1. No category

Treatment of High Risk Aortic Stenosis
Patients with Transcatheter Medtronic
CoreValve Implantation
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
Investigators
Axel Linke
University of Leipzig Heart Center, Leipzig, Germany
Ulrich Gerckens
Gemeinschaftskrankenhaus Bonn, Bonn, Germany
Peter Wenaweser
University Hospital Bern, Bern, Switzerland
Corrado Tamburino
Ferrarotto Hospital, University of Catania, Catania, Italy
Johan Bosmans
University Hospital Antwerp, Antwerp Belgium
Stephen Brecker
St. George’s Hospital, London, United Kingdom
Robert Bauernschmitt ISAR Heart Center, Munich, Germany
(on behalf of the ADVANCE investigators)
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
CoreValve® ADVANCE
Background
Transcatheter Aortic Valve Implant (TAVI) enables treatment of
aortic valve stenosis without open-heart surgery.
Balloon-expandable TAVI
• Superior to standard medical therapy in inoperable patients
• Non-inferior to surgical AVR in high-risk patients with AS in a
randomized controlled trial
Neither balloon-expandable or self-expanding TAVI have been
studied in a rigorous, monitored, independently adjudicated,
‘real world’ study.
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
CoreValve® ADVANCE
Background
Medtronic CoreValve® System
• Porcine pericardial tissue valve
sutured into a self-expanding
nitinol frame
• Supra-annular valve position
preserves circularity at level of
valve function
• 3 valve sizes
• 18Fr catheter delivery system
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
CoreValve® ADVANCE
Objective
The objective of the CoreValve ADVANCE study is
to evaluate the:
• safety
• efficacy
• clinical outcome according to VARC
of percutaneous aortic valve implantation using the Medtronic
CoreValve System in consecutive ‘real world’ patients with
severe aortic stenosis considered
• inoperable or high risk
for conventional AVR by the local ‘HEART TEAM’.
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
CoreValve® ADVANCE
Methods
1,015 patients enrolled
• From March 2010 to July 2011
Patients Enrolled
N = 1,015
19 – No Implant Attempted
• 5 year follow-up
44 centers
• 12 countries in Western Europe,
Asia and South America
All centers had conducted at least
40 TAVI procedures prior to the
study and had Heart Team in place
Clinical endpoints reported
according to Valve Academic
Research Consortium (VARC)
(e.g. death prior to procedure or
transapical access chosen prior
to procedure)
Patients Implanted
N = 996
45 – Deaths
1 – Withdrawal
30-Day Follow-Up
950/951 (99.9%)
79 – Deaths
9 – Withdrawals
6-Month Follow-Up
862/872 (98.9%)
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
CoreValve® ADVANCE
Primary Endpoint
Primary Endpoint—Major Adverse Cardiac & Cerebrovascular
Events (MACCE) at 30-days post procedure
• MACCE defined as a composite of:
• All cause mortality
• Myocardial infarction (Q-wave and non-Q-wave)
• Emergent cardiac surgery or percutaneous re-intervention
• Stroke
Clinical endpoints reported according to VARC
• All cause and cardiovascular mortality
• Myocardial infarction
• Stroke
• Life-threatening bleeding
• Major vascular complications
• Acute kidney injury
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
CoreValve® ADVANCE
Study Oversight
100% of all patients were monitored
All primary endpoint events adjudicated by an independent
Clinical Events Committee (CEC) consisting of TAVIexperienced Interventional Cardiologists and Cardiac Surgeon
All Cerebrovascular events adjudicated by an Independent
Neurologist
• Adjudication of events utilized all available relevant source documents;
including neuroimaging and systematic NIH Stroke Scale assessments
Core Laboratory
• Systematic review and assessment of ECGs and Procedural
Angiograms
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
CoreValve® ADVANCE
Baseline Characteristics
Characteristics (n=1015)
%
Age (yrs.)
Male
Logistic EuroSCORE
%
81 ± 6
Prior MI
16.0
49.4
Prior PCI
31.1
Permanent Pacemaker
12.8
19.2 ± 12.4
EuroSCORE Relevant Factors
NYHA
I or II
20.4
Prior CABG
21.4
III or IV
79.6
Cerebrovascular Disease
12.9
Diabetes
30.9
COPD
22.6
CAD
57.6
Pulmonary Hypertension
12.6
PVD
19.5
Prior Median Sternotomy
17.3
Atrial Fibrillation
32.8
Renal Failure
14.6
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
CoreValve® ADVANCE
Procedural Results
Procedural Parameters (N=996)
%
Successful vascular access, delivery & deployment of device
& successful retrieval of the delivery system
97.8
Correct position of the device in the proper anatomical location
98.7
Mean aortic valve gradient < 20 mmHg
96.2
No severe grade AR requiring intervention
97.9
Only one valve implanted in the proper anatomical location
96.0
Major Complications; Valve Related (N=996)
Annulus Rupture
0.0
Valve Embolization
0.3
Conversion to Open AVR
0.1
Coronary Compromised
0.1
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
CoreValve® ADVANCE
45.6
50
1.7
1.7
1.7
40
1.6
1.2
30
Effective Orifice Area (cm2)
Mean Gradient (mm Hg)
0.8
20
0.7
9.8
0.4
9.3
9.5
10
0
0
Baseline
Discharge
30-days
Follow-Up Visit
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
6-months
Mean Gradient (mm Hg)
Effective Orifice Area (cm2)
2
Valve Performance
CoreValve® ADVANCE
100%
Symptom Status
2%
1%
13%
12%
47%
44%
38%
43%
1 Month
6 Month
12%
80%
60%
67%
40%
20%
0%
17%
4%
Baseline
NYHA I
NYHA II
NYHA III
NYHA IV
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
CoreValve® ADVANCE
30-Day Outcomes
Primary Endpoint (N=996)
MACCE
Kaplan-Meier Estimates, %
8.3
All Cause Mortality
4.5
Myocardial Infarction
0.2
Emergent Cardiac Surgery or Percutaneous Re-Intervention
1.7
Stroke
2.9
Additional VARC Endpoints (N=996)
Kaplan-Meier Estimates, %
Cardiovascular Mortality
3.4
Major Bleeding
9.7
Life-Threatening Bleeding
4.0
Major Vascular Complications
10.7
Acute Kidney Injury – Stage III
0.4
Additional Endpoint (N=996)
New Pacemaker Implantation
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
Kaplan-Meier Estimates, %
26.3
6-Month Survival
CoreValve® ADVANCE
Kaplan-Meier Estimates of Freedom from All Cause Mortality (VARC)
and Cardiovascular Mortality (VARC)
Survival Distribution Function
1
96.6%
91.6%
95.5%
0.9
87.2%
0.8
0.7
P-value (log rank) < 0.001
All Cause Survival (N=996)
Cardiovascular Survival (N=996)
0.6
0.5
0
1
2
3
4
Months Post-Procedure
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
5
6
6-Month Survival
CoreValve® ADVANCE
Kaplan-Meier Estimates of Freedom from All Cause Mortality
by EuroSCORE Group
1
96.7%
Survival Distribution Function
92.3%
0.9
95.8%
94.2%
88.2%
82.7%
0.8
0.7
P-value (log rank) < 0.001
EuroSCORE 0-10 (N=241; 7.2 ± 2.1)
0.6
EuroSCORE 10-20 (N=408; 14.7 ± 2.8)
EuroSCORE >20 (N=346; 32.5 ± 11.1)
0.5
0
1
2
3
4
Months Post-Procedure
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
5
6
6-Month Survival
CoreValve® ADVANCE
Kaplan-Meier Estimates of Freedom from Cardiovascular Mortality
by EuroSCORE Group
Survival Distribution Function
1
97.5%
95.7%
96.8%
95.7%
0.9
92.4%
88.1%
0.8
0.7
P-value (log rank) = 0.006
EuroSCORE 0-10 (N=241; 7.2 ± 2.1)
0.6
EuroSCORE 10-20 (N=408; 14.7 ± 2.8)
EuroSCORE >20 (N=346; 32.5 ± 11.1)
0.5
0
1
2
3
4
Months Post-Procedure
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
5
6
6-Month Stroke
CoreValve® ADVANCE
Kaplan-Meier Estimates of Freedom from Stroke (VARC)
Survival Distribution Function
1
97.1%
96.6%
0.9
0.8
0.7
0.6
0.5
0
1
2
3
4
Months Post-Procedure
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
5
6
CoreValve® ADVANCE
Summary and Conclusions
The CoreValve ADVANCE study, which is the largest,
multicenter, prospective, fully monitored TAVI study, shows that
treatment of ‘real world’ inoperable and frail, high-risk patients
with the Medtronic CoreValve is:
• Safe
• Associated with:
• an improvement in aortic valve function
• low stroke and mortality rates at 1 month and 6 months follow-up
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
CoreValve® ADVANCE
Hospital
Universitat Leipzig Herzzentrum (DE)
Deutsches Herzzentrum Munchen (DE)
Leeds General Infirmary (UK)
Asklepios Klinik St. Georg Hamburg (DE)
Helios Klinikum Siegburg - Herzzentrum (DE)
Inselspital, University Hospital Bern (CH)
Azienda Ospedaliero Universitaria Policlinico
Vittorio Emanuele di Catania (IT)
Rigshospitalet (DK)
CardioVascular Center Frankfurt (DE)
Study Centers
Pts. Enrolled
100
79
57
54
49
47
Hospital
Amphia Hospital Breda (NL)
St. George's Hospital (UK)
Tel Aviv Sourasky Medical Center (IS)
St. Antonius Hospital Nieuwegein (NL)
ZNA Antwerpen Middelheim (BE)
Newcross Hospital Wolverhampton (UK)
Pts. Enrolled
18
15
14
12
10
9
43
University Hospital Zürich (CH)
8
39
39
Ospedale Civile (IT)
Catharina Hospital Eindhoven (NL)
Hospital de Santa Cruz Centro Hospitalar de
Lisboa Ocidental (PT)
The Heart Hospital (UK)
Glenfield Hospital (UK)
Angiografia de Occidente (CO)
Hopital Henri Mondor (FR)
Hopital Louis Pradel (FR)
Centro Hospitalar de Vila Nova de Gaia (PT)
The Chaim Sheba Medical Center (IS)
Azienda Ospedaliere Spedali Civili di Brescia
(IT)
AMC Hospital (NL)
Azienda Ospedaliero Universitaria Careggi (IT)
Institut Hospitalier Jacques Cartier (FR)
Onassis Cardiac Surgery Center (GR)
8
8
University Hospital Antwerp (BE)
36
Ospedale Niguarda Ca'Granda (IT)
Universitatsklinikum Aachen (DE)
Clinique Pasteur (FR)
Fondazione Centro San Raffaele (IT)
CHU Sart Tillman (BE)
Istituto Clinico S. Ambrogio (IT)
Groupe hospitalier Pitié-Salpêtrière (FR)
Immanuel Klinikum Bernau Herzzentrum
Brandenburg (DE)
Hadassah Medical Center (IS)
Istituto Clinico Humanitas (IT)
Brighton and Sussex Hospital (UK)
Hôpital Cardiologique - CHRU de Lille (FR)
35
32
30
29
29
24
24
23
20
20
18
18
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
7
7
6
6
6
6
5
5
5
5
4
4
2
INTERNATIONAL
CAUTION: For distribution only in markets where CoreValve has been approved. Not approved in the USA, Canada or Japan.
CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.