Evidence based LAA occlusion & appropriate technique occlusion (김중선).pdf · morbidity and...

Severance Cardiovascular Hospital Yonsei University College of Medicine

Kim, Jung-Sun, M.D. Ph D

Division of Cardiology, Severance Cardiovascular Hospital Yonsei University College of Medicine

Evidence based LAA occlusion & appropriate technique


Agenda

Why is Left Atrial Appendage Issued in AF ?

Appropriate Technique of LAA Closure Devices

Clinical Evidence of LAA Closure Devices


Agenda





AF related Stroke – Worse Prognosis

Stroke is one of main cause of morbidity and mortality. Especially, strokes related to AF have been known a higher

morbidity and mortality than non-AF stroke (Mortality at 3 months :

AF patients 33% vs Non-AF patients 20%).

Blackshear JL, et al. Ann Thorac Surg 1996;61:755–759. Landmesser U, et al. Eur Heart J 2012;33:698-704.


Prevention of stroke in AF: Treatment Options

Long Term antithrombotic therapy Coumadin therapy

New oral anticoagulants: Dabigatran, Rivaroxaban, Apixaban

Antiplatelet agents

Surgical Amputation or Ligation of LAA

Percutaneous Occlusion of the LAA The Watchman® System

Amplatzer Cardiac Plug


Challenges in Treating AF • Warfarin is cornerstone of therapy for AF (60-70 % reduction of stroke)

• However, warfarin is not always well-tolerated

• Narrow therapeutic range (INR between 2.0 – 3.0)

• Impacted by interactions with some foods and medications

• Requires frequent monitoring and dose adjustments

• 30-50% 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.

Hylek E, et al. Circulation. 2007(115):2689-2696. Landmesser U, et al. Eur Heart J 2012;33:698-704.


Persistent warfarin declined to 45% after 2 years

Glader EL, et al. Stroke 2010;41:397-401

a cohort of stroke survivors (21 077 survivors)


New Oral Agents versus Coumadin

Equivalent or slightly better in reduction of stroke Overall bleeding risk is similar (major bleedings ranging

from 1.4 to .3%/yr in clinical trials, which have excluded patients with a high risk of bleeding).

IC bleed is lower than coumadin

Does not require frequent monitoring

Shorter half life

Drug intolerance equivalent or higher than coumadine

Drug dosing in extreme body weight or renal failure patients is problematic

There is no free lunch: If it prevents clots, it will bleed.

Courtesy silde of Dr. Caibal Kar


Non Reumatic Reumatic

10%

90%

40%

60% Atrium

Appendage

Atrium

Appendage

The Contribution of Cardiac Embolic Stroke

Why is LAA important in non-valvular AF ?


Number of LAA publications in various periods

Johnson and colleagues described the LAA as “our most lethal human attachment” in a report of prophylactic LAA excision in 437 patients from 1995 to 1997.

MAZE Operation Use of TEE


Surgical Excision of LAA

(A) Epicardial suture exclusion. (B) Endocardial suture exclusion.

(C) Stapled excision. (Left panel) Stapler positioned across the base of the LAA; (Right panel)


LAA Structure

Courtesy Slide of Prof. D. Sanchez Quintana

Orifice: Oval shape


Common Morphologies of LAA

Courtesy slide of Dr. Tim Betts


When to close LAA ?

Non valvular AF and 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.


2012 ESC Guideline for AF Management. Eur Heart J. 2012; E-Pub Ahead of Print

ESC Guideline for AF Management


Courtesy slide of Park J-W


Septal Puncture

Anterior Posterior Superior Inferior


Agenda





PLAATO™Device

Courtesy slide of Dr. Horst Sievert

Limitations of the PLAATO device : Rather rigid and required 20–50% oversizing for the LAA orifice to achieve a stable position.


WATCHMAN® System (Boston Scientific)

•More operator dependent •Unique design – flexibility to work in varied anatomy •Small profile - 9F to 13F delivery sheath

Amplatzer Cardiac Plug (St Jude Medical)

Current Generation Devices

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

Polyester polyethylene terephthalate (PET)


M / 64

Clinical Diagnosis: • Atrial fibrillation for 8 yrs • Hypertension for 8 yrs • Diabetes for 4 yrs

Past History: • 2008.2 Right MCA infarction • 2008.4 Unstable angina

• CAD 1VD • s/p PTCA c stent implantation at mLAD

• 2009.6 UGI bleeding

KJH 5046973

CHADS2 4 CHA2DS2VASc 5 HAS-BLED 4


2008.4.14 Unstable angina CAOD 1VD S/P PTCA c stent at mLAD

Discharge Medication Astrix 100mg Plavix 75mg Concor 5mg Lipitor 40mg Digosin 0.125mg Tritace plus Diamicron MR 30mg Glupa 500mg Coumadin 7.5mg

Unstable angina (2008.4)


Dieulafoy's lesion & duodenum ulcer s/p Hemostasis

GI bleeding (2009.6)


INR F/U at OPD

Mon, Thur: 5mg Others: 7.5mg


Heart CT


Frame: Nitinol structure • Available sizes: 21, 24, 27, 30, 33

mm (diameter)

10 Fixation barbs around device perimeter engage LAA tissue

Contour shape accommodates most LAA anatomy

Fabric Cap: (PET) Fabric Polyethyl terephthalate

• Prevents harmful emboli from exiting during the healing process

• 160 micron filter

Barbs

PET fabric

WATCHMAN LAA Closure System Components

width

Leng

th

Length = Width of device


Landing Zone and Size

LCA/MVA to a point 2cm from tip of LUPV limbus

8-20 % oversize


135 degree : 27 mm

45 degree : 22 mm

Size Measurement and check thrombus inside LA and LAA

90 degree : 18 mm

Maximal size: 27 mm -> 30 mm Watchman device (11%)

No thrombus in LA and LAA


Angiography

LAO 36 CRA 0 RAO 32 CRA 30

LAO 36 CAU 0 RAO 32 CAU 30


Angiography of the LAA, RAO projection


LAA Oriface and Landing Zone

Angiography

TEE


Sheath navigation/ manipulation

• Counter clockwise torque on the Access system • Aligns the sheath more

anterior

• Clockwise torque on the Access system

• Aligns the sheath more posterior


RAO 28 CAU 21 RAO 28 CAU 21

Angiography


Recapture & deployment



Final Deployment

RAO 31 CRA 29

Maximal size: 27 mm -> 30 mm Watchman device

RAO 32 CAU 30


Final Echocardiography


25 % Compression Less than 20 % of protrusion into LA Jet measurements: 3mm± 2mm or less.


3D Echocardiography


CT Image

Axial Images Coronal Images


60 days F/U Echocardiography

90 degree 135 degree


Courtesy slide of Dr. Horst Sievert

AMPLATZER® Cardiac Plug


Mechanism of Action and Size

Lobe Landing Zone

Sealing the LAA Ostium


Configuration of Proper Device 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


Final Deployment



Final Echo


Proper Criteria After ACP Implantation

Angiography

TEE

Tire shape (Lobe) Concave (Disc) Separation between disc and lobe

At least 2/3 of inf. Edge of the ACP lobe should be inside the LCx


Echocardiography after 60 days


Initial ECG monitoring

ST elevation after LAA-OD deployment

Final ECG monitoring


ST-elevation during LAA occlusion


Agenda





PROTECT AF1,6 CAP2 ASAP3,4 PREVAIL5

Trial Design

Prospective RCT with patients able to take

warfarin

Prospective registry with patients able to take

warfarin

Prospective registry with patients contraindicated for warfarin

Prospective RCT with patients able to take

warfarin

Outcome

WATCHMAN was non-inferior to warfarin in patients at high-risk of

thromboembolism

Significantly improved safety results from early PROTECT AF experience

Ischemic stroke rate significantly reduced in warfarin contra-in

dicated patients

WATCHMAN device was safely implanted by new

operators

Mean age /CHADS2 72/2.2 74/2.4 72.4/2.8 74/2.6

Total Enrolled Subjects 707 randomized1 93 pts rolled in2 460 150 407

Total Patients Implanted 5422 437 142 269

Implantation Success 89.5%2 95.0% 94.7% 95.1%

Primary Efficacy (all-stroke, CV/unexplained death,

and systemic embolism)

40% reduction vs. warfarin6 29% reduction vs. warfarin N/A

0.064 Identical 18-month rates for WATCHMAN and warfa

rin

All-Stroke 32% reduction vs. warfarin6 23% reduction vs. warfarin 77% reduction vs. expected rate

per CHADS₂ score Data not yet available

Safety

(7 day procedure-related*) 8.7%5

4.1%5

53% reduction vs. PROTECT AF

Pericardial effusion with tamponade=1.3%

Major bleeding=2.7%

4.4% 49% reduction vs.

PROTECT AF

*Composite of vascular complications includes cardiac perforation, pericardial effusion with tamponade, ischemic stroke, device embolization, and Includes observed PE not necessitating intervention, AV fistula, major bleeding requiring transfusion, pseudoaneurysm, hematoma and groin bleeding

1 Holmes DR et al. Lancet 2009;374:534–42; 2 Reddy VY et al. Circulation. 2013; 127:720-729; 3 Sievert H. TCT 2011; 4 Reddy, JACC 2013; 5 Homes DR PREVAIL Mar 201 6 Reddy, et al. HRS LBCT 2013

WATCHMAN™ Clinical Program At 4yrs WATCHMAN was superior to warfarin in primary efficacy, all-cause mortality, & cardiovascular death


WATCHMAN™ PROTECT AF

3 2.3

0.7 0.3

4.9

3.2 2.7

0 0

1

2

3

4

5

6

7

8

9

10

Primary Efficacy All Stroke CV orUnexplained Death

Systemic embolism

PROTECT AF Investigators. Lancet 2009; 374: 534–42

WATCHMAN therapy is non-inferior to warfarin in the prevention of stroke and death. 38% reduction with WATCHMAN for the composite endpoint for efficacy (including

strokes, CV or unexplained death, and systemic embolism) when compared to warfarin Following the periprocedural period, the rate of ischemic stroke with the WATCHMAN

Device was 1.3 per 100 patient years vs. 1.6 with warfarin

Holmes, et al., Lancet 2009; 374: 534–42

Events in PROTECT AF trial at 1065 patient years

PNI >99.9% PNI >99.9% PNI > 99%

38% lower 29% lower 38% lower WATCHMAN Group

N=463

Warfarin Group N=244

PNI = Posterior non inferiority Probabilities

Rate

per

100

pat

ient

yea

rs PNI >99.9%

PNI >99.9% PNI > 99%


ASAP Registry: warfarin contraindicated patients

Observed rate of ischemic stroke represents a 77% reduction from the expected event rate

7.3%

5.0%

1.7%

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

6.0%

7.0%

8.0%

Expected, based onCHADS2 Score

Expected, ifClopidogrel was usedthroughout follow-upObserved rate in ASAP

77% Reduction

Expected and Observed Stroke Rates (per 100 patient-years)

Reddy V, et al. J Am Coll Cardiol 2013 In Press

mean follow-up 14.4 months


WATCHMAN™ Pilot: 6 Year Data

5.75%

0.5%

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

6.0%

7.0%

Expected, based on CHADS₂ Score

Observed rate in 6year follow up

Ischemic Stroke

Isch

emic

Str

oke

Rate

(%

/pt-

yr)

• 2 embolic strokes over 6 years of follow up*

• A 90% decrease when compared to CHADS₂ expected stroke rate

Sick PB, et al, ESC 2012

90% Reduction

*One stroke at 2 months and one at 39 months in the setting of severe carotid disease


PREVAIL Enrollment

Total Enrolled 461

Roll-In Patients 54

Implant Attempt 54

Device Implanted 51

Unable to Implant 3

Randomized Patients

407

WATCHMAN (Device)

269

Warfarin (Control)

138

Implant Attempt 265

No Implant Attempt 4

Device Implanted 252

Unable to Implant 13


PREVAIL Implant Success

PROTECT AF Implant Success

90.9%

CAP Implant Success

94.3%

PREVAIL Implant Success

95.0%

p = 0.01

95%

96.2%

93.2%

90.0% 92.0% 94.0% 96.0% 98.0%

Study Implant Success

Experienced Operators

New Operators

% of Successful Implants (PREVAIL)

p = 0.282

N= 26

N= 24

Holmes TCTMD 2013 PROTECT-AF and CAP data: Reddy, VY et al. Circulation. 2011;123:417-424.


PREVAIL Co-Primary Endpoints

6 events in device group = 2.2% (6/269)

Pre-specified criterion met for first primary endpoint (95% Upper confidence bound < 2.67%)

One-sided 95% upper CI bound for success

2.0% 2.5% 3.0% Percent of patients experiencing an event

2.2% 2.618%

95% upper CI bound for non-inferiority

0.5 1.0 1.5 18-month Rate Ratio

2.0

1.07

0.57 1.88

1.75 2.67%

Similar 18-month event rates in both control and device groups = 0.064

Upper 95% CI bound slightly higher than allowed to meet success criterion(<1.75)

Limited number of patients with follow-up through 18 months thus far (Control = 30 pts, Device = 58 pts)

95% upper CI bound for non-inferiority

-0.01 0 0.01 18-month Rate Difference

0.02

0.0051

-0.02 0.03 -0.03

-0.0191 0.0268

0.0275

Endpoint success in the presence of an over performing control group

Pre-specified non-inferiority criterion met for third primary endpoint (95% CI Upper Bound < 0.0275%)

Holmes D, TCTMD 2013

Acute (7-day) Procedural Safety


PROTECT AF Primary Efficacy Results -2.3-Yr FU 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

Reddy, VY et al. Circulation. 2013;127:720-729;.

Reddy VY, et al. Circulation 2013;12:720-29


Reddy V, et al. HRS LBCT 2013

40% Reduction in Primary Efficacy events vs. warfarin – Superior

PROTECT AF Long Term (4 Year) Follow-up

Primary Efficacy


PROTECT AF Long Term (4 Year) Follow-up All-Cause Mortality

34% Reduction in All-Cause Mortality vs. warfarin – Superior Reddy V, et al. HRS LBCT 2013


PROTECT AF Long Term (4 Year) Follow-up Summary

WATCHMAN Observed Rate per 100 pt-yrs

Warfarin Observed Rate per 100 pt-yrs

% Reduction (vs Warfarin)

Primary Efficacy Endpoint 2.3 3.8 40% Superior CV Death 1.0 2.4 60% Superior All-cause Death 3.2 4.8 34% Superior

Reddy R, et al. HRS LBCT 2013

2.3 1.0

3.2 3.8 2.4

4.8

0123456789

10

Primary Efficacy CV orUnexplained Death

All-Cause Death

Events in PROTECT AF trial at 2,621 patient years

Rate

per 100 p

atient years

PS >99% P=0.0379 P=0.0045

40% lower 60% lower 34% lower

Ps = Posterior Probability for Superiority

WATCHMAN Group N=463

Warfarin Group N=244


WATCHMAN™ PROTECT-AF - Quality of Life Assessment

There was a significant improvement in QOL for WATCHMAN patients compared to warfarin patients at 12-months, with the greatest differences observed in physical function.

Alli O, Doshi S, Kar S, et al. J Am Coll Cardiol 2013


WATCHMAN™ Net Clinical Benefit

The net clinical benefit of WATCHMAN LAAC is greatest for patients at higher risk of stroke.

Gangireddy, SR, et al. Eur Heart J 2012


WATCHMAN™ Net Clinical Benefit

In PROTECT AF the NCB shifted from warfarin to WATCHMAN between 6-9 months post implant.

Due to PEs and procedure-related stroke events. NCB favored WATCHMAN as early as 3 mo’s post implant in CAP registry.

Gangireddy, SR, et al. Eur Heart J 2012


Amplatzer Cardiac Plug


ACP European Prospective Observational Study

Walsh K, et al. EuroPCR 2012


Learning Curve for the Procedure


ACP in Pts with NVAF and ContraIx for Anticoagulation Tx

Urena M, et al. J Am Coll Cardiol 2013 In Press

Mean FU: 20 ± 5 Months 52 Pts

The procedure was successful in 98.1% of the patients and the main complications were device embolization (1.9%) and pericardial effusion (1.9%), with no cases of periprocedural stroke.


ACP in Pts with NVAF and ContraIx for Anticoagulation Tx

Urena M, et al. J Am Coll Cardiol 2013 In Press


Yonsei Experiences for LAA-OD

A total of 23 patients with permanent AF were tried for LAA-OD

From October 2010 to March 2013 17 males, 65 ± 10 (52 – 83) years 15 patients (65%); history of stroke or embolism LA size 54±8 mm, EF 61±11% 8 windsock, 8 chicken wing, 7 broccoli types

1 patient excluded for too large LAA os with 39 mm Risk of Stroke & Bleeding CHADS2 score 3.6±1.4 HAS-BLED score 3.2±0.8 HADS2 + HAS-BLED 6.8±2.0


Yonsei Experiences for LAA-OD

Acute Procedural Success Rate All 22 patients underwent successful LAA-OD No procedure failure 1 case of respiratory arrest & successful CPR No acute complication, no pericardial effusion

Clinical FU for mean 8 ± 8 months (2-29 months, 22 pts) No device failure or leak at 8 week on TEE (22 patients) Stop OAC in 20/22 patients (91 %) after FU TEE One pts was observed thrombus over Watchman One patient with severe SEC is continuing OAC and stroke. Two patient with leakage (1 & 3 mm) and contrast filling in CT.


Summary of Presentation

Percutaneous LAA occlusion has shown to be effective in the prevention of stroke in AF patients.

This therapy reduced the stroke rate compared with the CHADS2 predicted rates and is non-inferiority compared with warfarin has been reported.

Based on successful stroke prevention, LAA occlusion may eliminate the need for OAC and prevent OAC associated bleeding events.

This benefit may be offset by complications related to the implantation of the device .


Yonsei LAA Occluder Team

Intervention Part Jang, Yangsoo, MD, Ph D Kim, Jung-Sun, MD, Ph D

Electrophysiology Part Pak, Hui-Nam, MD, Ph D Uhm, Jae Sun, MD, Ph D

Non-Invasive Part Hong, Geu Ru, MD, Ph D

Shin , Sang-Hoon, MD

Anesthesiology Part Kwak, Young-Lan, MD, Ph D Shim, Jae-Gwang, MD, Ph D


Thanks for your Attention Cardiovascular Hospital Hybrid Cath Room

Preclinical Research Lab

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Evidence based LAA occlusion & appropriate technique occlusion (김중선).pdf · morbidity and...

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