Supplemental Figure 1: Forest Plot of Single center Experience: A. Showing the individual and
Pooled Event Rates for stroke (30 day/inhospital) using the Transfemoral (TF) and Transapical
(TA) approach for TAVR. B. Showing the Odds Ratio (OR) for stroke, comparing the Transfemoral and Transapical approach.

Supplemental Figure 2: Forest Plot of Single center Experience: A. Showing the individual and
Pooled Event Rates for stroke (30 day/inhospital) using the CoreValve (TF) or Edwards Valve (ES) for TAVR. B. Showing the Odds Ratio (OR) for stroke, comparing the CoreValve and Edwards
Valve.

Supplemental Figure 3: Forest Plot A. Showing the Odds Ratio (OR) for stroke, comparing TAVR and SAVR in high surgical risk patients B. Showing the Odds Ratio (OR) for stroke, comparing
TAVR and SAVR in intermediate surgical risk patients. Surgical Aortic Valve Replacement (SAVR) and TAVR (Transcatheter Aortic Valve Replacement)

Supplemental Figure 4: Forest Plot of Stroke after TAVR using the Transfemoral approach: A.
Showing the individual and Pooled Event Rates for stroke (30 day/inhospital) using the
CoreValve or Edwards Valve in Multicenter studies B. Showing the individual and Pooled Event
Rates for stroke (30 day/inhospital) using the CoreValve or Edwards Valve in Single center studies.

Supplemental Figure 5: Forest Plot of Stroke after TAVR using the Edwards Valve: A. Showing the individual and Pooled Event Rates for stroke (30 day/inhospital) using the Transfemoral (TF) and Transapical (TA) approach in Multicenter studies B. . Showing the individual and Pooled
Event Rates for stroke (30 day/inhospital) using the Transfemoral (TF) and Transapical (TA) approach in Single center studies.

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Zeitoun D, Francis F, Ibrahim H, Nataf P, Vahanian A. Results of transfemoral or transapical aortic valve implantation following a uniform assessment in high-risk patients with aortic stenosis. Journal of the American College of Cardiology.
2009;54:303-311 e81. Ussia GP, Scarabelli M, Mule M, Barbanti M, Cammalleri V, Imme S, Aruta P, Pistritto
AM, Carbonaro A, Deste W, Sciuto P, Licciardello G, Calvi V, Tamburino C.
Postprocedural management of patients after transcatheter aortic valve implantation procedure with self-expanding bioprosthesis. Catheterization and cardiovascular
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2010;76:757-766 e82. Grube E, Buellesfeld L, Mueller R, Sauren B, Zickmann B, Nair D, Beucher H, Felderhoff T,
Iversen S, Gerckens U. Progress and current status of percutaneous aortic valve replacement: Results of three device generations of the corevalve revalving system.
Circulation. Cardiovascular interventions. 2008;1:167-175 e83. Godino C, Maisano F, Montorfano M, Latib A, Chieffo A, Michev I, Al-Lamee R, Bande M,
Mussardo M, Arioli F, Ielasi A, Cioni M, Taramasso M, Arendar I, Grimaldi A, Spagnolo P,
Zangrillo A, La Canna G, Alfieri O, Colombo A. Outcomes after transcatheter aortic valve implantation with both edwards-sapien and corevalve devices in a single center: The milan experience. JACC. Cardiovascular interventions. 2010;3:1110-1121 e84. Nuis RJ, van Mieghem NM, van der Boon RM, van Geuns RJ, Schultz CJ, Oei FB, Galema
TW, Raap GB, Koudstaal PJ, Geleijnse ML, Kappetein AP, Serruys PW, de Jaegere PP.
Effect of experience on results of transcatheter aortic valve implantation using a medtronic corevalve system. The American journal of cardiology. 2011;107:1824-1829 e85. Pasic M, Buz S, Dreysse S, Drews T, Unbehaun A, Klein C, Kukucka M, Mladenow A,
Ivanitskaia-Kuhn E, Hetzer R. Transapical aortic valve implantation in 194 patients:
Problems, complications, and solutions. The Annals of thoracic surgery. 2010;90:1463-
1469; discussion 1469-1470 e86. Kempfert J, Rastan A, Holzhey D, Linke A, Schuler G, van Linden A, Blumenstein J, Mohr
FW, Walther T. Transapical aortic valve implantation: Analysis of risk factors and learning experience in 299 patients. Circulation. 2011;124:S124-129 e87. Higgins J, Ye J, Toggweiler S, Webb JG, Cheung A. Transapical aortic valve implantation:
The vancouver experience. Annals of cardiothoracic surgery. 2012;1:138-144 e88. Higgins J, Ye J, Humphries KH, Cheung A, Wood DA, Webb JG, Lichtenstein SV. Early clinical outcomes after transapical aortic valve implantation: A propensity-matched comparison with conventional aortic valve replacement. The Journal of thoracic and
cardiovascular surgery. 2011;142:e47-52 e89. Wilbring M, Tugtekin SM, Alexiou K, Simonis G, Matschke K, Kappert U. Transapical transcatheter aortic valve implantation vs conventional aortic valve replacement in highrisk patients with previous cardiac surgery: A propensity-score analysis. European journal of cardio-thoracic surgery : official journal of the European Association for
Cardio-thoracic Surgery. 2013;44:42-47 e90. Stohr R, Dohmen G, Herpertz R, Brehmer K, Aktug O, Koos R, Altiok E, Stegemann E,
Autschbach R, Marx N, Hoffmann R. Thirty-day outcome after transcatheter aortic valve implantation compared with surgical valve replacement in patients with high-risk aortic stenosis: A matched comparison. Coronary artery disease. 2011;22:595-600

e91. Holzhey DM, Shi W, Rastan A, Borger MA, Hansig M, Mohr FW. Transapical versus conventional aortic valve replacement--a propensity-matched comparison. The heart
surgery forum. 2012;15:E4-8 e92. Conradi L, Seiffert M, Treede H, Silaschi M, Baldus S, Schirmer J, Kersten JF, Meinertz T,
Reichenspurner H. Transcatheter aortic valve implantation versus surgical aortic valve replacement: A propensity score analysis in patients at high surgical risk. The Journal of
thoracic and cardiovascular surgery. 2012;143:64-71 e93. Nielsen HH, Klaaborg KE, Nissen H, Terp K, Mortensen PE, Kjeldsen BJ, Jakobsen CJ,
Andersen HR, Egeblad H, Krusell LR, Thuesen L, Hjortdal VE. A prospective, randomised trial of transapical transcatheter aortic valve implantation vs. Surgical aortic valve replacement in operable elderly patients with aortic stenosis: The staccato trial.
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Interventional Cardiology of the European Society of Cardiology. 2012;8:383-389 e94. Latib A, Maisano F, Bertoldi L, Giacomini A, Shannon J, Cioni M, Ielasi A, Figini F, Tagaki
K, Franco A, Covello RD, Grimaldi A, Spagnolo P, Buchannan GL, Carlino M, Chieffo A,
Montorfano M, Alfieri O, Colombo A. Transcatheter vs surgical aortic valve replacement in intermediate-surgical-risk patients with aortic stenosis: A propensity score-matched case-control study. American heart journal. 2012;164:910-917 e95. Osnabrugge RL, Head SJ, Genders TS, Van Mieghem NM, De Jaegere PP, van der Boon
RM, Kerkvliet JM, Kalesan B, Bogers AJ, Kappetein AP, Hunink MG. Costs of transcatheter versus surgical aortic valve replacement in intermediate-risk patients. The
Annals of thoracic surgery. 2012;94:1954-1960 e96. Pilgrim T, Kalesan B, Wenaweser P, Huber C, Stortecky S, Buellesfeld L, Khattab AA,
Eberle B, Gloekler S, Gsponer T, Meier B, Juni P, Carrel T, Windecker S. Predictors of clinical outcomes in patients with severe aortic stenosis undergoing tavi: A multistate analysis. Circulation. Cardiovascular interventions. 2012;5:856-861 e97. Fairbairn TA, Mather AN, Bijsterveld P, Worthy G, Currie S, Goddard AJ, Blackman DJ,
Plein S, Greenwood JP. Diffusion-weighted mri determined cerebral embolic infarction following transcatheter aortic valve implantation: Assessment of predictive risk factors and the relationship to subsequent health status. Heart. 2012;98:18-23 e98. Tay EL, Gurvitch R, Wijesinghe N, Nietlispach F, Wood D, Cheung A, Ye J, Lichtenstein SV,
Carere R, Thompson C, Webb JG. A high-risk period for cerebrovascular events exists after transcatheter aortic valve implantation. JACC. Cardiovascular interventions.
2011;4:1290-1297 e99. Stortecky S, Windecker S, Pilgrim T, Heg D, Buellesfeld L, Khattab AA, Huber C, Gloekler
S, Nietlispach F, Mattle H, Juni P, Wenaweser P. Cerebrovascular accidents complicating transcatheter aortic valve implantation: Frequency, timing and impact on outcomes.
EuroIntervention : journal of EuroPCR in collaboration with the Working Group on
Interventional Cardiology of the European Society of Cardiology. 2012;8:62-70 e100. Nombela-Franco L, Webb JG, de Jaegere PP, Toggweiler S, Nuis RJ, Dager AE, Amat-
Santos IJ, Cheung A, Ye J, Binder RK, van der Boon RM, Van Mieghem N, Benitez LM,
Perez S, Lopez J, San Roman JA, Doyle D, Delarochelliere R, Urena M, Leipsic J, Dumont
E, Rodes-Cabau J. Timing, predictive factors, and prognostic value of cerebrovascular events in a large cohort of patients undergoing transcatheter aortic valve implantation.
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Frequency and causes of stroke during or after transcatheter aortic valve implantation.
The American journal of cardiology. 2012;109:1637-1643 e103. Motloch LJ, Reda S, Rottlaender D, Khatib R, Muller-Ehmsen J, Seck C, Strauch J,
Madershahian N, Erdmann E, Wahlers T, Hoppe UC. Postprocedural atrial fibrillation after transcatheter aortic valve implantation versus surgical aortic valve replacement.
The Annals of thoracic surgery. 2012;93:124-131 e104. Erdoes G, Basciani R, Huber C, Stortecky S, Wenaweser P, Windecker S, Carrel T, Eberle
B. Transcranial doppler-detected cerebral embolic load during transcatheter aortic valve implantation. European journal of cardio-thoracic surgery : official journal of the
European Association for Cardio-thoracic Surgery. 2012;41:778-783; discussion 783-774 e105. Rodes-Cabau J, Dumont E, Boone RH, Larose E, Bagur R, Gurvitch R, Bedard F, Doyle D,
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Cardiovascular interventions. 2012;5:499-512

Registry
Name
18F EE e1,e2
ADVANCE e3
Locations
Europe
Center s (N)
51
ANZ
CoreValve e4
ANZ Source e5 Australia/N
Z
Asia TAVI e6
Worldwide 44
Australia/N
Z
Asia
10
8
14
Belgium
Brazil e8 e7 Belgium
Brazil
15
18
Study period
Study
(N)
2007-2009 1483 TF (100)
2010-2011 879
2010-2011 428
2008-2009 130
2009-2013 253
2008-2010 328
2008-2013 418
Approach
(%)
TF (100)
TF (100)
TF (52)
TA (48)
TF (78)
TA (17)
TF (70)
TA (30)
TF (96)
Canada
FRANCE e9,e10 e11
FRANCE 2
GARY e13
Greece e14 e12
Ibero-
American e15
I-TA e16
Canada
France
France
Germany
Greece
Europe/Sou th America
Italy
6
16
34
69
4
43
21
2005-2009 339
2009-2009 232
2010-2011 2419 TF (73)
TA (18)
2011-2011 3875 TF (65)
2009-2011 126
2007-2012 1170
2008-2012 774
TF (48)
TA (52)
TF (66)
TA (29)
TA (35)
TF (100)
TF (95)
TA (100)
Valve (%) Publication
Type
18F (100) Conference
18F (100)
18F (100)
Conference
Conference
Sa (100)
MC (52)
Sa (48)
18F (43)
Sa (57)
MC (86)
XT (14)
CE (17)
Sa (81) XT
(2)
18F (32)
Sa (68)
18F (33)
Sa (67)
18F (47)
Sa (53)
18F (54)
XT (46)
18F (100)
Conference
Conference
Publication
Conference
Publication
Publication
Publication
Conference
Publication
Publication
Publication
14 2007-2009 659 TF (100)
Sa (65)
XT (35)
18F (100) Publication Italian
CoreValve e17
PARTNER I
Cohort A e18
Italy
USA
PARTNER I
Cohort B e19
USA
PARTNER II e20 USA
25
21
28
2007-2009 348
2007-2009 171
TF (71)
TA (29)
TF (100)
Sa (100)
Sa (100)
Publication
Publication
Conference
PREVAIL TA e21 Europe
EORP/TCVT e22
SOURCE e23
SOURCE XT
U.K TAVI
STS/ACC TVT
Registry e26
CoreValve
Extreme
Risk e27 e25 e24
Europe
Europe
Europe
U.K
USA
USA
12
137
37
94
25
250
40
2011-2012 560
2009-2010 150
TF (100)
TA (100)
Sa (49)
XT (51)
XT (100)
2011-2012 4547 TF (74)
TA (16)
2007-2009 2307 TF (40)
TA (60)
2010-2011 2600 TF (63)
TA (33)
18F (43)
XT (57)
Sa (100)
XT (100)
2007-2009 870
2010-2013 487
TF (69)
TA (27)
2011-2013 8075 TF (64%)
TA (29%)
MC (52)
Sa (48)
Sa (100)
TF (100%) 18F (100)
Publication
Publication
Conference
Conference
Publication
Publication
Conference

Single center location
Country Study period Study N Approach (%) Valve used (%) Publication type
Supplemental Table 1: Included Multi center studies. TF= Transfemoral , TA= Transapical, 18F =18 F
CoreValve, MC= Medtronics CoreValve,Sa = Edwards Sapien Valve, XT = Edwards Sapient XT.
(Supplemental e reference 1-27)

Quebec City e28 Canada
Vancouver e29,e30 Canada
Skejby e31 Denmark
Créteil e32
Paris e33
France
France
Rouen e34,e35 France
Berlin –Charite e36 Germany
NA
2005-2011
2006-2010
2007-2011
2006-2010
2006-2011
2009-2011
Berlin -German
Heart e37
Bonn e38
Cologne e39
Essen e40
Frankfurt e41
Gottingen e42
Germany
Germany
Germany
Germany
Germany
Germany
Hamburg UHC e43 Germany
Heidelberg e44 Germany
Bochum e45
Leipzig e46
Lubeck e47
Munich e48.e49
Germany
Germany
Germany
Germany
Siegburg e50
Stuttgart e51
Germany
Germany
Jerusalem e52
Bologna e53
Milan e54,e55
Catania e56
Padova e57
Leiden e58
Rotterdam/
Colombia e59
Malaga e60
Israel
Italy
Italy
Italy
Italy
Netherlands
Netherlands
Spain
2008-2011
2008-2012
2008-2011
2006-2010
2005-2008
2008-2010
2008-2011
2008-2011
2008-2011
2006-2011
2007-2011
2007-2011
2004-2009
2008-2012
NA
2008-2010
2007-2010
2005-2011
2007-2011
NA
2005-2011
2008-2010
206
150
151
100
180
326
251
100
500
267
198
360
125
444
576
270
211
345
100
144
125
105
102
287
218
191
107
230
205
TF (100)
TF (100)
TF (69.6)
TA (30.4)
TA (55.1)
TF (54.9)
TF (100)
TF (100)
TA (100)
TA (54)
TF (46)
TF (45.7)
TA (54.3)
TF (87.6)
TA (12.4)
TF (100)
TA (100)
TF (100)
TF (67.8)
TA (32.2)
TF (100)
TA (100)
TF (100)
TF (64.7)
TF (15.8)
TA (84.2)
TF (59)
TA (41)
TA (76)
TF (24)
TF (100)
TF (100)
TF (75.6)
TA (24.4)
TF (100)
TA (100)
TF (100)
TA (100)
TF (100)
ES(100)
ES (100)
Sa (100)
Publication
Publication
Publication
MC (100)
Sa (NA)
18F (NA)
ES (100)
18F (97.9)
21F (2.1)
18F (100)
Publication
Publication
Publication
18F (83)
Sa (17)
Sa (81.2)
XT (18.8)
18F (100)
Sa (100)
MC (51)
Sa (49)
ES (100)
18F (13.4)
Sa (86.6)
18F (13.8)
ES (86.2)
18F(75.3)
Sa (24.7)
18F (100)
ES (100)
18F (100)
18F(67.7)
Sa(33.3)
18F(94.2)
21F (4.1)/25F (1.7)
Sa(80.3)
XT (15.9)
18F (84.8)
XT (15.2)
18F(64.7)
ES (35.3)
18F (31)
XT (45.9)/ Sa (23.1)
MC (89.1)
ES (10.9)
MC (45.5)
ES (54.5)
Sa (100)
Publication
Publication
Publication
Publication
Publication
Publication
Publication
Publication
Publication
Publication
Publication
Publication
Publication
Conference
Publication
Publication
Publication
Conference &
Publication
Publication
Publication
Publication
Publication
Publication

Santiago de
Compostela e61
Bern e62
Spain
Switzerland
London, Kings e63 UK
2008-2011
2007-2011
2007-2009
85
389
151
TF (100)
TF (79)
TA (21)
TA (56)
TF (44)
TA (84.2)
18F (100)
MC (58)
Sa (42)
Sa (100)
London, Guys e64 UK 2008-2011 108 Sa (100)
Supplemental Table 2: Included Single Center studies. TF= Transfemoral , TA= Transapical, MC=
Medtronics CoreValve (all/any generation), ES = Edwards valve (all/any generations) 18F =18 F CoreValve,
Sa = Edwards Sapien Valve, XT = Edwards Sapient XT. (Supplemental e reference 26-72)
Registry name
18F EE e1,e2
ADVANCE e3
ANZ CoreValve e4
ANZ Source e5
Asia TAVI e6
Belgium e7
Brazil e8
Canada e9,e10
FRANCE e11
FRANCE 2 e12
Euro score mean ± SD
22.6 ± 13.7
19.2 ± 12.4
17.6 ± 11.0
28.1
19.7 ± 13.9
28 ± 16
20.2 ± 13.8
NA
25.6 ± 11.4
STS score mean ± SD
NA
NA
5.9 ± 4.2
NA
NA
NA
14.2 ± 11.5
9.8 ± 6.4
18.9 ± 12.8
AV Area mean ± SD
0.64 ± 0.18
0.7
0.7 ± 0.2
0.7 ± 0.2
0.61 ± 0.15
0.63 ± 0.17
0.68 ± 0.16
82.7 ± 7.2 21.9 ± 14.3 14.4 ± 12.0 0.67 ± 0.2
GARY e13
Greece e14
75.5 ± 7.9 17.5
24.5 ± 13
NA 0.76 ± 0.4
8.1 ± 6.2 0.66 ± 0.16
Ibero-American e15 81.4 ± 6.3 17.8 ± 13.1
I-TA Registry e16 81 ± 6.7 25.6 ± 16.3
NA
10.3 ± 8.4
0.62 ± 0.18
0.48 ± 0.13
Italian CoreValve e17
80 ± 8
81 ± 6 23 ± 5 NA NA
83.6 ± 6.8 29.3 ± 16.5 11.8 ± 3.3 0.7 ± 0.2 PARTNER I Cohort
A e18
PARTNER I Cohort
B e19
PARTNER II e20
PREVAIL TA e21
EORP/TCVT e22
SOURCE e23
SOURCE XT e24
U.K TAVI e25
Age mean ± SD
81.2 ± 6.4
81 ± 6
83.9 ± 5.9
82.8
78.2 ± 7.2
83 ± 6
81.5 ± 7.7
81 ± 8
82.3 ± 7.3
83.1 ± 8.6
84.3 ± 8.7
81.6 ± 5.8
81.4 ± 7.1
81.2 ± 6.9
81 ± 6.5
81.9 ± 7.9
26.4 ± 17.2
NA
24.3 ± 7.0
20.2 ± 13.3
25.7 ± 15.2
20.4 ± 12.4
18.5
11.6 ± 6.0
10.6 ± 5.6
7.5 ± 4.4.
NA
NA
8.6 ± 7.1
NA
0.62
NA
0.6 ± 0.2
0.6 ± 0.2
0.7 ± 0.2
0.68 ± 0.26
NA
0.7
0.68
Prior stroke
(%)
7.6
13
NA
NA
NA
15
7.4
22.9
10.2
9.9
13.5
NA
11
8.5
7.3
29.3
27.4
11.8
22.7
12.1
5.9
8.5
NA
STS/ACC TVT
Registry e26
CoreValve
ExtremeRisk e27
84(78-88)
83.1
NA
NA
7(5-11)
NA
NA
NA
13
NA
Supplemental Table 3: Selected Baseline characteristics of patients in the included Multi center studies.
SD = Standard Deviation, AF= Atrial Fibrillation. NA – Not Available.
Prior AF
(%)
28.3
32.8
35.3
NA
NA
30
12.5
34.1
NA
26.6
20
NA
21.4
21.8
16
40.8
32.9
NA
38.6
NA
20.1
NA
25.6
NA
41
Publication
Publication
Publication
Publication

Registry name
Quebec City
Vancouver
Skejby
Study/Author Age (mean±SD) Euro score
(mean±SD)
79±8 24.9±15.2 Nombela-
Franco e28
Gurvitch e29 82.2±8.1
Lichtenstein e30 79.7±8.2
Moller Nielsen e31 80.6±6.7
NA
NA
21.5 (13.5)
Creteil
Paris *
Gallet e32
Dehedin e33
84±7
83 (78-87)
24±12
24 (16-31)
Rouen
Cologne
Essen
Frankfurt
Eltchaninoff e34
Litzler e35
Berlin -Charite Stangl e36
Berlin -German
Heart *
Bonn
Pasic e37
Sedaghat e38
Scherner e39
Bergmann e40
Doss e41
83.3±6.4
81±6.8
79±8
79.5±8.1
80.5±6.5
79.8 ± 13.1
80.2±6.5
85±6
21.9±11.9
27.5 ± 14.9
19.9±15.4
29.2±17.8
28.5 ± 19.8
21±14
36±12
STS score
(mean±SD)
NA
9.4±5.7
NA
NA
NA
13 (7-20)
NA
NA
NA
AV area
(mean±SD)
0.63±0.19
NA
NA
0.6±0.2
0.7±0.2
0.39 (0.31-
0.46)
0.67±0.56
0.68 ± 0.16
0.8±0.2
30.4 (21-48.5) 12.2 (6.7-21.6) 0.6 (0.6-0.8)
9.5±6.8
11.7 ± 3.2
NA
16±3
0.7±0.2
NA
NA
NA
Gottingen Puls e42
Hamburg UHC * Seiffert e43
Heidelberg
82.1±5.4 27±14
80.6 (79.8–81.3) 22.7 (21.2–
24.2)
81.8 ± 5.9 19.64 ± 13.15
NA
8.3 (7.7–8.9)
7.2 ± 4.01
NA
0.7 (0.7–0.7)
NA
Bochum
Leipzig
Lubeck
Munich
Siegburg
Stuttgart
Jerusalem
Bologna
Milan
Catania
Padova
Leiden
Beller e44
Gotzmann e45
Haensig e46
Abdel-Wahab e47
Muensterer e49
Bleiziffer e48
Grube e50
Goebel e51
Perlman e52
Saia e53
Buchanan e54
Mussardo e55
Tamburino e56
Thiene e57
Hooi Ewe e58
80±6
81.6 ± 6.4
81±6.95
80.2 ± 7.0
80.3±6.4
NA
81.6±5.7
80.7±6.6
NA
79.45±2.6
80.1±6.3
80.9±5.2
80.5 ± 6.9
80.6±7.9
22±16
30.0 ± 15.7
24.35±14.61
19.2 ± 12.8
21±13
NA
33.5±18.1
23.3±15.1
NA
21.25±3.94
26.5±1.6
21.1±14.2
21.43±13.37
21.3±11.8
NA
11.7 ± 7.8
NA
5.9 ± 4.1
6.1±3.8
NA
14±13
NA
NA
8.65±2.94
7.2±5.0
8.5±4.3
NA
8.7±3.6
0.7±0.1
0.56 ± 0.18
0.68±0.20
26.4
12
NA
62
0.687 ± 0.218 11
0.67±0.22
NA
0.6±0.2
0.65±0.41
NA
NA
NA
0.6±0.2
0.77 ± 0.20
0.7±0.2
Prior stroke (%)
21.8
18
5.3
9.8
10
22.6
NA
13
10
14
12
19.3
NA
NA
NA
10
35
NA
1.5
NA
NA
16.3
18.2
7.4
13.2
11.5
41.8
31.1
19
NA
Prior
AF (%)
22.3
NA
40
NA
NA
25
NA
NA
33.1
NA
NA
NA
NA
12.8
NA
21.2
NA
33
NA
NA
NA
NA
29
27
29
NA
33.2

Rotterdam/
Colombia *
Malaga
Santiago de
Compostela *
Bern
London, Kings
London, Guys
Van Der Boon e59
Munoz-Garcia e60
Lopez-Otero e61
Wenaweser e62
Dworakowski e63
Bapat e64
80.2±7.14
78±2.7
83±5.43
82.5+5.8
82.5±7.4
82.64±7.3
16.40 (9.32–
23.48)
24.3±3.08
4.90 (2.94–
6.87)
8.75±2.37
17.7 (11.3-23.4) NA
24.3+14.2
21.6±11.9
23.5±13.2
6.8+5.3
NA
NA
0.66±0.21
1.6±0.6
NA
0.6±0.2
0.62±0.16
NA
Supplemental Table 4: Selected Baseline characteristics of patients in the included Single center studies.
SD = Standard Deviation, AF= Atrial Fibrillation, NA – Not Available. *- Data presented as median and Inter
Quartile Range.
Registry Name
18FEE e1,e2
VARC
No
Stroke
Adjudication
NA
Major
Stroke
No
Minor
Stroke
No
TIA
Yes
24 -48 hrs
Stroke
Yes
In Hospital
Stroke
No
6.6
8.2
NA
8
18.5
16.5
30 day
Stroke
Yes
22.5
NA
NA
27
23.8
NA
ADVANCE e3 Yes
ANZ CoreValve e4 Yes
ANZ Source
Asia TAVI
Belgium e7 e5 e6
Yes
No
No
Neurologist
Independent
CEC
Independent
CEC
NA
Yes
No
No
No
No
Yes
No
No
No
No
No
No
No
Yes
Yes
No
No
No
No
No
No
No
No
No
No
Yes
Yes
Yes
Yes
Yes
Brazil
Canada e8 e9,e10
Yes
No
NA
Independent
CEC
NA
No
No
No
No
No
No
No
Yes
No
No
Yes
Yes
FRANCE e11
FRANCE 2 e12
GARY e13
Greece e14 Yes
Ibero-American e15 Yes
I-TA e16
Italian
CoreValve e17
No
Yes
No
Yes
Yes
NA
Independent
CEC
NA
NA
NA
NA
Independent
CEC
No
Yes
No
No
Yes
Yes
Yes
No
Yes
No
No
Yes
Yes
No
No
No
No
No
Yes
Yes
No
No
No
No
No
No
No
Yes
No
No
Yes
No
Yes
No
No
Yes
Yes
No
Yes
Yes
Yes
Yes

PARTNER I Cohort
A e18
PARTNER I Cohort
B e19
PARTNER II e20
No
No
Yes
Independent
CEC
Independent
CEC
Neurologist
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
No
No
No
No
Yes
Yes
Yes
PREVAIL TA e21 No Committee No No No No No Yes
EORP/TCVT
SOURCE e23
SOURCE XT e22 e24
Yes
No
Yes
NA
Principal
Investigator
Independent
CEC
NA
No
No
No
No
No
No
No
No
Yes
No
No
No
U.K TAVI e25 No No No Yes No
STS/ACC TVT
Registry e26
CoreValve
Extreme Risk e27
Yes
Yes
Cardiologist
NA
No
NA
No
NA
No
NA
Yes
NA
Supplemental Table 5: Reporting of stroke by multicenter studies. VARC= Valve Academic Research
Consortium, CEC= Clinical Events Committee.
Single Center Author VARC Stroke
Adjudication
Yes NA
Major
Stroke
Yes
Minor
Stroke
Yes
TIA
Yes
Yes
No
No
Yes
Yes
NA
Yes
Yes
Yes
No
Yes
NA
24 -48 hrs
Stroke
Yes
In Hospital
Stroke
No
30 day
Stroke
Yes Quebec City
Vancouver
Skejby
Creteil
Paris
Rouen
Nombela-
Franco e28
Gurvitch e29
Litchenstein e30
Nielsen e31
Gallet e32
Dehedin e33
Eltchaninoff e34
Litzler e35
Berlin-Charite Stangl e36
Berlin-German Heart Pasic e37
Bonn
Cologne
Essen
Frankfurt
Sedaghat e38
Scherner e39
Bergmann e40
Doss e41
Gottingen
Hamburg UHC
Heidelberg
Bochum
Leipzig
Puls e42
Seiffert e43
Beller e44
Gotzmann e45
Haensig e46
No
Yes
Yes
Yes
Yes
No
No
Yes
Yes
Yes
Yes
Yes
Yes
No
No
Yes
Yes
Yes
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
Neurologist
NA
NA
NA
NA
NA
Yes
No
No
Yes
Yes
No
Yes
Yes
Yes
No
No
Yes
No
No
No
No
Yes
No
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
Yes
No
Yes
Yes
No
No
Yes
No
No
No
No
Yes
No
No
Yes
No
No
Yes
Yes
No
No
Yes
Yes
No
No
No
No
Yes
No
Yes
Yes
No
Yes
No
No
No
Yes
No
No
Yes
Yes
No
No
No
No
Yes
No
Yes
Yes
No
Yes
No
No
No
Yes
Yes
No
Yes
Yes
No
Yes
No
No
Yes
No
Yes
Yes
No
No
No
Yes
Yes
Yes
Yes
Yes
No
Yes
Yes
No
Yes
No
Yes

Lubeck
Munich
Siegburg
Stuttgart
Jerusalem
Bologna
Abdel-Wahab e47 Yes
Bleiziffer e48 No
Muensterer e49
Gruebe e50
Yes
No
Goebel e51
Perlman e52
Saia e53
Buchanan e54
Yes
Yes
Yes
Yes Milan
Catania
Malaga de
Mussardo e55
Tamburino e56
Yes
Yes
Padova Fraccaro e57 Yes
Leiden Ewe e58 No
Rotterdam/Colombia Van der Boon e59 Yes
Munoz Garcia e60 Yes
Lopez-Otero e61 Yes Santiago
Compostela
Bern
London, Kings
London, Guys
Wenaweser e62 Yes
Dwarakowski e63 No
Bapat e64 No
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
Neurologist
NA
NA
NA
NA
NA
Yes
No
No
No
No
No
No
No
Yes
No
No
No
Yes
No
Yes
Yes
No
No
No
No
No
No
No
No
No
No
No
No
No
No
Yes
No
No
Yes
No
No
No
Yes
Yes
No
Yes
Yes
No
No
Yes
No
No
No
Yes
No
Yes
Yes
No
No
No
Yes
Yes
Yes
No
Yes
No
No
No
Supplemental Table 6: Reporting of stroke by multicenter studies. VARC= Valve Academic Research
Consortium, CEC= Clinical Events Committee.
Yes
Yes
No
Yes
No
No
Yes
No
No
Study
24F e65
21F e66
Walther e67
Walther e68
REVIVAL e69
REVIVE2 e70
REVIVAL2 e71
Walther e72
Vancouver
Exp e73
18F e74
PARTNER EU e75
TRAVERCE e76
Location
Germany
Germany/USA
USA
Europe
USA
Germany
Canada
Europe
Europe
Europe
Period
2005-2005
Germany/Canada 2005-2006
Germany 2006-2006
2006-2006
2005-2006
2006-2007
2006-2008
2006-2008
2007-2008
Valve
MC
MC
CE
Sa
CE
Sa
Sa
2006-2007 Sa
2005-2008 CE/Sa
MC
Sa
2006-2008 CE/Sa
Approach
TF
TF
TA
TA
TF
TF
TA
TA
TF/TA
TF
TF/TA
TA
Supplemental Table 7: Included Feasibility Studies. F = French scale, MC= Medtronics
CoreValve, CE= Cribier Edwards, Sa= Edwards Sapien, TF= Transfemoral and TA= Transapical.
Center Approach
Munich TF
Early
Bleiziffer e77
Late
Muensterer e49
Yes
No
Yes
Yes
Yes
No
No
No
No
Yes
No
No
Yes
No
No
No
No
No
Yes
Yes
No
No
No
Yes
No
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes

Vancouver
Bern
Paris
Rouen
Catania
Siegburg
Milan
Rotterdam
Berlin
Cologne
Leipzig
Munich
Vancouver
TF
TF
TF
TF
TF
TF
TF
TF
TA
TA
TA
TA
TA
Gurvitch e78
Stortecky e79
Himbert e80
Eltachninoff
Paolo Ussia
Grube e82
Godino e83
Nuis RJ e84
Pasic e85 e34 e81
Scherner e39
Kempfert e86
Bleiziffer e77
Higgins e87
Gurvitch e78
Wenaweser e62
Dehedin e33
Eltchaninoff e34
Tamburino
Grube e50 e56
Musssardo e55 /Buchanan e54
Van Der Boon e59
Pasic e35
Scherner e39
Haensig e46
Bleiziffer e48
Higgins e87
Supplemental Table 8: High volume centers with corresponding early and late publication. TF=
Transfemoral and TA = Transapical.
e88
e89
e90
e91
e92
e18
e93
e94
e95
Patient Specific Risk factors for Stroke:
Risk Factor
Age
BMI e96-98 e96,e99
History of Stroke e96-e100
New onset Atrial Fibrillation e100-103
Procedure Specific Predictors of Stroke
Procedural Step
Stroke Association
Increased age was significantly related to a higher number of new infarcts (r =0.37, p=0.042)-
Fairbairn et al.
BMI ≤20 kg/m 2 was a predictor of stroke and death. (HR 4.11, 95% CI 1.33-12.70)-Pilgrim et al.
Prior history of stroke is more frequent in patients that have a stroke after TAVR (21% vs. 7%)-
Stortecky et al.
Also associated with stroke beyond the first 30 days (HR 2.35, 95% CI 1.17-4.73)- Franco et al.
Is an important predictor of early (HR 2.96, 95% CI 1.21-7.25) and late stroke after TAVR (HR
1.93, 95% CI 1.15- 3.24) – Franco et al.
May be increased with TA approach- Santos et al.
Theories for stroke Supportive Evidence

Pre implantation Instrumentation –
Vessel puncture to
Valvuloplasty e97,e98,e104-e107
Rapid Ventricular Pacing (Testing
/BAV) e108-e110
Balloon Valvuloplasty of the Aortic
Valve e109,e111
Trafficking of the delivery catheter with mounted prosthetic valve across the aortic arch e97,e109 .
Valve positioning and
Implantation e104,e107,e111,e112
Valve Dislodgement/Embolization e100
Balloon Post Dilation (BPD) e100,e113
Thrombo embolism from catheters, Air embolization from repeated flushing and multiple exchanges of wires and catheters.
Temporary tachycardic cardiac arrest – cerebral hypoperfusion
Disruption of endothelial layer and subsequent embolization of calcific material from the aortic valve.
Large caliber less flexible delivery catheters are more traumatic and prone to dislodge atheromatous debris.
Embolization of calcific and atheromatous debris from valve manipulation and crushing.
Mechanical friction between prosthesis frame and aortic wall.
Additional dislodgement and embolization of calcific debris from the native aortic valve.
1. Prolonged procedural time increases the risk of stroke.
2. Total HITS load comparable to valve deployment.
1. Hyper intense signals on DW MRI without neurological or neurocognitive impairment.
1. The risk of stroke varies from 1-2%.
2. Second to valve deployment in load of HITS per unit time of procedure in transcranial Doppler studies during TAVR.
3. Smaller Aortic Valve Area increases the risk of stroke.
1. Atheromatous plaques > 5 mm in thickness or mobile atheroma in the arch and descending thoracic aorta increase the risk of stroke during aortic trafficking.
2. Declining risk of stroke with new generation delivery systems (current analysis).
1. Small valve areas and higher transvalvular gradients increase stroke risk (higher valve calcification).
2. Peak HITS load is observed during implantation.
3. Repeated attempts associated with increased risk of stroke
(2.8% vs. 12%).
1. More common with self expanding CoreValve.
Smaller valve area and higher degree of calcification are associated with an increased risk of BPD and hence stroke.
Supplemental Table 10: Risk factors for Stroke after Transcatheter Aortic Valve Replacement.
BMI = Body Mass Index, COPD = Chronic Obstructive Pulmonary Disease, HITS= High Intensity
Transcranial Doppler Signals, BAV = Balloon Aortic Valvuloplasty. r= regression coefficient, HR=
Hazards Ratio, CI= Confidence Intervals.