Atrial fibrillation in the context of cryptogenic strokes

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

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

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

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

Workup for a Cryptogenic Stroke in the early 2000’s

Workup for afib in PFO closure clinical trials 2002 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 therapy First patient enrolled 2003

Workup for afib in RESPECT Trial

Workup for afib in PFO closure clinical trials 2008 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 2008 HELEX transitioned to Cardioform

Workup for afib in REDUCE Trial

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%

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

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

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 ØLA dilation ØReduced LA emptying fraction ØLAA size and single lobe-morphology • Frequent atrial premature beats The presence of at least one risk factor indicates the need for prolonged monitoring

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

Current strategies for the detection of afib

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

Incidence of afib post PFO closure All PFO RCTS found an increase in afib after PFO closure – regardless of device Randomized controlled PFO trials: Atrial Fibrillation and Atrial Flutter Clinical Outcomes Gore REDUCE Clinical Study 1 Closure (N= 441) Amplatzer RESPECT Study 2 Closure (N = 499) Any atrial fibrillation 29 (6. 6%) 20 (4. 0%) Any atrial flutter 2 (0. 5%) 2 (0. 4%) Serious atrial fibrillation 10 (2. 3%) 6 (1. 2%) Serious atrial flutter 1 (0. 2%) 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.

Severity and time course of afib post PFO closure The REDUCE Study found: Gore REDUCE Clinical Study 1 Closure (N= 441) Non-Serious atrial fibrillation or atrial flutter 19/29 (66%) Atrial fibrillation detected within 45 days post-procedure 24 / 29 (83%) Cases that resolved within 2 weeks of onset 17 / 29 (59%) 1 Søndergaard L, Kasner SE, Rhodes JF, et al; Gore REDUCE Study Investigators. New England Journal of Medicine 2017; 377(11): 1033 -1042.

Clinical consequences of afib post PFO closure • Both REDUCE and RESPECT showed low risk of recurrent stroke due to postimplant atrial fibrillation Gore REDUCE Clinical Study 1 Closure (N= 441) Subjects with post-implant atrial fibrillation or flutter who had a recurrent stroke 1 (0. 2%) Amplatzer RESPECT Study 2 Closure (N = 499) 1 (0. 2%) 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.

Afib post PFO closure Key Points AFIB is more common with an implant but is typically transient and onset within 45 days post implant Serious AFIB is rare The relative risk of recurrent stroke is still Risk of recurrent stroke reduced by 77% with in patients with AFIB PFO closure even when post implant is low including the additional risk of AFIB

Balance between stroke reduction and risk for afib post PFO closure British Medical Journal Kuijpers T, Spencer FA 2, Siemieniuk RAC, et al. . BMJ 2018; 362: k 2515.

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

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

Thank you…