WHEN AND WHY TO CLOSE LAA ?

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WHEN AND WHY TO CLOSE LAA ?
Matteo Montorfano San Raffaele Hospital Milan,
Italy
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Magnitude of the Problem Stroke

• The World Health Organization estimates that in
  2001 there were over 20.5 million strokes
  worldwide, 5.5 million of these were fatal.1
• Europe averages approximately 650,000 deaths due
  to stroke each year.2
• Stroke is the 3rd leading cause of death behind
  diseases of the heart and cancer and the 1st
  cause of serious long-term disability.3
• Stroke social cost accounts approximately for the
  3 of total health care expenditures.4

1.World Health Report 2002 2. International
Cardiovascular Disease Statistics 3. 2003 Heart
and Stroke Statistical Update, American Heart
Association 4. Evers SM, et al. International
comparison of stroke cost studies. Stroke. 2004.
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MECHANISMS OF STROKE
OTHERS
LARGE ARTERY ATHEROSCLEROSIS
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CARDIOEMBOLISM
20
20
25
30
CRYPTOGENIC
LACUNES
Albers GW et al. Antithrombotic and Thrombolytic
Therapy for Ischemic Stroke Chest 2001.
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CARDIOEMBOLIC SOURCES
LV thrombus
Valvular heart disease
Acute MI
10
10
10
Prosthetic valves
5
15
50
Other less common sources (PFO, ASA, aortic
debris, etc.)
Nonvalvular Atrial Fibrillation
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Atrial Fibrillation Demographics by Age
Adapted from Feinberg WM. Arch Intern Med.
1995155469-43
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The Impact of Stroke in AF Patients is More
Severe Prevention is Paramount

• European Community Stroke Project of 4462
  patients (AF present in 18) evaluated after a
  first in a lifetime stroke1
• Mortality at 3 months
• AF patients 33 vs Non-AF patients
  20
• Morbidity AF increased by almost 50 the
  probability of remaining disabled or handicapped

1. Lamass M et al. Characteristics, Outcome, and
Care of Stroke Associated with AF in Europe
Stroke. 2001.
7
SEDE DELLE TROMBOSI NELLA FIBRILLAZIONE ATRIALE
NON REUMATICA
REUMATICA
40
10
ATRIO
ATRIO
90
60
AURICOLA
AURICOLA
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Non-Valvular AF Stroke PreventionMedical Rx

• Warfarin cornerstone of therapy
• Warfarin
• 60-70 risk reduction vs no treatment
• 30-40 risk reduction vs aspirin
• Direct thrombin inhibitors (Dabigatran, RE-LY
  Study).1

1 Connolly SJ et al., Dabigatran versus warfarin
in patients with atrial fibrillation. NEngl J Med
2009 361113951.
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Vitamin K Antagonists (VKA) in AF

• 38 reduction in strokes, compared to aspirin
• Increase in hemorrhage, compared to aspirin
• 70 increase extra-cranial
• 128 increase intra-cranial

• Recommended in high-risk patients
• Monitoring required
• Drug interactions
• Often not used

Hart RC et al. Meta-analysis Antithrombotic
therapy to prevent stroke in patients who have
non-valvular AF. Ann Intern Med 2007 146 857-67
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Anticoagulation in AFStroke risk reductions
Stroke RRR 62 All-cause mortality RRR 26
Severe bleedings 1.2/year
11

• Warfarin is the gold standard in patients with AF
  

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Narrow anticoagulant therapeutic window
Stroke risk increases at INR lt 2Bleeding risk
increases at INR gt3
Hylek EM et al, N Engl J Med 1996 335 540-546
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RCTs Warfarin INR at Stroke
1.8
4.0
1.7
1.6
3.0
PT
INR
1.5
Ratio
Ratio
1.4
(ISI 2.4)
2.0
1.3
1.2
1.1
1.0
1.0
AFASAK
SPAF I
BAATAF
SPINAF
CAFA
ACCP raccomandazioni INR 2.03.0
Target range per ogni studio
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HEMORRHAGIC COMPLICATIONS OF OAC IN PATIENTS WITH
AF

p 0.007 p 0.03

PER 100 PATIENTS-YEARS
(n 360)
(n 175)
(n 185)
Wehinger C. et al, Stroke 2001 32 2246-2252
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ORAL ANTICOAGULATION AND RISK OF BLEEDING
ISCOAT Study
2,745 pts
ns
PT / YEAR
N 461 Age lt 70 (56.5)
N 461 Age gt 75 (79.9)
Palareti et al, Arch Intern Med 2000 160 470-478
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Dual Antiplatelet Therapy After PCI with Stenting
in Pts Taking Chronic OAC
127 patients who underwent stent implantation and
were discharged on triple therapy (aspirin,
thienopyridines and warfarin) were analyzed.
Conclusion Major bleeding occurred in 5.6 of
patients on triple therapy. Half of the events
were fatal, and most occurred within the first
month.
Rogacka R, et al, JACC Interventions 2008156-61
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Hypothesis

• Stroke in patients with AF is largely due to the
  LAA as a thromboembolic source

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LAA SURGICAL OBLITERATION
During surgery for mitral stenosis amputation of
the left atrial appendage is recommended to
reduce the likelihood of postoperative
thromboembolic events
ACC/AHA 2006 Guidelines for valvular heart disease
Role of left atrial appendage obliteration in
stroke reduction in patients with mitral valve
prosthesis a transesophageal echocardiographic
study

• An incomplete LAA ligation during surgery of
  mitral valve replacement considered together with
  the absence of LAA ligation, increased risk of
  embolism at follow-up (up to 11.9 x)

Garcia-Fernandez MA et al, J Am Coll Cardiol
2003421253-8
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When to close LAA?

• Non valvular AF, high risk of stroke
• - Contraindication to OAC
• - High risk of bleeding with OAC
• - Difficult to maintain INR within the
  therapeutic range
• - Poor compliance
• - Difficulty to manage the patient because of
  logistic problems

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• High-risk factors
• - age gt 75 years
• - prior stroke / TIA or systemic embolism
• - Hx of hypertension
• - CHF or poor LV function
• - rheumatic mitral valve disease
• -prosthetic heart valves
• Moderate - risk factors
• - age 65-75 years
• - diabetes mellitus
• - CAD with preserved LV function

HIGH RISK
1 High Risk Factor 2 Moderate Risk Factor
AHA ACCP 2004
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CHAD2 Score - Congestive heart failure (1), -
Hypertension (1), - Age gt75 years (1), -
Diabetes (1), - history of stroke or TIA (2)
HIGH RISK gt1
The European Society for Cardiology recently
recommended that the CHADS2-VASc scoring system
be used if the CHADS2 score is 0 to 1 or when a
more detailed assessment of stroke risk is
indicated.
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CHA2DS2-Vasc Score - Congestive heart failure or
LVEF40 (1) - Hypertension (1) - Age75 years
(2) - Diabetes (1) - Stroke/TIA/thromboembolism
(2) - Vascular disease (MI, peripheral arterial
disease, or aortic plaque) (1) - Age 65 to 74
years (1) - Sex category female (1)
HIGH RISK 2
Low Risk CHA2DS2-VASc 0 Intermediate risk
CHA2DS2-VASc 1 High risk CHA2DS2-VASc 2
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WATCHMAN System Atritech
Current Generation Devices
Amplatzer Cardiac Plug AGA Medical

• User friendly simple repositioning and
  recapture
• Unique design flexibility to work in varied
  anatomy
• Small profile - 9F to 13F delivery sheath

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Clinical Studies
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PROTECT-AF Clinical Trial

• Prospective, randomized study of WATCHMAN LAA
  Device vs Long-Term Warfarin Therapy
• 21 allocation ratio device to control
• Non-inferiority study
• 704 randomized patients with non-valvular AF
• Mean age 72 years
• Permanent atrial Fib 36
• Paroxysmal atrial fib 41
• CHADS2 1 31
• CHADS2 2 35

Holmes DR, et al. The Lancet 2009374534-542.
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PROTECT AF TRIAL

• Randomized, controlled, statistically valid study
  to evaluate the WATCHMAN device compared to
  warfarin.
• In PROTECT AF
• 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
• In PROTECT AF, there are early safety adverse
  events, specifically pericardial effusion these
  events have decreased over time

Holmes DR, et al. The Lancet 2009374534-542.
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Safety Event Rates PROTECT AF vs CAP
From tests comparing the PROTECT AF cohort with
CAP From tests for differences across three
groups (early PROTECT AF, late PROTECT AF, and
CAP)
Kar et al. TCT 2010
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Warfarin Discontinuation
87 of implanted subjects were able to cease
warfarin at 45 days and the rate further
increased at later timepoints
Visit Watchman No. 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 (n30)
• Physician order (n13)
• Other (n9)

Holmes DR, et al. The Lancet 2009374534-542.
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Summary

• Hemorrhagic stroke risk is significantly lower
  with the device
• When hemorrhagic stroke occurred, risk of death
  was markedly increased
• All cause stroke and all cause mortality risk are
  non-inferior to warfarin
• There were early safety events, specifically
  pericardial effusion these events have decreased
  over time

Holmes DR, et al. The Lancet 2009374534-542.
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LAA Closure with Amplatzer Cardiac Plug for
Stroke Prevention in AF Initial Asia-Pacific
Experience

• Methods
• 20 NVAF pts (16 males, age 689 years) with high
  risk for stroke (CHADS2 score 2.31.3) and
  contraindications to OAC received ACP implants
  from June 2009 to May 2010.
• - Procedures guided by fluoroscopy and TEE.
• - Clinical F-UP at 1 month and then every
  3-month.
• - TEE 1 month (completion of dual anti-platelet
  therapy).
• - All patients were prescribed aspirin,
  80-160mg per day indefinitely, and clopidogrel,
  75mg per day for 4 weeks after the procedure.

Lam YY et al., Catheter Cardiovasc Interv. 2011
May 3. doi 10.1002/ccd.23136.
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LAA Closure with Amplatzer Cardiac Plug for
Stroke Prevention in AF Initial Asia-Pacific
Experience

• Results
• - LAA successfully occluded in 19/20 pts (95 1
  procedure abandoned because of catheter-related
  thrombus formation).
• - Complications coronary artery air embolism
  (n1) and TEE-attributed esophageal injury (n1).
  
• - Mean size of implant 23.63.1 mm.
• - Average hospital stay 1.81.1 days.
• - F-UP TEE showed all the LAA orifices sealed
  without device-related thrombus formation.
• - No stroke or death at a mean follow-up of
  12.73.1 months.

Lam YY et al., Catheter Cardiovasc Interv. 2011
May 3. doi 10.1002/ccd.23136.
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LAA Closure with Amplatzer Cardiac Plug in AF
Initial European Experience

• Methods
• An investigator-initiated retrospective data
  collection to evaluate the initial European
  experience in pts treated with the ACP between
  December 2008 and November 2009, beginning with
  the FIM.
• Procedures guided by fluoroscopy and TEE.
• Clinical F-UP up to 24 hr after the procedure
  (the study aimed to assess solely periprocedural
  technical and safety issues).

Jai-Wun Park et al., Catheter Cardiovasc Interv.
77700706 (2011).
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LAA Closure with Amplatzer Cardiac Plug in AF
Initial European Experience

• Results
• In 137 of 143 pts, LAA occlusion was attempted,
  and successfully performed in 132 (96).
• Major complications in 10 (7.0) pts 3 ischemic
  stroke 2 device embolization, both
  percutaneously recaptured 5 clinically
  significant pericardial effusions.
• Minor complications 4 pericardial effusions, 2
  transient myocardial ischemia, 1 loss of the
  device in the venous system.

Jai-Wun Park et al., Catheter Cardiovasc Interv.
77700706 (2011).
34
WATCHMAN System Atritech
Current Generation Devices
Amplatzer Cardiac Plug AGA Medical

• User friendly simple repositioning and
  recapture
• Unique design flexibility to work in varied
  anatomy
• Small profile - 9F to 13F delivery sheath

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Distribution of number of lobes (1 to 4) of LAA
3 lobes 23
4 lobes 3
1 lobe 20
2 lobes 54
Veinont etal. Anatomy of normal LAA Circulation
1997
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The Amplatzer Cardiac Plug

• 1. Consists of a lobe and a disc connected by a
  central waist.
• 2. Designed to sit in the ostium of the appendage
  requiring only 10mm of depth

Disk
Waist
Lobe
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Catheter Delivery

• 9 F, 10 F 13 Delivery Catheter
• 100 cm length
• 3 dimensional curve to facilitate access to left
  atrial appendage.
• 0.035 guide wire compatible dilator
• Alignment during device delivery
• Where to place transseptal puncture

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Flexible Delivery Cable
2 inch Floppy distal Section to aid in
assessing ACP placement and stability
stiff proximal section for pushability and
control
Heat shrink cover for Hemostasis
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Pre-Implant Echo and Angio Measurement
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Pre-procedural TEE measurements of LAA in
multiple views
00
450

• 00 view
• 1350 Views are most important views for
  measurements and deployment
• Size of device should be gt20 of max LAA diameter

1350
900
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Access into LAA and angiogramRAO caudal (Echo
135)

• Pig tail advanced into LAA
• Advance sheath over pig tail
• LAA angio (Right Cranial view)
• Sizing of Device
• 20 larger than max diameter

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Configuration of Proper Device Size
Proper Size
Over Size
Under Size
Tire shaped-- Proper tension on the device by
the LAA
Square shaped No tension on the device from
the LAA wall
Strawberry shaped the device is being
squeezed
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Correct Deployed Configuration of ACP
Small amount of tenting on the lobe
Concave disc
Separation between the disc and lobe
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Figure of 8 subcutaneous suture
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Acute
2 days
Necropsy Photos
3 months
1 month
Proprietary Confidential. For Internal Use
Only
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Summary Conclusions

• Important complications of LAA occlusion are
• Cardiac tamponade
• Stroke
• Residual leak
• Vascular complications
• Attention to detail at every step and proper use
  of imaging (Fluoro/Echo) can help prevent these
  complications

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• Thank you

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Conclusions

• Dabigatran 150 mg significantly reduced stoke
  compared to warfarin with similar risk of major
  bleeding
• Dabigatran 110 mg had a similar rate of stroke as
  warfarin with significantly reduced major
  bleeding
• Both doses markedly reduced intra-cerebral,
  life-threatening and total bleeding
• Dabigatran had no major toxicity, but did
  increase dyspepsia and GI bleeding

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Percutaneous Left Atrial Appendage Transcatheter
Occlusion to Prevent Stroke in High-Risk Patients
With Atrial Fibrillation Early Clinical
Experience Horst Sievert, MD Michael D. Lesh,
MD Thomas Trepels Heyder Omran, MD Antonio
Bartorelli, MD Paolo Della Bella, MD Toshiko
Nakai, MD Mark Reisman, MD Carlo DiMario, MD
Peter Block, MD Paul Kramer, MD Dirk
Fleschenberg Ulrike Krumsdorf Detlef Scherer,
MD. Circulation 2002 105 1887-1889
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Procedure-LAA TEE
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Results Estimated Stroke Reduction
Estimated 43 reduction in stroke risk

• Observed incidence of stroke to date
• 6 strokes/168 patient years of follow-up
• 3.6 annual rate
• Expected risk of stroke based on patients
  baseline adjusted CHADS2 score distribution
• 6.3 annual rate

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WATCHMAN LAA Closure Device in situ
3000838-18