy in rate control? 5. In patients with permanent AF, what is the efficacy of beta-blockers in combination with digoxin compared with beta-blocker monotherapy in rate control? 6. In patients with permanent AF, what is the efficacy of AV node ablation with permanent pacemaker therapy in rate control?G. ong-term rhythm control L 1. In patients with paroxysmal AF, is flecainide/propafenone better than beta-blockers in reducing the frequency of paroxysms? 2. In patients with paroxysmal AF, is amiodarone or sotalol better than beta-blockers in reducing the frequency of paroxysms? 3. In patients with paroxysmal AF, is flecainide/propefanone better than amiodarone or sotalol in reducing the frequency of paroxysms? 73
    • 4. In patients with AF, is flecainide or propafenone better than beta- blockers in maintaining sinus rhythm post cardioversion? 5. In patients with AF, is amiodarone or sotalol better than beta-blockers in maintaining sinus rhythm post cardioversion? 6. In patients with AF, is flecainide/propafenone better than amiodarone or sotalol in maintaining sinus rhythm post cardioversion? 7. Which antiarrhythmic agents should be chosen to maintain sinus rhythm for patients with normal hearts? 8. Which antiarrhythmic agents should be chosen to maintain sinus rhythm for patients with structural heart disease? 9. What is the efficacy of left atrial catheter ablation and surgical ablation therapy for rhythm control in patients with a) paroxysmal AF b) persistent AF? 10. What is the efficacy of cardiac pacing therapy for rhythm control in patients with paroxysmal AF?H. Referrals 1. Which patients with AF benefit from referral to specialist services for assessment and management? 2. Which patients with AF benefit from referral to specialist services for non-pharmacological treatment or electrophysiological studies?APPENDIX CC. WARFARIN IN PRACTICEBarriers that may prevent people accessing medication and INR testing include:• Financial barriers (including the ability to take time off work)• Travel difficulties• Lack of access to a telephone• Fear or dislike of regular blood tests• Difficulties with general practitioner monitoring.Possible solutions include the following:• Financial assistance from relevant agencies• Provision of transport (e.g., shuttle service, taxi chits)• Domiciliary testing, either at home or the work place• Testing people in groups at a public health centre using a point-of-care monitorC.1 INITIATION OF WARFARIN THERAPYLoading doses are not recommended because they may increase the risk ofbleedingInitiation of warfarin should be 5 mg daily in most patients (usually achieves INR 2 in 4-5 days)A starting dose < 5 mg should be considered for patients >65 yrs, liver disease,malnourished, severe heart failure, 74 concomitant drugs affecting warfarin ormetabolism.
    • • Difficulties with general practitioner monitoring.Possible solutions include the following:• Financial assistance from relevant agencies• Provision of transport (e.g., shuttle service, taxi chits)• Domiciliary testing, either at home or the work place• Testing people in groups at a public health centre using a point-of-care monitorC.1 INITIATION OF WARFARIN THERAPYLoading doses are not recommended because they may increase the risk ofbleedingInitiation of warfarin should be 5 mg daily in most patients (usually achieves INR 2 in 4-5 days)A starting dose < 5 mg should be considered for patients >65 yrs, liver disease,malnourished, severe heart failure, or concomitant drugs affecting warfarinmetabolism.If overlapping LMWH or heparin with warfarin, overlap for at least 5 days.Discontinue LMWH or heparin when INR is therapeutic on two consecutivemeasurements 24 hr apart.C.1.2 Frequency of INR Monitoring:Check baseline INR prior to ordering warfarinCheck INR daily (AM lab) until therapeutic for two consecutive days then two-three times weekly during initiationC.1.2.1 StandardTraditionally patients come into the clinic (or the hospital) to have venous blooddrawn for routine laboratory INR determination.C.1.2.2 Point of CareFinger tip capillary blood can be used with small, light weight and portableinstruments. The clinical trials result have compared favorably with traditionalINR determination.Use in anticoagulation clinic.Home use or Patient Self Test (PST) Need good quality control for point of care INR measurement. o Patient selection is essential. o Patients must have long-term indication for anticoagulation therapy. o Patients must be willing and able to perform self-management. o Patients must be willing to record results accurately and attend clinics regularly for quality assurance. o Patients must demonstrate competence in using the instrument and interpreting the results. o Patients must not have shown previous noncompliance in terms of clinic attendance or medication management. Can increase INR testing frequency and decrease complications associated with oral anticoagulation therapy.C.1.3 Therapeutic INR Ranges:AF alone: INR 2 – 3Prosthetic Heart Valve: INR 2.5 – 3.5C.1.4 Average Daily DoseThere are differences among various ethnic groups 75
    • Can increase INR testing frequency and decrease complications associated with oral anticoagulation therapy.C.1.3 Therapeutic INR Ranges:AF alone: INR 2 – 3Prosthetic Heart Valve: INR 2.5 – 3.5C.1.4 Average Daily DoseThere are differences among various ethnic groupsAbout 4-5 mg/day or 28-35 mg/week for caucasian for target INR of 2.5 (2.0-3.0)About 3-4 mg/day or 21-28 mg/week for Pacific-Asian (exclude caucasian in thisregion). This dose will be less if target INR is recommended at <2.0.C.1.5 Factors Effecting the Daily Dose Age ( For caucasian) o <35 yr ----- 8.1 mg/day. o 35-49 yr --- 6.4 mg/day. o 50-59 yr --- 5.1 mg/day. o 60-69 yr --- 4.2 mg/day. o >70 yr ----- 3.6 mg/day. Genetic. Hereditary warfarin sensitive and resistance. Medicine noncompliance. Drugs interaction, including herbal medicine. Concurrent illness, fever, diarrhea, post op major surgery (i.e.. heart valve replacement), malignancy, lupus anticoagulants. Impaired liver function, CHF with liver congestion. Food effect, vitamin K intake, alcohol. Hyperthyroidism, renal disease. During heparin and direct thrombin inhibitors treatment.C.1.6 Warfarin InitiationDay 1(If there is an active or acute thromboembolic condition, warfarin should bestarted along with heparin, unless there is a contraindication or patient cannottake medicine orally. Following warfarin initiation, heparin should be continueduntil INR reaches therapeutic level for 2 days).5 mg (2.5-7.5). This dose is a good choice since it is known that average dailydose is close to 5 mg. Using higher dose than necessary may lead to bleedingcomplication due to rapidly and severely reduce factor VII. It may deplete proteinC too quick, and theoretically can cause hypercoagulable state. The 5 mg sizetablet is recommended for both inpatient and outpatient use, making inpatient tooutpatient transition more convenient. It is the most commonly used size tabletby the majority of anticoagulation clinics today.The higher dose warfarin initiation has also been tested successfully by usingnormogram. It may be considered in patient who may need shorter period of timeto reach therapeutic INR. It should be done as inpatient. INR have to be donefrequently enough to prevent over anticoagulation and bleeding complicationUse lower dose (2.5 mg). >80 yr. Concurrent illness. On interaction drug. 76 S/P major surgery, i.e. heart valve surgery.
    • outpatient transition more convenient. It is the most commonly used size tabletby the majority of anticoagulation clinics today.The higher dose warfarin initiation has also been tested successfully by usingnormogram. It may be considered in patient who may need shorter period of timeto reach therapeutic INR. It should be done as inpatient. INR have to be donefrequently enough to prevent over anticoagulation and bleeding complicationUse lower dose (2.5 mg). >80 yr. Concurrent illness. On interaction drug. S/P major surgery, i.e. heart valve surgery. Chronic malnourished. Impaired liver function, liver congestion.�Use higher dose (7.5-10.0 mg). Young healthy subject. In the first two days.Day 2A. If INR <1.5, continue the same dose.B. If INR >1.5, give lower dose (2.5 mg or none)Day 3For #A. of Day 2 If INR <1.5, suggests a higher than average maintenance dose of 5 mg/day or 35 mg/week will be needed. Give higher dose than 5 mg. i.e.7.5 mg for now. If INR 1.5-2.0, suggests an average maintenance dose close to 5 mg/day or close to 35 mg/week will be needed, and continue 5 mg for now. If INR >2.0, suggests a lower than average maintenance dose of 5 mg/day or 35 mg/week will be needed. Give less than 5 mg, i.e.2.5 mg or none for now.For #B. of Day 2 If INR 1.5-2.0, suggests daily dose will be close to or less than 5 mg/day or close to 35 mg/week or less. May give 5 mg or less for now. If INR >2.0, suggests daily dose will be lower than 5 mg/day or less than 35 mg/week. May give 2.5 mg or none for now.Day 4If there is no need for heparin therapy, the patient may have been discharged bynow, and warfarin initiation is continued as an outpatient. INR 2 times a week until INR is in target range twice in a row, then INR 1 time weekly until INR is in target range twice in a row, then INR 1 time in 2 week until INR is in target range twice in a row, then enter the patient in to maintenance schedule (usually INR every 4 weeks). Patients during an acute illness, or post operative of major surgeries may be more sensitive to warfarin than when they become more stable.Out patient (See also "Day 4" above) Obtain baseline INR Start with 5 mg daily. See more detail for dose variation in "Inpatient guideline" Check INR 2 times a week, or more often if necessary, during the first week or so. Adjust warfarin dose and timing for INR check as outline in "Inpatient" guidelines. 77C.1.7 Ethnic Difference for Chinese-Asian or Pacific-Asian (exclude caucasian in
    • Obtain baseline INR Start with 5 mg daily. See more detail for dose variation in "Inpatient guideline" Check INR 2 times a week, or more often if necessary, during the first week or so. Adjust warfarin dose and timing for INR check as outline in "Inpatient" guidelines.C.1.7 Ethnic Difference for Chinese-Asian or Pacific-Asian (exclude caucasian inthis region) Average daily dose of Warfarin for Pacific-Asian (exclude caucasian in this region) or Chinese-Asian is about 3 mg. Weekly dose is about 21-28 mg, or lower if "target INR" for various diagnoses are about 0.4-0.5 lower than those of Caucasian-American-European level. "Target INR" for or Pacific-Asian (exclude caucasian in this region) or Chinese-Asian should be lower than those of Caucasian-American- European. The suggest level for nonvalvular atrial fibrillation is 1.6-2.6, to achieve less combine thromboembolic and major bleeding events. (Need more database for confirmation) Difference in polymorphism of CYP 2C9 and VKORC1which will influence Warfarin dosageWarfarin Initiation Table for average daily dose of 5 mg and 3 mg further INR DOSE DAY INPATIENT OUTPATIENT (Usually with daily INR) Normal 5.0 mg 5.0 mg 1 (2.5 or 7.5-10.0 mg in patients listed in the (2.5 or 7.5-10.0 mg in patients listed in the text) text) < 1.5 5.0 mg 5.0 mg > 1.5 0.0 - 2.5 mg 0.0 - 2.5 mg 2 [If INR is not measured 5.0 mg] < 1.5 5.0 - 10 mg 5.0 - 10 mg 1.5 - 1.9 2.5 - 5.0 mg 2.5 - 5.0 mg 2.0 - 3.0 0.0 - 2.5 mg 0.0 - 2.5 mg 3 > 3.0 0.0 mg 0.0 mg INR should be measured today. If INR is not measured, may use the same dose as day 2, and should not > 5 mg < 1.5 10.0 mg 10.0 mg 1.5 - 1.9 5.0 - 7.5 mg 5.0 - 7.5 mg 2.0 - 3.0 0.0 - 5.0 mg 0.0 - 5.0 mg 4 > 3.0 0.0 mg 0.0 mg INR measurement should be done, if INR on day 3 is < 1.5 or > 3.0 < 1.5 10.0 - mg 10.0 - mg 1.5 - 1.9 7.5 - 10.0 mg 7.5 - 10.0 mg 2.0 - 3.0 0.0 - 5.0 mg 0.0 - 5.0 mg 5 > 3.0 0.0 mg 0.0 mg INR measurement should be done, if INR on day 4 is < 1.5 or > 3.0 < 1.5 7.5 - 12.5 mg 7.5 - 12.5 mg 1.5 - 1.9 5.0 - 10.0 mg 5.0 - 10.0 mg 2.0 - 3.0 0.0 - 7.5 mg 0.0 - 7.5 mg > 3.0 0.0 mg 0.0 mg INR measurement should be done, if INR on day 5 is < 1.5 or > 3.0Note: Frequent INR measurement during warfarin initiation helps prevent bleeding from over anticoagulation and helps reaching target INRsooner. 78
    • DOSE DAY INR INPATIENT OUTPATIENT (Usually with daily INR) Normal 3.0 mg 3.0 mg 1 (1.5 or 3.0-6.0 mg in patients listed in the text) (1.5 or 3.0-6.0 mg in patients listed in the text) 3.0 mg 3.0 mg < 1.3 0.0 - 1.5 mg 0.0 - 1.5 mg > 1.3 2 [If INR is not measured 3.0 mg (1.5-4.5)] < 1.3 3.0 - 6 mg 3.0 - 6 mg 1.3 - 1.6 1.5 - 3.0 mg 1.5 - 3.0 mg 1.6 - 2.6 0.0 - 1.5 mg 0.0 - 1.5 mg > 2.6 0.0 mg 0.0 mg 3 INR should be measured today. If INR is not measured, may use the same dose as day 2, and should not > 3.0 mg < 1.3 4.5 - 6.0 mg 4.5 - 6.0 mg 1.3 - 1.6 3.0 - 4.5 mg 3.0 - 4.5 mg 1.6 - 2.6 1.5 - 3.0 mg 0.0 - 3.0 mg 4 > 2.6 0.0 mg 0.0 mg INR measurement should be done, if INR on day 3 is < 1.3 or > 2.6 < 1.3 6.0 - 7.5 mg 6.0 - 7.5 mg 1.3 - 1.6 3.0 - 4.5 mg 3.0 - 4.5 mg 1.6 - 2.6 1.5 - 3.0 mg 1.5 - 3.0 mg 5 > 2.6 0.0 mg 0.0 mg INR measurement should be done, if INR on day 4 is < 1.3 or > 2.6 < 1.3 6.0 - 7.5 mg 6.0 - 7.5 mg 1.3 - 1.6 4.5 - 6.0 mg 4.5 - 6.0 mg 1.6 - 2.6 1.5 - 3.0 mg 1.5 - 3.0 mg 6 > 2.6 0.0 mg 0.0 mg INR measurement should be done, if INR on day 5 is < 1.3 or > 2.6 Note: Frequent INR measurement during warfarin initiation helps prevent bleeding from over anticoagulation and helps reaching target INR sooner.C.1.8 Dose Adjustments for Warfarin Maintenance Therapy (Target INR 2.0-3.0) C.1.8 Dose Adjustments for Warfarin Maintenance Therapy 2.0-3.0) INR INR Dose Adjustments Dose Adjustments 1.5 1.5 Increase weekly dose by Increase weekly dose by 20% 1.5-1.9 1.5-1.9 Increase weekly dose Increase weekly dose by 10% 2.0-3.0 2.0-3.0 No change No change 3.1-3.9 3.1-3.9 No change; ififpersistent decrease weekly dose by 10-20% No change; persistent decrease weekly dose by 10-20% 4.0-5.0 4.0-5.0 Omit 11dose; decrease weekly dose by 10-20% Omit dose; decrease weekly dose by 10-20% 5.0 5.0 See recommendations for managing elevated INR See recommendations for managing elevated INR When resume decrease weekly dose 20-50% When resume decrease weekly dose 20-50% 79
    • C.1.8.1 Recommendations for Managing Elevated INRs or Bleeding in Patients C.1.8.1 Recommendations for Managing Elevated INRs or BleedingReceivingRecommendations for Managing Elevated INRs or Bleeding in Patients C.1.8.1 Warfarin: Receiving Warfarin: Receiving Warfarin: Condition Condition Recommendation Recommendation INR aboveCondition INR above Recommendation Lower the dose or omit a dose and resume with lower dose Lower the dose or omit a dose and resume with lower dose INR above Lower the therapeutic; dose and resume with lower dose when INR dose or omit aonly minimally above therapeutic therapeutic range when INR therapeutic; ififonly minimally above therapeutic therapeutic range but 5; 5; no range range, no dose reduction only minimally above therapeutic therapeutic but no when no therapeutic; if may be required. range,INR dose reductionmay be required. significantnobleeding range, no dose reduction may be required. but 5; bleeding significant significant bleeding Omit next one or two doses, monitor INR more frequently, INR 5 but 9;9; no Omit next one or two doses, monitor INR more frequently, INR 5 but no Omit next one or two doses, monitor INR more frequently, significant but 9; no and resume with lower dose when INR therapeutic. If risk of INR 5 bleeding significant bleeding and resume with lower dose when INR therapeutic. If risk of significant bleeding bleeding, omitwith lowerdose and give vitamin K 1-2.5 risk of and resume the next bleeding, omitthe next dose when INR therapeutic. If mg and give vitamin K 1-2.5 mg bleeding, omit the next dose and give vitamin K 1-2.5 mg PO. PO. PO. INR 9;9; no INR no Hold warfarin and give Vitamin K 2.5-5 mg orally; expect Hold warfarin and give Vitamin K 2.5-5 mg orally; expect significant bleeding substantial INR reduction in 24-48hr. Monitor INRexpect INR 9; no Hold warfarin and give Vitamin K 2.5-5 mg orally; more significant bleeding substantial INR reduction in 24-48hr. Monitor INR more substantial INR reduction in 24-48hr. Monitor INR more significant bleeding frequently and repeat vitamin K if necessary. Resume frequently and repeat vitamin K if necessary. Resume frequently an repeat vitamin K if necessary. Resume warfarin atandadjusted dose when INR therapeutic. warfarin at an adjusted dose when INR therapeutic. warfarin at an adjusted dose when INR therapeutic. Serious bleeding at Hold warfarin and give vitamin K 10 mg slow IV infusion, Serious bleeding atat Hold warfarin and give vitamin K 10 mg slow IV infusion, Serious bleeding any elevation of Hold warfarin and give vitamin K 10 mg slow IV infusion, supplemented with FFP, prothrombin complex concentrate any elevation ofof any elevation INR supplemented with FFP, prothrombin complex concentrate supplemented with FFP, prothrombin complex concentrate or rVIIa, depending on urgency of situation. Vitamin K can INRINR or rVIIa, depending on urgency of situation. Vitamin K can or rVIIa, depending on urgency of situation. Vitamin K can be repeated q12hr Life threatening be repeated q12hr give FFP, prothrombin complex be repeated q12hr Hold warfarin and Life threatening Life threatening bleeding Hold warfarin and give FFP, prothrombin vitamin K 10 mg Hold warfarinor rVIIa supplemented with complex concentrate, and give FFP, prothrombin complex bleeding bleeding concentrate, or rVIIa supplemented withdepending 10 mg concentrate, or rVIIa supplemented with vitamin K on mg slow IV infusion. Repeat, if necessary, vitamin K 10 INR. slow IV infusion. Repeat, ififnecessary, depending on INR. slow IV infusion. Repeat, necessary, depending on INR. C.1.9 Interruption of Warfarin Therapy for SurgeryC.1.9 Interruption ofof Warfarin Therapyfor Surgery C.1.9 Interruption Warfarin Therapy for Surgery Condition Recommendations Condition Condition Low risk of Recommendations Stop warfarin 5 daysRecommendations before surgery allowing INR to return Low risk ofof Low risk thromboembolism Stop warfarin 55days before surgery allowing INR to return Stop warfarin Bridge therapy with allowing return to near normal. days before surgery low dose LMWH or no thromboembolism thromboembolism tobridging. to near normal. Bridge therapy with low dose LMWH or no near normal. Bridge therapy with low dose no Moderate risk of bridging. bridging. Stop warfarin 5 days before surgery allowing INR to fall, Moderate risk ofof Moderate risk thromboembolism Stop warfarin days before surgery dose LMWH to fall, start bridge 55days before surgery allowing Stop warfarintherapy with therapeutic allowing INR 2-3 days thromboembolism thromboembolism start bridge therapy when therapeutic dose LMWH 2-3 days start to surgery (or with INR is sub-therapeutic). 2-3 days prior bridge therapywith therapeutic dose prior to surgery (or when INR is sub-therapeutic). prior to surgery (or whenLMWH 24 hrs before surgery. Administer last dose of INR is sub-therapeutic). High risk of Administer last 5 doseof LMWH 24 hrs before surgery. Administer lastdose of LMWH 24 hrs before surgery. Stop warfarin days before surgery allowing INR to fall, High risk ofof High risk thromboembolism Stop bridge 55days before surgery allowing INR to fall, start warfarin days before surgery dose LMWH to fall, Stop warfarintherapy with therapeutic allowing INR 2-3 days thromboembolism thromboembolism start bridge therapy when therapeutic dose LMWH 2-3 days start bridge therapywith therapeutic dose LMWH 2-3 days prior to surgery (or with INR is sub-therapeutic). prior to surgery dose of INR is sub-therapeutic). Administer last (or when INR is sub-therapeutic). prior to surgery (or whenLMWH 24hrs before surgery. Low risk of Administer last dose of LMWH 24hrs before surgery. and operate at before surgery. Administer last dose of LMWH 24hrsan INR of 1.3-1.5; the Lower warfarin Low risk ofof Low risk bleeding Lower warfarinlowered 4-5operate at an surgery;1.3-1.5; the Lower warfarin dose and days before INR of warfarin can dose may be dose and operate at an INR of 1.3-1.5; the bleeding bleeding doserestarted lowered 4-5 days before surgery; warfarin can dose may be lowered 4-5 days before LMWH if necessary. be may be post-op, supplement with surgery; warfarin can be restarted post-op, supplement with LMWH if necessary. be restarted post-op, supplement with LMWH if necessary. Urgent surgical or For immediate reversal give FFP, prothrombin complex Urgent surgical oror Urgent surgical other invasive For immediatein reversalgive FFP, prothrombinpo or by slow For immediate addition to vitamin K 2.5-5 mg complex concentrate reversal give FFP, prothrombin complex other invasive procedure (within concentrate IV infusion. in addition to vitamin K 2.5-5 mg po or by slow other invasive concentrate in addition to vitamin K 2.5-5 mg po or by slow procedure 12 hours) (within IV infusion. procedure (within IV infusion. 12 hours) 12Urgent surgical or hours) If surgery is urgent but can be delayed for 18-24 hrs give Urgent surgical or If surgery is urgent but can be delayed for 18-24 hrs give Urgent surgical or If surgery is urgent but can be delayed for 18-24 hrs give 80
    • other invasive vitamin K 2.5- 5 mg po or by slow IV infusion. If INR is still procedure (within high, additional vitamin K 1-2 mg po can be given. 18-24 hours)Low risk: VTE: Single VTE occurred >12 months ago and no other risk factors,AF: (CHADS2 score 0-2) without a history of stroke or other risk factors, Mechheart valve: bileaflet aortic valve without AF and no other risk factors for stroke.Moderate risk: VTE: VTE within 3-12 months, non-severe thrombophilicconditions, recurrent VTE, active cancer, AF: (CHADS2 score 3 or 4), Mech heartvalve: bileaflet aortic valve and one of the following: AF, prior stroke or TIA, HTN,DM, CHF, age >75 yr.High risk: VTE: recent (within 3mo) VTE, severe thrombophilia, AF:(CHADS2score 5 or 6), recent (within 3 months) stroke or TIA, rheumatic valvular heartdisease,Mech heart valve: any mitral valve prosthesis, older aortic valve prosthesis(caged-ball or tilting disc), recent (within 6 months) stroke or TIA Resume warfarin therapy 12-24 hrs after surgery and when there is adequate hemostasis. Resume bridge therapy: o Minor surgery or other invasive procedure and receiving therapeutic dose LMWH: Resume 24 hrs after the procedure when there is adequate hemostasis o Major surgery or high bleeding risk surgery/procedure where post- op therapeutic dose LMWH is planned: delay initiation of therapeutic dose LMWH for 48-72 hours after surgery when hemostasis is secured or administering low dose LMWH after surgery when hemostasis is secured or completely avoiding LMWH after surgery. 81
    • APPENDIX DVaughn Williams Classification of Antiarrhythmic DrugsType IA Disopyramide Procainamide QuinidineType IB Lignocaine MexilitineType IC Flecainide PropafenoneType II Beta blockers (e.g. propranolol)Type III Amiodarone Dronedarone Bretylium Dofetilide Ibutilide SotalolType IV Nondihydropyridine calcium channel antagonist (verapamil and diltiazem)Table includes compounds introduced after publication of the original classification. 82
    • GlossaryACEI Angiotensin Converting Enzyme InhibitorACS Acute Coronary SyndromeAF Atrial fibrillationAFl Atrial FlutterAFFIRM Atrial Fibrillation Follow-up Investigation of Rhythm ManagementAP Accessory PathwayAV AtrioventricularARB Angiotensin Receptor BlockerBAFTA Birmingham Atrial Fibrillation Treatment of the Agedbpm Beats per minuteCCB Calcium Channel BlockerCAD Coronary Artery DiseaseCCS-SAF Canadian Cardiovascular Society Severity in Atrial FibrillationCHA2DS2VASc Congestive Heart Failure, Hypertension, Age, Diabetes Mellitus and Stroke, Vascular DiseaseCHADS2 Congestive Heart Failure, Hypertension, Age, Diabetes Mellitus and StrokeCHF Congestive Heart FailureCOPD Chronic Obstructive Pulmonary DiseaseCPR Cardiopulmonary ResuscitationCRT Cardiac Resynchronisation TherapyCT Computed tomographyCV CardioversionCYP Cytochrome PDCCV Direct Current CardioversionDM Diabetes MellitusEAPCI European Association of Percutaneous Cardiovascular InterventionsECG ElectrocardiogramEHRA European Heart Rhythm AssociationGPI Glycoprotein IIb/IIIa InhibitorHAS-BLED Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile INR, Elderly, DrugsHCM Hypertrophic CardiomyopathyHF Heart FailureHOT CAFÉ HOw to Treat Chronic Atrial FibrillationHTN HypertensionICD Implantable Cardioverter Defibrillator 83
    • INR International Normalised RatioIV IntravenousJ-RHYTHM Japanese Rhythm Management Trial for Atrial FibrillationLA Left atriumLAA Left atrial appendageLMWH Low molecular weight heparinLoE Level of EvidenceLV Left ventricleLVEF Left Ventricular Ejection FractionLVH Left Ventricular HypertrophyMI Myocardial InfarctionN/A Not availableND Not DeterminedNYHA New York Heart AssociationOAC Oral AnticoagulantPAD Peripheral Artery DiseasePAF Paroxysmal atrial fibrillationPCI Percutaneous InterventionPIAF Pharmacological Intervention in Atrial FibrillationPUFA Polyunsaturated fatty acidsPVI Pulmonary Vein IsolationRACE RAte Control versus Electrical CardioversionFor Persistent Atrial FibrillationRE-LY Randomised Evaluation of Long-Term Anticoagulation TherapySCD Sudden Cardiac DeathSR Sinus RhythmSTAF Strategies of Treatment of Atrial FibrillationTE ThromboembolismTE risk Thrombo-embolic riskTIA Transient ischemic attackTOE Transesophageal echocardiogramTTE Transthoracic echocardiogramUFH Unfractionated HeparinVHD Valvular Heart DiseaseVKA Vitamin K AntagonistVTE Venous Thromboembolism ProphylaxisWPW Wolff-Parkinson-White Syndrome 84
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    • Copyright:© European Society of Cardiology 2010 - All Rights Reserved.This clinical practice guideline comprises [a] figure[s] from the ESCGuidelines for the Management of Atrial Fibrillation (“ESC Guidelines”)originally published in the English language in the European Heart Journal2010; 31:2369-2429; by Oxford University Press under licence from theEuropean Society of Cardiology (“ESC”). This publication is for personaland educational use only. No commercial use is authorized. No part ofthis publication or the original ESC Guidelines from which it is derivedmay be translated or reproduced in any form without written permissionfrom the ESC. Permission may be obtained upon submission of a writtenrequest to Oxford University Press, the publisher of the European HeartJournal and the party authorized to handle such permissions by the ESC.National Heart Association of Malaysia (NHAM), Ministry of Health (MOH)and the Academy of Medicine Malaysia (AMM) have obtained permissionto publish this guideline and to distribute it to healthcare professionalswithin Malaysia.For permissions, please contact journals.permissions@oup.comAll rights reserved; no part of this publication may be reproduced, stored ina retrieval system, or transmitted in any form or by any means, electronic,mechanical, photocopying, recording, or otherwise without the prior writtenpermission of Oxford University Press or its licensee Oxford PublishingLimited (“OPL”).Disclaimers:The original ESC Guidelines represent the views of the ESC and werearrived at after careful consideration of the available evidence at the timethey were written. Health professionals are encouraged to take them fullyinto account when exercising their clinical judgment. The ESC Guidelines donot, however, override the individual responsibility of health professionals tomake appropriate decisions in the circumstances of the individual patients,in consultation with that patient, and where appropriate and necessary thepatient’s guardian or carer, including without limitation in relation to the useand dosage of drugs mentioned in the ESC Guidelines. It is also the healthprofessional’s responsibility to verify the rules and regulations applicableto drugs and devices at the time of prescription. Oxford University Press,OPL and the ESC cannot accept any liability whatsoever in respect of anyclaim for damages or otherwise arising therefrom.Please visit: www.escardio.org/guidelines 99
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