Atrial fibrillation in the context of cryptogenic strokes and transcatheter PFO closure

1. Atrial fibrillation in the context of cryptogenic strokes and transcatheter PFO closure Ignacio Inglessis, MD Director Structural Heart Disease Program Massachusetts General Hospital Harvard Medical School

2. Proctor and Consultant for: - Gore Medical - St Jude Medical Disclosures

3. Lecture Objectives • Importance of afib as a risk factor for cryptogenic strokes • Ideal methodology for afib detection in cryptogenic strokes • Incidence, time course, and clinical consequences of afib in patients that undergo transcatheter PFO closure • Treatment recommendations for post-PFO closure afib

4. Lecture Objectives • Importance of afib as a risk factor for cryptogenic strokes • Ideal methodology for afib detection in cryptogenic strokes • Incidence, time course, and clinical consequences of afib in patients that undergo transcatheter PFO closure • Treatment recommendations for post-PFO closure afib

5. Cryptogenic Stroke • CS is a stroke in which no cause is identified during initial standard evaluation • CS account for 10-40% of all ischemic causes • Atrial fibrillation is now increasingly recognized as a cause of cryptogenic strokes

6. Workup for a Cryptogenic Stroke in the early 2000’s

7. Workup for afib in PFO closure clinical trials RESPECT Trial Initiated (Second US Randomized, Prospective Trial) Stroke patients only, randomized 1:1 to medical therapy alone or to PFO closure with Amplatzer device plus medical therapyFirst patient enrolled 2003 2002

8. Workup for afib in RESPECT Trial

9. Workup for afib in PFO closure clinical trials REDUCE Trial Initiated (Third Randomized, Prospective US/OUS Trial) Stroke patients only, randomized 2:1 to PFO closure plus medical therapy or to medical therapy alone. First patient enrolled 2008HELEX transitioned to Cardioform 2008

10. Workup for afib in REDUCE Trial

11. Impact of long-term monitoring technology 2014 Randomized trial evaluating Implantable cardiac monitoring versus EKG/Holter for detection of afib in patients with CS Detection of Afib at 6 months Detection of Afib at 12 months 15%

12. What afib duration impacts the stroke risk? Duration of detected afib Do all afib episodes have the same risk? Afib > 1 hour is clinically significant

13. Lecture objectives • Importance of afib as a risk factor for cryptogenic strokes • Ideal methodology for afib detection in cryptogenic strokes • Incidence, time course, and clinical consequences of afib in patients that undergo transcatheter PFO closure • Treatment recommendations for post-PFO closure afib

14. The strategy for afib detection depends on the risk Factors that increase risk for afib detection in CS • Older age (>40) • Higher CHADS-VASC score (Hypertension, diabetes, CHF, PVD) • MRI consistent with embolic stroke (i.e. multiple vascular territories) • LA atrial cardiopathy • LA dilation • Reduced LA emptying fraction • LAA size and single lobe-morphology • Frequent atrial premature beats The presence of at least one risk factor indicates the need for prolonged monitoring

15. Current strategies for the detection of afib REDUCE Post Approval Study adopted this strategy to rule out afib before enrollment

16. Current strategies for the detection of afib

17. Lecture objectives • Importance of afib as a risk factor for cryptogenic strokes • Ideal methodology for afib detection in cryptogenic strokes • Incidence, time course, and clinical consequences of afib in patients that undergo transcatheter PFO closure • Treatment recommendations for post-PFO closure afib

18. Incidence of afib post PFO closure Randomized controlled PFO trials: Atrial Fibrillation and Atrial Flutter Clinical Outcomes • All PFO RCTS found an increase in afib after PFO closure – regardless of device 1 Søndergaard L, Kasner SE, Rhodes JF, et al; Gore REDUCE Study Investigators. New England Journal of Medicine 2017;377(11):1033-1042. 2. Saver JL, Carroll JD, Thaler DE, et al; RESPECT Investigators.. New England Journal of Medicine 2017;377(11):1022-1032.

19. Severity and time course of afib post PFO closure The REDUCE Study found: 1 Søndergaard L, Kasner SE, Rhodes JF, et al; Gore REDUCE Study Investigators. New England Journal of Medicine 2017;377(11):1033-1042.

20. Clinical consequences of afib post PFO closure • Both REDUCE and RESPECT showed low risk of recurrent stroke due to post-implant atrial fibrillation 1 1. Søndergaard L, Kasner SE, Rhodes JF, et al; Gore REDUCE Study Investigators. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. New England Journal of Medicine 2017;377(11):1033-1042. 2. Saver JL, Carroll JD, Thaler DE, et al; RESPECT Investigators. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. New England Journal of Medicine 2017;377(11):1022-1032.

21. Afib post PFO closure

22. Balance between stroke reduction and risk for afib post PFO closure British Medical Journal Kuijpers T, Spencer FA2, Siemieniuk RAC, et al.. BMJ 2018;362:k2515.

23. Lecture objectives • Importance of afib as a risk factor for cryptogenic strokes • Ideal methodology for afib detection in cryptogenic strokes • Incidence, time course, and clinical consequences of afib in patients that undergo transcatheter PFO closure • Treatment recommendations for post-PFO closure afib

24. Strategies for management of post PFO closure afib • Start anticoagulation • Implant a cardiac monitor • Monitor patient for duration of monitor’s battery (3 years) • Consider discontinuation of anticoagulation if no recurrent significant events (> 1 hour) for at least 1 year

25. Thank you…