2. John D. Hummel, MD Ohio State University Medical Center Ross Heart Hospital Columbus, Ohio Current Management of Atrial Fibrillation: An Evidence-Based Approach

3. Learning Objectives Understand the guidelines for anticoagulation and where there is latitude for physician decision making. Be able to discriminate between patients requiring restoration of sinus rhythm vs. rate control alone. Be able to determine when patients should be evaluated for curative ablation.

4. Atrial Fibrillation Easily recognized. Seems to bother healthcare workers as much as patients. Who’s Problem? Internists cardiologists EP.

5. Go A, et al. JAMA. 2001;285:2370-2375. Projected Number of Adults With AF in the US: 1995 to 2050.

6. Atrial Fibrillation: Costs to the Health Care System 35% of arrhythmia hospitalizations Average hospital stay = 5 days Mean cost of hospitalization = $18,800 Does not include: Costs of outpatient cardioversions Costs of drugs/side effects/monitoring Costs of AF-induced strokes Estimated US cost burden 15.7 billion ALOT!!

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

8. DIAGNOSTIC WORKUP Minimum Evaluation History and physical – Sx with AF, CV dz Electrocardiogram – WPW, LVH, MI Echocardiogram – LVH, LAE, EF, Valve Dz Labs – TSH, Renal fxn, LFTs Additional Testing ETT – CAD, Exercise induced SVT / AF Holter / Event Monitor – Confirm AF and Sxs TEE – LA clot EPS – SVT triggered AF AHA / ACC / ECS Guidelines 2006

9. 20 – 15 – 10 – 5 – 0 – Years Cumulative Frequency of AF (%) OSA Gami, et al. JACC 2007;49:565-71 Cumulative frequency curves for incident atrial fibrillation (AF) for subjects < 65 years of age with and without obstructive sleep apnea (OSA) during an average 4.7 years of follow-up. p = 0.002 0123456789101112131415 Number at Risk OSA No OSA 844 2,209 709 1,902 569 1,616 478 1,317 397 1,037 333 848 273 641 214 502 173 393 134 296 110 217 94 195 70 130 46 94 29 69 8 28 Incidence of AF Based on Presence or Absence of OSA No OSA

10. Maintenance of SR Pharmacologic Stroke prevention Nonpharmacologic Class IA Class IC Class III  -blocker Catheter ablation Surgery (MAZE) Pacing Pharmacologic Warfarin Thrombin inhibitor Heparin Aspirin Nonpharmacologic Removal / isolation LA appendage Rate control Pharmacologic Ca 2+ blockers  -blockers Digitalis Amiodarone Nonpharmacologic Ablate and pace Prevent remodeling ACE-I ARB AF: TREATMENT OPTIONS Adapted from Prystowsky, Am J Cardiol. 2000;85:3D-11D.

11. Risk Factors for Thromboembolism in AF High-Risk Factors=2Recommended Therapy Previous CVA / TIA / EmbolismHigh-risk factor or > 2 Mitral Stenosismoderate-risk factors Prosthetic heart valveCoumadin INR 2-3 Moderate-Risk Factors=1(mechanical valve INR > 2.5) Age > 75 yrs HTN1 moderate-risk factor CHFASA or Coumadin DM EF < 35%No risk factors Weaker-Risk Factors~½ASA 81-325mg daily Female CAD Thyrotoxicosis Age 65 – 74 yrs AHA / ACC / ECS Guidelines 2006

12. AF THERAPY ANTITHROMBOTIC RX RHYTHM CONTROL RATE CONTROL OR ? AND

13. The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833. AFFIRM Trial: Rate vs Rhythm Control Management Strategy Trial Design –5-year, randomized, parallel-group study comparing rate control vs. AARx attempt at NSR –Primary endpoint: overall mortality Patient population –4060 patients with AF and risk factors for stroke –Minimal symptoms –Mean Age = 69 yo –Hx of hypertension: 70.8% –CAD: 38.2% –Enlarged LA: 64.7% –Depressed EF: 26.0%

14. 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.

15. RateRhythm Ischemic stroke 77 (5.5%)* 80 (7.1%)* INR < 2.027 (35%)17 (21%) Not taking warfarin 25 (32%)44 (55%) * p=0.79 The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833. AFFIRM: Adverse Events

16. Atrial fibrillation Rate control – Drug Therapy: Digoxin – controls resting rate, OK in CHF patients. Beta, Ca+2 blockers – controls resting and exercise rates. Best therapy – combination of beta blocker and digoxin. Even in the best of circumstances pacing support is sometimes required Goal: Chronic afib – mean 24hr HR < 80-90 bpm

17. Atrial fibrillation: Why Control Rate? Rate control – the problem: Increased rates – more symptomatic, greater hemodynamic impact. Persistent increased rates – tachycardia induced cardiomyopathy Rate control – the goal: PAF – control symptomatic tachycardia Chronic afib – mean 24hr HR < 80-90 bpm

18. AF Rate vs. Rhythm Control Trials: Implications AFFIRM has demonstrated that rate control is an acceptable primary therapy in a selected high-risk subgroup of AF patients Continuous anticoagulation seems warranted in all patients with risk factors for stroke –Asymptomatic recurrences Is there a role for rhythm control?

19. 100 – 80 – 60 – 40 – 20 – 0 – Time (years) Percent With AF Recurrence Rate Control Raitt, et al. Am H J 2006 0123456 N, Events (%) Rate control: Rhythm control: 563, 3 (0) 729, 2 (0) 167, 383 (69) 344, 356 (50) 98, 440 (80) 250, 422 (60) 42, 472 (87) 143, 470 (69) 10, 481 (92) 73, 494 (75) 2, 484 (95) 18, 503 (79) Time to first recurrence of AF. Time 0 is the day of randomization Rhythm Control Log rank statistic = 58.62 p < 0.0001

20. Benjamin, E. J. et al. Circulation 1998;98:946-952 Kaplan-Meier mortality curves for age and sex matched subjects (independent of cardiac conditions and risk factors) Impact of AF on Risk of Death: Framingham Heart Study

21. Improvement in Left Ventricular (LV) Function and Dimensions after Ablation in Patients with Congestive Heart Failure Hsu, L. et al. N Engl J Med 2004;351:2373-2383

22. Class IA Quinidine Procainamide Disopyramide Class IC Propafenone Propafenone SR Flecainide Class III Sotalol Amiodarone Dofetilide Miller and Zipes. In: Braunwald, et al (eds). Heart Disease. 6th ed. 2001. Procainamide, disopyramide, and amiodarone are not FDA-approved for treatment of AF. Rhythm Control for AF: Commonly Used Oral Antiarrhythmic Drugs

23. CTAF Trial*: Maintenance of SR * Excluded recurrence in first 21 days. Roy D, et al. N Engl J Med. 2000;342:913-920. Patients without recurrence, % 100 80 60 40 20 0100 0 200300400500600 Amiodarone 10 mg/kg/2 wk, 300 mg/4 wk, 200 mg/d (n=201) Propafenone 300-450 mg/d (n=101) Sotalol 160 mg BID or 80 mg TID (n=101) Days of follow-up

24. ORGAN TOXICITY Examples: –Lupus, agranulocytosis, thrombocytopenia, optic neuritis, pulmonary fibrosis, hepatitis, etc. Negligible: –Dofetilide, flecainide, propafenone, sotalol Acceptable: –Azimilide, disopyramide High: –Amiodarone, procainamide, quinidine

25. Drug-Induced Proarrhythmia - Torsades

26. Factors Which Influence Ventricular Proarrhythmia Risk Hypokalemia, hypomagnesemia Long QT at baseline CHF / Decreased EF / Ventricular hypertrophy Bradycardia Female gender Reduced drug metabolism or clearance Amiodarone has lowest risk

27. Alternatives to Drug therapy “Non-Pharmacologic Therapy”  Coumadin – LAA closure (Watchman)  Rate Control – AVN RFA + PCMK  AARx – Adjunctive AFL RFA  AARX – Curative Afib RFA

28. WATCHMAN ® LAA Filter System

29. Complete AVN ablation

30. Pacemaker Placement

31. AVN RF ablation

32. Objective Benefits of AV nodal Ablation Rodriguez LM. Am J Cardiol. 1993;72:1137-1141. A Left ventricular ejection fraction (%) B Left ventricular end systolic diameter (mm) 70 60 50 40 30 20 BeforeAfter LVEF (%) mean 54 + 7 p < 0.001 mean 43 + 8 55 50 45 35 30 20 BeforeAfter LVESD (mm) mean 34 + 5 p < 0.003 mean 40 + 5 40 25

33. Complete AVN Ablation Advantages: 100% efficacy 85% symptomatic improvement Improved EF (LV remodeling) Eliminates need for rate control drugs Disadvantages: Pacemaker dependant Good Candidates: Tachy / Brady Syndrome PCMK in Place – CHF with BiV device Medication refractory / intolerant Elderly

34. 60 F with PAF treated with Rythmol Presented with recurrent tachycardia

35. Atrial Flutter Circuit

37. Atrial Flutter Ablation

38. Atrial Flutter RFA

39. Atrial Flutter Ablation Approximately 15% of AF patients treated with an AA will develop AFL Advantages: 95% efficacy ≈ 80% arrhythmia control if AARx continued As primary Rx: RFA more effective than AARx Disadvantages: Invasive Good Candidates: Typical AFL (IVC / TV isthmus) Primary AFL or AARx related AFL

40. Pathophysiology of AF Initiation –Pulmonary vein atrial ectopy Maintenance –Atrial myocardium Termination

41. Normal Sinus Rhythm Right & Left Atria

42. Electrograms During AF Surface, Right & Left Atria Right Atrium Surface Organized Disorganized Left Atrium

43. Complex Atrial Anatomy Around Pulmonary Veins

44. Beginnings of “Non Pharmacologic ” Therapies for AFib Minneapolis Feb 1999 Haisseguerre – Bordeaux, France Designed a circular catheter to map the pulmonary veins “Pulmonary Vein Isolation” Atrial muscle bundles span the transition zone from the pulmonary veins into the atria – trigger for AFib Ablation – use energy in the radiowave frequency to dessicate tissue at culprit sites Fib

45. Focal Origin of Atrial Fibrillation Hassaiguerre M, NEJM, 1998 94% of AF triggers from Pulmonary Veins “90 – 95% of all AF is initiated by PV ectopy” RALA CS FO SVC IVC Pulmonary Veins 17 31 611

46. 74 yo medically refractory AF, Echo – Normal AA Rx - Verapamil, Rythmol, Betapace, Norpace I II III V1 RSPV dist RSPV prox LIPV RA *

47. Lasso Catheter

48. Circular Mapping & Ablation Catheter in Right Superior Pulmonary Vein

49. Atrial Fibrillation Ablation Atrial Shell and Cardiac MRI

50. 45 yo F with medically refractory Highly Symptomatic PAF

51. 45 yo F with Medically Refractory PAF CT Scan / Carto Images – PA View

52. 45 yo with PAF Conversion of AF to NSR, LSPV with AF Lasso LSPV CS Abl

53. Who Should Have Ablation Symptomatic Patients Failed Class I or III Drug therapy Pts. not tolerating chronic medical therapy

54. Procedure Arrive on day of procedure “Table-time” - 4 hours Usually discharged the next day Limited activity for 3-5 days then no restrictions

55. Success Rates >1000 procedures Cure rate is about 80-85% at 1 year 1.45 procedures per pt Success rate is highly dependent on other variables: –High blood pressure –Sleep apnea –Number of years with AFib –Size of the atria –Other heart disease

56. Complications Complications ≈ 1.5% –Tamponade – 0.6% –Pulmonary vein stenosis – 0.6% –TIA / CVA – 0.5% –Esophageal-LA fistula - 0 –Groin Bleeding / Hematoma No deaths No inadvertent damage to the esophagus (Last 200 pts complications < 1%)

57. New Technology Coming to Increase Efficacy and Decrease Risk of Complications Stereotactic – Magnetic Catheter Navigation Energy Sources High Intensity Focused Ultrasound (HIFU) Cryoablation Lasar Left Atrial Appendage Closure

58. Stereotactic Navigation

59. Automatic Catheter Access to Pulmonary Veins

60. Automatic Catheter Access to Right Inferior Pulmonary Vein

62. Point and Click: Mapping Near Site of Early Activation

63. Atrial Fibrillation Ablation Evolution of the Moving Target Early Rumors (20 hr cases) 2006 Mid 90’s Right Sided Linear Phrenic Nerve Injury Left Sided Focal Tamponade TIA/CVA PV Isolation PV Stenosis WACA + Linear Esophageal Fistulas Left Atrial Flutters Fractionated Egms Back to the Right Side Hybrid Approaches Need for Stereotaxis, Cryoablation, HIFU? IVUS / TranseptalLasso3D Mapping CT integration The Trouble With a Moving Target

64. A-Fib vs. EP Labs

65. AF TREATMENT GOALS AF is rarely life-threatening and is typically recurrent Treatment goals in symptomatic pts –  frequency of recurrences –  duration of recurrences –  severity of recurrences Minimize risk of tachycardia induced cardiomyopathy Safety is primary concern

66. Atrial Fibrillation: Ablation vs Drug Rx. Ablation 80% success PV stenosis AE fistula TIA/CVA Drug Rx. 50% success Proarrhythmia End Organ Toxicity No Free Lunch PV stenosis AE fistula Torsades