Innovations in AF Management

Transcription

1 Innovations in AF Management Barry Boilson MD PhD FRCPI

2 Disclosures Relevant None financial relationship(s) with industry None Off Label Usage None

3 Overview Mechanisms of AF AF as a syndrome, not a disease The role of ablation The role of medical therapy, AADs Anticoagulation

4 Atrial Fibrillation Chaotic rhythm in atria, variably conducted to ventricles - irregular rate Common - up to 6 million in US Increasing prevalence due to increased longevity (like HF)

5 Understanding of AF changed over time Focal Multiple Wavelet 1947 Scherf D et al. Proc Soc Exp Bio 1962 Moe G et al. Arch Int Pharm Ther

6 Whatever the mechanism, MAZE works.. Multiple incision lines, including around PVs Up to 30% in need for PPM postop

7 The Pulmonary Veins.. Haissaguerre M et al. NEJM 1998 Sep 3;339(10):659-66

8 However, AF begets AF The longer you are in AF, the more likely to stay in it Dittrich HC et al. Am J Cario 1989;63:

9 However, AF begets AF There must be something changing in the substrate as well Wijffels MC et al. Circulation 1995 Oct 1:92(7):

10 Atrial Remodelling Electrical Remodelling Shortening of atrial AP duration Structural Remodelling Fibrosis Shortening of action potential duration Decrease in Ica(L) Bosch et al. CV Res Oct;44(1):

11 Autonomic Input Nademanee K et al. J Cardiology 2010; 55; 1-12

12 Scherf and Moe are both correct Paroxysmal Persistent Permanent Trigger/ initiation Substrate/ maintenance AF duration

13 Ablation LA ablation - PV isolation AV node ablation - PPM implant Ablate and Pace

14 Left Atrial Ablation Ablating Focal Triggers - Parosxysmal Substrate Modification - Persistent PV isolation (PVI) Ablating rotors CFAE Mapping Linear ablation lesions

15 LA Ablation -The Harsh Reality HRS/EHRA/ECAS 2017 AF Guidelines Only Class 1 indication for LA ablation is paroxysmal patients breaking through Class 1 or III AAD. For persistent AF, ablation of identified focal triggers IIa, all other substrate modification techniques (CFAE, lines) IIb. Calkins et al. Heart Rhythm 2017

16 STAR AF II Verma et al. N Engl J Med 2015; 372:

17 Ablation complications PV Stenosis

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19 Antral PV ablation - WACA PV isolation (PVI) Wide area circumferential ablation (WACA)

20 Atrio-esophageal Fistula

21 Phrenic nerve injury

22 Cryoballoon Kuck et al. N Engl J Med 2016; 374:

23 Fire and Ice Study Kuck et al. N Engl J Med 2016; 374:

24 CMAP Dubuc et al.heart Rhythm. 2011;8(7):

25 Pharmacologic treatment of AF Rate control Rhythm Control Pharmacologic Ca 2+ blockers -blockers Digitalis Nonpharmacologic AVN ablation and pace Pharmacologic Antiarrhythmics Class I / III agents Nonpharmacologic Catheter ablation Pacing Implantable atrial defibrillator Surgery maze

26 Q: A dialysis dependent 64 year old patient with EF35% has symptomatic atrial fibrillation The antiarrhythmic drug of choice would be: 1. Dofetililde 2. Sotalol 3. Amiodarone 4. Dronedarone

27 Q: A dialysis dependent 64 year old patient with EF35% has symptomatic atrial fibrillation The antiarrhythmic drug of choice would be: 1. Dofetililde 2. Sotalol 3. Amiodarone 4. Dronedarone

28 Flecainide (and, by association, propafenone) mortality in patients with CAD: Cardiac Arrhythmia Suppression Trial (CAST) 100 Survival (%) Class I agents Contraindicated with structural heart disease / CAD Placebo (n=725) Encainide or flecainide (n=730) P= Days after randomization NEJM, 1989

29 Safety of Dofetilide in Patients with Congestive Heart Failure, Left Ventricular Dysfunction and prior MI Probability survival Placebo Dofetilide No Increase in Mortality No. at risk Dofetilide Placebo Months Torp-Pederson: N Eng J Med 341:857, 1999

30 Drug Choices: Rhythm control in Atrial Fibrillation Heart disease? No Yes Renal Failure Flecainide Propafenone CHF? CAD? Amiodarone Sotalol Amiodarone, Dronedarone dofetilide Amiodarone, dofetilide Sotalol Amiodarone, Dronedarone dofetilide

31 Drug Choices: Rhythm control in Atrial Fibrillation Heart disease? No Yes Renal Failure Flecainide Propafenone Sotalol Amiodarone, Dronedarone dofetilide CHF? AVOID Flecainide Propafenone Amiodarone, dofetilide CAD? Sotalol Amiodarone, Dronedarone dofetilide Amiodarone Caution with Sotalol Dofetilide

32 Is ablation better than drug? Primary Endpoint (Death, Disabling Stroke, Serious Bleeding, or Cardiac Arrest) (ITT) Packer, DL et al. JAMA. March

33 Is ablation better than drug? Estimates of All-Cause Mortality Risk (ITT) Packer, DL et al. JAMA. March

34 Is ablation better than drug? All-Cause Mortality or Cardiovascular Hospitalization (ITT) Packer, DL et al. JAMA. March

35 Is ablation better than drug? Recurrent Atrial Fibrillation After Blanking by Intention-to-Treat Analysis Packer, DL et al. JAMA. March

36 CABANA Trial Key points AF ablation reduces AF Burden significantly more than medical management AF ablation reduces hospitalization significantly more than medical management No difference in all cause mortality or combined endpoint by intention to treat analysis Significant crossover in both arms on treatment effect showed significant mortality benefit and decrease in combined endpoint

37 Ablation in Heart Failure AF-CHF Trial Roy D et al: N Engl J Med. 2008;358(25):2667

38 Ablation in Heart Failure Catheter Ablation in CHF ARC-CHF PABA-CHF CAMTAF n=52 n=81 n=50 Jones DG et al. JACC 2013;61(18):1894 Hunter RJ Circ Arrhythm Electrophysiol. 2014;7(1):31 Khan M et al. N Engl J Med 2008;359:

39 Ablation in Heart Failure CASTLE-AF Death or hospitalization for worsening HF Marrouche et al. NEJM (5):

40 Ablation in Heart Failure CASTLE-AF All cause mortality Marrouche et al. NEJM (5):

41 Ablation in Heart Failure CASTLE-AF Freedom from heart failure hospitalization Marrouche et al. NEJM (5):

42 Better than ablation..? 70% AF free at one year without ablation 90% AF free at 5 years with ablation Pathak et al. JACC May 2015

43 What is the intervention? 1. Amiodarone therapy 2. Dronedarone therapy 3. Weight loss 4. CPAP for sleep apnea

44 LEGACY-AF >10% weight loss if BMI>27 70% AF free at one year without ablation 90% AF free at 5 years with ablation Pathak et al. JACC May 2015

45 Anticoagulation in AF CHA2DS2-VASc acronym Score Congestive HF 1 Hypertension 1 Age 75 years 2 Diabetes mellitus 1 Stroke/TIA/TE 2 Vascular disease (prior MI, PAD, or aortic plaque) Age 65 to 74 years 1 Sex category (ie, female sex) Maximum score Risk of ischemic stroke 0 points: 0.2% per year 1 point : 0.6% per year 2 points: 2.2% per year 3 points: 3.2% per year 4 points: 4.8% per year 5 points: 7.2% per year 6 points: 9.7% per year 7 points: 11.2% per year 8 points: 10.8% per year 9 points: 12.2% per year

46 Anticoagulation in AF Letter Clinical characteristic* Points HAS-BLED score (total points) Bleeds per 100 patient-years H Hypertension (ie, uncontrolled blood pressure) A Abnormal renal and liver function (1 point each) 1 or S Stroke B Bleeding tendency or predisposition L Labile INRs (for patients taking warfarin) E Elderly (age greater than 65 years) 1 5 to 9 Insufficient data D Drugs (concomittant aspirin or NSAIDs) or alcohol abuse (1 point each) 1 or 2 Maximum 9 points

47 Anticoagulation in AF Warfarin was historically standard therapy 3 meta-analyses compared to warfarin NOACs are associated with: A significant reduction in stroke/systemic embolism (OR 0.85) and major bleeding (OR 0.86) A significant and marked relative reduction in hemorrhagic stroke (RR 0.48) and a significant reduction in all-cause mortality (RR 0.88) Trend toward reduced major bleeding with the NOAC agents (RR 0.86). Dentali F et al. Circulation. 2012;126(20):2381 Adam SS et al. Ann Intern Med. 2012;157(11):796 Nitaios et al. Stroke Dec;43(12):

48 Focused Update of the AHA/ACC/HRS Atrial Fibrillation Guidelines NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) are recommended over warfarin in NOAC-eligible patients with AF (except moderate-to-severe mitral stenosis or mechanical heart valve) Idarucizumab (I) or Andexanet alfa (IIa) for urgent reversal Watchman device (IIb) if AC necessary but high risk of bleeding Catheter ablation for AF may have mortality benefit in selected patients with heart failure For overweight and obese patients with AF, weight loss, combined with risk factor modification, is recommended January CT et al. JACC 2019, in press

49 Conclusions Role of left atrial ablation for AF is primarily for symptomatic patients with paroxysmal AF Ablation may decrease AF burden and hospitalization more than AAD, but no mortality advantage (CABANA) Ablation may provide mortality benefit in some heart failure patients (CASTLE-AF) NOACs now favoured over Warfarin with exception of mechanical valves or mitral stenosis

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