The Risk and Extent of Neurological
Events Are Equivalent for High-Risk
Patients Treated With Transcatheter or
Surgical Aortic Valve Replacement
Thomas G. Gleason, MD
On Behalf of the CoreValve US Clinical Investigators
Disclosure Statement of Financial Interest
Within the past 1 year, I or my spouse/partner have had a financial
interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
Company
Institutional Grants
Medtronic, Inc.
Under direction from Dr. Gleason, Medtronic performed all statistical analyses and assisted in the graphical display of the data.
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Background & Objectives
• Post-procedural strokes significantly affect both quality of life and
survival.
• Rigorous neurologist-adjudicated stroke assessment has not been
applied to most of the previously reported trials comparing TAVR
and SAVR.
• Thus the extent and characteristics of stroke following AVR have
not previously been well described.
• Neurological events from the CoreValve US Pivotal High Risk Trial
and comprehensive cognitive assessments for a neurological
substudy were carefully evaluated.
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Patients
CoreValve US Pivotal High Risk Trial
TAVR
N=391
SAVR
N=359
Assessed
neurological
events through
2 years
Enrolled in Neurological Substudy*
TAVR
N=111
SAVR
N=88
Assessed
neurological
events in detail
through 1 year
Substudy Cohort
N=199
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*Pivotal high-risk patients volunteered for additional testing
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Stroke Assessment
• The CoreValve US Pivotal High Risk Trial:
– Systematically collected National Institute of Health Stroke Scale (NIHSS) in all
patients
– Modified Rankin Scale (MRS), neurology consultation and neuroimaging
triggered in any patient with neurologic abnormality and serially after any
stroke
• Neurological substudy patients underwent comprehensive cognitive
assessments by a neurologist:
–
–
–
–
Minimental State Examination
Visual fields testing
Gait & motor assessment
Writing & drawing evaluation
• Stroke was defined by VARC-1 criteria
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Study Device and Access Routes
4 Valve Sizes (23, 26, 29, 31 mm)
(18-29 mm Annular Range)
18F Delivery System
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Transfemoral
Subclavian
Direct Aortic
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Neurological Outcomes From the
CoreValve Pivotal High Risk Trial
30 Days
Event*
Stroke
TAVR SAVR
1 Year
P
TAVR SAVR
2 Years
P
TAVR SAVR
P
4.9
6.2
0.46
8.7
12.5
0.11
10.9
16.6
0.05
Major stroke
3.9
3.1
0.55
5.8
6.9
0.61
6.8
9.8
0.25
Ischemic
3.6
2.5
0.39
5.0
5.4
0.87
5.7
6.7
0.70
Hemorrhagic
0.3
0.0
0.34
0.8
0.9
0.88
1.2
1.8
0.58
Undetermined
0.0
0.6
0.14
0.0
0.6
0.14
0.3
1.4
0.13
1.0
3.4
0.03
3.0
6.0
0.05
4.2
7.3
0.08
0.8
0.3
0.36
1.6
1.6
0.92
2.6
1.6
0.41
Minor stroke
TIA
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CoreValve High Risk Pivotal Trial
Stroke or TIA
No. at Risk
TAVR
SAVR
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391
359
361
323
313
251
198
165
8
CoreValve High Risk Pivotal Trial
Major Stroke
No. at Risk
TAVR
SAVR
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391
359
368
335
326
271
214
184
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Neurological Outcomes From the
CoreValve Pivotal High Risk Trial By Access Route
30 Days
1 Year
2 Years
Iliofemoral
NonIliofemoral
Iliofemoral
NonIliofemoral
Iliofemoral
NonIliofemoral
TAVR
SAVR
TAVR
SAVR
TAVR
SAVR
TAVR
SAVR
TAVR
SAVR
TAVR
SAVR
5.9
5.3
4.5
12.3
10.8
12.5
7.7
22.3
14.2
15.6
7.7
30.0
5.0
5.0
4.5
12.3
8.9
10.7
7.7
22.3
11.5
14.1
7.7
30.0
Major stroke
3.7
2.0
4.5
8.8
5.7
4.6
6.1
18.7
6.9
7.1
6.1
23.8
Minor stroke
1.3
3.0
0.0
5.3
3.2
6.1
1.6
5.3
4.7
7.1
1.6
8.3
0.9
0.3
0.0
0.0
2.0
1.9
0.0
0.0
3.1
1.9
0.0
0.0
Event*
Any stroke or TIA
Stroke
TIA
*Kaplan-Meier rates. Yellow Text = P <0.05.
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Timing of TIA, Major & Minor Strokes
to 30 Days
Days from Implant to Event
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Timing of TIA, Major & Minor Strokes
to 2 Years
Time from Implant to Event
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Mortality in Patients with Any Stroke
Within 30 Days for TAVR & SAVR
No. at Risk
TAVR
SAVR
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19
22
13
19
7
14
3
9
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Mortality in Patients with Major Stroke
Within 30 Days for TAVR & SAVR
No. at Risk
TAVR
SAVR
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15
11
9
8
5
5
2
2
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Mortality in TAVR Patients with
& without a Major Stroke Within 30 Days of Implant
No. at Risk
Major Stroke
No Major
Stroke
15 10
376 368
5
329
2
217
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Mortality in SAVR Patients with
& without a Major Stroke Within 30 Days of Implant
No. at Risk
Major Stroke
No Major
Stroke
11 8
348 335
5
277
2
189
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Predictors of Early Stroke
Predictors of Early (0-30 Days) Stroke Following TAVR*
Kaplan Meier Rate
[95% CI] no.
Univariable Analysis
Multivariable
HR
95% CI
P Value
HR
95% CI
P
Value
3.16
1.18, 8.44
0.02
3.18
1.23, 8.21
0.02
Peripheral vascular
disease
8.3 [4.9, 13.9] 159
3.21
1.22, 8.44
0.02
Nocturnal bipap
13.8 [5.4, 32.7] 29
3.32
1.10, 10.0
0.03
Falls in past 6
months
9.9 [4.8, 19.6] 72
2.91
1.13, 7.51
0.03
*There were no univariable or multivariable predictors of early stroke found for the SAVR group.
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Predictors of Stroke at 1 Year
Predictors of 1-Year Stroke Following TAVR*
Univariable
Peripheral vascular
disease
Severe aortic
calcification
History of
hypertension
Severe Charlson
Comorbidity Score (≥5)
Multivariable
Kaplan Meier Rate
[95% CI] no.
HR
95% CI
P
Value
HR
95% CI
P
Value
12.4 [8.1, 18.7] 159
2.06
1.03, 4.10
0.04
17.7 [9.2, 32. 3] 47
2.42
1.09, 5.36
0.03
2.37
1.07, 5.26
0.03
7.8 [5.4, 11.1] 372
0.28
0.11, 0.73
0.009
0.26
0.10, 0.68
0.006
13.3 [9.3, 18.9] 211
3.95
1.63, 9.57
0.002
3.91
1.61, 9.48
0.003
0.15, 0.97
0.04
Predictors of 1-Year Stroke Following SAVR
NYHA class III/IV
11.1 [7.9, 15.3] 312
0.47
0.23, 0.96
0.04
Angina
6.0 [2.5, 13.9] 91
0.38
0.15, 0.96
0.04
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Baseline Demographics for Patients in the
Neurological Substudy
TAVR
N=111
SAVR
N=88
82.3 ± 7.4
83.7 ± 7.3
55.0
59.1
7.0 ± 3.0
7.4± 3.7
17.2 ± 13.8
18.6 ± 14.1
Modified Rankin 0 or 1
89.2
40.5
35.1
17.1
72.2
87.5
42.0
36.4
14.8
91.7
Modified Rankin >1
27.8
8.3
NIH Stroke Scale 0
NIH Stroke Scale 1-5
Prior TIA
72.2
63.6
27.8
18.1
36.4
15.9
Characteristic, % or mean ± SD
Age (years)
Men
STS Predicted Risk of Mortality (%)
Logistic EuroSCORE (%)
NYHA Class III/IV
Atrial fibrillation/flutter
Diabetes mellitus
Prior stroke
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Non-STS Comorbidity, Frailty, Disability
for the Neurological Substudy
TAVR
N=111
SAVR
N=88
Home oxygen
9.1
9.1
Anemia
14.2
11.1
Albumin < 3.3mg/dL
10.1
13.3
Severe (≥5) Charlson comorbidity
51.4
62.5
Falls in past 6 months
20.7
20.5
5-Meter gait speed >6 seconds
78.4
79.3
Katz ≥2 ADLs deficits
0.0
2.3
26.7 ± 2.6
26.4 ± 2.8
Assessment, % or mean ± SD
Mini-Mental State Examination
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Neurological Assessment Changes
from Baseline to Discharge in Substudy Patients
Assessment
TAVR
SAVR
P Value
NIH Stroke Scale – Increase by ≥ 2
3.5 (3/85)
12.7 (8/63)
0.05
Mini-Mental State Examination Decreased by > 4
2.5 (2/79)
10.9 (6/55)
0.06
New Gait Abnormality
7.8 (6/77)
15.5 (9/58)
0.16
Weakness in Left Hand Motor Function
7.2 (5/69)
6.5 (3/46)
>0.99
Weakness in Right Hand Motor Function
7.2 (5/69)
10.4 (5/48)
0.74
Failed Writing Evaluation
5.1 (4/79)
8.5 (5/59)
0.50
Failed Drawing Evaluation
23.5 (12/51)
25.6 (10/39)
0.82
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Neurological Assessment Changes
from Baseline to 1 Year in Substudy Patients
Assessment
TAVR
SAVR
P Value
NIH Stroke Scale – Increase by ≥ 2
1.5 (1/65)
4.9 (2/41)
0.56
Mini-Mental State Examination Decreased by > 4
8.1 (5/62)
2.5 (1/40)
0.40
New Gait Abnormality
6.8 (4/59)
7.7 (3/39)
>0.99
Weakness in Left Hand Motor Function
0.0 (0/56)
5.7 (2/35)
0.15
Weakness in Right Hand Motor Function
0.0 (0/55)
5.4 (2/37)
0.16
Failed Writing Evaluation
1.6 (1/61)
10.0 (4/40)
0.08
Failed Drawing Evaluation
10.9 (5/46)
11.1 (3/27)
>0.99
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Conclusions
• This study demonstrates equivalent post-procedural, neurologistadjudicated stroke risk and extent of neurological injury following
TAVR or SAVR in a high risk population.
• Vascular disease, fall history, severe aortic calcification, and a
severe Charlson Score appear to be predictors of stroke after
TAVR.
• Two-year mortality rate after an early TAVR- or SAVR-associated
stroke is very high.
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