1. Preventive Role of Embolic Protection Devices:
Silent Cerebral Injury after TAVI and the
Preventive Role of Embolic Protection Devices:
A Systematic Review and Meta-Analysis
Matteo Pagnesi, MD; Enrico A. Martino, MD; Mauro Chiarito, MD; Antonio Mangieri, MD; Richard J. Jabbour, MD; Nicolas M. Van Mieghem, MD, PhD; Susheel K. Kodali, MD; Cosmo Godino, MD; Giovanni Landoni, MD; Antonio Colombo, MD; Azeem Latib, MD
San Raffaele Scientific Institute, Milan, Italy

2. Potential conflicts of interest
Speaker’s name: Matteo Pagnesi
I do not have any potential conflict of interest

3. Background
Overall stroke rate after TAVI: 1.5% at 24 h; 3.3% at 1 m; 4.3%
at 6 m; 5.2% at 1 y (Eggebrecht et al. EuroIntervention 2014)
30-day major stroke 2.4% with 2nd generation THVs (Athappan et al. EuroIntervention 2016)
30-day all-stroke rate 5.5% in PARTNER IIA trial (Leon et al. New Eng J Med 2016)
Most ischemic CVEs result from cerebral embolization of aortic debris or thrombotic material (Van Mieghem et al. Circulation 2013)
Silent cerebral injury is dramatically more frequent than clinically apparent CVEs and has controversial prognostic significance
EPDs may reduce the risk of early neurological injury during or
after TAVI

4. Embolic protection devices
Claret Montage and Sentinel CPS
(Claret Medical, Santa Rosa, California)
EMBOL-X system
(Edwards Llifesciences, Irvine, California)
TriGuard HDH device
(Keystone Heart, Caesarea, Israel)
Embrella Embolic Deflector system
(Edwards Lifesciences, Irvine, California)

5. Aims
To perform a pooled analysis of all prospective studies reporting DW-MRI outcomes after unprotected TAVI
Evaluation of the incidence and features of TAVI-related silent cerebral injury
To perform a meta-analysis of studies evaluating EPDs during TAVI
Assessment of the efficacy of EPDs on DW-MRI endpoints

6. Study selection process

7. Pooled analysis Characteristics of the pooled studies
Study
Design n
Approach
Device
Age (years)
Male (%)
Log EuroSCORE (%)
Timing of DW- MRI (days)
Kahlert et al. 2010
Prospective 32 TF
22 SAPIEN, 10 CoreValve
80.0 ± 3.0*
14 (44)
21.3 ± 9.0*†
3.5 ± 1.8*†
Ghanem et al. 2010 22
CoreValve
79.3 ± 4.8
8 (37)
19.4 ± 13.5
2.2 ± 0.4
Arnold et al. 2010 25 TA
SAPIEN
81.0 ± 5.0
10 (40)
32.3 ± 10.0
6.0 ± 2.0
Rodés-Cabau et al. 2011 60
29 TF, 31 TA
SAPIEN/XT
83.0 ± 7.0
30 (50)
18.9 ± 12.8
4.0 ± 1.0
Astarci et al. 2011 35
21 TF, 14 TA
85.2 ± 4.4†
26 (74)
33.2 ± 16.2†
2 days
Fairbairn et al. 2012 31
81.0 ± 5.9
11 (36)
23.9 ± 16.4
5.0 ± 1.5*
Ghanem et al. 2013
111
16 SAPIEN, 95 CoreValve
80.0 ± 6.0
60 (54)
24.3 ± 14.7
3 days
Knipp et al. 2013 27
82.2 ± 4.7
7 (26)
36.4 ± 13.2
11.7 ± 6.2
Astarci et al. 2013 44
26 TF, 18 TA
84.8 ± 5.1†
31 (71)
31.7 ± 15.3†
2-3 days 61
30 (49)
26.4 ± 18.1
3.0 ± 1.0
Alassar et al. 2015 85
64 TF, 18 TAo, 3 SC
4 SAPIEN, 81 CoreValve
81.0 ± 5.9*
46 (54)
26.7 ± 20.7*
6 days
Uddin et al. 2015 71
65 TF, 5 SC, 1 CA
80.5 ± 6.3
31 (44)
18.2 ± 10.9
<7 days
Samim et al. 2015 42
37 TF, 4 TA, 1 SC
26 SAPIEN XT, 16 CoreValve
81.3 ± 4.4*
25 (60)
13.2 ± 7.3*
<4 days
Bijuklic et al. 2015 87
19 SAPIEN XT, 68 SAPIEN 3
83.2 ± 6.1†
43 (49)
22.2 ± 15.6†
4.8 ± 2.4
Altisent et al. 2015 46
33 TF, 7 TA, 6 TAo
SAPIEN XT
79.0 ± 8.1*
29 (63)
14.1 ± 9.9
6.5 ± 3.5
Fanning et al. 2015** 36 -
82.2 ± 6.6§
Leclercq et al. 2015** 28
SAPIEN 3
83.0 ± 5.9*
10 (36)
8.4 ± 3.2*
<3 days
Bijuklic et al. 2015**
152
23 SAPIEN XT, 87 SAPIEN 3, 35
DirectFlow, 7 others
2-4 days
Lansky et al. 2015**
TAo
29 SAPIEN/XT, 15 CoreValve
82.3††
44 (66)
4.0 ± 2.0
Wendt et al. 2015
RCT 16
82.1 ± 4.1
8 (50)
39.5 ± 10.5
6.1 ± 2.8
Lansky et al. 2015 39
TF, TA
SAPIEN/XT/3, CoreValve, others
82.3 ± 6.0
19 (49)
Linke et al. 2014** 50
79.0 ± 4.0
23 (46)
14.6 ± 8.6
Van Mieghem et al. 2015** 33
SAPIEN XT/3, CoreValve, others
81.7 ± 6.7*
17 (52)
5.0 ± 0.0*
Rodés-Cabau et al. 2014 11
83.7 ± 8.1*
8 (73)
19.3 ± 12.6*
3.7 ± 3.0* 37
22 SAPIEN XT, 15 CoreValve
81.0 ± 4.4*
21 (57)
13.1 ± 7.5*
Pooled estimate rate (95% CI)
1225
81.6 ( )
50.0 ( )
22.9 ( )
4.5 ( )

8. Pooled analysis. Pooled DW-MRI outcomes

9. Pooled analysis Pooled DW-MRI outcomes
100 90 80 70 60 50 40 30 20 10
77.5%
Patients with new cerebral lesions (%)

10. Meta-analysis Characteristics of the included studies
Study
Design
Study Population
EPD No EPD Approach
N=384
(n=198) (n=186)
Device
EPD type
Timing of
DW-MRI
(days)
Age (y)
EPD
No EPD
Wendt et al. 2015
RCT 30 14 16
TAo
SAPIEN XT
EMBOL-X
6.5 ± 2.6†
81.0 ± 5.0
82.1 ± 4.1
Lansky et al. 2015 85 46 39
82 TF, 3 TA 54
SAPIEN/XT/3,
26 CoreValve, 3 others
TriGuard HDH
4.0 ± 2.0
82.5 ± 6.5
82.3 ± 6.0
Linke et al. 2014**
100 50 TF
CoreValve
Claret Montage CPS
2 days
80.0 ± 5.0
79.0 ± 4.0
Van Mieghem et al. 2015** 65 32 33 -
10 SAPIEN XT,
35 SAPIEN 3, 16
CoreValve, 4 others
Claret Sentinel CPS
5.0 ± 0.0*
81.3 ± 3.7*
81.7 ± 6.7*
Rodés-Cabau et al. 2014
Prospective 52 41 11
Embrella Embolic Deflector
3.2 ± 3.0*†
82.7 ± 5.2*
83.7 ± 8.1*
Samim et al. 2015
Consecutive patients 15 37
33 SAPIEN XT,
19 CoreValve
<4 days
81.3 ± 10.4*
81.0 ± 4.4*
Primary endpoints
Secondary endpoints
Number of new lesions
per patient
Total lesion volume
Number of patients with
new lesions
Single lesion volume

11. Primary endpoints Number of new lesions per patient
Total lesion volume

12. Secondary endpoints Number of patients with new lesions
Single lesion volume

13. Sub-group analysis
Cerebral protection filters: Claret Sentinel/Montage; EMBOL-X
Number of new lesions per patient
Total lesion volume
P interaction = 0.10
Embolic deflection systems: TriGuard HDH; Embrella Embolic Deflector
P interaction = 0.23
Number of new lesions per patient
Total lesion volume

14. Limitations Lack of patient-level data
High heterogeneity: different populations, valves,
approaches, and EPDs
MRI-related limitations: 1.5-T vs 3-T MRI; high drop out
rate; different timing of DW-MRI scan
Only 4 RCTs out of 6 studies in the meta-analysis

15. Conclusions Silent cerebral injury after TAVI occurs in 77.5% of pts
The main pooled DW-MRI outcomes are consistent with cerebral embolization (multiple, disseminated, ischemic lesions of different size)
The use of EPDs is associated with significantly lower
total lesion volume and single lesion volume
Larger RCTs are needed before drawing definitive
conclusions (SENTINEL, REFLECT)