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Management of Atrial Fibrillation Dr.Ajmal Khan TMO Cardiology HMC.

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Presentation on theme: "Management of Atrial Fibrillation Dr.Ajmal Khan TMO Cardiology HMC."— Presentation transcript:

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2 Management of Atrial Fibrillation Dr.Ajmal Khan TMO Cardiology HMC

3 The Consequences of AF Thromboembolism  Stroke: 4.5  increased risk  Microemboli: reduced cognitive function  Prothrombotic state Mortality  2  increased risk independent of comorbid CV disease  Sudden death in HF and HCM Hospitalizations  Most common arrhythmia requiring hospitalization  2-3  increased risk for hospitalization Impaired Hemodynamics  Loss of atrial kick  Irregular ventricular contractions  HF  Tachycardia-induced cardiomyopathy Reduced QoL  Palpitations, dyspnea, fatigue, reduced exercise tolerance AF is an enormous contributor AF is an enormous contributor to the growing cost of medical care

4 Definition  AF 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.

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7 Classification Recurrent AF :(1) paroxysmal AF (2) persistent AF (3) permanent AF

8 Paroxysmal (Self-terminating) First Detected Permanent Classification of Atrial Fibrillation ACC/AHA/ESC Guidelines Persistent (Not self-terminating)

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 by 2050. Lifetime risk of developing AF: 1 in 4 for men and women ≥ 40 years of age.

10 Prevalence of Diagnosed AF Go AS, et al. JAMA. 2001;285:2370-2375. Prevalence (%) 0 2 4 6 8 10 12 < 5555–5960–6465–6970–7475–7980–84 ≥ 85 Women Age (years) 11.1 9.1 10.3 7.2 7.3 5.0 3.4 3.0 1.7 1.0 0.9 0.40.2 0.1 1.89 million adults in study population; N = 17,974 with AF Men

11 Projected Number of Patients with AF by 2050 ATRIA = Anticoagulation and Risk Factors in Atrial Fibrillation. Naccarelli GV, et al. Am J Cardiol. 2009;104(11):1534-1539. Year 2.08 2.44 5.1 0 2 4 6 8 12 14 16 1990199520002005201020152020202520302035204020452050 Patients with AF (millions) 3.03 7.56 5.42 11.7 15.2 4.34 9.4 11.7 3.33 7.5 8.9 2.94 6.8 7.7 8.4 10.2 3.80 4.78 10.3 13.1 5.16 11.1 14.3 5.61 12.1 15.9 5.6 5.9 2.66 6.1 6.7 MarketScan and Thomson Reuters Medicare Databases, 2009 Olmsted County Data, 2006 (assuming a continued increase in AF incidence) ATRIA Study Data, 2000 Olmsted County Data, 2006 (assuming no further increase in AF incidence)

12 Etiologies and factors predisposing patients to AF Electrophysiological abnormalities Enhanced automaticity (focal AF) Conduction abnormality (reentry) Atrial pressure elevation Mitral 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 ischemia Coronary artery disease

13 Etiologies and factors predisposing patients to AF Inflammatory or infiltrative atrial disease Pericarditis Amyloidosis Myocarditis Age-induced atrial fibrotic changes Drugs Alcohol Caffeine Endocrine disorders Hyperthyroidism Pheochromocytoma

14 Etiologies and factors predisposing patients to AF Changes in autonomic tone Increased parasympathetic activity Increased sympathetic activity Primary or metastatic disease in or adjacent to the atrial wall Postoperative Cardiac, pulmonary, or esophageal Congenital heart disease Neurogenic Subarachnoid hemorrhage Nonhemorrhagic, major stroke Idiopathic (lone AF) Familial AF

15 Diagnosis

16 CLINICAL FINDINGS History Mild symptoms : palpitations,sweating,fatigue. Severe symptoms :hypotension,myocardial ischemia,myocardial dysfunctions,stroke,mesenteric ischemia,lower limb ischemia Presentations of precipitating factors Asymptomatic

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 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 therapy

19 Clinical evaluation in patients with AF 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 disease Blood tests of thyroid, renal, and hepatic function For a first episode of AF, when the ventricular rate is difficult to control

20 Clinical evaluation in patients with AF Additional testing One or several tests may be necessary. 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 drug Holter monitoring or event recording If diagnosis of the type of arrhythmia is in question As a means of evaluating rate control Transesophageal echocardiography To identify LA thrombus (in the LA appendage)

21 Management

22 Prevention of thrombo- embolism Reduction of AF burden*  QoL  Symptoms Reduction in the risk of CV events and hospitalizati ons and costs Reduction in mortality Goals of AF Management

23 AFib Management Treatment Options VENTRICULAR RATE CONTROL PharmacologicNonpharmacologic ACHIEVEMENT AND MAINTENANCE OF SINUS RHYTHM PharmacologicNonpharmacologic ANTITHROMBOTIC THERAPY

24 Guideline-Based AF Treatment Options Maintenance of SR Pharmacologic Class IA Class IC Class III  -blockers Nonpharmacologic Catheter ablation Pacing Surgery Implantable devices Stroke prevention Pharmacologic Warfarin Aspirin +/- clopidogrel Dabigatran Factor Xa inhibitors Nonpharmacologic Removal/isolation LA appendage Rate control Prevent remodeling CCBs ACE-Is, ARBs Statins Fish oil Pharmacologic CCBs  -blockers Digitalis Amiodarone Dronedarone Nonpharmacologic Ablate and pace

25 Rate and Rhythm Control Definitions Rate control – Rest and exertion control of ventricular response – No commitment to maintaining SR Rhythm control – Attempts restoration and maintenance of SR – Rate control required as needed Can switch from rhythm control to rate control Difficult to switch from rate to rhythm control as duration of AF becomes longer ANTICOAGULATION NEEDED for either strategy Fuster V, et al. J Am Coll Cardiol. 2006;48:854-906.

26 Major Trials Comparing Rhythm Strategy and Rate Strategy Major trials include – AFFIRM – RACE – PIAF, STAF, HOT CAFE – AF-CHF

27 Trials comparing rate control and rhythm control strategies in patients with AF

28 AFFIRM: All-Cause Mortality Rate N: Rhythm N: 2027 2033 1925 1932 1825 1807 1328 1316 774 780 236 255 0 5 10 15 20 25 30 01 2 3 4 5 Mortality, % Rate Rhythm p=0.078 unadjusted Time (years) p=0.068 adjusted The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833.

29 Favors Rate ControlFavors Rhythm Control Persistent AFParoxysmal AF Newly Detected AF Less SymptomaticMore Symptomatic >65 years of age< 65 years of age HypertensionNo Hypertension No History of Congestive Heart Failure Congestive Heart Failure clearly exacerbated by AF Previous Antiarrhythmic Drug FailureNo Previous Antiarrhythmic Drug Failure Canadian Cardiovascular Society Recommendations 2011

30 Cardioversion of AFib Pharmacological – Early onset AFib – Long-standing AFib Electrical

31 Pharmacological Cardioversion

32 Our Goal

33 Pharmacological Cardioversion More effective in recent-onset AFib – Class IA-IC-III drugs administered IV – Class IC favoured in non-cardiopathic patients – Class III favoured in cardiopathic patients or those with delays in conduction Oral loading can be performed with class IC drugs – Flecainide (200-300 mg) – Propafenone (450-600 mg)

34 Treatment Out-of-Hospital with Class IC Drugs Symptomatic, rare episodes of AFib Recent onset AFib No structural heart disease Prior hospital experience Good physician-patient relationship Resting conditions for at least 4 hours

35 Pill-in-the-Pocket In a selected (no or mild HD), risk-stratified patient population with recurrent AFib not currently taking AADs – 79% developed ≥ 1 episodes of recurrent AFib during 15 ± 5m follow-up – Acute oral flecainide or propafenone successfully terminated 94% of episodes within 113 ± 84 min, with side effects in 7% of patients Alboni P, et al. N Engl J Med (2004) 351: 2384

36 Amiodarone for Cardioversion of Recent-Onset AFib: Meta-analysis Amiodarone IV (3-7 mg/kg ± infusion 0.9-3.0 g/day) Amiodarone oral (25-30 mg/kg) Time to conversion > 6-8 h Amiodarone > 1.5 g/day IV > placebo Amiodarone 25-30 mg/kg oral > placebo Amiodarone not > other AADs Safe in patients with structural cardiopathies and low LVEF 100 80 60 40 20 Conversion (%) Bolus only Bolus+infusion 2-4 h8 h8 h 0 34 55 69 95

37 Electrical Cardioversion

38 Indications Failure 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.

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40 A Safety-Driven Approach 2011 ACC/AHA/HRS Guidelines: Antiarrhythmic Approaches to Maintain SR in Patients with Recurrent PAF or Persistent AF* HF Amiodarone Dofetilide Maintenance of SR Amiodarone Dofetilide Catheter ablation Dronedarone Flecainide Propafenone Sotalol No (or minimal) heart disease Dronedarone Flecainide Propafenone Sotalol Amiodarone NoYes Amiodarone Dofetilide Catheter ablation HTN Substantial LVH CAD Catheter ablation Amiodarone Catheter ablation Dofetilide Dronedrone Sotalol

41 Efficacy of AADs in AF Trials Dronedarone Sotalol Amiodarone Class IC Placebo 100 80 60 40 20 0 Patients in SR at 1 Year (%) CTAFSAFE-TAFFIRMDAFNE*EURIDIS*ADONISEURIDIS/ ADONIS Pooled DIONYSOS †

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 recurrence Alternative treatment to maintain sinus rhythm

44 Favors Rate ControlFavors Rhythm Control Persistent AFParoxysmal AF Newly Detected AF Less SymptomaticMore Symptomatic >65 years of age< 65 years of age HypertensionNo Hypertension No History of Congestive Heart Failure Congestive Heart Failure clearly exacerbated by AF Previous Antiarrhythmic Drug FailureNo Previous Antiarrhythmic Drug Failure Canadian Cardiovascular Society Recommendations 2011

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46 Anticoagulation and Antiplatelet Therapy

47 Intermittent AF Permanent AF Annual Stroke Rate (%) AF and Stroke AF increases stroke risk 4- to 5-fold Stroke is the most common and devastating complication of AF – Incidence of all-cause stroke in patients with AF is 5% AF is an independent risk factor for stroke. – Risk for stroke increases with age Stroke risk persists even in asymptomatic AF Stroke risk persists in patients with a “high-risk” profile despite a strategy of rhythm control (AFFIRM study, RACE study) Low Risk Moderate Risk High Risk 10 8 6 4 2 0

48 Approach to thromboprophylaxis in patients with AF

49 Stroke Risk Stratification in AF CHADS 2 Risk criteria score Risk FactorScore Cardiac failure1 HTN1 Age ≥75 y1 Diabetes1 Stroke2 Lip GY, Halperin JL. Am J Med. 2010;123(6):484-488.

50 CHAD2 score and stroke rate

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52 Antithrombotic therapy for patients with atrial fibrillation

53 Warfarin vs Placebo in Stroke Prevention in AF 100 % 50 % 0 % -50 % -100 % AFASAK-1 SPAF BAATAF CAFA SPINAF EAFT ALL Trials Favors WarfarinFavors Placebo/ Control Hart R, et al. Ann Intern Med. 2007;146:857-867. Warfarin reduces incidence of stroke by about 64%

54 ACTIVE = AF Clopidogrel Trial with Irbesartan for Prevention of Vascular Events. Antiplatelet Therapy in AF ACTIVE-W: 6706 randomized patients; trial stopped 6 4 0 2 Outcome/Year (%) StrokeVascular Event Major Bleeding 5 3 1 P =.0003 P =.001P =.53 Warfarin Clopidogrel +ASA

55 Active = AF Clopidogrel Trial with Irbesartan for Prevention of Vascular Events. ACTIVE Investigators. N Engl J Med. 2009;360(20):2066-2078. Antiplatelet Therapy in AF ACTIVE-A: 7554 randomized patients; median follow-up of 3.6 years 8 6 4 0 2 Outcome/Year (%) StrokeVascular Event Major Bleeding 7 5 3 1 P =.01 P<.001 ASA Clopidogrel +ASA

56 NEW ANTICOAGULANTS

57 Characteristics of new oral anticoagulants Sobieraj-Teague M, et al. Semin Thromb Hemost. 2009;35:515-524. Agent Mechanism of Action DosingOnsetHalf LifeReversibility Clinical Development Apixaban Direct factor Xa inhibitor Oral 2x daily 3 hr12 hrNo Phase 3; ARISTOTLE, AVERROES Rivaroxaban Direct factor Xa inhibitor Oral 1–2x daily 3 hr9 hrNo Phase 3; ROCKET AF DU 176b Direct factor Xa inhibitor Oral 1–2x daily 1–2 hr9–11 hrNo Phase 3; ENGAGE-AF Betrixaban Direct factor Xa inhibitor Oral 2x daily Not reported 19 hrNo Phase 2; EXPLORE Xa YM 150 Direct factor Xa inhibitor Not reported NoPhase 2 Idrabiotaparinux Indirect factor Xa inhibitor Weekly SC Injection 1–2 hr80–130 hrYes, IV avidin Phase 3; BOREALIS–AF Dabigatran etexilate Direct thrombin inhibitor Oral 1–2x daily 1–2 hr12–17 hrNoPhase 3; RE–LY AZD 0837 Direct thrombin inhibitor Oral 1–2x daily 1 hr9 hrNoPhase 2 ATI-5923 Tecarfarin Vitamin K antagonist Variable Oral 1x daily Not reported 136 hrYes, vitamin K Phase 2/3; EMBRACE AC

58 Connolly S, et al. N Engl J Med. 2009;361:1139-1151. Stroke Prevention in Atrial Fibrillation Dabigatran etexilate vs warfarin (RE-LY) 0.00 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 Stroke/Systemic Embolism Major BleedIntracranial Hemorrhage Percent/Year Dabigatran 110 mg Dabigatran 150 mg Warfarin INR 2.0–3.0 * ** † †† § Dabigatran vs warfarin * P < 0.001 Non-inferiority **P < 0.001 Non-inferiority, superiority † P = 0.003 †† P < 0.001 § P < 0.001

59 AVERROES Trial ASA (81-324 mg daily; up to 36 mo/end of study) Apixaban (5 mg twice daily; 2.5 mg in selected patients up to 36 mo/end of study) E Unsuitable for warfarin therapy N= 5600 Double-blind AVERROES, Apixaban Versus ASA to Reduce the Risk Of Stroke. R

60 Cumulative Risk 0.0 0.01 0.03 0.05 036 9 121821 ASA Apixaban* No. at Risk ASA Apix 27912720254121241541626329 28092761256721271523617353 Months RR=0.45 95% CI, 0.32-0.62 P<.001 AVERROES: Stroke or Systemic Embolic Event

61 Clinical Challenges With New Anticoagulants No validated tests to measure anticoagulation effect No established therapeutic range No antidote for most agents Assessment of compliance more difficult than with vitamin K antagonists Potential for unknown long-term adverse events Balancing cost against efficacy Lack 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 fraction Presence of an LA thrombus is contraindication to catheter ablation of AF Discontinuation of anticoagulation is not an indication for ablation

63 A.Circumferential ablation around left and right PV antra B.and C. Additional linear lesion sets for the roof, mitral isthmus, carinae, SVC, and cavotricuspid isthmus D.Targeting fractionated electrograms and/or ganglionic plexi Common Lesions Performed in AF Ablation A.B. LSPV LIPV RSPV IVC RIPV LSPV LIPV RSPV IVC RIPV LSPV LIPV RSPV IVC RIPV SVC C.D. LSPV LIPV RSPV IVC RIPV SVC

64 Treatment of atrial fibrillation in special population

65 Management of atrial fibrillation associated with the Wolff-Parkinson-White (WPW) preexcitation syndrome  Immediate 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 Hyperthyroidism  Administration 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 control  Guidelines provide recommendations for the management of patients with AF  Anticoagulation is essential in AF patients with risk markers, regardless of any restoration of SR  New agents and procedures may provide antiarrhythmic and antithrombotic options with improved outcomes for managing AF

71 Thank you for your attention!


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