2 Management of Atrial Fibrillation Dr.Ajmal KhanTMO Cardiology HMC
3 The Consequences of AF Thromboembolism Mortality Hospitalizations Stroke: 4.5 increased riskMicroemboli: reduced cognitive functionProthrombotic stateMortality2 increased risk independent of comorbid CV diseaseSudden death in HF and HCMHospitalizationsMost common arrhythmia requiring hospitalization2-3 increased risk for hospitalizationImpaired HemodynamicsLoss of atrial kickIrregular ventricular contractionsHFTachycardia-induced cardiomyopathyReduced QoLPalpitations, dyspnea, fatigue, reduced exercise toleranceAF is an enormous contributorto the growing cost of medical care
4 DefinitionAF is a supraventricular tachyarrhythmia characterized by uncoordinated atrial activation with consequent deterioration of mechanical function.ECG shows, rapid oscillations, or fibrillatory waves that vary in amplitude, shape, and timing, replace consistent P waves, and there is an irregular ventricular response.
7 Classification Recurrent AF :(1) paroxysmal AF (2) persistent AF (3) permanent AF
8 Classification of Atrial Fibrillation ACC/AHA/ESC Guidelines First DetectedParoxysmal (Self-terminating)Persistent (Not self-terminating)PermanentFuster V, Rydén LE, Asinger RW, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation.) J Am Coll Cardiol. 2001;38:
9 Epidemiology of Atrial Fibrillation Most common sustained cardiac arrhythmia.0.4% to 1% in the general population.8% in those older than 80 y.Currently affects > 2.3 million Americans, or 1% of population.Preferentially affects men and the elderly .Prevalence expected to increase by ≥ 2.5-fold byLifetime risk of developing AF: 1 in 4 for men and women ≥ 40 years of age .Page 9
10 Prevalence of Diagnosed AF 12Women11.1Men10.3126.96.36.199Prevalence (%)65.05.043.43.021.71.71.00.188.8.131.52< 5555–5960–6465–6970–7475–7980–84≥ 85Age (years)1.89 million adults in study population; N = 17,974 with AFGo AS, et al. JAMA. 2001;285:
11 Projected Number of Patients with AF by 2050 MarketScan and Thomson Reuters Medicare Databases, 2009Olmsted County Data, 2006(assuming a continued increase in AF incidence)15.915.216Olmsted County Data, 2006(assuming no further increase in AF incidence)14.313.114ATRIA Study Data, 200011.71184.108.40.206.9220.127.116.11Patients with AF (millions)9.418.104.22.16822.214.171.124.86.1Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001;285:Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna WP, Seward JB, Tsang TS. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 2006;114:5.65.425.6126.96.36.1993.034.343.803.3322.662.942.442.081990199520002005201020152020202520302035204020452050YearATRIA = Anticoagulation and Risk Factors in Atrial Fibrillation.Naccarelli GV, et al. Am J Cardiol. 2009;104(11):
12 Etiologies and factors predisposing patients to AF Electrophysiological abnormalitiesEnhanced automaticity (focal AF) Conduction abnormality (reentry) Atrial pressure elevationMitral or tricuspid valve disease Myocardial disease (primary or secondary, leading to systolic or diastolic dysfunction) Semilunar valvular abnormalities (causing ventricular hypertrophy) Systemic or pulmonary hypertension (pulmonary embolism) Intracardiac tumors or thrombi Atrial ischemiaCoronary artery disease
13 Etiologies and factors predisposing patients to AF Inflammatory or infiltrative atrial diseasePericarditis Amyloidosis Myocarditis Age-induced atrial fibrotic changes DrugsAlcohol Caffeine Endocrine disordersHyperthyroidism Pheochromocytoma
14 Etiologies and factors predisposing patients to AF Changes in autonomic toneIncreased parasympathetic activity Increased sympathetic activity Primary or metastatic disease in or adjacent to the atrial wallPostoperativeCardiac, pulmonary, or esophageal Congenital heart diseaseNeurogenicSubarachnoid hemorrhage Nonhemorrhagic, major stroke Idiopathic (lone AF)Familial AF
17 Examination Irregularly irregular pulse Pulse deficit Also look for Hypertension ,Thyrotoxicosis ,CCF ,MS, Pulmonary diseases ,Other causative factors.
18 Clinical evaluation in patients with AF Electrocardiogram, to identifyRhythm (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 therapy
19 Clinical evaluation in patients with AF Transthoracic echocardiogram, to identifyValvular heart disease LA and RA size LV size and function Peak RV pressure (pulmonary hypertension) LV hypertrophy LA thrombus (low sensitivity) Pericardial disease Blood tests of thyroid, renal, and hepatic functionFor a first episode of AF, when the ventricular rate is difficult to control
20 Clinical evaluation in patients with AF Additional testingOne or several tests may be necessary. Exercise testingIf 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 drug Holter monitoring or event recordingIf diagnosis of the type of arrhythmia is in question As a means of evaluating rate control Transesophageal echocardiographyTo identify LA thrombus (in the LA appendage)
22 Goals of AF ManagementReduction in the risk of CV events and hospitalizations and costsPrevention of thrombo-embolismReduction of AF burden* QoL SymptomsReduction in mortality
23 AFib Management Treatment Options 4/14/2017 9:24 PMAFib Management Treatment OptionsVENTRICULARRATE CONTROLPharmacologicNonpharmacologicACHIEVEMENT AND MAINTENANCE OF SINUS RHYTHMPharmacologicNonpharmacologicAFib Management Treatment OptionsMajor treatment strategies for atrial fibrillation are listed here and includeVentricular rate control, mediated by drugs, devices or ablationAchievement and maintenance of sinus rhythm, mediated by cardioversion and/or antiarrhythmic drugs, and/or ablationAntithrombotic therapy to reduce the risk of thromboembolic complications, in combination with rate control, and as needed, with rhythm controlThe clinical history and cardiovascular comorbidities of the patient presenting with atrial fibrillation will dictate the most suitable treatment option____________________Miller JM, Zipes DP. Therapy for cardiac arrhythmias. In: Zipes DP, Libby P, Bonow RO, Braunwald E, eds. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 7th ed. Philadelphia, Pa: Elsevier Saunders; 2005;I:Fuster V, Ryden LE, Asinger RW, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences. J Am Coll Cardiol. 2001;38:1266i-1266lxx.ANTITHROMBOTIC THERAPY
24 Guideline-Based AF Treatment Options Rate controlMaintenance of SRStroke preventionPharmacologicCCBs-blockersDigitalisAmiodaroneDronedaroneNonpharmacologicAblate and pacePharmacologicNonpharmacologicPharmacologicWarfarinAspirin +/- clopidogrelDabigatranFactor Xa inhibitorsNonpharmacologicRemoval/isolation LA appendageClass IA Class IC Class III-blockersCatheter ablationPacingSurgeryImplantable devicesCCBsACE-Is, ARBsStatinsFish oilPrevent remodeling24
25 Rate and Rhythm Control Definitions Rate controlRest and exertion control of ventricular responseNo commitment to maintaining SRRhythm controlAttempts restoration and maintenance of SRRate control required as neededCan switch from rhythm control to rate controlDifficult to switch from rate to rhythm control as duration of AF becomes longerANTICOAGULATION NEEDED for either strategyFuster V, et al. J Am Coll Cardiol. 2006;48:25
26 Major Trials Comparing Rhythm Strategy and Rate Strategy Major trials includeAFFIRMRACEPIAF, STAF, HOT CAFEAF-CHFPage 2626
27 Trials comparing rate control and rhythm control strategies in patients with AF ReferencePatients (n)AF durationFollow-up (y)Age (mean y ±SD)Clinical events (n)Stroke/embolismDeathRateRhythmAFFIRM (2002)1284060b/NR3.570±988/202793/2033310/2027356/2033RACE (2002)1245221 to 399 d2.368±97/25616/26618/25618/266PIAF (2000)1302527 to 360 d161±100/1252/1272/125
29 Canadian Cardiovascular Society Recommendations 2011 Favors Rate ControlFavors Rhythm ControlPersistent AFParoxysmal AFNewly Detected AFLess SymptomaticMore Symptomatic>65 years of age< 65 years of ageHypertensionNo HypertensionNo History of Congestive Heart FailureCongestive Heart Failure clearly exacerbated by AFPrevious Antiarrhythmic Drug FailureNo Previous Antiarrhythmic Drug Failure
30 Cardioversion of AFib Pharmacological Electrical Early onset AFib Long-standing AFibElectrical
33 Pharmacological Cardioversion More effective in recent-onset AFibClass IA-IC-III drugs administered IVClass IC favoured in non-cardiopathic patientsClass III favoured in cardiopathic patients or those with delays in conductionOral loading can be performed with class IC drugsFlecainide ( mg)Propafenone ( mg)
34 Treatment Out-of-Hospital with Class IC Drugs Symptomatic, rare episodes of AFibRecent onset AFibNo structural heart diseasePrior hospital experienceGood physician-patient relationshipResting conditions for at least 4 hours
35 Pill-in-the-PocketIn a selected (no or mild HD), risk-stratified patient population with recurrent AFib not currently taking AADs79% developed ≥ 1 episodes of recurrent AFib during 15 ± 5m follow-upAcute oral flecainide or propafenone successfully terminated 94% of episodes within 113 ± 84 min, with side effects in 7% of patientsAlboni P, et al. N Engl J Med (2004) 351: 2384
36 Amiodarone for Cardioversion of Recent-Onset AFib: Meta-analysis Bolus onlyBolus+infusion10095Amiodarone IV (3-7 mg/kg ± infusion g/day)Amiodarone oral (25-30 mg/kg)Time to conversion > 6-8 hAmiodarone > 1.5 g/day IV > placeboAmiodarone mg/kg oral > placeboAmiodarone not > other AADsSafe in patients with structural cardiopathies and low LVEF80696055Conversion (%)4034202-4 h8 h
38 IndicationsFailure of pharmacological measures for patients with AF with ongoing myocardial ischemia, symptomatic hypotension, angina, or HF.Immediate direct-current cardioversion is recommended for patients with AF involving preexcitation when very rapid tachycardia or hemodynamic instability occurs.AF of <48hr ---cardioversion without prior anticoagulation.For high risk patients---IV UFH or LMWH before cardioversion.AF of > 48 hr or uncertain duration follow the protocol of anticoagulation.
40 2011 ACC/AHA/HRS Guidelines: Antiarrhythmic Approaches to Maintain SR in Patients with Recurrent PAF or Persistent AF*Maintenance of SRNo (or minimal) heart diseaseHTNCADHFDronedaroneFlecainide Propafenone SotalolSubstantial LVHDofetilideDronedrone SotalolAmiodarone DofetilideNoYesAmiodarone DofetilideCatheter ablationDronedaroneFlecainide Propafenone SotalolAmiodaroneAmiodaroneCatheter ablationCatheter ablationDronedarone is added in parentheses here as a possible position in this table where it may become recommended in future guidelines statements.A Safety-Driven ApproachAmiodarone DofetilideCatheter ablationCatheter ablation
41 Efficacy of AADs in AF Trials 100AmiodaroneDronedarone80SotalolClass IC60PlaceboPatients in SR at 1 Year (%)4020CTAFSAFE-TAFFIRMDAFNE*EURIDIS*ADONISEURIDIS/ADONIS PooledDIONYSOS†
42 Treatment Options for AFib Drugs to Control Ventricular Rate
43 Permanent AFib and Ventricular Rate Control Indications for control of ventricular rate:Failure of antiarrhythmic therapy for preventing recurrenceAlternative treatment to maintain sinus rhythm
44 Canadian Cardiovascular Society Recommendations 2011 Favors Rate ControlFavors Rhythm ControlPersistent AFParoxysmal AFNewly Detected AFLess SymptomaticMore Symptomatic>65 years of age< 65 years of ageHypertensionNo HypertensionNo History of Congestive Heart FailureCongestive Heart Failure clearly exacerbated by AFPrevious Antiarrhythmic Drug FailureNo Previous Antiarrhythmic Drug Failure
51 Less validated or weaker risk factors Moderate-risk factors High-risk factorsFemale genderAge greater than or equal to 75 yPrevious stroke, TIA or embolismAge 65 to 74 yHypertensionMitral stenosisCoronary artery diseaseHeart failureProsthetic heart valveaThyrotoxicosisLV ejection fraction 35% or lessDiabetes mellitus
52 Antithrombotic therapy for patients with atrial fibrillation Risk categoryRecommended therapyNo risk factorsAspirin, 81 to 325 mg dailyOne moderate-risk factorAspirin, 81 to 325 mg daily, or warfarin (INR 2.0 to 3.0, target 2.5)Any high-risk factor or more than 1 moderate-risk factorWarfarin (INR 2.0 to 3.0, target 2.5)
53 Stroke Prevention in AF Warfarin vs Placebo inStroke Prevention in AFAFASAK-1SPAFBAATAFCAFASPINAFEAFTALL Trials100% % % % %Favors WarfarinFavors Placebo/ControlWarfarin reduces incidenceof stroke by about 64%Hart R, et al. Ann Intern Med. 2007;146:
54 Antiplatelet Therapy in AF ACTIVE-W: 6706 randomized patients; trial stoppedClopidogrel +ASAWarfarinP = .0003654Outcome/Year (%)3P = .001P = .5321Vascular EventStrokeMajor BleedingACTIVE = AF Clopidogrel Trial with Irbesartan for Prevention of Vascular Events.
55 Antiplatelet Therapy in AF ACTIVE-A: 7554 randomized patients; median follow-up of 3.6 yearsP = .018Clopidogrel +ASA7ASA65Outcome/Year (%)4P<.0013P<.00121Vascular EventStrokeMajor BleedingActive = AF Clopidogrel Trial with Irbesartan for Prevention of Vascular Events.ACTIVE Investigators. N Engl J Med. 2009;360(20):
57 Characteristics of new oral anticoagulants AgentMechanism of ActionDosingOnsetHalf LifeReversibilityClinical DevelopmentApixabanDirect factor Xa inhibitorOral2x daily3 hr12 hrNoPhase 3; ARISTOTLE, AVERROESRivaroxaban1–2x daily9 hrPhase 3; ROCKET AFDU 176b1–2 hr9–11 hrPhase 3; ENGAGE-AFBetrixabanNot reported19 hrPhase 2; EXPLORE XaYM 150Phase 2IdrabiotaparinuxIndirect factor Xa inhibitorWeeklySC Injection80–130 hrYes, IV avidinPhase 3; BOREALIS–AFDabigatran etexilateDirect thrombin inhibitor12–17 hrPhase 3; RE–LYAZD 08371 hrATI-5923TecarfarinVitamin K antagonistVariableOral 1x daily136 hrYes, vitamin KPhase 2/3; EMBRACE ACSobieraj-Teague M, et al. Semin Thromb Hemost. 2009;35:
58 Stroke Prevention in Atrial Fibrillation Dabigatran etexilate vs warfarin (RE-LY)4.00Dabigatran 110 mg3.50Dabigatran 150 mgWarfarin INR 2.0–3.03.00†Dabigatran vs warfarin* P < Non-inferiority**P < Non-inferiority, superiority†P = 0.003††P < 0.001§ P < 0.0012.50Percent/Year2.00*1.50**1.000.50††0.00Stroke/SystemicMajor BleedIntracranialEmbolismHemorrhageConnolly S, et al. N Engl J Med. 2009;361:
59 AVERROES Trial E R ASA (81-324 mg daily; up to 36 mo/end of study) Unsuitable for warfarin therapyN= 5600ERDouble-blindApixaban(5 mg twice daily; 2.5 mg in selected patients up to 36 mo/end of study)AVERROES, Apixaban Versus ASA to Reduce the Risk Of Stroke.
60 AVERROES: Stroke or Systemic Embolic Event 95% CI,P<.0010.05ASACumulative Risk0.03Apixaban*0.010.0369121821MonthsNo. at RiskASA27912720254121241541626329Apix28092761256721271523617353
61 Clinical Challenges With New Anticoagulants No validated tests to measure anticoagulation effectNo established therapeutic rangeNo antidote for most agentsAssessment of compliance more difficult than with vitamin K antagonistsPotential for unknown long-term adverse eventsBalancing cost against efficacyLack of head-to-head studies comparing new agents
62 Catheter AF Ablation Indications: Symptomatic AF refractory or intolerant to at least 1 class I or III AAD.Selected symptomatic patients with HF and/or reduced ejection fractionPresence of an LA thrombus is contraindication to catheter ablation of AFDiscontinuation of anticoagulation is not an indication for ablationCARDProgress Indicators9. Recognize ablation as an option for treating patients with AF. (knowledge — for PCPs and GenCards only)Learning Objectives3. Select the optimal treatment strategy—ie, appropriate pharmacotherapy (including antiarrhythmic therapy), ablation—for patients with AF based on patient characteristics [Progress Indicators 6, 9, 11] and make appropriate referral for ablation [Progress Indicator 10]Instructional Objectives9. Presented with treatment options for AF patients, participants will recognize ablation as an acceptable optionPCP5. Select the optimal treatment strategy—ie, appropriate pharmacotherapy (including antiarrhythmic therapy), ablation—for patients with AF based on patient characteristics [Progress Indicators 6, 9, 11]
63 Common Lesions Performed in AF Ablation A. Circumferential ablation around left and right PV antraB. and C. Additional linear lesion sets for the roof, mitral isthmus, carinae, SVC, and cavotricuspid isthmusD. Targeting fractionated electrograms and/or ganglionic plexiSVCSVCA.B.RSPVRSPVLSPVLSPVLIPVLIPVRIPVRIPVIVCIVCSVCSVCC.D.RSPVRSPVLSPVLSPVLIPVRIPVLIPVRIPVIVCIVC
64 Treatment of atrial fibrillation in special population
65 Management of atrial fibrillation associated with the Wolff-Parkinson-White (WPW) preexcitation syndromeImmediate direct-current cardioversion is recommended in hemodynamically unstable patients.Intravenous procainamide , ibutilide ,flecainide or amiodarone is recommended to restore sinus rhythm in hemodynamically stable patients.Intravenous administration of AV nodal blocking drugs i.e. digitalis glycosides or nondihydropyridine calcium channel antagonists is not recommended.Catheter ablation of the accessory pathway is recommended in symptomatic patients.
66 HyperthyroidismAdministration of a beta blocker to control the rate of ventricular response .Alternative is nondihydropyridine calcium channel antagonist (diltiazem or verapamil).Oral anticoagulation (INR 2.0 to 3.0) is recommended in the presence of risk factors for stroke.
67 Management of atrial fibrillation during pregnancy Digoxin, a beta blocker, or nondihydropyridine calcium channel to control the rate .Flecainide , ibutilide , quinidine or procainamide to restore sinus rhythm in hemodynamically stable patient.Direct-current cardioversion in hemodynamically unstable patient.Anticoagulation in the presence of risk factor for stroke.
68 Management of atrial fibrillation in patients with pulmonary disease Correction of hypoxemia and acidosis .A nondihydropyridine calcium channel antagonist (diltiazem or verapamil) to control the ventricular rate.Direct-current cardioversion in hemodynamically unstable patient.IV flecainide may be used to restore sinus rhythm in hemodynenicall y stable patient.
69 Interruption of anticoagulation for diagnostic or therapeutic procedures Anticoagulation may be interrupted for a period of up to 1 wk for surgical or diagnostic procedures.In high-risk patients (particularly those with prior stroke, TIA, or systemic embolism), or when a series of procedures requires interruption of oral anticoagulant therapy for longer periods, unfractionated or low-molecular-weight heparin may be administered.
70 Summary AF is a common disease that is increasing in prevalence For any patient with AF, decisions need to be made regarding antithrombotic therapy, rate control, and/or rhythm controlGuidelines provide recommendations for the management of patients with AFAnticoagulation is essential in AF patients with risk markers, regardless of any restoration of SRNew agents and procedures may provide antiarrhythmic and antithrombotic options with improved outcomes for managing AF