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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