David J Wilber MD Loyola University Chicago DECAAF II UPDATE David J Wilber MD Loyola University Chicago Disclosures: Abbott: Investigator. ACCF: Consultant. Biosense / Webster: Consultant, Investigator; Medtronic: Consultant, Investigator

DECAAF I: MRI IN PREDICTING ABLATION OUTCOME Baseline Scan Marrouche et al, JAMA 2014. 311(5):498-506.

IS FIBROSIS AN ABLATION TARGET? Retrospective analysis of DECAAF data Age 59+11 yrs, 64% PAF Baseline fibrosis quantified in 273 of 330 pts (83%) Post ablation fibrosis quantified in 177 pts 1 year recurrence in 36% Multivariate predictors Baseline fibrosis (p<0.001) adjusted HR 1.089 (1.055-1.121) Residual fibrosis (p<0.001) adjusted HR 1.09 (1.054- 1.126) PVI not a predictor Akoum et al, JCE 2015; 26:473-805

ATRIAL MYOPATHY? DE-MRI Prediction of Ablation Outcomes Mild Moderate Extensive <15% (N=43) 15-35% (N=30) >35% (N=8) 81 pts (50% PAF) Moderate/extensive enhancement more frequent in persistent AF (70% vs 32%) Extent of DE strongest predictor of recurrence in multivariate analysis, LA volume and persistent AF weaker predictors Oakes et al, Circulation 2009; 119:1758-1767

DECAAF II Prospective RCT of PVI + Fibrosis guided ablation vs PVI alone Inclusion: persistent AF (> 7 days), first AF ablation, age > 18 yrs Exclusion: contraindication or inability to obtain acceptable quality MRI No access or ability for daily ECG upload via smart phone or tablet Prior valve surgery Power and sample size 517 arrhythmia recurrence events 90% power to detect a 25% reduction in recurrence (2 sided α 0.05) 888 pts assuming 60% 1 year recurrence in conventional treatment group DSMB conducts interim analysis after 1/3 and 2/3 of total projected events with Obrien-Fleming boundaries to guide early termination.

DECAAF II ENDPOINTS Primary efficacy endpoint: any nonself-terminating episode of atrial tachyarrhyhmia (AF, flutter, AT) demonstrated by at least 2 consecutive valid ECG tracings within 6 hours to a maximum of 7 days, after 3 mo blanking period Secondary efficacy endpoint: Quality of Life (Toronto AFSS, SF-36) 3 and 12 mo Primary Safety Endpoint: composite of stroke, PV stenosis, bleeding, heart failure, death Data Coordinating Center: CARMA

DECAAF DESIGN MRI-fibrosis images not made available Images made available to site clinician

Group 1--PVI

Group 2—Targeting fibrosis

Targeting Fibrosis

DECAAF WORKFLOW

Progress To Date Planned enrollment: 900 pts 1st Subject Enrolled: July 2016 660 pts randomized as of Feb 13, 2019 43 Activated Trial Sites US 17 Europe 22 Australia 4 - Would also like to mention the study is being diligently monitored by the Data Monitoring Committee who have performed quarterly safety reviews with full endorsement of the continuation of the trial w/o modification.

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