Structural Heart Disease:" Innovations in Intervention!

Transcription

1 Structural Heart Disease:" Innovations in Intervention! Jon C. George, MD, FACC, FSCAI! Director, Clinical Research! Assistant Director, Cardiac Catheterization Lab! Deborah Heart and Lung Center! Aortic Stenosis Gross specimen of minimally diseased aortic valve (left) and severely stenotic aortic valve (right)! Images courtesy of Renu Virmani MD at the CVPath Institute! 3! 1!

2 Prevalence of Aortic Stenosis!!! Aortic stenosis is estimated to be prevalent in up to 7% of the population over the age of 65 1! 16.5 Million People in US Over the Age of 65 2! Percentage Diagnosed with Aortic Stenosis! 7%! It is more likely to affect men than women; 80% of adults with symptomatic aortic stenosis are male 3! 4! What Causes Aortic Stenosis in Adults?! More Common! Age-Related Calcific Aortic Stenosis! Infection! Aortic stenosis in patients over the age of 65 is usually caused by calcific (calcium) deposits associated with aging! Aortic stenosis can be caused by various infections! Less Common! Rheumatic Fever! Congenital Abnormality! Adults who have had rheumatic fever may also be at risk for aortic stenosis! In some cases adults may develop aortic stenosis resulting from a congenital abnormality! 5! Major Risk Factors! Independent clinical factors associated with degenerative aortic valve disease include the following: 4!! Increasing age! Male gender! Hypertension! Smoking!! Elevated lipoprotein A!! Elevated LDL cholesterol! 6! 2!

3 Multiple Modalities May Be Used to " Diagnose Severe Aortic Stenosis 6! Auscultation! TTE! Cardiac Cath! Chest! X-ray! ECG! 7! Echocardiographic Guidelines are the Gold Standard in Assessing Severe Aortic Stenosis 6 *! *Doppler-Echocardiographic measurements!! According to the 2008 ACC/AHA guidelines, severe aortic stenosis is defined as:!! Aortic valve area (AVA) less than 1.0 cm 2!! Mean gradient greater than 40 mmhg or jet velocity greater than 4.0 m/s! 8! Aortic Stenosis Is Life Threatening and Progresses Rapidly 7!! Survival after onset of symptoms is 50% at 2 years 1 Surgical intervention for severe aortic stenosis should be performed promptly once even minor symptoms occur 1 9! 3!

4 AVR, no Sx No AVR, no Sx AVR, Sx No AVR, Sx 9/13/14! Addressing a Serious Unmet Need! Studies show at least 40% of SAS patients are not treated with an AVR 9-15! 10! Aortic Valve Replacement Greatly Improves Survival! Patient Survival 16! AVR, No Symptoms! AVR, Symptoms! No AVR, No Symptoms! No AVR, Symptoms! Survival, % Years! Study data demonstrate that early and late outcomes were similarly good in both symptomatic and asymptomatic patients!! It is important to note that among asymptomatic patients with SAS, omission of surgical treatment was the most important risk factor for late mortality! 11! Standard Therapies are Inadequate Treatments for Severe Aortic Stenosis Patients! All-Cause Mortality, %! 100! 80! 60! 40! 20! 0! The PARTNER Trial! 68.0%! 50.7%! Months! Numbers at Risk Control Group Control Group (Med Rx and BAV)! As seen previously, survival after onset of symptoms in patients with aortic stenosis is 50% at 2 years 1 The PARTNER Trial showed that in inoperable patients with severe aortic stenosis who did not receive a valve replacement, 50% died within 1 year! Despite the frequent utilization of BAV, standard therapy did not do much to alter the dismal course of disease for inoperable patients with severe aortic stenosis! 12! 4!

5 Options for Aortic Valve Replacement! Transapical Transcatheter Aortic Valve Replacement (TAVR)! High Risk! Patients! Transfemoral Transcatheter Aortic Valve Replacement (TAVR)! Surgical Aortic Valve Replacement! (SAVR)! Inoperable Patients! Transfemoral Transcatheter Aortic Valve Replacement (TAVR)! Transapical Approach! Transfemoral Approach! Minimal Incision Valve Surgery! (MIVS)! Transfemoral Approach! 13! Edwards SAPIEN Transcatheter Heart Valve The Edwards SAPIEN transcatheter heart valve is indicated for patients with severe symptomatic calcified native aortic valve stenosis who have been examined by a Heart Team including an experienced cardiac surgeon and cardiologist and found to be either inoperable or at high risk for surgical aortic valve replacement.! 14! What is TAVR? For patients who are either at high risk or too sick for open-heart surgery, TAVR may be an alternative! This less invasive procedure allows the aortic valve to be replaced with a new valve while the heart is still beating! 15! 5!

6 Edwards SAPIEN Transcatheter Heart Valve Bovine pericardial tissue! Leaflets matched for thickness and elasticity! Stainless steel frame! PET skirt! 16! Transfemoral Procedural Animation 17! Balloon Aortic Valvuloplasty 18! 6!

7 Edwards SAPIEN Transcatheter Heart Valve Deployment 19! An Alternative Option for Patients Without Vascular Access! Some patients may not have adequate vascular access to accommodate the sheath used during transfemoral procedures! For these patients, the transapical procedure may be an option! During the transapical approach, the Edwards SAPIEN transcatheter heart valve is delivered through the apex of the heart by making a small incision between the ribs! 20! Transapical Procedural Animation! 21! 7!

8 Definitive Results Through Rigorous Design! THE PARTNER TRIAL COHORT B! 22! Definitive Results Through Rigorous Design! *Patient selection required at least two cardiothoracic surgeons and a cardiologist to agree that patients were not suitable candidates for surgery.! This mean score reflects enrolled patient group; not required for inclusion.! THE PARTNER TRIAL COHORT B! 23! Definitive Results Through Rigorous Design! THE PARTNER TRIAL COHORT B! 24! 8!

9 Edwards SAPIEN THV Improved Survival! THE PARTNER TRIAL COHORT B! 25! Edwards SAPIEN THV Improved Cardiac Function! THE PARTNER TRIAL COHORT B! Error bars = ± 1 Std Dev! 26! Time-to-Event Analyses of Key End Points during 2 Years of Follow-up. Makkar RR et al. N Engl J Med 2012;366: ! 9!

10 Two-Year Mortality, Stratified According to the Society of Thoracic Surgeons (STS) Risk Score. Makkar RR et al. N Engl J Med 2012;366: ! Edwards SAPIEN THV Reduced Symptoms! THE PARTNER TRIAL COHORT B! 29! Edwards SAPIEN THV Improved Quality of Life! THE PARTNER TRIAL COHORT B! MCID, minimum clinically important difference.! 30! 10!

11 Complications! Stroke was defined as follows: Neurological deficit lasting # 24 hours or lasting less than 24 hours with a brain imaging study showing an infarction.!! Major vascular complications were defined as any thoracic aortic dissection, access site or access-related vascular injury (dissection, stenosis, perforation, rupture, arteriovenous fistula, pseudoaneurysm, or hematoma) leading to either death, need for significant blood transfusion (> 3 units), or percutaneous or surgical intervention, and/or distal embolization (non-cerebral) from a vascular source requiring surgery or resulting in amputation or irreversible end-organ damage.!! Bleeding event is defined as # 2 units within the index procedure.! THE PARTNER TRIAL COHORT B! 31! Critical Insights! THE PARTNER TRIAL COHORT B! 32! Study Design & Inclusion Criteria THE PARTNER TRIAL COHORT A! 33! 11!

12 " All-Cause Mortality "! THE PARTNER TRIAL COHORT A! 34! NYHA Class! THE PARTNER TRIAL COHORT A! 35! All Strokes! THE PARTNER TRIAL COHORT A! 36! 12!

13 Major Vascular Complications! THE PARTNER TRIAL COHORT A! 37! Major Bleeding! THE PARTNER TRIAL COHORT A! 38! Following Patient Referral, the TAVR Team will Perform Further Evaluation 1! 2! 3! 4! 5! 6! Confirm the patient is diagnosed with severe symptomatic native aortic stenosis! Confirm the patient has been evaluated by two cardiac surgeons and meets the indication for TAVR! Evaluate the " aortic valvular complex using echocardiography! Evaluate the aortic valvular complex and peripheral vasculature using CT! Evaluate the aortic valvular complex and peripheral vasculature using catheterization! Determine access route for transcatheter aortic valve replacement! Note: The above is a suggested flow for the patient screening process, however, the order in which screening tests are conducted varies depending on the patient s profile and should be at the discretion of the Heart Team.! 39! 13!

14 Devising a Treatment Plan A Collaborative Process Multiple treatment pathways are now available to treat severe aortic stenosis TAVR For inoperable and high risk patients Surgical or MIS AVR For patients who are suitable for open-chest aortic valve replacement Medical Management and BAV For patients not suitable for invasive procedures Treatment decision discussed with referring physician! Multidisciplinary review & treatment decision by TAVR Heart Team! Patient with severe aortic stenosis identified by referring physician! Ultimate treatment choice is a collaborative decision between the physicians, patient, and patient s family Patient referred to TAVR valve clinic! Additional testing completed! 40! Mitral Regurgitation (MR) o Occurs when the mitral valve fails to close tightly, allowing blood to flow backwards into the heart.! o Severity scale of 1+ (mild) to 4+ (severe)!! o Two kinds:! o Degenerative MR (DMR) - includes stretching or rupture of the chordae tendineae.! o Funtional MR (FMR) - normal valve anatomy; impaired ventricular wall function and dilation.! 14!

15 MitraClip System Chip Delivery System (CDS): Consists of 3 main parts:! o Delivery Catheter! o Steerable Sleeve! o MitraClip Device! * The Delivery Catheter and Steerable Sleeve plant the device! Steerable Guide Catheter (SDC): o Contains a handle made up of knobs and levers, which control the system, and is attached to a dilator.! o Positions the CDS into the appropriate location.! 15!

16 A cardiac disease that kills by producing emboli! AF MECHANISM FOR STROKE Irregular Heartbeat Pumping of Blood Disrupted Location of Thrombus in Patients with AF!!"##$%& '(#)*+,-$($%( '($%(.// 1($%(.// *"2"*"%3"./0.//!"" #$ ## %%& '()**+,*-./011.2%%3!"" %$& ,:;<+=)7.2%%5 5$ 43 $5& 0AB,9-.0:(+C.6B*C.':+7C.2%#%!"" 5 D 3E&!?+8-./F60.2%%E!"" 24 2D %D& G<B87-.H7(./.1+,*.HI %%4!"".J.K>B,+=)7 22 L $4& ,:;<+=)7 'M0F.HHH.J.!"" DE 2% %3& G<B87-.18,:;<+=)7.2%%5 Blood Stagnates in LAA Incubator for Thrombus!"" 2% 2% 2EE& NB;79-./011.2%%5!"" # # 2EE& O+,(-.'(,)PB.2%%5 #+#/ Clot dislodges from LAA Next Stop: BRAIN?? 16!

17 Who requires anticoagulation? Annals of Internal Medicine, 2003:139; !

18 How do we determine stroke risk? CHADS2 (Gage, et al.: JAMA 2001) Congestive heart failure - 1pt Hypertension - 1pt Age > 75-1 pt Diabetes - 1pt Stroke or TIA - 2 pts 0 points low risk ( strokes per 100 patient years) 1-2 points moderate risk ( strokes per 100 patient years) > 3 points high risk ( strokes per 100 patient years) Lip Y, et al. Chest 2010, 137(2):263 Lip Y, et al. Chest 2010, 137(2):263 18!

19 CHADS 2 vs. CHA 2 DS 2 VASc CHADS 2 score 0: 1.4% events CHA 2 DS 2 -VASc 0: 0 events CHA 2 DS 2 -VASc score 1: 0.6% events CHA 2 DS 2 -VASc score 2: 1.6% events Our approach: anticoagulation when Isch stroke risk > 0.9%/year 1,2! Treatments for Chronic A-Fib! 3! DRUGS! IMPLANT! SURGERY! A! B! C! A! B! C! A! B! C! A. Aspirin! B. Warfarin (Coumadin)! C. Xa Inhibitors (Dabigatran, Apixaban)! A. BSX (Atritech) Watchman! B. SJM (AGA) Amplatz Cardiac Plug! C. Coherex Wavecrest! A. Suture (Ethicon, Teleflex)! B. Clips (Atricure, LAAx)! C. Staplers (Ethicon, Covidien)! Not a permanent solution! Age is #1 contraindication! Bleeding complications >5%! 4! History of compliance <55%! Not suited! Serious risks of bleeding with implants! Requires invasive surgery, often with Anticoagulants required applicable?! CPB! Requires post procedure management! Technique affects clinical outcomes! Niche for patients eligible to anticoagulation! Anatomically challenging to achieve! Not available until safety studies completed! Not a stand-alone option! target market of patients! 1 Fuster V,, et al. ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation. Circulation 2006; 114:e257-e354.! 2. Miyasaka Y, et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota 1980 to 2000, and implications Circulation 2006; 114: ! 3. No implants are presently approved for sale in the USA! 4. Annals of Int Medi, Warfarin Use in AF Patients 1999; 131 (12): ! 19!

20 Non-Valvular Atrial Fibrillation Warfarin " Use in AF Patients by Age! %! < !. Only 55% of AF patients with no contraindications have evidence of warfarin use in previous 3 months! Other studies cite warfarin use in AF patients from 17-50%! Elderly patients with increased absolute risk least likely to be taking warfarin! Contraindications 30-40%! Ann Int Med 131(12), 1999! 4EEEL4LQ24. Atrial fibrillation 2009 Target INR 2-3 Non-Valvular Atrial Fibrillation " Adequacy of Anticoagulation in Clinic! Low INR <1.6! Therapeutic" INR 2-3! Efficacy " 4-fold! High INR >3.2! Bungard: Pharmacotherapy 20:1060, 2001! %! 4EEEL4LQ25. 20!

21 Atrial fibrillation a. Triggers: p. veins b. Sustainer: left atrium enlarged fibrosed Pulmonary Vein Isolation RIPV RSPV LSPV LAA LIPV MV The WATCHMAN product is a device for percutaneous closure of the left atrial appendage! WATCHMAN is a self-expanding nitinol frame with fixation anchors and a permeable fabric cover It is designed to be permanently implanted at or slightly distal to the opening of the LAA to trap potential emboli before they exit the LAA WATCHMAN LAA Closure Device Images on file at Boston Scientific Corporation Five sizes of device (21, 24, 27, 30 and 33 mm) allow for precise fit within ostium It is implanted via a transseptal approach by use of a catheter-based delivery system The delivery catheter is capable of recapturing the device if necessary Received CE mark in !

22 LAA: Watchman! PROTECT AF" Primary Efficacy Results! Device Control Posterior Probabilities! Observed rate " (events per 100 pt-yrs)! (95% CrI) Observed rate " (events per 100 pt-yrs)! (95% CrI) Rate Ratio " Intervention/Control! (95% CrI) Non-inferiority! Superiority! Primary " Efficacy 3.0! (2.1, 4.3) 4.3! (2.6, 5.9) 0.71! (0.44, 1.30) >0.99! 0.88! Event Free Probability Control Device Control Device Time (Days) Reddy, VY et al. Circulation. 2013;127: ;.! PREVAIL " Control (Warfarin) Group Performance! In spite of the high average CHADS 2 score of 2.6 in the control group, the observed rate of stroke in the PREVAIL Control group was lower than in other published warfarin studies! PREVAIL control group rate = 0.7 (95% CI 0.1, 5.1)! Control (Warfarin) Group! Trial Stroke, Systemic Embolism Rate! (Per 100 PY)! PROTECT AF1! 1.6! RE-LY (Dabigatran) 2! 1.7! ARISTOTLE (Apixaban) 3! 1.6! ROCKET AF (Rivaroxaban) 4! 2.2! PREVAIL! 0.7! Results are preliminary; final validation not yet complete 1 Ischemic stroke rate from Holmes et al. Lancet 2009; 374: Connolly et al. N Engl J Med 2009; 361: Granger et al. N Engl J Med 2011; 365: Patel et al. N Engl J Med 2011; 365: !

23 JOHN L. MADDEN, M.D. Department of Surgery, Long Island College of Medicine, Kings County Hospital, Brooklyn, NY AND! Laurence H. Coffin, M.D., F.A.C.S., Burlington, VT VJ DiSesa, S Tam, LH Cohn Division of Cardiac Surgery, Brigham & Women s Hospital, Boston, MA JL Blackshear, MD, JA Odell, FGRCS(Ed) Division of Cardiovascular Diseases, Mayo Clinic Jacksonville FL & Mayo Clinic, Rochester, MN 9/13/14! LAA: Amplatzer Cardiac Plug! Different from Amplatzer Septal Occluder! Registry; 141 pts; 24 hour FU! Indication: Permanent/paroxysmal AF! Early experience: Stroke 2.1%, device embolization 1.4%, tamponade 3.5%! Clinical trial pending! CE 12/2008! Minimally invasive surgical ablation! Atricure! Estech! History of Suture Closure! 1947! 1949! 1955! 1985! USE OF THE SURGICAL Resection of the Left SYSTEMIC EMBOLISM STAPLER TO Auricular Appendix AND LEFT AURICULAR OBLITERATE A Prophylaxis for Recurrent THROMBOSIS IN THE LEFT ATRIAL Arterial Emboli RELATION TO MITRAL APPENDAGE VALVOTOMY BY! J. R. BELCHER, M.S., F.R.C.S. Surgeon, London Chest Hospital; Assistant Thoracic Surgeon, the Middlesex Hospital! Appendage Obliteration to Reduce Stroke in Cardiac Surgical Patients with Atrial Fibrillation 2000! 2011! Ligation of the Left Atrial Appendage Using an Automatic Stapler Amputation of the Canine Atrial Appendages! Hellerstein, HK! 23!

24 Variable Surgical Outcomes! Multiple techniques. Suture vs clips/ bands vs staples?! What is being closed? Appendage vs Atrium. Closure location?! Operator variability. Suture tensioning?! Anatomical variability! Benefit of LAA Closure AF, Hx TE, No OAC! AF, No TE, No OAC! AF, Hx TE, OAC! AF, No TE, OAC! AF, No Risk, No TE, No OAC! Post maze, No OAC, No LAA! Cox J., et al. J Thorac Cardiovasc Surg 1999;118: Cox Maze III Cut and sew Maze! 24!

25 Long Term Efficacy of Cox III Maze Prasad SM. J Thorac Cardiovasc Surg. 2003;126: Percutaneous LAA Exclusion (LARIAT Suture Delivery Device! FDA cleared! Percutaneous, not open! Cath lab, not OR! General Anesthesia! TEE/Fluoro Guidance! Two access points! Femoral approach to enter the LAA! Epicardial approach to tie off the LAA! ç $ Epicardial Access! Femoral! Access! ç $ Innovation of Tradition! LAA Before! Cath-Lab Intuitive! Immediate, complete, permanent closure with nothing left inside! LAA! After! CATH-LAB CLOSURE WITHOUT COMPROMISE! 25!

26 TM! PLACE Procedure! PERMANENT LIGATION APPROXIMATION CLOSURE & EXCLUSION! ACCESS! DELIVER! CAPTURE/CLOSE! REMOVE! Standard techniques and technology for pericardial and transseptal access are utilized for placement. The.025 FindrWIRE & EndoCATH are positioned.! The SofTIP is oriented to the target and the.035 FindrWIRE is delivered to connect to the. 025 FindrWIRE at the target. The LARIAT is then advanced.! With the snare opened, the LARIAT is advanced over the target and closed. After confirmation, the suture is released & tightened.! All catheters are removed, reverse heparin and all that remains with the patient is a small remnant of suture. Band- Aid closure! Target Patient Population! Patient should be on anticoagulation!! o AF and CHADs2 of at least 2, some guidelines are CHADs2 of 1! Contraindicated Patients:! o GI bleeds! o Hemorragic stroke! o Elderly that are at high risk of falling with documented complication from anticoagulation! Anticoagulation failures: LAA thrombus or embolic event while on anticoagulation! Intolerant patients:! " Does not tolerate anticoagulation therapy due to side effects (i.e., dyspepsia from dabigatrin)! " Labile INR! " Complication of trauma resulting from being on anticoagulation.! " Multiple admissions for bleeding! Access! Delivery! Capture! Close! Remove! PRE-PROCEDURE Confirm position of target for best access approach Confirm origin, shape, size & trajectory of target is compatible with LARIAT Identify exclusions such as thrombus, adhesions or other anatomic factors 26!

27 AP View! Access! Delivery! Capture! Close! Remove! ACCESS AP View! Lateral View! Courtesy of Miguel Valderrábano, MD! Lateral View! Courtesy of Miguel Valderrábano, MD! Identify approach to deliver LARIAT to apical aspect of exclusion target Confirm absence of anatomical factors for delivery, e.g. adhesions Access! Delivery! Capture! Close! Remove! Dilate access site to >4.3mm Advance SofTIP guide cannula Replace guide wire with.035 FindrWIRE ACCESS! DELIVERY! CAPTURE! CLOSE! REMOVE! Routine Access Technique" Transseptal Puncture! 8.5F transseptal access! Standard catheterization! Nothing new required! 27!

28 Access! Delivery! Capture! Close! Remove! IDENTIFY Echo Probe Appendage Heart Guide wire in sac 8.5f transseptal catheter Diaphragm Access! Delivery! Capture! Close! Remove! EndoCATH prepped & advanced over.025 FindrWIRE EndoCATH FindrWIRE Transseptal SofTIP Angiogram performed to visualize placement ACCESS! DELIVERY! CAPTURE! CLOSE! REMOVE! 28!

29 TM! PLACE Procedure! PERMANENT LIGATION APPROXIMATION CLOSURE & EXCLUSION! Pericardial & transseptal access achieved. SofTIP positioned! EndoCATH & endo FindrWIRE placed into LAA! Confirmation of closure site location on echo & fluoro! Epi FindrWIRE connects to endo FindrWIRE! LARIAT advanced, placed and closed! EndoCATH removed. Suture released & tightened! Remnant suture cut with SureCUT! Contraindications for the PLACE procedure! R!,;B.1)7(,+87*8:+=)7?.?BB7.)7.1!. R MB:(;?."S:+T+(;I. R N00.U,+>>879.ABV87*.(VB.M;<I)7+,@.0,(B,@. R N00?.U8(V.+7.+>>,)+:V.U8*(V.9,B+(B,.(V+7.5EII. R 1Q'V+>B*.),.?;>B,8),<@.),8B7(B*.+>>B7*+9B?.+(.5EII.),.U8(V. :)7:B,7.)W.,BI)T+<.)W.(VB.N0XH0!.*BT8:B. R M,BT8);?.1+,*8+:.';,9B,@.Y.G7)U7.0*VB?8)7?. Access! Delivery! Capture! Close! Remove! Pre-LARIAT exclusion 30 day TEE Acute LARIAT exclusion Traditional Procedure New Approach! Offers Immediate & Complete Exclusion! Nothing Left Inside that can Break, Move, Infect 29!

30 Closure Without Compromise! LAA Pre-procedure! 30 day Post-procedure! Pre-Clinical Results! Objective! Evaluate safety & effectiveness in canine model of percutaneous LAA closure with the LARIAT! N=26 canines! Attempts to Capture! 1 attempt: 23/26 ( 88%)! 2 attempt: 3/26 ( 12%)! Complete Acute Closure: 26/26 (100%)! 7d Closure: 3/3 (100%)! 30d Closure: 3/3 (100%)! 90d Closure: 4/4 (100%)! Histological Examination (all)! Inflammatory response: 0/10 ( 0%)! Complete Endothelioization: 10/10 (100%)! Circ Cardiovasc Interv: June 2010! Clinical Results PLACE I! Total Patients! N=13! AF History! Persistent 12 (92%)! Flutter 1 ( 8%)! Age! Avg: 57.3; Hi 64, Low 43! Sex! M = 8 (62%)! Type Procedure! LAA w/ MVR 2 (15%)! LAA w/ ablation 10 (77%)! Ablation w/ LAA 1 ( 8%)! Type Access! Median Sternotomy 2 (15%)! Minimally Invasive 2 (15%)! Percutaneous 9 (70%)! Intent to Treat! 12/13 (92%)! Acute Closure! 12/12 (100%)! Heart Rhythm: 2011:8: ! Complications! 1/13 (8%) non-serious (anatomic)! Procedural Times! Avg: 85.7 min; Median min! 30!

31 Clinical Results PLACE II! Objective! # Patients! 109! Peri-Procedural Safety (24h)! Efficacy (Closure) at 90days! 85 (96%)! Able to PLACE! 89! Attempted! 4 (4%)! Unable to PLACE! Age! Median: ! Avg: 62 Hi: 81 Lo: 35! Sex! M: 67 (61%)! CHADS 2! Median: Avg: 1.9! CHA 2 DS 2 -VASc! Median: Avg: 2.9! (95%)! Complete Closure! >12 mos! 4 (3.6%)! Complications! Pericardial Effusion 3 (2.6%)! Device Related 1 (1.0%)! Adhesions at LAA 1! Unable to complete transseptal 1! Effusion at start of case 2! PLACE II study (Dec 2009 Mar 2011) EC# KBET/90/B/2008! Under editorial review for publication 4Q11 1Q12! LAA Closure Efficacy! LARIAT! PLACE II Study! WATCHMAN! AMPLATZER! PROTECT AF Trial I! European Registry II! # Patients! 89! 463! 143! Intent-to-Treat! 85 (96%)! 408 (88%)! 132 (92%)! Closure Definition! <1mm! <5mm! <5mm! >90d Closure! 100 (95%)! 346 (85%)! No Data! 5 pts with PLACE closure >1mm! All 5 pts with <3mm residual leak! 100% Closure Success by implant criteria! I PROTECT AF Trial defined complete closure as <3mm+2mm residual.! II Retrospective Registry data - No closure data included! Safety! Device Related! Other! Complications! All! 0 (0%)! LARIAT I! N=89! I Place II!! Effusion: Non- Serious 3 (3.0%)!! Pericardial 2 (2.0%)! Transseptal 1 (1.0%)! 3 (3.3%)! Device Replacement 171 (42.0%)! Cardiac Tamponade 24 (5.8%)! Device Thrombus 15 (3.9%)! Effusion- Non Serious 9 (2.2%)! Stroke - Ischemic 6 (1.4%)! Bleeding w/ Transfusion 4 (1.0%)! Device Embolization 3 (0.7%)! Watchman II! n=408!! II Protect AF! FDA Executive Summary! Serious 16 (3.9%)! Non-Serious 16 (3.9%)! 109 (26.2%)! Device Surgical Explant 2 (0.4%)! Trans Ischemic Attack 1 (0.2%)! Tamponade 4 (3.4%)! Device Embolization 4 (3.4%)! Pericardial Effusion 3 (2.6%)! Ischemic Stroke 2 (1.7%)! PA Puncture 1 (0.9%)! Amplatzer III Cardiac Plug! n=125!! III Registry! 14 (12%)! 31!

32 Goals of AF Therapy: Restore Maintain Protect Drugs Devices 32!