WHEN AND WHY TO CLOSE LAA ?

WHEN AND WHY TO CLOSE LAA ?

Matteo MontorfanoSan Raffaele Hospital

Milan, Italy

Matteo MontorfanoSan Raffaele Hospital

Milan, Italy

Magnitude of the Problem: Stroke Magnitude of the Problem: Stroke

1. The World Health Organization estimates that in 2001 there were over 20.5 million strokes worldwide, 5.5 million of these were fatal.1

2. Europe averages approximately 650,000 deaths due to stroke each year.2

3. 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

4. Stroke social cost accounts approximately for the 3% of total health care expenditures.4

1. The World Health Organization estimates that in 2001 there were over 20.5 million strokes worldwide, 5.5 million of these were fatal.1

2. Europe averages approximately 650,000 deaths due to stroke each year.2

3. 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

4. Stroke social cost accounts approximately for the 3% of total health care expenditures.4

1.World Health Report 20022. International Cardiovascular Disease Statistics3. 2003 Heart and Stroke Statistical Update, American Heart Association4. Evers SM, et al. International comparison of stroke cost studies. Stroke. 2004.

MECHANISMS OF STROKEMECHANISMS OF STROKEMECHANISMS OF STROKEMECHANISMS OF STROKE

5%5%

20%20%

25%25%

20%20%

30%30%

CARDIOEMBOLISMCARDIOEMBOLISM

CRYPTOGENICCRYPTOGENICLACUNESLACUNES

LARGE ARTERYATHEROSCLEROSISLARGE ARTERYATHEROSCLEROSIS

OTHERSOTHERS

Albers GW et al. Antithrombotic and Thrombolytic Therapy for Ischemic Stroke; Chest 2001.

50%50%50%50%15%15%15%15%

10%10%10%10%

5%5%5%5%

10%10% 10%10%

CARDIOEMBOLIC SOURCESCARDIOEMBOLIC SOURCESCARDIOEMBOLIC SOURCESCARDIOEMBOLIC SOURCES

NonvalvularAtrial Fibrillation

NonvalvularAtrial Fibrillation

Acute MIAcute MILV thrombusLV thrombus

Valvular heartdisease

Valvular heartdisease

Prostheticvalves

Prostheticvalves

Other lesscommon sources

(PFO, ASA,aortic debris, etc.)

Other lesscommon sources

(PFO, ASA,aortic debris, etc.)

Atrial Fibrillation Demographics by AgeAtrial Fibrillation Demographics by Age

Adapted from Feinberg WM. Arch Intern Med. 1995;155:469-43

The Impact of Stroke in AF Patients is More Severe

Prevention is Paramount

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

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.

Non-Valvular AF Stroke PreventionNon-Valvular AF Stroke PreventionMedical RxMedical Rx

Non-Valvular AF Stroke PreventionNon-Valvular AF Stroke PreventionMedical RxMedical Rx

• Warfarin cornerstone of therapyWarfarin cornerstone of therapy

• WarfarinWarfarin60-70% risk reduction vs no treatment60-70% risk reduction vs no treatment30-40% risk reduction vs aspirin30-40% risk reduction vs aspirin

• Direct thrombin inhibitors (Dabigatran, RE-LY Direct thrombin inhibitors (Dabigatran, RE-LY Study).Study).11

• Warfarin cornerstone of therapyWarfarin cornerstone of therapy

• WarfarinWarfarin60-70% risk reduction vs no treatment60-70% risk reduction vs no treatment30-40% risk reduction vs aspirin30-40% risk reduction vs aspirin

• Direct thrombin inhibitors (Dabigatran, RE-LY Direct thrombin inhibitors (Dabigatran, RE-LY Study).Study).11

1 Connolly SJ et al., Dabigatran versus warfarin in patients with atrial fibrillation. NEngl J Med 2009; 361:1139–51.1 Connolly SJ et al., Dabigatran versus warfarin in patients with atrial fibrillation. NEngl J Med 2009; 361:1139–51.

Narrow anticoagulant therapeutic windowNarrow anticoagulant therapeutic window

Stroke risk increases at INR < 2Stroke risk increases at INR < 2Bleeding risk increases at INR >3Bleeding risk increases at INR >3

Hylek EM et al, N Engl J Med 1996; 335: 540-546

RCT’s & Warfarin INR at StrokeINR at Stroke

AFASAK SPAF I BAATAF SPINAFCAFA1.0

2.0

3.0

4.01.7

1.6

1.51.41.31.21.11.0

INRRatio

PTRatio

(ISI 2.4)

ACCP raccomandazioni: INR: 2.0–3.0

1.8

Target range per ogni studio

HEMORRHAGIC COMPLICATIONS OF OACHEMORRHAGIC COMPLICATIONS OF OACIN PATIENTS WITH AFIN PATIENTS WITH AF

HEMORRHAGIC COMPLICATIONS OF OACHEMORRHAGIC COMPLICATIONS OF OACIN PATIENTS WITH AFIN PATIENTS WITH AF

13.1

6.7 5.8

3.41.4 1.7

22.2

11.8

9.6

0

5

10

15

20

25

All patients Taking < 3 drugs Taking > 3 drugs

Total bleeds

Serious bleeds

Minor bleeds

% P

ER 1

00 P

ATI

ENTS

-YEA

RS

(n= 360) (n= 175) (n= 185)

Wehinger C. et al, Stroke 2001; 32: 2246-2252

** p= 0.007** p= 0.03

**

21-month Follow-Up21-month Follow-Up DESDESn = 71n = 71

BMSBMSn = 56n = 56 p-p-ValueValue

Major Bleeding (%)Major Bleeding (%) 5.65.6 3.63.6 NSNS

MACCE (%)MACCE (%) 19.719.7 28.628.6 NSNS

TVR (%)TVR (%) 14.114.1 26.826.8 0.0410.041

No significant differences were found between DES vs. BMS, except in TVR No significant differences were found between DES vs. BMS, except in TVR risk.risk.

Dual Antiplatelet Therapy After PCI with Stenting in Dual Antiplatelet Therapy After PCI with Stenting in Pts Taking Chronic OACPts Taking Chronic OAC

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.

127 patients who underwent stent implantation and were discharged on triple 127 patients who underwent stent implantation and were discharged on triple therapy (aspirin, thienopyridines and warfarin) were analyzed.therapy (aspirin, thienopyridines and warfarin) were analyzed.

Rogacka R, et al, JACC Interventions 2008;1:56-61

HypothesisHypothesis

• Stroke in patients with AF is largely

due to the LAA as a

thromboembolic source

• Stroke in patients with AF is largely

due to the LAA as a

thromboembolic source

During surgery for mitral stenosis “amputation of the left atrial appendage is recommended to reduce the likelihood of postoperative thromboembolic events”

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

Role of left atrial appendage obliteration in stroke reduction in patients with mitral valve prosthesis: a

transesophageal echocardiographic study

LAA SURGICAL OBLITERATIONLAA SURGICAL OBLITERATION

“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)”

“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 2003;42:1253-8

When to close LAA?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

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

CHADCHAD22 Score Score- - Congestive heart failure (1), Congestive heart failure (1), - Hypertension (1),- Hypertension (1),- Age >75 years (1), - Age >75 years (1), - Diabetes (1), - Diabetes (1), - history of stroke or TIA (2)- history of stroke or TIA (2)

CHADCHAD22 Score Score- - Congestive heart failure (1), Congestive heart failure (1), - Hypertension (1),- Hypertension (1),- Age >75 years (1), - Age >75 years (1), - Diabetes (1), - Diabetes (1), - history of stroke or TIA (2)- history of stroke or TIA (2)

HIGH HIGH RISKRISK>1>1

The European Society for Cardiology recently The European Society for Cardiology recently recommended that the recommended that the CHADSCHADS22-VASc-VASc scoring system scoring system be used be used if the CHADS2 score is 0 to 1if the CHADS2 score is 0 to 1 or when a more or when a more detailed assessment of stroke risk is indicated.detailed assessment of stroke risk is indicated.

The European Society for Cardiology recently The European Society for Cardiology recently recommended that the recommended that the CHADSCHADS22-VASc-VASc scoring system scoring system be used be used if the CHADS2 score is 0 to 1if the CHADS2 score is 0 to 1 or when a more or when a more detailed assessment of stroke risk is indicated.detailed assessment of stroke risk is indicated.

CHACHA22DSDS22-Vasc Score-Vasc Score- Congestive heart failure or LVEF≤40% (1);- Congestive heart failure or LVEF≤40% (1);- Hypertension (1);- Hypertension (1);- Age≥75 years (2);- Age≥75 years (2);- Diabetes (1);- Diabetes (1);- Stroke/TIA/thromboembolism (2);- Stroke/TIA/thromboembolism (2);- Vascular disease (MI, peripheral- Vascular disease (MI, peripheral

arterial disease, or aortic plaque) (1);arterial disease, or aortic plaque) (1);- Age 65 to 74 years (1); - Age 65 to 74 years (1); - Sex category female (1); - Sex category female (1);

CHACHA22DSDS22-Vasc Score-Vasc Score- Congestive heart failure or LVEF≤40% (1);- Congestive heart failure or LVEF≤40% (1);- Hypertension (1);- Hypertension (1);- Age≥75 years (2);- Age≥75 years (2);- Diabetes (1);- Diabetes (1);- Stroke/TIA/thromboembolism (2);- Stroke/TIA/thromboembolism (2);- Vascular disease (MI, peripheral- Vascular disease (MI, peripheral

arterial disease, or aortic plaque) (1);arterial disease, or aortic plaque) (1);- Age 65 to 74 years (1); - Age 65 to 74 years (1); - Sex category female (1); - Sex category female (1);

HIGH HIGH RISKRISK≥≥22

Low Risk: CHALow Risk: CHA22DSDS22-VASc = 0-VASc = 0Intermediate risk: CHAIntermediate risk: CHA22DSDS22-VASc = 1 -VASc = 1 High risk: CHAHigh risk: CHA22DSDS22-VASc ≥ 2-VASc ≥ 2

Low Risk: CHALow Risk: CHA22DSDS22-VASc = 0-VASc = 0Intermediate risk: CHAIntermediate risk: CHA22DSDS22-VASc = 1 -VASc = 1 High risk: CHAHigh risk: CHA22DSDS22-VASc ≥ 2-VASc ≥ 2

WATCHMANWATCHMAN®® System Atritech System Atritech

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

Amplatzer Cardiac Plug AGA Amplatzer Cardiac Plug AGA MedicalMedical

Current Generation DevicesCurrent Generation Devices

•Nitinol with 160 micron PET filter)•21, 24, 27, 30, 33 mm •TEE, Angiography •12 F •45 days of Coumadin

PROTECT AF TRIAL• Randomized, controlled, statistically valid study to evaluate the Randomized, controlled, statistically valid study to evaluate the

WATCHMAN device compared to warfarin.WATCHMAN device compared to warfarin.

• In PROTECT AF:In PROTECT AF:

• NoninferiorityNoninferiority for all strokes – 26% lower in device group for all strokes – 26% lower in device group

• SuperioritySuperiority for hemorrhagic stroke – 91% lower in device group for hemorrhagic stroke – 91% lower in device group

• NoninferiorityNoninferiority for mortality rate – 39% lower rate in device group for mortality rate – 39% lower rate in device group

In PROTECT AF, there are In PROTECT AF, there are early safety adverse eventsearly safety adverse events, specifically , specifically pericardial effusion; these events have pericardial effusion; these events have decreased over timedecreased over time

Holmes DR, et al. The Lancet2009;374:534-542.

Safety Event Rates PROTECT AF vs CAP

PROTECT AF

PROTECT AF

CAP p-value* p-value±Early Late

Procedure/Device Related Safety Adverse Events within 7 Days

42/542(7.7%)

27/271(10.0%)

15/271(5.5%)

17/460(3.7%)

0.007 0.006

Serious Pericardial Effusions within 7 Days

27/542(5.0%)

17/271(6.3%)

10/271(3.7%)

10/460(2.2%)

0.019 0.018

Procedure Related Stroke

5/542(0.9%)

3/271(1.1%)

2/271(0.7%)

0/460(0.0%)

0.039 0.039

*From tests comparing the PROTECT AF cohort with CAP ±From tests for differences across three groups (early PROTECT AF, late PROTECT AF, and CAP)

• Improvements seen over time for acute safety events

• Fewer total procedure/device related events

Kar et al. TCT 2010

LAA Closure with Amplatzer Cardiac Plug for Stroke Prevention in AF: Initial Asia-Pacific

Experience

Methods

20 NVAF pts (16 males, age 68±9 years) with high risk for stroke (CHADS2 score: 2.3±1.3) 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.

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 (n=1) and TEE-attributed esophageal injury (n=1).

- Mean size of implant: 23.6±3.1 mm.

- Average hospital stay: 1.8±1.1 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 12.7±3.1 months.

Lam YY et al., Catheter Cardiovasc Interv. 2011 May 3. doi: 10.1002/ccd.23136.

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. 77:700–706 (2011).

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. 77:700–706 (2011).

WATCHMANWATCHMAN®® System Atritech System Atritech

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

Amplatzer Cardiac Plug AGA Amplatzer Cardiac Plug AGA MedicalMedical

Current Generation DevicesCurrent Generation Devices

•Nitinol with 160 micron PET filter)•21, 24, 27, 30, 33 mm •TEE, Angiography •12 F •45 days of Coumadin

Distribution of number of lobes (1 to 4) of LAA

Distribution of number of lobes (1 to 4) of LAA

Veinont etal. Anatomy of normal LAA Circulation 1997

2 lobes 54%2 lobes 54%

1 lobe 20%1 lobe 20%

3 lobes 23%3 lobes 23%

4 lobes 3%4 lobes 3%

The Amplatzer Cardiac PlugThe 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

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

LobeLobe

WaistWaist

DiskDisk

Catheter DeliveryCatheter 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

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

Flexible Delivery CableFlexible Delivery Cable

“stiff” proximal section for pushability and control

“stiff” proximal section for pushability and control

2 inch “Floppy” distal Section to aid in assessing ACP placement and stability

2 inch “Floppy” distal Section to aid in assessing ACP placement and stability

Heat shrink cover for Hemostasis

Heat shrink cover for Hemostasis

Pre-Implant Echo and Angio Measurement Pre-Implant Echo and Angio Measurement

00 450

900 1350

Pre-procedural TEE measurements of LAA in multiple viewsPre-procedural TEE measurements of LAA in multiple views

• 000 0 view &view &

• 13513500 Views are Views are most important most important views for views for measurements measurements and deploymentand deployment

• Size of device Size of device should be >20 % should be >20 % of max LAA of max LAA diameterdiameter

• 000 0 view &view &

• 13513500 Views are Views are most important most important views for views for measurements measurements and deploymentand deployment

• Size of device Size of device should be >20 % should be >20 % of max LAA of max LAA diameterdiameter

Access into LAA and angiogramAccess into LAA and angiogramRAO caudal (Echo 135°)RAO caudal (Echo 135°)

Access into LAA and angiogramAccess into LAA and angiogramRAO caudal (Echo 135°)RAO caudal (Echo 135°)

• Pig tail advanced Pig tail advanced into LAAinto LAA

• Advance sheath over Advance sheath over pig tail pig tail

• LAA angio (Right LAA angio (Right Cranial view)Cranial view)

• Sizing of DeviceSizing of Device

• 20% larger than max 20% larger than max diameterdiameter

• Pig tail advanced Pig tail advanced into LAAinto LAA

• Advance sheath over Advance sheath over pig tail pig tail

• LAA angio (Right LAA angio (Right Cranial view)Cranial view)

• Sizing of DeviceSizing of Device

• 20% larger than max 20% larger than max diameterdiameter

Configuration of Proper Device SizeConfiguration of Proper Device Size

“Tire” shaped-- Proper tension on the device by the LAA

“Tire” shaped-- Proper tension on the device by the LAA

“Square” shaped – No tension on the device from the LAA wall

“Square” shaped – No tension on the device from the LAA wall

“Strawberry” shaped – the device is being squeezed

“Strawberry” shaped – the device is being squeezed

Correct Deployed Configuration of ACP

Correct Deployed Configuration of ACP

Small amount of tenting on the lobeSmall amount of tenting on the lobe

Separation between the disc and lobeSeparation between the disc and lobe

Concave discConcave disc

Figure of 8 subcutaneous sutureFigure of 8 subcutaneous suture

Acute 2 days

1 month

3 months

Necropsy Photos

* Proprietary & Confidential. For Internal Use Only

1.1. Important complications of LAA occlusion are:Important complications of LAA occlusion are:

Cardiac tamponade Cardiac tamponade

StrokeStroke

Residual leak Residual leak

Vascular complicationsVascular complications

2.2. Attention to detail at every step and proper use Attention to detail at every step and proper use of imaging (Fluoro/Echo) can help prevent these of imaging (Fluoro/Echo) can help prevent these complicationscomplications

1.1. Important complications of LAA occlusion are:Important complications of LAA occlusion are:

Cardiac tamponade Cardiac tamponade

StrokeStroke

Residual leak Residual leak

Vascular complicationsVascular complications

2.2. Attention to detail at every step and proper use Attention to detail at every step and proper use of imaging (Fluoro/Echo) can help prevent these of imaging (Fluoro/Echo) can help prevent these complicationscomplications

Summary ConclusionsSummary ConclusionsSummary ConclusionsSummary Conclusions

Thank youThank you