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Section II: Clinical Management of AFib

Section II: Clinical Management of AFib. Section II. Clinical Management of AFib. Clinical Evaluation of AFib Treatment Options for AFib Cardioversion Drugs to prevent AFib Drugs to control ventricular rate Drugs to reduce thromboembolic risk Non-pharmacological options.

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Section II: Clinical Management of AFib

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  1. Section II:Clinical Management of AFib

  2. Section II. Clinical Management of AFib • Clinical Evaluation of AFib • Treatment Options for AFib • Cardioversion • Drugs to prevent AFib • Drugs to control ventricular rate • Drugs to reduce thromboembolic risk • Non-pharmacological options

  3. 1. Clinical Evaluation of AFib

  4. Clinical Evaluation • Minimum • History and Physical examination • Electrocardiogram • Trans-thoracic echocardiogram • Blood tests of thyroid, renal and hepatic function • Discretionary • Six-minute walk test • Exercise testing • Holter monitoring or event recording • Trans-oesophageal echocardiography • Electrophysiological study • Chest radiograph ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation J Am Coll Cardiol (2006) 48: 854

  5. Opportunistic Case Finding • In patients presenting with symptoms commonly associated with AFib: • breathlessness/dyspnoea • palpitations • syncope/dizziness • chest discomfort • Manual pulse palpation should be performed to determine the presence of an irregular pulse that may indicate underlying AFib • NICE recommendation: Developed by National Collaborating Centre for Chronic • Conditions at the Royal College of Physicians; Atrial fibrillation: full guideline DRAFT (January 2006)

  6. Primary Therapeutic Aims in AFib • Restore and maintain sinus rhythm whenever possible • Prevent thromboembolic events In order to: • Reduce symptoms and improve QoL • Minimize impact of AFib on cardiac performance • Reduce risk of stroke • Minimize cardiac remodeling ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation J Am Coll Cardiol (2006) 48: 854

  7. 2. Treatment Options for AFib

  8. Treatment Options for AFib Cardioversion • Pharmacological • Electrical Drugs to prevent AFib • Antiarrhythmic drugs • Non-antiarrhythmic drugs Drugs to control ventricular rate Drugs to reduce thromboembolic risk Non-pharmacological options • Electrical devices (implantable pacemaker and defibrillator) • AV node ablation and pacemaker implantation (ablate & pace) • Catheter ablation • Surgery (Maze, mini-Maze)

  9. Treatment Options for AFibCardioversion

  10. Cardioversion of AFib • Pharmacological • Early onset AFib • Long-standing AFib • Electrical • Transthoracic

  11. Cardioversion of AFib Prompt treatment essential • Limit duration to minimize cardiac remodelling • Avoid anticoagulation therapy • (necessary for arrhythmias that last >48 hours) • Avoid prolonged hospital recovery • Improve quality of life

  12. Pharmacological Cardioversion

  13. 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)

  14. Pharmacological CardioversionRecent onset AFib

  15. 100 60 80 40 20 Propafenone 600 mg Placebo 0 Oral Loading with Class IC Drugs for Recent Onset AFib Flecainide 300 mg p<0.001 vs. placebo p<0.001 vs. placebo 78 72 59 51 SR (%) 39 18 3 hours 8 hours Capucci A, et al. Am J Cardiol (1994) 74: 503

  16. Cardioversion of Paroxysmal AFib with Class IC Drugs Paroxysmal AFib (<48h), good LVEF Class IC drugs (propafenone, flecainide) • IV 2 mg/kg + 0.007 mg/kg/min, maintenance • Oral administration flecainide 300 mg propafenone 600 mg • Mean efficacy: 80% • Mean time of efficacy: 3h • Proarrhythmia: FLA 1:1 ECG monitoring necessary(<0.5%) with patients in resting condition

  17. Risk with Class IC Drugs: Transformation of AFib into Atrial Flutter with 1:1 AV Conduction Flecainide

  18. 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

  19. 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

  20. Pill-in-the-Pocket Prior to enrolment During follow-up 50 50 45.6 p<0.001 p<0.001 Number per month Number per month 25 25 15 4.9 1.6 0 0 Calls to ER Hospitalisation Alboni P, et al. N Engl J Med (2004) 351: 2384

  21. Conversion to SR with AmiodaroneIV (randomized studies) Connolly SJ Circulation (1999) 100: 2025

  22. 100 80 60 40 20 0 Amiodarone for Cardioversion of Recent-Onset AFib: Meta-analysis Bolus only 95 Bolus + infusion • 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 69 55 Conversion (%) 34 2-4 h 8 h Khan IA, et al. Int J Cardiol (2003) 89: 239

  23. Placebo 100 60 80 40 20 Amiodarone 0 Amiodarone Single Oral Administration for Cardioversion of Recent Onset AFib Patients in AFib (%) 0 2 4 6 8 10 12 14 16 18 20 22 24 26 Time to conversion (hours) Peuhkurinen K, et al. Am J Cardiol (2000) 85: 462

  24. 32 24 28 16 12 20 8 4 0 Flecainide IV vs Amiodarone IV for Cardioversion in Recent-Onset AFib Amiodarone Flecainide Placebo p=0.001 p=0.007 Cardioversion (%) 0 1 2 3 4 5 6 7 8 (hours) Donovan KD, et al. Am J Cardiol (1995) 75: 693

  25. Pharmacological CardioversionLong-lasting AFib

  26. 100 20 40 60 80 0 Effect of Duration on Efficacy of Pharmacological Cardioversion • 106 patients with AFib <6 months Flecainide Sotalol * p=0.005 69* 52* 44 31 23 17 0 0 Total <24 hours <7 days <6 months Reisinger J, et al. Am J Cardiol (1998) 81: 1450

  27. 100 60 80 40 20 77 48 30 0 0 Total AFib (m) >1 <1 Amiodarone Cardioversion in Persistent AFib • 67 patients with AFib >48 hours A B Amiodarone Placebo p<0.001 82 65 Sinus rhythm (%) 32 31 LA (mm) >45 <45 LVEF (%) >50 <50 Kochiadakis GE, et al. Am J Cardiol (1999) 83: 61

  28. Conversion of Atrial Flutter or AFib with Ibutilide IV • 266 patients 100 100 p<0.0001 p<0.0001 80 80 60 60 Sinus rhythm (%) Sinus rhythm (%) 40 40 20 20 0 0 Ibutilide Placebo AFlutter AFib Adverse effects: 8.3% polymorphic ventricular tachycardia Stambler BS, et al. Circulation (1996) 94: 1613

  29. Conversion of Atrial Flutter or AFib with Ibutilide IV • Effect “on top” of long-term amiodarone 80 60 54 70 patients(57 AFib, 13 AFlutter) Ibutilide 2 mg 39 Recovery of SR (%) 40 20 0 AFlutter AFib Glatter K, et al. Circulation (2001) 103: 253

  30. Electrical Cardioversion(transthoracic)

  31. Technical Aspects • The efficacy of electrical cardioversion depends on the density of current delivered to the atrial myocardium, which is dependent on: • Impedence • Position of paddles • Pressure applied to paddles • Waveform

  32. Transthoracic Cardioversion of Atrial FibrillationComparison of Rectilinear Biphasic vs Damped Sine Wave Monophasic Shocks • Suneet Mittal, Shervin Ayati, Kenneth M. Stein,David Schwartzman, Doris Cavlovich, Patrick J. Tchou,Steven M. Markowitz, David J. Slotwiner, Marc A. Scheiner,Bruce B. Lerman. • Circulation 2000; 101: 1282-7

  33. 10 0 Defibrillation Waves Monophasic wave Biphasic wave 30 10 20 Ampere Ampere 0 -10 0 4 8 12 0 4 8 12 msec msec Mittal S, et al. Circulation (2000) 101: 1282

  34. 100 60 80 40 20 0 Cumulative Efficacy of Cardioversion • Monophasic or biphasic shock p<0.005 p<0.0001 94 91 85 79 68 68 44 Efficacy of cardioversion (%) 21 100 J 200 J 300 J 360 J 70 J 120 J 150 J 170 J Monophasic Biphasic Mittal S, et al. Circulation (2000) 101: 1282

  35. Biphasic vs Monophasic Shock Waveform for Conversion of Atrial FibrillationThe Results of an International Randomized, Double-Blind Multicenter Trial • RL Page, RE Kerber, JK Russel, T Trouton, J Waktare, D Gallik,JE Olgin, P Ricard, GW Dalzell, R Reddy, R Lazzara, K Lee,M Carlson, B Halperin, GH Bardy, for the BiCard Investigators. • JACC (2002) 39: 1956-63

  36. 60 40 50 30 20 10 0 Dermal Injury Dependent on Waveform Monophasic Biphasic None(no erythema) Mild(no tenderness) Moderate(tenderness) Severe(blistering) Page RL, et al. J Am Coll Cardiol (2002) 39: 1956

  37. Success of Monophasic (MP) and Biphasic (BP) Waveforms at Cumulative Energy Levels Adgey AA & Walsh SJ Heart (2004) 90: 1493

  38. Success of Cumulative Shocks for Different Biphasic Devices Adgey AA & Walsh SJ Heart (2004) 90: 1493

  39. Electrical CardioversionPharmacological pretreatment and management of recurrence

  40. No conversion 100 30 70 50 20 10 80 60 90 40 Immediate recurrent AFib Early recurrent AFib Late recurrence AFib 0 Failure of Electrical Cardioversion Sinus rhythm (%) 2 min 2 weeks 1 year cardioversion Van Gelder IC, et al. Am J Cardiol (1999) 84: 147R

  41. Treatment Arm Rate control Rhythm control Recurrence Following Cardioversion: AFFIRM Study • AFFIRM:most recurrences occur within 2 monthsof cardioversion 100 80 60 Patients with AF Recurrence (%) 40 Log rank statistic = 58.62 p<0.0001 20 0 0 1 2 3 4 5 6 Time (years) N, Events (%) Raitt MN, et al. Am Heart J (2006) 151: 390

  42. Immediate Recurrence of AFib Following Successful Electrical Cardioversion

  43. Immediate/Early Recurrence of AFib After Electrical Cardioversion

  44. Effect of Atrial Fibrillation Duration on Probability of Immediate Recurrence after Transthoracic Cardioversion • H Oral, M Ozadyn, C Sticherling, H Tada, C Scharf, A Chugh, SWK Lai, F Pelosi, BP Knight, SA Strickeberger, F Morady. • JCE 2003; 14: 182-5

  45. 100 70 90 60 40 30 80 50 20 10 0 Immediate Recurrence of AFib (IRAF) According to the Duration of Arrhythmia 48 Prevalence of IRAF (%) 27 45 34 13 36 40 72 £1hr 1-24hrs 1-7days 7-30days 31-90days 91-180days 181-365days >365days Duration of AFib Oral H, et al. J Cardiovasc Electrophysiol (2003) 14: 182

  46. Propafenone 100 70 Placebo 90 60 50 40 30 20 10 80 70 60 50 0 Oral Propafenone Before Electrical Cardioversion in Persistent AFib • Effect on early recurrence of arrhythmia p<0.01 p<0.002 52 Sinus rhythm (%) Complex atrial arrhythmia (%) 18 0 10 min 24 min 48 min 10 minutes Bianconi L, et al. J Am Coll Cardiol (1996) 28: 700

  47. Amiodarone Amiodarone GIK GIK No treatment No treatment Effect of Pre-treatment with Oral Amiodarone 30 100 p<0.005 p<0.05 24 80 18 60 Conversion (%) Conversion (%) 12 40 6 20 0 0 SR before ECV SR with cardioversion No differences in energy for cardioversion Capucci A, et al. Eur Heart J (2000) 21: 66

  48. Short- and Long-term Treatment with Amiodarone after Cardioversion Reduces Recurrence Stable anticoagulation for 2 weeks Randomization172 Protocol violation = 4; Withdrew consent = 7 Placebo38 Short-term Amiodarone62 Long-term Amiodarone61 30 32 38 16 10 Sinus Rhythm DCCV100 Chemical26 Placebo30 Short-term Amiodarone48 Long-term Amiodarone48 Sinus Rhythm at 8 weeks Placebo6 (16%) Short-term Amiodarone29 (47%) Long-term Amiodarone34 (56%) Sinus Rhythm at 52 weeks Placebo2 (5%) Short-term Amiodarone20 (32%) Long-term Amiodarone30 (49%) Chenner KS, et al. Eur Heart J (2004) 25: 144

  49. SR before ECV SR after ECV Effect of Pre-treatment with Ibutilide IV AFib • Successful cardioversion in all patients given ibutilide and in 14/50 patients failing cardioversion alone • The mean energy for defibrillation was less with ibutilide • Sustained polymorphic tachycardia in 2/64 (3%) patients treated with ibutilide within 15 minof the infusion 50 40 30 Patients (%) 20 10 0 IBU No IBU Oral H, et al. N Engl J Med (1999) 340: 1849

  50. Pre-treatment with Verapamil in Patients with Persistent or Chronic Atrial Fibrillation Who Underwent Electrical Cardioversion • A De Simone, G Stabile, DF Vitale, P Turco, M Di Stasio,F Petrazzuoli, M Gasparini, C De Matteis, R Rotunno, T Di Napoli. • J Am Coll Cardiol (1999) 34: 810-4

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