current trends in the management of atrial …...source: martinez c, et al. therapy persistence in...

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Current Trends in the Management of Atrial Fibrillation: Left Atrial Appendage Occlusion

Benjamin A. D’Souza, MD, FACC, FHRS

Assistant Professor of Clinical Medicine

Penn Presbyterian Medical Center

Cardiac Electrophysiology

Perelman School of Medicine at the University of Pennsylvania

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Atrial fibrillation: Scope of the problem• Higher stroke risk for older patients and those with prior stroke or TIA

• 15-20% of all strokes are Atrial fibrillation (AF)-related

• AF results in greater disability compared to non-AF-related stroke

• High mortality and stroke recurrence rate

~5 Mpeople with AF in U.S., expected to more than

double by 20501

AF = most common cardiac arrhythmia,

and growing

AF increases risk of stroke

5xgreater risk of stroke

with AF2

<

‘15 ‘20 ‘30 ’40 ‘50

5M

12M

1. Go AS. et al, Heart Disease and Stroke Statistics—2013 Update: A Report From the American Heart Association. Circulation. 2013; 127: e6-e245.

2. Holmes DR, Atrial Fibrillation and Stroke Management: Present and Future, Seminars in Neurology 2010;30:528–536.

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Atrial fibrillation: Scope of the problem

AF related hospitalizations

almost tripled in 2000 compared with two decades ago

In 2001 the total annual costs for treatment of AF were estimated at

$6.65 billion in the US

As a result of increasing age and improved survival rates in those with coronary artery disease, heart failure, and hypertension, an

increase in the prevalence of atrial fibrillation is likely to be exponential and sustained in the foreseeable future.

As a result of increasing age and improved survival rates in those with coronary artery disease, heart failure, and hypertension, an

increase in the prevalence of atrial fibrillation is likely to be exponential and sustained in the foreseeable future.

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ParoxysmalParoxysmal

Recurrent, ≥2 episodes

Terminates spontaneously within 7 days

PersistentPersistent

Episodes lasting > 7 days

OR

Episodes that require intervention to terminate (medicationor electrical cardioversion)

Long-Standing PersistentLong-Standing Persistent

Continuous AF of > 1 year

Permanent Permanent

Mutual decision between patient and physician has been made to cease further attempts to restore/ maintain normal sinus rhythm by any means, including catheter ablation and surgery

Sub-types of AF

January 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary, Journal of the American College of Cardiology (2014), doi: 10.1016/j.jacc.2014.03.021.

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Progression of AF

of patients progress from Paroxysmal to Persistent AF within 1 year of diagnosis

20%

Typical ProgressionTypical Progression

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Over 60 Yrs of Age

Diabetes

Hypertension

Prior Myocardial Infarctions

Coronary Artery Disease

Structural Heart Disease

Untreated Atrial Flutter Chronic Lung

Disease

Congestive Heart Failure

Prior Open Heart Surgery

Thyroid Disease

Sleep Apnea

Excessive Alcohol Use

Serious IllnessOr Infection

Risk Factors of AF

http://www.hrsonline.org/Patient-Resources/Heart-Diseases-Disorders/Atrial-Fibrillation-AFib/Risk-Factors-for-AFib#sthash.vIHHAtio.dpuf

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Mechanisms of AF

Triggers Rotors

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AF ablation

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AF ablation versus medications

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Evolution of AF ablation technology

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Success rates with newer AF technology

ABLATION

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Stroke prevention in AF

CHA2DS2VASc STROKE RISK CRITERIA SCORE

C Congestive Heart Failure 1

H Hypertension 1

A Age ≥ 75 2

D Diabetes mellitus 1

S Stroke/TIA/Embolism 2

V Vascular Disease 1

A Age 65-74 Years 1

S Sex (female) 1

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Oral anticoagulation in AFWarfarin

• Bleeding risk

• Daily regimen

• High non-adherence rates

• Regular INR monitoring

• Food and drug interaction issues

• Complicates surgical procedures

Novel Oral Anticoagulants• Bleeding risk

• Daily regimen

• High non-adherence rates

• Complicates surgical procedures

• Lack of reversal agents

• High cost

CHADS2 Score

p < 0.001(n=27,164)

AF

Pat

ien

ts U

sin

g

An

tico

agu

lati

on

Anticoagulation Use Declines with Increased

Stroke Risk1

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2014 ACC/AHA/HRS Treatment Guidelines to Prevent Thromboembolism in Patients with AF

Score 1: Annual stroke risk 1%, oral anticoagulants or aspirin may be considered

Score ≥2: Annual stroke risk 2%-15%, oral anticoagulants are recommended

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AF and bleeding risk

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Use of NOAC at 2 years

Source: Martinez C, et al. Therapy Persistence in Newly Diagnosed Non-Valvular Atrial Fibrillation Treated with Warfarin or NOAC. A Cohort Study. Thromb Haemost. 2015 Dec 22;115(1):31-9. doi: 10.1160/TH15-04-0350.

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AF and Stroke risk

> 33Mpeople with AF Worldwide1

Many patients are unprotected

AF is the most common cardiac arrhythmia

AF increases risk of stroke

Blood clots form in the left atrial appendage

5xgreater risk of stroke with

AF2

>90%of stroke-causing clots that come from the left atrium in non-valvular

AF are formed in the LAA3

<90%

ThrombusOriginate LAA

10%Non-LAA

90%Thrombus

Originate LAA

10%Non-LAA

15%

15%70%

Treated with

WarfarinContraindicated

Intolerant

~45%of patients eligible for warfarin are untreated (tolerance/adherence)4

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AF and Stroke

Stasis-related LA thrombus is a predictor of TIA and ischemic stroke

In non-valvular AF, >90% of stroke-causing clots that come from the left atrium are formed in the LAA

1. Stoddard et al. Am Heart J. (2003)2. Goldman et al. J Am Soc Echocardiogr (1999)3 Blackshear JL. Odell JA., Annals of Thoracic Surg (1996)

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Left atrial appendage closure

For atrial fibrillation patients not undergoing cardiac surgery who should be treated with long-term oral anticoagulation to prevent embolization but for whom such therapy poses an unacceptably high risk of bleeding • Thrombocytopenia or known coagulation defect associated with

bleeding

• Recurrent gastrointestinal bleeding

• Prior severe bleeding, including intracranial hemorrhage

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LAA anatomy

Wind Sock:

An anatomy in which one

dominant lobe of sufficient

length is the primary structure

Chicken Wing:

An anatomy whose main feature is a

sharp bend in the dominant lobe of

the LAA at some distance from the

perceived LAA ostium

Broccoli:

An anatomy whose main feature

is an LAA that has limited overall

length with more complex

internal characteristics

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Transseptal puncture

Bicaval view: Poster

Short axis: Inferior

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Delivery system

Marker bands

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TEE and anatomy of LAA

Device should be at or just distal to the LAA ostium

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Endothelization of device

Canine Model – 30 Day

Canine Model – 45 Day Human Pathology - 9 Months Post-implant (Non-device related death)

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LAA closure video

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Time line for LAA closure

2005 – PROTECT AFRandomizedComparison: warfarin

2008 – CAP Registrynon-randomizedAdd’l patients and follow-up

2009 – ASAPnon-randomizedPatients Contra-indicated to warfarin*

2010 – PREVAILRandomizedComparison: warfarin

2013 EWOLUTION, WASP Registriesnon-randomizedReal-world, All comers

2012 – CAP2 Registrynon-randomizedAdd’l patients and follow-up

Apr 2009FDA Panel #1

Dec 2013FDA Panel #2

Oct 2014FDA Panel #3

2002 – PilotnonrandomizedFeasibility and Safety

Mar 2015FDA Approval

2016 NESTed SAPPost-approval statistical analysisfrom NCDR LAAO Registry data

2017 ASAP TOORandomizedUS Indication Expansion Worldwide study

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Clinical trials for LAA closure

Key Trials N Highlights

PROTECT AF1

(2005-2008)707

Prospective, randomized 2:1, non-inferiority trial of LAA closure vs. warfarin.

CAP2

(2008-2010)566

Prospective registry allowing continued access to the WATCHMAN Device and gain further information prior to PMA approval.

PREVAIL3

(2010-2012)407

Prospective, randomized 2:1, non-inferiority trial to collect additional information on the WATCHMAN Device.

CAP2(2012-2014)

579Prospective registry allowing continued access to the WATCHMAN Device prior to PMA approval.

EWOLUTION(2013-2015)4* 1025

Prospective registry allowing all patients receiving a WATCHMAN Device at participating centers in Europe, Middle East and Russia

Total patients

>3,000 ~9,000 Patient-Years of Follow-up

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Clinical Trial data

PROTECT AFCAP

Registry PREVAILCAP2

Registry

Enrollment 2005-2008 2008-2010 2010-2012 2012-2014

Purpose

Demonstrate safety and effectiveness of the

WATCHMAN implant compared to long-term

warfarin

Continued Access Registry

Demonstrate safety and effectiveness of

the WATCHMAN implant compared to long-term warfarin

Continued Access Registry

Study Design 2:1 Randomized, non-inferiority

Non-randomized2:1 Randomized,

non-inferiorityNon-randomized

Primary Endpoints

1. Effectiveness: Stroke, systemic embolism and cardiovascular/unexplained death

2. Safety: Life-threatening events, which include device embolization requiring retrieval and

bleeding events

1. Effectiveness: Stroke, systemic embolism and cardiovascular/unexplained death

2. Effectiveness: Ischemic stroke or systemic embolism, occurring after 7 days post-randomization or WATCHMAN implant

procedure3. Safety: Death, ischemic stroke, systemic

embolism and procedure/device-related complications within 7 days of implantation

procedure

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CHADS scores in trials

PROTECT AF

CHA2DS2-VASc Score ≥2

93%

High Risk

CAPPREVAILCAP2

Patients(%)

CHA2DS2-VASc Score

96%100%100%

Anticoagulation Eligible

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HAS BLED scores in the trials

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Implant success rates

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Complication rates

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Registry data for LAA closure devices

JAAC patient-level meta-analysis of 5 year data from two randomized clinical trials: PROTECT AF and PREVAIL,

5-Year Outcomes After Left Atrial Appendage Closure: From the PREVAIL and PROTECT AF Trials

• 55% reduction in disabling and fatal stroke

• 80% reduction in hemorrhagic stroke

• 52% reduction in non-procedure related major bleeding

• 27% reduction in all-cause mortality

• 41% reduction in cardiovascular/unexplained death

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New ACC/AHA guidelines

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current trends in the management of atrial …...source: martinez c, et al. therapy persistence in...

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