Linker hartoor sluiting: WATCHMAN

Linker hartoor sluiting: WATCHMAN Y.J. Stevenhagen, cardioloog, Medisch Spectrum Twente DRES 1

Inhoud Workshop Casus Achtergrond behandeling atriumfibrilleren Waarom linker hartoor afsluiting Procedure en interpretatie van images Klinisch bewijs voor de Watchman Conclusies Demo materiaal 2

Casus 1 Man, 60 jaar Paroxysmaal atriumfibrilleren Diabetes Hypertensie Vaatlijden CHA2DS2VASc score 3 Gebruik VKA 3

Intracerebrale bloeding INR 3.2 VKA stop tijdelijk 4

Staken VKA 2 maal TIA MRI ischaemisch CVA Wat zijn je opties? 5

Casus 2 Vrouw 71 jaar Persisterend atriumfibrilleren Nierfunctiestoornissen Hypertensie CHA2DS2Vasc score 3 Recidiverende TIA s meerdere stroomgebieden onder adequate VKA instelling Wat zijn je opties? 6

Achtergrond Patienten met atriumfibrilleren 5 keer meer risico op CVA Ernstiger CVA Occlusie grotere vaten Groter ischaemisch gebied Hogere mortaliteit Frequent recidief 40% relatieve/absolute contra- indicatie OAC 90% thrombus afkomstig vanuit linker hartoor 7

Waarom linker hartoorsluiting 8

Stroke profylaxe Stroke preventie Vermijden bloedingen 9

Behandeling opties AF Ablatie en/of Stroke preventie Pacing VKA NOAC Interventie Rate controle Chirurgisch LAA Clip Percutaan LAAC 10

CHA2DS2VASc score CHA 2 DS 2 -VASc C Congestive heart failure 1 H Hypertension 1 18% 15% Annual Risk of Stroke 1,2 15,2 A Age 75 2 D Diabetes mellitus 1 13% S Stroke/TIA 2 V Vascular disease 1 A Age 65-74 1 Sc Sex category (female) 1 10% 5% 3% 1,3 2,2 3,2 4,0 6,7 9,8 9,6 6,7 Maximum Score: 9 0% 0 1 2 3 4 5 6 7 8 9 11

1 jaars bloedingsrisico HAS-BLED H Hypertension 1 Keuze voor embolie profylaxe: Balans tussen stroke risico en risico op grote bloedingen A Renal / Liver dysfunction 1 or 2 S Stroke 1 B Bleeding 2 L E D Labile INRs 1 Elderly (age 65 years) 1 Drugs or alcohol abuse 1 or 2 Maximum Score: 9 Score Bleeds per 100 patient-years 0 1.13 1 1.02 2 1.88 3 3.74 4 8.70 12

Risicoreductie CVA 13

ESC guideline 14

VKA praktijk 33% 67% N= 5333 EuroHeart survey 1 VKA No anticoagulation 15

VKA praktijk INR Smalle range 2-3 Interactie voedsel medicatie Frequente monitoring Bloedingen Hospitalisering Time outside therapeutic INR 36 64 Time in therapeutic INR 16

NOAC Voordeel Geen monitoring Goede stroke preventie Vermindering intracraniele bloedingen Nadeel Bloeding nagenoeg evenveel 10% gestopt na 1 jaar ivm bijwerkingen Study Treatment Major Bleeding Hemorrhagic Stroke Discontinuation in the study RE-LY 1 Dabigatran (150mg) 3.11 % 0.10 % 21.2 % Dabigatran (110mg) 2.71 % 0.12 % 20.7 % Warfarin 3.36 % 0.38 % 16.6 % ROCKET-AF 2 Rivaroxaban 3.6 % 0.5% 23.7% Warfarin 3.4 % 0.7 % 22.2 % ARISTOLE 3 Apixaban 2.13 % 0.24 % 25.3 % Warfarin 3.09 % 0.47 % nc 17

WATCHMAN Procedure Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Indications, Information for contraindications, the use only warnings warnings countries and instructions and with instructions applicable for use health can for use be found authority can in be the found product in registrations. the labeling product supplied labeling SH-218301-AA with each supplied device. JAN with 2014 each device. Information for the use only in countries with applicable health authority product registrations. SH-218301-AA JAN 2014 Information for the use only in countries with applicable health authority product registrations. Page Page # of # 32of 32

Hartoor anatomie Cactus (30%) Chicken Wing (30%) Windstock (19%) Cauliflower (3%) 19

Watchman procedure 20

Watchman LAAC device Nitinol Frame Radially expands to maintain position in LAA Contour shape accommodates most LAA anatomies 160 Micron Membrane Polyethylene terephthalate (PET) cap Designed to block emboli from exiting the LAA Intended to promote healing process Anchors 10 Active fixation anchors around device perimeter designed to engage LAA tissue for stability and retention Sizes: 21, 24, 27, 30, 33 mm (Diameter) 21

Watchman device 22

Watchman System Components Access Sheath Delivery System Double Curve Single Curve Deployment Knob Hemostasis Valve Core Wire Preassembled 12Fr (4 mm) Delivery System Compatible with all device sizes >> Designed for Safety and Ease of Use << Double or Single Curve styles 14F O.D. (4.7 mm), 12F I.D. (4 mm) 75 cm working length Preloaded Device Saves time Distal Marker Band Guides placement 23

Implantatie procedure LAA dimensie bepaling TEE Bevestig afwezigheid trombus Metingen TEE 0, 45, 90, 135 graden Lengte LAA 24

Implantatie procedure Sheat in LAA Pigtail voor manipulatie Selectieve angiogram Zo distaal mogelijk Marker bands 25

Implantatie procedure Sheat plaatsing Access Sheath Marker Band 21mm 24mm 27mm 30mm 33mm Loaded Device Length 20.2mm 22.9mm 26.5mm 29.4mm 31.5mm Radiopaque marker bands bepalen diepte sheet in LAA Allignment marker band met ostium afhankelijk device lengte 26

Implantatie procedure Device positioneren Unsheat device rustig NIET naar voren verplaatsen 27

Implantatie procedure Optimale positie 28

Implantatie procedure Release criteria (PASS) All criteria must be met prior to device release Position device is distal to or at the ostium of the LAA Anchor (stability) fixation barbs engaged / device is stable Size device is compressed at least 8-20% of original size Seal - device spans ostium, all lobes of LAA are covered If necessary, device can be recaptured (partial or full) 29

Implantatie procedure Lekkage Jet moet < 5mm Tracht repositonering, partiele recapture of volledige recapture 30

Positie Watchman 31

Implantatie procedure Samenvatting 32

Klinisch bewijs voor de Watchman 2008 CAP Registry Endpoints: Collect additional safety and efficacy data to be pooled with PROTECT AF Incl/Excl: same as PROTECT AF 2002 Pilot Endpoints: Feasibility and Safety Comparison: Nonrandomzed Incl/Excl: CHADS2 1, able to tolerate warfarin 2010 PREVAIL Endpoint: Safety and Efficacy Comparison: warfarin Incl/Excl: CHADS2 2, some exceptions for CHADS2=1 no clopidegrel 7 days prior to procedure 2005 PROTECT AF Endpoints: Safety and Efficacy Comparison: warfarin Incl/Excl: CHADS2 1, able to tolerate warfarin 2012 ESC Guidelines & Expanded Indication 2009 ASAP Endpoint: Efficacy Comparison: CHADS2 score expected stroke rate Incl/Excl: intolerant or contra-indicated for warfarin 2013 EWOLUTION* 1000 patient Real Life Registry in Europe Endpoint: Additional information in a real-world setting Incl/Excl: All comers * In planning phase 33

Studies > 2000 ptn in meerdere gerandomiseerde trials > 4000 patient jaren follow- up Study Patients Sites Comments Pilot 66 8 PROTECT AF 707 59 CAP (Continued Access Registry) 402 patient years of follow-up 6 years of follow-up 1500 patient years of follow-up 2.3 years average follow-up per patient 460 26 Significantly improved safety results ASAP 150 4 Treat patients contra-indicated for warfarin EVOLVE 69 3 Evaluate design changes of a non-commercialized WATCHMAN device PREVAIL 453 41 CAP2 579 48 Same endpoints as PROTECT AFRevised inclusion/exclusion criteria Results presented in March 2013 Prospective, multicenter, single-arm registry (PROTECT AF or PREVAIL) Total Patients: 2484 34

PROTECT AF Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. SH-242301-AA MAY 2014 2014 Boston Scientific Corporation or its affiliates. All rights reserved. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information contained herein for distribution outside the USA, France and Japan only. and only in countries with applicable health authority product registrations. SH-231502-AA MAR 2014 2014 Boston Scientific Corporation or its affiliates. All rights reserved. 35

WATCHMAN PROTECT AF Study Objective Study Design Effectiveness and safety of LAA closure for prevention of stroke in comparison to Coumadin for non-valvular A-fib patients Prospective, randomized (2:1), non-inferiority trial of LAA closure vs. warfarin in A-fib patients for prevention of stroke Primary Endpoint Efficacy: Composite end point of stroke, cardiovascular death or systemic embolization Safety: Major bleeding, device embolization or pericardial effusion Patient Population n = 707 Mean CHADS2=2.2 Mean Follow-Up Number of Sites 1065 Patient-years, 18 months (Holmes, et al., Lancet 2009; 374: 534 42) 1588 Patient-years, 2.3±1.1 years (Reddy, et al., Circ 2013) 2,621 patient-years, 4 years (Reddy, et al., HRS LBCT 2013) 59 in the United States and Europe Holmes, et al., Lancet 2009; 374: 534 42 Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. SH-242301-AA MAY 2014 2014 Boston Scientific Corporation or its affiliates. All rights reserved. 36

WATCHMAN PROTECT AF 4 Yrs. WATCHMAN Observed Rate per 100 pt-yrs Warfarin Observed Rate per 100 pt-yrs % Reduction (vs Warfarin) Primary Endpoint 2.3 3.8 40% SUPERIOR CV Death 1.0 2.4 60% SUPERIOR All-cause Death 3.2 4.8 34% SUPERIOR Events in PROTECT AF trial at 2,621 patient years Rate per 100 patient years 10 7,5 5 2,5 0 40% lower 32% lower 60% lower P S = 0.96 2,3 Ps = Posterior Probability for Superiority 3,8 P S > 82.5% 1,5 Primary Efficacy All Stroke CV or Unexplained Death 2,2 P=0.0045 1 2,4 34% lower P=0,0379 4,8 3,2 All-Cause Death WATCHMAN Group N=463 Warfarin Group N=244 Reddy, et al., HRS LBCT 2013 Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. SH-242301-AA MAY 2014 2014 Boston Scientific Corporation or its affiliates. All rights reserved.

WATCHMAN PROTECT AF & Continued Access Protocol (CAP) Average Time (Minutes) Procedure Time 70 67 63 58 55 48 40 PROTECT AF EarlyPROTECT AF Late 50 CAP Success % 100 95 90 85 80 88 Implant Success 91 PROTECT AF EarlyPROTECT AF Late 95 CAP Discon3nua3o n % 100 85 70 45 Day Discontinuation Rate Among Implanted 83 91 PROTECT AF Early PROTECT AF Late 95 CAP With increased operator experience The average procedure time reduced from 67 minutes to 50 minutes Implant success improved from 88% to 95% Discontinuation of Warfarin improved from 83% to 95% of patients Reddy VY et al. Circulation. 2011;123:417-424 Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. SH-242301-AA MAY 2014 2014 Boston Scientific Corporation or its affiliates. All rights reserved. 38

WATCHMAN PROTECT AF & Continued Access Protocol (CAP) Incidence % Incidence % 15 11,3 7,5 3,8 0 5 3,8 2,5 1,3 0 Procedure/Device Related Safety Adverse Event Within 7 Days 10 5,5 PROTECT AF EarlyPROTECT AF Late 3,7 CAP Procedure Related Stroke 1,1 0,7 PROTECT AF Early PROTECT AF Late 0 CAP Incidence % 10 5 0 Serious Pericardial Effusion Within 7 Days 6,3 3,7 PROTECT AF EarlyPROTECT AF Late With increased operator experience Procedure related adverse events and serious pericardial effusions were reduced significantly Peri-procedural strokes were eliminated 2,2 CAP Reddy VY et al. Circulation. 2011;123:417-424 Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. SH-242301-AA MAY 2014 2014 Boston Scientific Corporation or its affiliates. All rights reserved. 39

Implant Success p = 0.01 90.9% 94.3% 95.1% Implant success defined as deployment and release of the device into the left atrial appendage Warfarin Cessation Study 45-day 12-month PROTECT AF 86.6% 93.2% PREVAIL 92.2% 99.3% PREVAIL Implant Success No difference between new and experienced operators Experienced Operators: n=26 96.2% New Operators: n=24 93.2% Holmes DR et al. Randomized Trial of LAA Occlusion. JACC. Vol. 64: 1-12, 2014 PROTECT-AF and CAP data: Reddy, VY et al. Circulation. 2011;123:417-424. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. SH-242301-AA MAY 2014 2014 Boston Scientific Corporation or its affiliates. All rights reserved. 40

WATCHMAN Preliminary Results ASA Plavix Feasibility Study Study Objective Study Design To evaluate the safety and feasibility of the WATCHMAN Left Atrial Appendage Closure device for the treatment of non-valvular atrial fibrillation in patients with a contraindication to warfarin Multicenter, nonrandomized, feasibility study Primary Endpoint Patient Population Mean Follow-Up Number of Sites The primary efficacy endpoint was defined as the combined events of ischemic stroke, hemorrhagic stroke, systemic embolism, and cardiovascular/unexplained death. n = 150 Mean age 72.5 ± 4 yrs. Mean CHADS2=2.8 Mean CHA2DS2-VASc=4.4 14.4 months 4 centers (Prague, Leipzig, Regensburg, and Frankfurt) Reddy, et al. JACC. 2013 Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. SH-242301-AA MAY 2014 2014 Boston Scientific Corporation or its affiliates. All rights reserved.

WATCHMAN Preliminary Results ASA Plavix Feasibility Study 5.0% 64% WATCHMAN Implantation for contra-indicated AF warfarin patients is: Feasible Low, but manageable, rate of device thrombus Decreases the rate of stroke by 77% Reddy, et al. JACC. 2013 Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. SH-242301-AA MAY 2014 2014 Boston Scientific Corporation or its affiliates. All rights reserved.

Therapie aanbevelingen ESC 2012 Effectiviteit ascal voor stroke preventie beperkt Gebruik CHA2DS2VASc score Schat bloedingsrisico in Overweeg hartoor afsluiting Contra- indicatie (N)OAC Verhoogd bloedingsrisico bv HASBLED > 3 Stroke onder (N)OAC Patient voorkeur Noodzaak langdurige triple therapie Nierfalen (ernstig) 43

Samenvattende Thrombo- embolie bij atriumfibrilleren grote veroorzaker morbiditeit en mortaliteit (N)OAC zijn effectief echter veroorzaken ook bloedingen Hartoor afsluiting middels Watchman is een alternatieve optie naast (N)OAC om het stroke risico te verminderen zonder bloedingen te veroorzaken Watchman heeft zich bewezen in meerdere gerandomiseerde studies voor reductie embolie vanuit linker hartoor 44

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