1. Left Atrial Appendage Closure for Stroke Prevention in Atrial Fibrillation
Ramon Quesada, MD, FACP,FACC, FSCAI,
Medical Director, Interventional Cardiology
Baptist Cardiac & Vascular Institute
Miami, Florida

2. Ramon Quesada, MD DISCLOSURES
I have no real or apparent conflicts of interest to report.

3. Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship Company
Grant/Research Support None
Consulting Fees/Honoraria Abbott, Cordis, St. Jude, W.L. Gore, NMT Medical, Terumo & Boston Scientific Corporation
Major Stock Shareholder/Equity None
Royalty Income None
Ownership/Founder None
Intellectual Property Rights None
Other Financial Benefit None

4. A major source of cardiogenic embolism-related stroke
Atrial Fibrillation
A major source of cardiogenic embolism-related stroke
500,000 strokes per year
AHA estimates that 15 – 20% of strokes/year are related to AF
90% of thrombus originate in LAA
Source: Neurology, 1978; Stroke, 1985; European Heart Journal, 1987; Lancet, 1987

5. Challenges in Treating AF
However warfarin is not always well-tolerated
Narrow therapeutic range (INR between 2.0 – 3.0)
Effectiveness is impacted by interactions with some foods and medications
Requires frequent monitoring and dose adjustments
Published reports indicate that less than 50% of patients eligible are being treated with warfarin due to tolerance or non-compliance issues
SPORTIF trials suggest only 60% of patients treated are within a therapeutic INR range, while 29% have INR levels below 2.0 and 15% have levels above 3.0

6. CHADS Score Is Anticoagulation Warranted?
Medical Condition
# points
Prior Stroke 2
Congestive Heart Failure 1
High Blood Pressure
Diabetes
Age 75 or Older
Washington University St. Louis

7. CHADS Score Estimate of Yearly Stroke Risk
Yearly Risk of Stroke
1.9% 1
2.8% 2
4.0% 3
5.9% 4
8.5% 5
12.5% 6
18.2%
Washington University St. Louis

8. Surgical Closure of Left Atrial Appendage as a Source of Emboli
An Alternative to Medical Therapy:
Surgical Closure of Left Atrial Appendage as a Source of Emboli

10. Mechanical Closure of Left Atrial Appendage as a Source of Emboli
An Alternative to Medical Therapy:
Mechanical Closure of Left Atrial Appendage as a Source of Emboli

11. 2D TEE for measures/thrombus assessment of LAA

12. 3D TEE for LAA assessment

13. PLAATO Implant

14. WATCHMAN® LAA Device Fully Deployed 8-20% Compressed 160 µ PET Fabric
Nitinol Frame
Barbs

15. WATCHMAN® LAA System Access Catheters
14F Double Curve
14F Single Curve

16. WATCHMAN® LAA System Delivery Catheter
WATCHMAN® 12F Device

17. Release Criteria Details
All criteria must be met prior to device release
Stability - fixation barbs engaged / device is stable
Position – device is distal to or at the ostium of the LAA
Size – device is compressed 10-20% of original size
Seal - device spans ostium, all lobes of LAA are covered
If necessary, device can be recaptured (partially or full)
If full recapture – new device must be used
Implant face distal to ostium
Radial force at shoulders
Fixation barbs engage LAA wall

18. WATCHMAN® LAA Delivery Catheter Device Deployment
Pre-deployment angio to define the LAA (20% of patients have multiple lobes).
1.5 laa mora

19. WATCHMAN® LAA Delivery Catheter Device Deployment
Pre-deployment positioning to ensure adequate coverage of the LAA “neck”
2/5 laa mora

20. WATCHMAN® LAA Delivery Catheter Device Deployment
Pre-deployment testing of fixation of the device to the walls of the LAA to prevent migration of the device.
3/5 laa mora

21. WATCHMAN® LAA Delivery Catheter Device Deployment
Release of the device once all “pre-testing” of placement and fixation is complete.
4/5 laa mora

22. WATCHMAN® LAA Delivery Catheter Device Deployment
Post deployment angio
5/5 laa mora

23. WATCHMAN® LAA Device: Final Placement

24. Human pathology: 9 months post-implant (non-device related)
WATCHMAN® LAA Device
Healing Response
Canine model – 30 day
Human pathology: 9 months post-implant (non-device related)
Canine model – 45 day

26. WATCHMAN® LAA Device: 45 Day Follow-up

27. Sick, J Am Coll Cardiol 2007;49: 1490–5
66 pts. underwent device implantation. Mean follow-up was 740 ±341 days.
ACC 2009: Duration of f/u now out to 5 years (mean >1300 days)
At 45 days, 93% (54 of 58) devices showed successful sealing of LAA
No strokes occurred during follow-up despite 90% of patients with discontinuation of anticoagulation. The expected annual risk of stroke based on the CHADS2 score in this study cohort was calculated to be 1.9/year.
In long term follow up 63/66 (95%) patients were off warfarin. Two patients experienced a TIA and one patient had an embolic stroke with severe carotid disease at 39 months. This reflects an actual stroke rate of 1 in 251 patient years (0.4%), whereas the expected stroke rate according to the CHADS2 Score would have been 5.75%. Although the number of patients does not provide sufficient power to demonstrate equivalence or superiority to anticoagulation, the results appear generally comparable to those reported for the PLAATO System (ev3 Inc.,Plymouth, Minnesota), which has also been demonstrated in 205 of 210 implanted patients to have a lower event rate of stroke (5 strokes at a mean follow-up of 14.7 months) compared with the expected stroke rate predicted by the CHADS2 score
Sick, J Am Coll Cardiol 2007;49: 1490–5

28. What We’ve Learned From This Pilot Series
Appreciation of the variability of the anatomy of the LAA
Use of additional imaging tools
Variability and the fragility of the LAA required modifications to the device

29. LAA Comes In All Shapes And Sizes

30. LAA Comes In All Shapes And Sizes. Imaging The Left Atrium
MRA and computed tomographic (CT) imaging allow for precise 3D reconstruction of structures such as the LAA, which may prove complementary to intraprocedural transesophageal echocardiographic data in selecting and sizing occlusion devices.
Pre-procedural MRA and CT imaging of the LA and pulmonary veins now is used in conjunction with other imaging modalities to direct catheter ablation of AF in many centers.

31. CT LAA Reconstruction Compared To TEE

32. Improvements in Device Technology
Shorter length device
Modification in the delivery sheath with markers and a softer tip

33. Improvements in Device Technology
Shorter length device
Modification in the delivery sheath with markers and a softer tip

34. WATCHMAN Device, Access Sheath And Adjunctive Procedure Tools
A shorter WATCHMAN device has become the preferred implant of choice in the study as it may allow additional patients with limited LAA depth to be further considered for device implantation

35. Bilobar LAA

36. Short Device Sealing One Lobe

37. Post Deployment - Complete Sealing of LAA

38. Improvements in Device Technology
Shorter length device
Modification in the delivery sheath with markers and a softer tip

39. WATCHMAN® LAA Access Sheath
14F Double Curve
14F Single Curve

40. Delacruz 19 20
The use of the radiopaque marker bands permits more accurate positioning prior to device deployment

41. Pre-deployment 21 mm device
Dela cruz 15

42. Device deployed in “perfect” position
Dela Cruz 5

43. PROTECT AF Clinical Trial Design
Prospective, randomized study of WATCHMAN LAA Device vs. Long-term Warfarin Therapy
2:1 allocation ratio device to control
800 Patients enrolled from Feb 2005 to Jun 2008
Device Group (463)
Control Group (244)
Roll-in Group (93)
59 Enrolling Centers (U.S. & Europe)
Follow-up Requirements
TEE follow-up at 45 days, 6 months and 1 year
Clinical follow-up biannually up to 5 years
Regular INR monitoring while taking warfarin
Enrollment continues in Continued Access Registry

44. Patient Study Timeline
Day 45
postimplant
Day 0
Day 2-14
Ongoing to 5 years
Device subject takes warfarin
Device subject has ceased warfarin
Preimplant interval
Device
Device subject gets implant
Randomize
Control
Control subject takes warfarin
Day 0
Ongoing to 5 years

45. Warfarin Discontinuation
87% of implanted subjects were able to cease warfarin at 45 days and the rate further increased at later time points
Visit
Watchman
N/Total (%)
45 day
349/401 (87.0)
6 month
347/375 (92.5)
12 month
261/280 (93.2)
24 month
95/101 (94.1)
Reasons for remaining on warfarin therapy after 45-days:
Observation of flow in the LAA (n = 30)
Physician Order (n = 13)
Other (n = 9)

46. PROTECT AF Trial Endpoints
Primary Efficacy Endpoint
All stroke: ischemic or hemorrhagic
deficit with symptoms persisting more than 24 hours or
symptoms less than 24 hours confirmed by CT or MRI
Cardiovascular and unexplained death: includes sudden death, MI, CVA, cardiac arrhythmia and heart failure
Systemic embolization
Primary Safety Endpoint
Device embolization requiring retrieval
Pericardial effusion requiring intervention
Cranial bleeds and gastrointestinal bleeds
Any bleed that requires ≥ 2uPRBC
NB: Primary effectiveness endpoint contains safety events

47. Key Participation Criteria
Key Inclusion Criteria
Age 18 years or older
Documented non-valvular AF
Eligible for long-term warfarin therapy, and no other conditions that would require long-term warfarin therapy
Calculated CHADS2 score > 1
Key Exclusion Criteria
NYHA Class IV Congestive Heart Failure
ASD and/or atrial septal repair or closure device
Planned ablation procedure within 30 days of potential WATCHMAN Device implant
Symptomatic carotid disease
LVEF < 30%
TEE Criteria: Suspected or known intracardiac thrombus (dense spontaneous echo contract)

48. Patient Demographics Baseline Demographics Characteristic WATCHMAN
Control
N= 244
P-value
Age (years)
71.7 ± 8.8
463 (46.0, 95.0)
72.7 ± 9.2
244 (41.0, 95.0)
0.1800
Height (inches)
68.2 ± 4.2
462 (54.0, 82.0)
68.4 ± 4.2
244 (59.0, 78.0)
0.6067
Weight (lbs)
195.3 ± 44.4
463 (85.0, 376.0)
194.6 ± 43.1
244 (105.0, 312.0)
0.8339
Gender
Female
Male
137/463 (29.6)
326/463 (70.4)
73/244 (29.9)
171/244 (70.1)
0.9276

49. Patient Demographics Baseline Risk Factors WATCHMAN N= 463 Control
P-value
CHADS2 Score 1 2 3 4 5 6
158/463 (34.1)
157/463 (33.9)
88/463 (19.0)
37/463 (8.0)
19/463 (4.1)
4/463 (0.9)
66/244 (27.0)
88/244 (36.1)
51/244 (20.9)
24/244 (9.8)
10/244 (4.1)
5/244 (2.0)
0.3662
AF Pattern
Paroxysmal
Persistent
Permanent
Unknown
200/463 (43.2)
97/463 (21.0)
160/463 (34.6)
6/463 (1.3)
99/244 (40.6)
50/244 (20.5)
93/244 (38.1)
2/244 (0.8)
0.7623
LVEF %
57.3 ± 9.7
460 (30.0, 82.0)
56.7 ± 10.1
239 (30.0, 86.0)
0.4246

50. Potential Safety Endpoints Device
Procedural complications
Pericardial effusion
Stroke – ischemic
Bleeding during 45 days of Warfarin

51. Protect AF: Lancet: August 15, 2009

52. Safety Events Stroke Safety stroke events
Also counted as efficacy events in efficacy analyses
5 events in device group classified as “ischemic stroke”
All periprocedural: extended hospitalization by 7 days
3 were related to air embolism
1 hemorrhagic stroke in device group vs 6 in control group
Device event occurred 15 days post implant while patient was on warfarin
4/6 stroke events in control group patients resulted in death

53. Protect AF: Lancet: August 15, 2009

54. Protect AF: Lancet: August 15, 2009

55. Protect AF: Lancet: August 15, 2009

56. Primary efficacy results by patient subgroup
Protect AF: Lancet: August 15, 2009

57. Risk/Benefit Analysis
Intent-to-treat analysis
Primary endpoint (intent to treat) achieved
Other statistically significant endpoint findings
Noninferiority for the primary efficacy event rate – 32% lower in device group
Noninferiority for all strokes – 26% lower in device group
Superiority for hemorrhagic stroke – 91% lower in device group
Noninferiority for mortality rate – 39% lower rate in device group
Increased rate of primary safety events for the device group relative to the control group
Most events in the device group were procedural effusions that decreased over the course of the study
87% of patients were able to discontinue warfarin at 45 days

58. Conclusion
The WATCHMAN LAA Technology offers a safe and effective alternative to warfarin in patients with non-valvular atrial fibrillation at risk for stroke and who are eligible for warfarin therapy

59. International Symposium on Endovascular Therapy
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January, 2011
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