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Transcatheter Aortic Valve
Replacement: Expanding to
“Intermediate Risk” Patients
Jeffrey J. Popma, MD
Director, Interventional Cardiology
Clinical Services
Beth Israel Deaconess Medical Center
Associate Professor of Medicine
Harvard Medical School
Boston, MA
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Jeffrey J. Popma, MD
Contracted Research / Grant Support:
Abbott Vascular
Abiomed, Inc.
Atrium Medical Corporation
Boston Scientific Corporation
Cordis Corporation
IDEV Technologies, Inc.
Medtronic, Inc.
Consulting Fees:
Abbott Vascular
Boston Scientific Corporation
My presentation will include off label
discussions:
Percutaneous aortic valves
Better TAVR Outcomes in Lower Risk Patients
N=420 patients (105 per quartile)
Quartile 1
Quartile 4
81.1 years
78.9 years
Logistic Euroscore, %
25.4%
17.8%
STS-PROM, %
7.13%
4.8%
Crude 30 day Mortality, %
11.4%
3.8%
Age, years
Lange JACC 2012;59:280–7
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European ‘’On-Label’’ and ‘’Off-Label ’’ Use
Piazza Heart 2010;96:19–26.
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European ‘’On-Label’’ and ‘’Off-Label ’’ Use
Better Survival in “Off-Label”
No Change in Stroke
But at an increased risk of bleeding (5% on-label; 14% off label)
Piazza Heart 2010;96:19–26.
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Intermediate Populations
“Risk Creep”
Favors TAVR
Preferentially
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“Risk Creep” Favors TAVR Preferentially
Bern Windecker
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Expanding Into Risk Populations
Top 33% Surgical Risk
STS ≥ 4
30-Day Mortality < 2-4%
Intermediate
≈ 26%
Surgical Aortic Valve Replacements 70-90,000 yearly
PARTNER B
CoreValve Extreme
Risk
STS PROM < 4%
PARTNER IIA
SURTAVI
PARTNER A
CoreValve High Risk
Two-thirds of patients will
remain optimal surgical
candidates
Top 7% Surgical Risk
“Cohort C”
STS > 8
Extreme
Risk
Inoperable 20-50K
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Patient Selection
Presented By Prof. Patrick Serruys, MD on behalf of
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SURTAVI Trial Leadership
Chairmen:
• Prof. P.W. Serruys (Chair)
• Dr. N. van Mieghem (Deputy Chair)
Principal Investigators:
• Prof. S. Windecker
• Prof. A.P. Kappetein
• Prof. R. Lange
• Prof. T. Walther
• Dr. J. Popma
• Dr. D. Adams
• Dr. M. Reardon
Serruys SURTAVI TCT2011
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Identifying Intermediate Risk Patients
Serruys SURTAVI TCT2011
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Identifying Intermediate Risk Patients
Serruys SURTAVI TCT2011
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Operability is a Risk Continuum
¿
TAVR
or
AVR
Low
Risk
Intermed
Risk
High
Risk
< 5%
5-15%
>15%
~20-25%
~10%
Surgery (AVR)
OR risk
% patients
~65-70%
Serruys SURTAVI TCT2011
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STS PROM (2006-2010)
STS ≥ 3
STS ≥ 4
STS ≥ 5
Leon PARTNERII A TCT2011
46%
33%
25%
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BERMUDA Results
Serruys SURTAVI TCT2011
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Heart Team Assesment May Vary From STS
Serruys SURTAVI TCT2011
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BERn – MUnich – rotterDAm Registry
3666 patients enrolled
TAVI – 782
SAVR – 2884
2882 patients excluded based
on propensity scores
784 matched patients
TAVI – 392
SAVR - 392
274 patients excluded based
on STS score <3% and >8%
510 matched patients (STS scores 3-8%)
TAVI
255 patients analyzed
Serruys SURTAVI TCT2011
SAVR
255 patients analyzed
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BERn – MUnich – rotterDAm Registry
Matched Cohort
Age (years)
STS
<3
n=184
STS
3-8
n=510
STS
>8
n=90
77.3 (4.7)
80.1(5.3)
81.7 (5.3)
17.6 (10.5)
25.1(17.1)
Logistic ES (%) 13.5 (8.4)
TAVI vs. SAVR
92 vs. 92
Serruys SURTAVI TCT2011
255 vs.
255
45 vs. 45
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BERn – MUnich – rotterDAm Registry
One Year Outcome In Intermediate Risk Patients
Serruys SURTAVI TCT2011
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SURTAVI: Primary Objective
Evaluate in a prospective randomized
fashion whether TAVI is non-inferior to
SAVR with respect to the event free
survival of the combined endpoint of allcause mortality and major stroke at 24
months in patients with symptomatic
severe aortic stenosis and at
intermediate surgical risk.
Serruys SURTAVI TCT2011
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SURTAVI: Study Design
• Patient population
– Symptomatic severe aortic stenosis
– Intermediate surgical risk, defined by
Society of Thoracic Surgeons (STS)
mortality risk:
• ≥ 3% and ≤ 8-10% (OUS)
• ≥ 4% and ≤ 8-10% (US)
• Long-term follow-up through 5 years
– Enrollment phase ~ 20 months
– Trial duration ~ 7 years
Serruys SURTAVI TCT2011
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SURTAVI: Inclusion Criteria
1. Subject must have STS mortality risk score ≥ 3%
and ≤ 8% (in United States, STS mortality risk
score ≥4% and ≤8%)
2. Heart Team consisting of at least one
interventional cardiologist and one cardiac
surgeon agree on indication, treatment proposal,
and eligibility for randomization based on their
clinical judgment
3. Critical aortic valve area defined as an initial
aortic valve area of ≤1.0 cm2 or aortic valve area
index < 0.6 cm2/m2
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SURTAVI: Inclusion Criteria
4. In presence of normal LV function: mean gradient >
40mmHg OR Vmax > 4m/sec.
5. In the presence of reduced LV function and a mean
gradient < 40 mmHg AND Vmax < 4 m/sec,
dobutamine stress echo may be give to increase
the mean gradient >40mmHg or Vmax < 4 m/sec
5. Subject is symptomatic from his/her aortic valve
stenosis, as demonstrated by New York Heart
Association (NYHA) Functional Class II or greater
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SURTAVI: Exclusion Criteria
9.
Active Gastrointestinal (GI) bleeding within the
past 3 months
10. Subject refuses a blood transfusion
11. Severe dementia (resulting in either inability to
provide informed consent for the trial/procedure,
prevents independent lifestyle outside of a
chronic care facility, or will fundamentally
complicate rehabilitation from the procedure or
compliance with follow-up visits)
12. Multivessel coronary artery disease with a
Syntax score >22
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SURTAVI: Exclusion Criteria
18.
19.
20.
21.
True porcelain aorta
Extensive mediastinal radiation
Liver failure (Child-C)
Reduced ventricular function with left ventricular
ejection fraction (LVEF) <30% as measured by
resting echocardiogram
22. Uncontrolled atrial fibrillation
23. Pregnancy or intent to become pregnant prior to
completion of all protocol follow-up requirements
24. End stage renal disease requiring chronic dialysis
or creatinine clearance < 20 cc/min
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SURTAVI: Exclusion Criteria
25. Native aortic annulus size < 20 mm or > 29 mm
26. Pre-existing prosthetic heart valve in any position
27. Mixed aortic valve disease [AS and AR with
predominant AR (3-4+)]
28. Severe mitral or severe tricuspid regurgitation
29. Severe mitral stenosis
30. Hypertrophic obstructive cardiomyopathy
31. Echocardiographic or Multislice Computed
Tomography (MSCT) evidence of intracardiac mass,
thrombus or vegetation
32. Ascending aorta diameter > 43 mm unless the
aortic annulus is 20-23 mm in which case the
ascending aorta diameter > 40 mm
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SURTAVI: Study Design
OUS
US
STS mortality risk
≥3% and ≤8%
STS mortality risk
≥4% and ≤8%
Heart Team Evaluation
including assessment for significant
CAD with determination of need for
revascularization
Meet I/E Criteria
and eligible for
SAVR and TAVI
QoL Questionnaire
Randomization
Neurological
Assessments
with 5 year follow up
Presence of
significant CAD
with intended
revascularization
TAVI + PCI
SAVR + CABG
No intended
revascularization
TAVI
SAVR
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PARTNER II – Intermediate Risk
Symptomatic Severe Aortic Stenosis
ASSESSMENT by Heart Valve Team
2 Parallel RCTs:
Individually Powered
Intermediate Risk
Inoperable
ASSESSMENT:
Yes
Transfemoral (TF)
1:1 Randomization
TF TAVR
Sapien XT
AVR
VS
ASSESSMENT:
No
Transfemoral
Access
Transfemoral
Access
Transapical (TA)
1:1 Randomization
TA TAVR
Ascendra 2
AVR
VS
Primary Endpoint: All-Cause Mortality +
Major Stroke at Two Years
(Non-inferiority)
Yes
No
1:1 Randomization
TF TAVR
Sapien XT
Not In Study
TF TAVR
Sapien
VS
Primary Endpoint: All-Cause Mortality +
Major Stroke + Repeat Hospitalization at One Year
(Non-inferiority)
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PARTNER II – Intermediate Risk
• Severe, symptomatic calcific AS (echo criteria)
• Intermediate risk = STS score ≥ 4% OR specific qualifying
intermediate risk criteria
• Includes AS patients with CAD requiring treatment…
 AS + CAD patients substratified to compared (TAVR + PCI vs.
AVR + CABG)
 “Complex” CAD excluded (unprotected LM lesions, MVD with
Syntax score ≥ 33)
 All CAD treatment patients reviewed by EC sub-committee for
study inclusion
 Less aggressive complete revascularization acceptable (both
for TAVR and AVR)
• TF-TAVR includes vascular anatomy appropriate for lower
profile Sapien XT + Novaflex system
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PARTNER II – Intermediate Risk
• Non-inferiority of TAVR-Sapien XT vs. sAVR for the
primary endpoint for the duration of the study (all patients
followed for at least 2 years)
• Primary endpoint is a nonhierarchical composite of allcause mortality and major stroke (mRankin score ≥ 2 at 90
days)
• Non-inferior if one-sided 95% upper confidence limit for
the treatment difference (∆) is < 20% of control; α =0.05
and power = 80%
• Based on PARTNER 1 High-risk study results in AVR
control arm (death + stroke at 1-year = 28%); assumed
event rate for primary endpoint in control 30% (discounted
for intermediate risk and adjusted for longer 2-year FU)
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PARTNER II – Intermediate Risk
• 1:1 randomization between TAVR (Sapien XT)
vs. AVR
• Estimated sample size = 1744 patients (872
patients per arm); study sample size = 2,000
patients to account for lost-to-FU, withdrawals,
and other study contingencies; (? mid-course
pre-specified adjustment in final SAP)
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PARTNER II – Intermediate Risk
• FDA approved for enrollment Nov 4, 2011
• Up to 50 study sites (all U.S.)
• VARC definitions
• More intense neurologic assessments (100%
qualified neurology pre- and post-evaluations) and
neurocognitive function substudies
• Detailed frailty assessments
• Incorporate TAVR Best Clinical Practices, including
adjunctive pharmacology regimens (anti-platelet
and anti-thrombin therapy)
• ? Incorporate cerebral embolic protection (later
portion of study)
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Intermediate Risk Populations: Summary
• Outcomes will definitely be better with
TAVI in lower risk populations, but so will
the outcomes in patients undergoing sAVR
• Two big concerns: Perivalvular AR and
Stroke
• Aim to lower PPM rate with good
implantation technique
• Randomized trials are essential
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