LAA Closure: Beyond the Bleeding Patient Rahul N. Doshi, MD, FHRS, FACC

1. LAA Closure: Beyond the Bleeding Patient Rahul N. Doshi, MD, FHRS, FACC Directorof Electrophysiology, CCEP Fellowship Director Associate Professor of Medicine Keck School of Medicine of USC, USC Cardiovascular Thoracic Institute, LAC + USC Medical Center

2. Relevant Disclosures • Abbott/St.Jude Medical: Consultant, Clinical Research, Fellowship Support • Biosense-Webster (Johnson & Johnson): Consultant • Boston Scientific: Consultant, Clinical Research, Fellowship Support • Medtronic: Clinical Research, Fellowship Support

3. “The left atrial appendage itself is one of the most ‘lethal’ structures that exists in the human body” -DeSimone CV…Asirvatham SJ J Atrial Fibrillation Aug-Sep 2015 Last year, I tried to convince you that there is an argument to do AF ablation and LAA occlusion simultaneously… John P. Veinot et al. Circulation. 1997;96:3112-3115

4. 2019 ACC/AHA/HRS Focused Update on Atrial Fibrillation “Oral anticoagulation remains the preferred therapy for stroke prevention for most patients with AF and elevated stroke risk. However, for patients who are poor candidates for long-term oral anticoagulation (because of the propensity for bleeding or poor drug tolerance or adherence),the Watchman device provides an alternative.”

5. Reddy VY et.al. JACC 2017

6. ACC, HRS, SCAI Consensus Memo to CMSContra-Indications to Long-Term Warfarin Therapy The CMS NCD for LAAC (20.34) indicates that patients must have "A suitability for short-term warfarin but deemed unable to take long-term oral anticoagulation…." Although not part of the NCD, the professional societies (HRS/ACC/SCAI) recommended the list below to CMS during the public comment period, to describe the population they view as contraindicated to long-term anticoagulation. Source: ACC, HRS, SCAI LAAC NCD consensus memo to CMS

7. Importance of the LAA: The AF argument • AF ablation closely mirrors surgical MAZE except… • LAA ligation alone shown to decrease AF burden1 • Triggers present in LAA 30% of the time in persistent AF2 • BELIEVE Trial: 76% success at 24 months with LPAF with LAA isolation versus 56% without3 • AMAZE trial4 • Potential for increased risk of thrombus (20%) after LAA isolation despite OAC5 • Afzal MR, Kanmanthareddy A, Earnest M, et.al. Heart Rhythm 2015;12:52–59 • Di Biase L, Burkhardt JD, Mohanty P, et al. Circulation 2010;122:109–126. • DiBiase L, Burkhardt JD, Mohanty P, et.al. JAmCollCardiol 2016;68:1929–40 • Lee RJ, Lakkireddy D, MittalS, et.al. Am Heart J 2015;170:1184-94 • Rillig A, Tilz RR, Lin T et.al. CircArrhythmElectrophysiol. 2016;9:e003461

8. LAA electrical isolation meta analysis • Friedman DJ et.al • 7 studies, 1037 patients, 566 patients with electrical isolation • Lower rate AT/AF p<0.02 • No increased risk of thromboembolism though incorporated LAA occlusion Friedman DJ et.al., J Am CollCardiol EP 2018;4:112–20

9. 50 patients with LAA isolation compared to 50 patients without • OAC recommended in all patients • TEE performed 47/50 patients with LAA isolation, thrombus seen in 10/47 (21%) with 9/10 on OAC; none in control • 2 CVA and 1 TIA in LAA group; none in control 21%incidence thrombus despite OAC 3/50 patients with CVA/TIA despite OAC • Rillig A, Tilz RR, Lin T et.al. CircArrhythmElectrophysiol. 2016;9:e003461

10. Beyond the bleeding patient…how about when OAC doesn’t work?

11. 2352 patients in AF registry, 39 (1.7%) with LAA isolation Adjusted HR for CVA/TIA 11.3 if LAA electrically isolated No difference in LAA flow velocity with or without CVA Kim YG et.al. Heart Rhythm 2018

12. Retrospective, two-centers • 162 patients (140 Watchman, 22 Lariat), median follow-up 18.5 months • 84 patients (51.8%) had LAAO because of thromboembolic event post LAAEI • After 45-day TEE, 150 (92.6%) off OAC • No thromboembolism in group off OAC • Four patients with CVA while on OAC following LAAO, two of four were fatal Gadiyaram VK et.al. JCE 2019

13. 20/22 patients had LAA successfully isolated 1/20 with subsequent >5 mm leak 19/20 with freedom AF off AAD at 12 months Panniker S, Jarman JWE, Virmani R, et.al. CircArrhythmElectrophysiol. 2016;9:e003710.

14. Patients with AF CHA2DS2-VASc ≥ 2 (n = 54) Keck-USC experience combining LAA electrical isolation and LAA occlusion Persistent AF WACA + LAAEI (n = 42) De novo (n = 20) Re-do (n = 22) TEE sizing and LAA occlusion using WATCHMAN™ performed successfully in 100% of patients Kita K et.al., unpublished data

15. Kita K et.al., unpublished data

16. Kita K et.al., unpublished data

17. OPTION Trial To determine if left atrial appendage closure with the WATCHMAN Device is a reasonable alternative to oral anticoagulation following catheter ablation for patients with NVAF. Approximately 1600 subjects at 130 sites world-wide Randomized 1:1 (Device to OAC) Follow-Up at 3, 12, 24, and 36 months Patient Populations Sequential Prior ablation procedure for NVAF between 3 and 6 months prior to randomization Concomitant* Planning to have catheter ablation within 10 days of randomization OR Medication Regimens Device Group Market approved OAC and aspirin (75-100mg recommended) for 90 days followed by aspirin through at least 12-months post-implant (recommended for duration of the trial). Control (OAC) Group Market approved OAC used per IFU for atrial fibrillation stroke preventions for the duration of the trial.

18. LAA: Beyond the Bleeding Patient • Need for DAPT (PCI, TAVR)? • High risk subgroups? • AF and post CABG • AF and post TAVR • LAA Morphologic characteristics? • Thromboembolism despite OAC? • Lifestyle considerations?