1. Percutaneous Device Occlusions for Left Atrial Appendage (LAA)
Julie Logan, RN
Foundation for Cardiovascular Medicine
La Jolla, CA
Julie Logan, RN
Foundation for Cardiovascular Medicine

2. Julie Logan, RN DISCLOSURES
I have no real or apparent conflicts of interest to report.

3. Conflict of Interest Speaker’s name: Julie Logan, RN
 I have the following potential conflicts of interest to report:
 Consulting
 Employment in industry
 Stockholder of a healthcare company
 Owner of a healthcare company
 I do not have any potential conflict of interest
Julie Logan, RN
Foundation for Cardiovascular Medicine

4. Facts about Atrial Fibrillation (AF)
AF is the most common cardiac arrhythmia
Affects more than 3 million individuals in the US
Projected to increase to 16 million by 2050
Patients with AF have a 5-fold higher risk of stroke
Over 87% of strokes are thromboembolic
Greater than 90% of thrombus accumulation originates in the Left Atrial Appendage (LAA)
Stroke is the number one cause of long-term disability and the third leading cause of death in patients with AF
Julie Logan, RN
Foundation for Cardiovascular Medicine

5. Atrial fibrillation is a major source of cardiogenic embolic related stroke
500,000++strokes per year (U.S only)
AHA estimates that 20% of strokes/year are related to AF
Julie Logan, RN
Foundation for Cardiovascular Medicine
Source: Neurology, 1978; Stroke, 1985; European Heart Journal, 1987; Lancet, 1987

6. Stroke: A Life Threatening and Debilitating Disease
Functional impact of AF-related strokes
Julie Logan, RN
Foundation for Cardiovascular Medicine

7. Atrial fibrillation patients have a much higher incidence of stroke
Cardiovascular patients with atrial fibrillation are six times more likely to have stroke than patients without AF
Comparison of stroke risk for patients with and without AF
Source: Neurology, 1978; Stroke, 1985; European Heart Journal, 1987; Lancet, 1987
Julie Logan, RN
Foundation for Cardiovascular Medicine

8. Warfarin Use in AF Patients by Age
58.1%
60.7%
57.3%
44.3%
35.4%
Only 55% of AF patients with no contraindications to warfarin had evidence of warfarin use in previous 3 months
Other studies site warfarin use among AF patients from 17% - 50%
Elderly patients with an increased absolute risk of stroke were least likely to be taking warfarin
Julie Logan, RN
Foundation for Cardiovascular Medicine

9. AF Strokes: Occur primarily with sub-therapeutic INR.
Adequacy of anticoagulation in patients with AF coming to a hospital clinic
LOW INR < 1.6
79.3%
Therapeutic INR 2 - 3
17.2%
HIGH INR > 3.2
3.5%
Julie Logan, RN
Foundation for Cardiovascular Medicine

10. Dual and Triple Anticoagulation Therapy
Julie Logan, RN
Foundation for Cardiovascular Medicine
American Journal of Cardiology

11. Left atrial appendage is a major source of thrombi that cause stroke in AF patients
91% of all thrombus in patients with AF is found in the left atrial appendage (LAA)
The four largest TEE studies comprising 1,181 patients showed that 98% of thrombi were found in the LAA
Location of thrombi in non-rheumatic atrial-fibrillation 1
Julie Logan, RN
Foundation for Cardiovascular Medicine

12. Thrombi Formation in the LAA
Julie Logan, RN
Foundation for Cardiovascular Medicine

13. LAA – What does it do?
May mediate thirst in hypovolemia via stretch receptors
Modulates relationship between pressure & volume
Improve filling of LV
Endocrine organ – ANP 40-fold higher in LAA than in the rest of the atrial free wall or ventricle
Julie Logan, RN
Foundation for Cardiovascular Medicine

14. Left Atrial Appendage Post Mortem LAA Casts
LAA body – variable size and morphology 0.77 to cm2 and trabeculated
Julie Logan, RN
Foundation for Cardiovascular Medicine

15. Why not make it go away? Left Atrial Appendage Julie Logan, RN
Foundation for Cardiovascular Medicine

16. Surgical LAA Closure Julie Logan, RN
Foundation for Cardiovascular Medicine
JACC vol.52, No11, Sept, 2008;Kanderian et al

17. Left Appendage Closure Devices
PLATTO™
WATCHMAN®
Julie Logan, RN
Foundation for Cardiovascular Medicine
Amplatzer Cardiac Plug

18. Non-Warfarin Candidates
What can we learn from the
PLAATO™ device feasibility trial?
LA Side
LAA Side
Julie Logan, RN
Foundation for Cardiovascular Medicine

19. PLAATO European Registry
(90% 2 mos echo proven closure)
Stroke: 3 strokes / 129 patient years F/U
8.2%
2.3%
72% Stroke Reduction:
(based on 129 documented pt years)
Julie Logan, RN
Foundation for Cardiovascular Medicine 19

20. North American PLAATO 5 yr F/U Annualized Stroke Rate.
North American PLAATO
N=64
Treatment 30 days
= 100% by TEE
30 day freedom from major
adverse events = 98%
N=64
6.6%
3.3%
Predicted
Actual
Julie Logan, RN
Foundation for Cardiovascular Medicine

21. WATCHMAN® Device Frame: Nitinol (shape memory)
160 µ PET fabric
Device available in various sizes:
21, 24, 27, 30 and 33 mm (diameter)
Device diameter is measured across face of device
Device Length = Device Diameter
Barbs
Frame: Nitinol (shape memory)
Contour shape accommodates most LAA anatomy
Barbs engage the LAA tissue
Fabric Cap: Polyethyl terephthalate (PET) Fabric
Prevents harmful emboli from exiting during the healing process
Julie Logan, RN
Foundation for Cardiovascular Medicine

22. WATCHMAN® LAA closure system
Procedure consists of percutaneous placement via transseptal of a filter device just distal to the ostium of the left atrial appendage to keep harmful sized emboli from exiting.
Julie Logan, RN
Foundation for Cardiovascular Medicine

23. WATCHMAN® Procedure Julie Logan, RN
Foundation for Cardiovascular Medicine

24. RAO “Long Axis” View
On the left is a 3D surface reconstruction of the LA-PVs derived from a CT Angiogram.
Julie Logan, RN
Foundation for Cardiovascular Medicine

25. Positioning the Sheath
The pigtail is “twirled” to ensure that the sheath is free in the LAA.
Julie Logan, RN
Foundation for Cardiovascular Medicine

26. Sizing / Positioning the Device
Top left: Endo luminal view of the left-sided structures: LAA on right and left PVs on the left.
Bottom left: TEE…measuring the appendage
Right: Positioning the Watchman within the sheath to the ostium of the LAA.
TEE
Julie Logan, RN
Foundation for Cardiovascular Medicine

27. Deploying the Device TEE Julie Logan, RN
Foundation for Cardiovascular Medicine

28. Deploying the Device Assessing Stability Releasing the Device
Julie Logan, RN
Foundation for Cardiovascular Medicine

29. WATCHMAN® LAA System – Internal view of Complete Healing of LA
Canine – 45 days
Autopsy – 9 mos
Julie Logan, RN
Foundation for Cardiovascular Medicine

30. WATCHMAN® Left Atrial Appendage System for Embolic PROTECTion in Patients with Atrial Fibrillation (PROTECT AF)
Julie Logan, RN
Foundation for Cardiovascular Medicine

31. 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
Julie Logan, RN
Foundation for Cardiovascular Medicine

32. Enrollment Among Sites
Average patients enrolled per site: 14
Interventional cardiologists and electrophysiologists participated
Enrollment was 53% / 47% between specialists
Top enrolling site = 9.3% of patients
Julie Logan, RN
Foundation for Cardiovascular Medicine

33. 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
Julie Logan, RN
Foundation for Cardiovascular Medicine

34. 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
Julie Logan, RN
Foundation for Cardiovascular Medicine

35. INR Measurements – Control Group
INR Values
Total Measurements With
N/Total (%)
Patients Ever Having
INR < 2.0
1170/3948
29.6%
189/202
93.6%
INR > 2.0 to < 3.0
2170/3948
55.0%
197/202
97.5%
INR > 3.0 to < 4.0
446/3948
11.3%
149/202
73.8%
INR > 4.0
162/3948
4.1%
86/202
42.6%
55% within therapeutic range - consistent with clinical practice
Most patients had an INR outside of the recommended range at least once during the study
34% of Control Patients interrupted Warfarin therapy
Julie Logan, RN
Foundation for Cardiovascular Medicine

36. Warfarin Discontinuation- Watchman group
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)
Julie Logan, RN
Foundation for Cardiovascular Medicine

37. PROTECT AF Efficacy Endpoint
Primary Efficacy Endpoint
All stroke: ischemic or hemorrhagic
Cardiovascular and unexplained death
Systemic thromboembolism
Julie Logan, RN
Foundation for Cardiovascular Medicine

38. Intent-to-Treat: Primary Efficacy Results
Cohort
WATCHMAN
Control
Rel. Risk (95% CI)
Posterior Probabilities
Rate (95% CI)
Non-inferiority
Superiority
600 pt-yrs
4.4
2.6, 6.7
5.8
3.0, 9.1
0.76
0.39, 1.67
0.992
0.734
900 pt-yrs
3.4
2.1, 5.2
5.0
2.8, 7.6
0.68
0.37, 1.41
0.998
0.837
Endpoint criteria met
32% lower relative risk in WATCHMAN Group
Julie Logan, RN
Foundation for Cardiovascular Medicine

39. Intent-to-Treat: All Stroke
Cohort
WATCHMAN
Control
Rel. Risk (95% CI)
Posterior Probabilities*
Rate (95% CI)
Non-inferiority
Superiority
600 pt-yrs
3.4
1.9, 5.5
3.6
1.5, 6.3
0.96
0.43, 2.57
0.927
0.488
900 pt-yrs
2.6
1.5, 4.1
3.5
1.7, 5.7
0.74
0.36, 1.76
0.998
0.731
26% lower relative risk in WATCHMAN Group
Julie Logan, RN
Foundation for Cardiovascular Medicine

40. Primary Efficacy Kaplan-Meier Estimates
Cohort
1 Year
Event Rate (95% CI)
2 Year
Event Rate
(95% CI)
3 Year
WATCHMAN
3.6 (1.8, 5.3)
6.5 (3.1, 10.0)
7.9 (3.6, 12.2)
Control
4.3 (1.5, 7.0)
9.7 (4.6, 14.8)
12.3 (5.2, 19.5)
Julie Logan, RN
Foundation for Cardiovascular Medicine

41. Pericardial Effusions by Experience
Pericardial effusions – most common safety issue
Throughout PROTECT AF Trial, procedural modifications and training enhancements were implemented
Procedural events would be expected to decrease over time
Site implant group
Any
Serious
No. % No. %
Early patients (1-3) 13/ /
Late patients (4) 27/ /
Total 40/ /
Continued ACCESS Registry- CAP
Any
Serious
No. % No. %
1/ /88 1.1
Julie Logan, RN
Foundation for Cardiovascular Medicine

42. Intent-to-Treat: All-Cause Mortality
Cohort
WATCHMAN
Control
Rel. Risk
(95% CI)
Posterior Probabilities*
Rate (95% CI)
Non-inferiority
Superiority
600 pt-yrs
3.4
1.8, 5.4
4.9
2.3, 7.8
0.69
0.33, 1.66
0.991
0.779
900 pt-yrs
2.9
1.7, 4.4
4.7
2.5, 7.1
0.61
0.32, 1.32
0.999
0.889
39% lower relative risk in WATCHMAN Group
Julie Logan, RN
Foundation for Cardiovascular Medicine

43. Learning Curve Early vs. Late Patients
Investigational; no claims can be made from this slide.
Julie Logan, RN
Foundation for Cardiovascular Medicine 43
April 23, 2009 43

44. Learning Curve Tertiles by Enrollment Date and CAP
Investigational; no claims can be made from this slide.
Julie Logan, RN
Foundation for Cardiovascular Medicine 44
April 23, 2009 44

45. Conclusion - Warfarin
Long-term Warfarin treatment of patients with AF has been found effective, but presents considerable difficulties and risks
Difficult to maintain patients in therapeutic range/compliance
Increased risk of hemorrhagic stroke and fatal bleeds over time
PROTECT AF trial evaluated the WATCHMAN device compared to Warfarin
Only study comparing device to drug for stroke prevention in AF
Prospective, randomized, controlled study of 800 patients
86% of WATCHMAN patients successfully implanted and able to discontinue Warfarin therapy
Julie Logan, RN
Foundation for Cardiovascular Medicine

46. Conclusion - Safety Any invasive procedure has potential complications
Majority of WATCHMAN safety events occurred in the first 7 days (mostly pericardial effusions and procedural ischemic strokes)
Pericardial effusions did NOT cause death or long-term disability
With experience (procedural / training modifications), positive trends were observed in all procedural categories
Procedure safety events:
Serious pericardial effusion:
All-cause mortality was 39% lower in the WATCHMAN group (2.9 vs. 4.7) 9% 4% 1% 7% 4% 1%
Julie Logan, RN
Foundation for Cardiovascular Medicine

47. Conclusion - Efficacy
Efficacy Events - 32% fewer in the WATCHMAN group (3.4 vs. 5.0)
Composite of ischemic stroke, hemorrhagic stroke, systemic embolism, CV or unexplained death
Non-inferiority was achieved
Strokes - 26% fewer in the WATCHMAN group (2.6 vs. 3.5)
Procedural ischemic strokes occurred in 1.1% of WATCHMAN patients (0% in CAP)
After Day 0, WATCHMAN ischemic stroke rate is 1.7% versus 2.0% for Control
No hemorrhagic stroke risk in WATCHMAN after warfarin discontinuation versus 2% for Control
Risk of death was markedly increased with hemorrhagic stroke
Potentially, 26,000 strokes per year are preventable with WATCHMAN
Julie Logan, RN
Foundation for Cardiovascular Medicine