Case 70 yo with longstanding persistent AF. Paroxysmal AF diagnosed - PDF document

12/8/19 Should We Ablate Asymptomatic AF in a Young Patient? Pro Edward Paul Gerstenfeld, MD, FHRS @Ed_Gerst Professor of Medicine University of California, San Francisco 2.0 1 Case 70 yo with longstanding persistent AF. Paroxysmal AF diagnosed 1992 (44 yo) AF became persistent 2002. Asymptomatic. EF 67%. Rx ASA+diltiazem. 2018 developed DOE. Echo: EF 40-45%, severe RAE, LAE, mod MR/mild-mod TR Holter: Mean rate 82 bpm 2 1

12/8/19 AFFIRM Ø 4060 pts randomized to rate vs. rhythm control Ø Enrolled 1996-1999. Followed for mean 3.5 years Wyse et al. N Engl J Med. 2002 Dec 5;347(23):1825-33. 3 4 2

12/8/19 AFFIRM – Predictors of Survival 5 AF-Mediated Cardiomyopathy Ø 67 pts with baseline EF ≤ 50% and “ controlled ” ventricular rate (<90 bpm) 80 70 57% 60 50 44% LVEF 40 30 20 10 0 LVEF Baseline LVEF Follow up LV EF increased by > 5% in 82% patients Ø Ø LV EF normalized to ≥ 55% in 72% patients Gentlesk et al. JCE 2004. 6 3

12/8/19 CASTLE AF Primary endpoint: All-cause death or unplanned hospitalization due to worsening of heart failure Marrouche et al. NEJM 2018 378(5):417.427. 7 Overall Mortality 13.4% 25.0% Marrouche et al. NEJM 2018 378(5):417.427. 8 4

12/8/19 CHF Trials: Total Mortality 100 80 Mortality (%) 60 36.1 28.9 24.6 25 20.4 40 13.4 9.8 7.2 20 Control 0 Intervention BHAT SAVE SCD-HeFT CASTLE AF 9 Ø 68 pts with Per AF and LVEF≤45%. Ø Randomized to Medical Rate Control vs. RFA Ø CMR pre-ablation Ø 1°endpoint LVEF by CMR Ø 6-months post RFA Prabhu …. Kistler. J Am Coll Cardiol 2017;70:1949–61 10 5

12/8/19 CAMERA-MRI Prabhu …. Kistler. J Am Coll Cardiol 2017;70:1949–61 11 12 6

12/8/19 CABANA Trial Design Enroll patients with new onset or Ablation Therapy (1108) under-treated paroxysmal, Primary ablation: persistent, or longstanding • PVI/WACA persistent AF who warrant therapy Ancillary ablation: • Linear lesions R Key Inclusion Criteria • CFAE • ³ 65 years of age Anticoagulation 1:1 •<65 years of age with ³ 1 CVA/CV risk factor Drug Therapy (1096) •Eligible for ablation and ≥2 • Rate Control or rhythm or rate control drugs • Rhythm Control • Anticoagulation No Exclusion Criteria Identified Packer D. et al JAMA. 2019;321(13):1261-1274. 13 Primary Endpoint (Death, Disabling Stroke, Serious Bleeding, or Cardiac Arrest) (ITT) Packer D. et al JAMA. 2019;321(13):1261-1274. 14 7

12/8/19 Estimates of All-Cause Mortality Risk (ITT) Packer D. et al JAMA. 2019;321(13):1261-1274. 15 CABANA: Patient Randomization Subjects 2204 Ablation Therapy Drug Therapy 1108 1096 Drug Treated Ablated 1092 (99.6%) 1006 (90.8%) rhythm control 953 (87.2%) repeat ablation 215 (19.4%) rate control only 126 (11.5%) Not ablated Cross Over Ablated Crossovers 102 (9.2%) 301 (27.5%) Completed FU Completed FU 1002 (90.4%) 48.9 mo 966 (88%) 48.2 mo * Withdrew <3 years 16 8

12/8/19 Primary and Secondary Outcomes (Treatment Received)* Ablation Drug Hazard Ratio P- (N = 1307) (N = 897) (95% CI) Value Primary Outcome 92 (7.0%) 98 (10.9%) 0.67 (0.50, 0.89) 0.006 Death, Disabling Stroke, Serious Bleeding, or Cardiac Arrest Secondary Outcomes All-cause mortality 58 (4.4%) 67 (7.5%) 0.60 (0.42, 0.86) 0.005 Death or CV 538 (41.2%) 672 (74.9%) 0.83 (0.74, 0.94) 0.002 hospitalization *pre-specified Packer D. et al JAMA. 2019 Apr 2;321(13):1261-1274. 17 Primary Endpoint Sub-group Analysis All-Cause Mortality, Disabling Stroke, Serious Bleeding, Cardiac Arrest * Minority=Hispanic or Latino or non-white race 18 9

12/8/19 Adverse Events in CABANA 19 N=309 N=583 N=768 N=378 Leong-Sit et al. Circ Arrhythm Electrophysiol. 2010;3(5):452-7. 20 10

12/8/19 21 Ø 180 patients with paroxysmal/persistent AF compared to 90 CTRLS Ø OAT: 0% CTRL vs. 88% AF Ø # SCI Persist > Parox > CTRL (41±28 vs. 33±23 vs. 12±27 p <0.01) Cognitive Function * Control * * * * Paroxysmal Persistent * Visio-spatial Immediate Language Attention Delayed Memory abilities Memory J Am Coll Cardiol 2013;62:1990–7 *P<0.05 22 11

12/8/19 1 year 3 years 23 STAR AF II - Primary Outcome • Documented AF > 30 seconds after one procedure with or without AAD p=0.15 59% 48% 44% Verma et al N Engl J Med. 2015 May 7;372(19):1812-22 24 12

12/8/19 STAR AF II AF Burden Verma et al N Engl J Med. 2015 May 7;372(19):1812-22 25 HRS/EHRA/ECAS 2017 Atrial Fibrillation Consensus Statement ∗∗ A decision to perform AF ablation in an asymptomatic patient requires additional discussion with the patient because the potential benefits of the procedure for the patient without symptoms are uncertain 26 13

12/8/19 Reasons to consider ablating asymptomatic AF in a young patient: Ø Randomized trial data only extend for 3-5 years. No data on 20-30+ years with AF. Ø Patients with AF who underwent ablation in CABANA had lower mortality over only 3.5 years. Ø For young AF patients, future risk of LA dilatation -> MR -> CHF. May be too late to address AF later. Early ablation better success. Ø Association of AF with dementia may be modifiable 27 When is it appropriate to consider ablation for asymptomatic AF*? Ø Young age (< ~60 years old) Ø Paroxysmal or recent persistent (<1 year) AF (echo surrogate mild-mod LAE) Ø Tachy or AF-mediated cardiomyopathy Ø Tachy/brady with conversion pauses otherwise requiring pacemaker Ø High risk occupation (pilot) with AF *After a thorough discussion of the risks/benefits 28 14

12/8/19 Thank you 29 30 15

12/8/19 Cases 1) 50 yo male attorney Found to be in AF prior to wisdom teeth extraction Last ECG 2009 during insurance physical SR Meds: Lipitor, ASA 81mg Echo: Normal LV EF 65%, trace MR, moderate LAE 46ml/m 2 Feels fine. Referred for AF ablation 2) 50 yo male engineer PAF since 2001. Progressed to persistent AF 2012 – recurred after CV x2. Meds: Mg++, Eliquis, MVI Echo: LV EF 40-45%; mild MR, moderate LAE 46ml/m 2 Referred for AF ablation given declining EF 31 Cases 1) 50 yo attorney Lost 20# Sleep study found moderate OSA – started CPAP CV – SR with marked first degree AV delay – AF recurred 2 after hours Loaded with dofetilide 500ug bid. CV to SR with Mobitz I AVB. Syncope. Dofetilide stopped. Back in persistent AF. 2) 50 yo engineer Loaded with dofetilide + CV Remained in SR for ~3 weeks and then AF recurred Wife felt he had more energy in SR Elected to undergo AF ablation. 32 16

12/8/19 33 42 yo Commercial Airline Pilot 34 17

12/8/19 AF Onset R I P V LSP V C S R A 35 First Recurrence AF – Post Blanking* (ITT) Packer D. et al Heart Rhythm Late Breaking Clinical Trials 2018 *Using CABANA Monitors 36 18

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