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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Registry Name

Locations Centers (N)

Study period

Study

(N)

Approach (%)

Valve (%) Publication Type

18F EEe1,e2 Europe 51 2007-2009 1483 TF (100) 18F (100) Conference

ADVANCEe3 Worldwide 44 2010-2011 879 TF (100) 18F (100) Conference

ANZ CoreValvee4

Australia/NZ

10 2010-2011 428 TF (100) 18F (100) Conference

ANZ Sourcee5 Australia/NZ

8 2008-2009 130 TF (52)

TA (48)

Sa (100) Conference

Asia TAVIe6 Asia 14 2009-2013 253 TF (78)

TA (17)

MC (52)

Sa (48)

Conference

Belgiume7 Belgium 15 2008-2010 328 TF (70)

TA (30)

18F (43)

Sa (57)

Publication

Brazile8 Brazil 18 2008-2013 418 TF (96) MC (86)

XT (14)

Conference

Canadae9,e10 Canada 6 2005-2009 339 TF (48)

TA (52)

CE (17)

Sa (81) XT (2)

Publication

FRANCEe11 France 16 2009-2009 232 TF (66)

TA (29)

18F (32)

Sa (68)

Publication

FRANCE 2e12 France 34 2010-2011 2419 TF (73)

TA (18)

18F (33)

Sa (67)

Publication

GARYe13 Germany 69 2011-2011 3875 TF (65)

TA (35)

18F (47)

Sa (53)

Conference

Greecee14 Greece 4 2009-2011 126 TF (100) 18F (54)

XT (46)

Publication

Ibero-Americane15

Europe/South America

43 2007-2012 1170 TF (95) 18F (100) Publication

I-TAe16 Italy 21 2008-2012 774 TA (100) Sa (65)

XT (35)

Publication

Italian CoreValvee17

Italy 14 2007-2009 659 TF (100) 18F (100) Publication

PARTNER I Cohort Ae18

USA 25 2007-2009 348 TF (71)

TA (29)

Sa (100) Publication

PARTNER I Cohort Be19

USA 21 2007-2009 171 TF (100) Sa (100) Publication

PARTNER IIe20 USA 28 2011-2012 560 TF (100) Sa (49)

XT (51)

Conference

PREVAIL TAe21 Europe 12 2009-2010 150 TA (100) XT (100) Publication

EORP/TCVTe22 Europe 137 2011-2012 4547 TF (74)

TA (16)

18F (43)

XT (57)

Publication

SOURCEe23 Europe 37 2007-2009 2307 TF (40)

TA (60)

Sa (100) Conference

SOURCE XTe24 Europe 94 2010-2011 2600 TF (63)

TA (33)

XT (100) Conference

U.K TAVIe25 U.K 25 2007-2009 870 TF (69)

TA (27)

MC (52)

Sa (48)

Publication

STS/ACC TVT Registrye26

USA 250 2011-2013 8075 TF (64%)

TA (29%)

Sa (100) Publication

CoreValve Extreme Riske27

USA 40 2010-2013 487 TF (100%) 18F (100) Conference

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)

Single center location

Country Study period Study N Approach (%) Valve used (%) Publication type

Quebec Citye28 Canada NA 211 TF (15.8)

TA (84.2)

ES(100) Publication

Vancouvere29,e30 Canada 2005-2011 345 TF (59)

TA (41)

ES (100) Publication

Skejbye31 Denmark 2006-2010 100 TA (76)

TF (24)

Sa (100) Publication

Créteile32 France 2007-2011 144 TF (100) MC (100) Publication

Parise33 France 2006-2010 125 TF (100) Sa (NA)

18F (NA)

Publication

Rouene34,e35 France 2006-2011 251 TF (75.6)

TA (24.4)

ES (100) Publication

Berlin –Charitee36 Germany 2009-2011 100 TF (100) 18F (83)

Sa (17)

Publication

Berlin -German Hearte37

Germany 2008-2011 500 TA (100) Sa (81.2)

XT (18.8)

Publication

Bonne38 Germany 2008-2012 206 TF (100) 18F (100) Publication

Colognee39 Germany 2008-2011 150 TA (100) Sa (100) Publication

Essene40 Germany 2006-2010 151 TF (100) MC (51)

Sa (49)

Publication

Frankfurte41 Germany 2005-2008 100 TA (100) ES (100) Publication

Gottingene42 Germany 2008-2010 180 TA (54)

TF (46)

18F (13.4)

Sa (86.6)

Publication

Hamburg UHCe43 Germany 2008-2011 326 TF (45.7)

TA (54.3)

18F (13.8)

ES (86.2)

Publication

Heidelberge44 Germany 2008-2011 267 TF (87.6)

TA (12.4)

18F(75.3)

Sa (24.7)

Publication

Bochume45 Germany 2008-2011 198 TF (100) 18F (100) Publication

Leipzige46 Germany 2006-2011 360 TA (100) ES (100) Publication

Lubecke47 Germany 2007-2011 125 TF (100) 18F (100) Publication

Muniche48.e49 Germany 2007-2011 444 TF (67.8)

TA (32.2)

18F(67.7)

Sa(33.3)

Publication

Siegburge50 Germany 2004-2009 576 TF (100) 18F(94.2)

21F (4.1)/25F (1.7)

Conference

Stuttgarte51 Germany 2008-2012 270 TA (100) Sa(80.3)

XT (15.9)

Publication

Jerusaleme52 Israel NA 105 TF (100) 18F (84.8)

XT (15.2)

Publication

Bolognae53 Italy 2008-2010 102 TF (64.7) 18F(64.7)

ES (35.3)

Publication

Milane54,e55 Italy 2007-2010 287 TF (100) 18F (31)

XT (45.9)/ Sa (23.1)

Conference & Publication

Cataniae56 Italy 2005-2011 218 TF (100) MC (89.1)

ES (10.9)

Publication

Padovae57 Italy 2007-2011 191 TF (69.6)

TA (30.4)

MC (45.5)

ES (54.5)

Publication

Leidene58 Netherlands NA 107 TA (55.1)

TF (54.9)

Sa (100) Publication

Rotterdam/ Colombiae59

Netherlands 2005-2011 230 TF (100) 18F (97.9)

21F (2.1)

Publication

Malagae60 Spain 2008-2010 205 TF (100) 18F (100) Publication

Santiago de Spain 2008-2011 85 TF (100) 18F (100) Publication

Compostelae61

Berne62 Switzerland 2007-2011 389 TF (79)

TA (21)

MC (58)

Sa (42)

Publication

London, Kingse63 UK 2007-2009 151 TA (56)

TF (44)

Sa (100) Publication

London, Guyse64 UK 2008-2011 108 TA (84.2) Sa (100) Publication

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 Age

mean ± SD

Euro score

mean ± SD

STS score

mean ± SD

AV Area

mean ± SD

Prior stroke

(%)

Prior AF

(%)

18F EEe1,e2 81.2 ± 6.4 22.6 ± 13.7 NA 0.64 ± 0.18 7.6 28.3

ADVANCEe3 81 ± 6 19.2 ± 12.4 NA 0.7 13 32.8

ANZ CoreValvee4 83.9 ± 5.9 17.6 ± 11.0 5.9 ± 4.2 0.7 ± 0.2 NA 35.3

ANZ Sourcee5 82.8 28.1 NA 0.62 NA NA

Asia TAVIe6 78.2 ± 7.2 19.7 ± 13.9 NA 0.7 ± 0.2 NA NA

Belgiume7 83 ± 6 28 ± 16 NA 0.61 ± 0.15 15 30

Brazile8 81.5 ± 7.7 20.2 ± 13.8 14.2 ± 11.5 NA 7.4 12.5

Canadae9,e10 81 ± 8 NA 9.8 ± 6.4 0.63 ± 0.17 22.9 34.1

FRANCEe11 82.3 ± 7.3 25.6 ± 11.4 18.9 ± 12.8 0.68 ± 0.16 10.2 NA

FRANCE 2e12 82.7 ± 7.2 21.9 ± 14.3 14.4 ± 12.0 0.67 ± 0.2 9.9 26.6

GARYe13 75.5 ± 7.9 17.5 NA 0.76 ± 0.4 13.5 20

Greecee14 80 ± 8 24.5 ± 13 8.1 ± 6.2 0.66 ± 0.16 NA NA

Ibero-Americane15 81.4 ± 6.3 17.8 ± 13.1 NA 0.62 ± 0.18 11 21.4

I-TA Registrye16 81 ± 6.7 25.6 ± 16.3 10.3 ± 8.4 0.48 ± 0.13 8.5 21.8

Italian CoreValvee17 81 ± 6 23 ± 5 NA NA 7.3 16

PARTNER I Cohort Ae18

83.6 ± 6.8 29.3 ± 16.5 11.8 ± 3.3 0.7 ± 0.2 29.3 40.8

PARTNER I Cohort Be19

83.1 ± 8.6 26.4 ± 17.2 11.6 ± 6.0 0.6 ± 0.2 27.4 32.9

PARTNER IIe20 84.3 ± 8.7 NA 10.6 ± 5.6 0.6 ± 0.2 11.8 38.6

PREVAIL TAe21 81.6 ± 5.8 24.3 ± 7.0 7.5 ± 4.4. 0.7 ± 0.2 22.7 NA

EORP/TCVTe22 81.4 ± 7.1 20.2 ± 13.3 NA 0.68 ± 0.26 12.1 20.1

SOURCEe23 81.2 ± 6.9 25.7 ± 15.2 NA NA 5.9 NA

SOURCE XTe24 81 ± 6.5 20.4 ± 12.4 8.6 ± 7.1 0.7 8.5 25.6

U.K TAVIe25 81.9 ± 7.9 18.5 NA 0.68 NA NA

STS/ACC TVT Registrye26

84(78-88) NA 7(5-11) NA 13 41

CoreValve ExtremeRiske27

83.1 NA NA NA NA NA

Supplemental Table 3: Selected Baseline characteristics of patients in the included Multi center studies. SD = Standard Deviation, AF= Atrial Fibrillation. NA – Not Available.

Registry name Study/Author Age (mean±SD) Euro score (mean±SD)

STS score (mean±SD)

AV area (mean±SD)

Prior stroke (%)

Quebec City Nombela-Francoe28

79±8 24.9±15.2 NA 0.63±0.19 21.8

Vancouver Gurvitche29 82.2±8.1 NA 9.4±5.7 NA 18

Lichtensteine30 79.7±8.2 NA NA NA 26.4

Skejby Moller Nielsene31 80.6±6.7 21.5 (13.5) NA 0.6±0.2 12

Creteil Gallete32 84±7 24±12 NA 0.7±0.2 NA

Paris* Dehedine33 83 (78-87) 24 (16-31) 13 (7-20) 0.39 (0.31-0.46)

62

Rouen Eltchaninoffe34 83.3±6.4 21.9±11.9 NA 0.67±0.56 5.3

Litzlere35 81±6.8 27.5 ± 14.9 NA 0.68 ± 0.16 9.8

Berlin -Charite Stangle36 79±8 19.9±15.4 NA 0.8±0.2 10

Berlin -German Heart*

Pasice37 79.5±8.1 30.4 (21-48.5) 12.2 (6.7-21.6) 0.6 (0.6-0.8) 22.6

Bonn Sedaghate38 80.5±6.5 29.2±17.8 9.5±6.8 0.7±0.2 NA

Cologne Schernere39 79.8 ± 13.1 28.5 ± 19.8 11.7 ± 3.2 NA 13

Essen Bergmanne40 80.2±6.5 21±14 NA NA 10

Frankfurt Dosse41 85±6 36±12 16±3 NA 14

Gottingen Pulse42 82.1±5.4 27±14 NA NA 12

Hamburg UHC* Seifferte43 80.6 (79.8–81.3) 22.7 (21.2–24.2)

8.3 (7.7–8.9) 0.7 (0.7–0.7) 19.3

Heidelberg Bellere44 81.8 ± 5.9 19.64 ± 13.15 7.2 ± 4.01 NA NA

Bochum Gotzmanne45 80±6 22±16 NA 0.7±0.1 NA

Leipzig Haensige46 81.6 ± 6.4 30.0 ± 15.7 11.7 ± 7.8 0.56 ± 0.18 NA

Lubeck Abdel-Wahabe47 81±6.95 24.35±14.61 NA 0.68±0.20 10

Munich Muensterere49 80.2 ± 7.0 19.2 ± 12.8 5.9 ± 4.1 0.687 ± 0.218 11

Bleiziffere48 80.3±6.4 21±13 6.1±3.8 0.67±0.22 35

Siegburg Grubee50 NA NA NA NA NA

Stuttgart Goebele51 81.6±5.7 33.5±18.1 14±13 0.6±0.2 1.5

Jerusalem Perlmane52 80.7±6.6 23.3±15.1 NA 0.65±0.41 NA

Bologna Saiae53 NA NA NA NA NA

Milan Buchanane54 79.45±2.6 21.25±3.94 8.65±2.94 NA 16.3

Mussardoe55 80.1±6.3 26.5±1.6 7.2±5.0 NA 18.2

Catania Tamburinoe56 80.9±5.2 21.1±14.2 8.5±4.3 0.6±0.2 7.4

Padova Thienee57 80.5 ± 6.9 21.43±13.37 NA 0.77 ± 0.20 13.2

Leiden Hooi Ewee58 80.6±7.9 21.3±11.8 8.7±3.6 0.7±0.2 11.5

Rotterdam/ Colombia*

Van Der Boone59 80.2±7.14 16.40 (9.32–23.48)

4.90 (2.94–6.87)

0.66±0.21 6.6

Malaga Munoz-Garciae60 78±2.7 24.3±3.08 8.75±2.37 1.6±0.6 8.2

Santiago de Compostela*

Lopez-Oteroe61 83±5.43 17.7 (11.3-23.4) NA NA NA

Bern Wenawesere62 82.5+5.8 24.3+14.2 6.8+5.3 0.6±0.2 8

London, Kings Dworakowskie63 82.5±7.4 21.6±11.9 NA 0.62±0.16 18.5

London, Guys Bapate64 82.64±7.3 23.5±13.2 NA NA 16.5

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 VARCStroke

AdjudicationMajor Stroke

Minor Stroke

TIA24 -48 hrs

StrokeIn Hospital

Stroke30 day Stroke

18FEEe1,e2 No NA No No Yes Yes No Yes

ADVANCEe3 Yes Neurologist Yes Yes No No No Yes

ANZ CoreValvee4 YesIndependent

CECNo No No No No Yes

ANZ Sourcee5 YesIndependent

CECNo No No No No Yes

Asia TAVIe6 No NA No No Yes No No Yes

Belgiume7 No NA No No Yes No No Yes

Brazile8 YesIndependent

CECNo No No No No Yes

Canadae9,e10 No NA No No No Yes No Yes

FRANCEe11 No NA No No No No No Yes

FRANCE 2e12 YesIndependent

CECYes Yes No No No Yes

GARYe13 No NA No No No No Yes No

Greecee14 Yes NA No No No No No Yes

Ibero-Americane15 Yes NA Yes Yes Yes No Yes Yes

I-TAe16 Yes NA Yes Yes Yes No No Yes

Italian CoreValvee17 Yes

Independent CEC

Yes No No Yes No Yes

PARTNER I Cohort Ae18 No

Independent CEC

Yes Yes Yes Yes No Yes

PARTNER I Cohort Be19 No

Independent CEC

Yes Yes Yes No No Yes

PARTNER IIe20 Yes Neurologist Yes Yes Yes No No Yes

PREVAIL TAe21 No Committee No No No No No Yes

EORP/TCVTe22 Yes NA No No No No Yes Yes

SOURCEe23 NoPrincipal

InvestigatorNo No No No No Yes

SOURCE XTe24 YesIndependent

CECNo No Yes No No Yes

U.K TAVIe25 No NA No No Yes No Yes No

STS/ACC TVT Registrye26 Yes Cardiologist No No No Yes Yes Yes

CoreValve Extreme Riske27 Yes NA NA NA NA NA NA NA

Supplemental Table 5: Reporting of stroke by multicenter studies. VARC= Valve Academic Research Consortium, CEC= Clinical Events Committee.

Single Center Author VARC Stroke Major Minor TIA 24 -48 hrs In Hospital 30 day

Adjudication Stroke Stroke Stroke Stroke Stroke

Quebec City Nombela-Francoe28

Yes NA Yes Yes Yes Yes No Yes

Vancouver Gurvitche29 Yes Neurologist Yes Yes Yes No No Yes

Litchensteine30 No NA No No No No No Yes

Skejby Nielsene31 No NA Yes No No Yes No No

Creteil Gallete32 Yes NA No No No No No Yes

Paris Dehedine33 Yes NA No No No No Yes No

Rouen Eltchaninoffe34 Yes NA Yes Yes Yes No No Yes

Litzlere35 No NA No No No Yes Yes No

Berlin-Charite Stangle36 Yes NA Yes Yes Yes Yes No Yes

Berlin-German Heart Pasice37 Yes NA Yes Yes No No No Yes

Bonn Sedaghate38 Yes NA No No No Yes Yes No

Cologne Schernere39 Yes NA Yes Yes Yes Yes Yes No

Essen Bergmanne40 No NA No No No Yes No No

Frankfurt Dosse41 No NA No No No Yes Yes Yes

Gottingen Pulse42 Yes NA No No Yes Yes Yes Yes

Hamburg UHC Seifferte43 Yes NA Yes Yes Yes Yes Yes Yes

Heidelberg Bellere44 Yes NA Yes No No No No Yes

Bochum Gotzmanne45 Yes NA No No No Yes No Yes

Leipzig Haensige46 Yes NA Yes Yes Yes Yes Yes No

Lubeck Abdel-Wahabe47 Yes NA Yes No No No No Yes

Munich Bleiziffere48 No NA No No Yes Yes No Yes

Muensterere49 Yes NA No No Yes Yes Yes No

Siegburg Gruebee50 No NA No No No No No Yes

Stuttgart Goebele51 Yes NA No No Yes No No Yes

Jerusalem Perlmane52 Yes NA No No Yes Yes Yes Yes

Bologna Saiae53 Yes NA No No No No No Yes

Milan Buchanane54 Yes NA No No No No No Yes

Mussardoe55 Yes NA Yes No Yes Yes Yes Yes

Catania Tamburinoe56 Yes NA No No No No No Yes

Padova Fraccaroe57 Yes NA No No No Yes Yes No

Leiden Ewee58 No NA No No No Yes Yes No

Rotterdam/Colombia Van der Boone59 Yes Neurologist Yes Yes Yes Yes Yes No

Malaga Munoz Garciae60 Yes NA No No No No No Yes

Santiago de Compostela

Lopez-Oteroe61 Yes NA Yes No Yes Yes No No

Bern Wenawesere62 Yes NA Yes Yes Yes No No Yes

London, Kings Dwarakowskie63 No NA No No No No No Yes

London, Guys Bapate64 No NA No No No No No Yes

Supplemental Table 6: Reporting of stroke by multicenter studies. VARC= Valve Academic Research Consortium, CEC= Clinical Events Committee.

Study Location Period Valve Approach

24Fe65 Germany 2005-2005 MC TF

21Fe66 Germany/Canada 2005-2006 MC TF

Walthere67 Germany 2006-2006 CE TA

Walthere68 Germany/USA 2006-2006 Sa TA

REVIVALe69 USA 2005-2006 CE TF

REVIVE2e70 Europe 2006-2007 Sa TF

REVIVAL2e71 USA 2006-2008 Sa TA

Walthere72 Germany 2006-2007 Sa TA

Vancouver Canada 2005-2008 CE/Sa TF/TA

Expe73

18Fe74 Europe 2006-2008 MC TF

PARTNER EUe75 Europe 2007-2008 Sa TF/TA

TRAVERCEe76 Europe 2006-2008 CE/Sa 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

Early Late

Munich TF Bleiziffere77 Muensterere49

Vancouver

TF Gurvitche78 Gurvitche78

Bern TF Storteckye79 Wenawesere62

Paris TF Himberte80 Dehedine33

Rouen TF Eltachninoffe34

Eltchaninoffe34

Catania TF Paolo Ussiae81

Tamburinoe56

Siegburg

TF Grubee82 Grubee50

Milan TF Godinoe83 Musssardoe55/Buchanane54

Rotterdam

TF Nuis RJe84 Van Der Boone59

Berlin TA Pasice85 Pasice35

Cologne TA Schernere39 Schernere39

Leipzig TA Kempferte86 Haensige46

Munich TA Bleiziffere77 Bleiziffere48

Vancouver

TA Higginse87 Higginse87

Supplemental Table 8: High volume centers with corresponding early and late publication. TF= Transfemoral and TA = Transapical.

Study Name Surgical Risk group

Higginse88 High Risk

Wilbringe89 High Risk

Stohre90 High Risk

Holzheye91 High Risk

Conradie92 High Risk

PARTNER Ie18 High Risk

Staccatoe93 Intermediate Risk

Latibe94 Intermediate Risk

Osnabruggee95 Intermediate Risk

Supplemental Table 9: Studies comparing Transcatheter Aortic Valve Replacement (TAVR) vs. Surgical aortic valve replacement (SAVR) – TAVR vs. SAVR.

Patient Specific Risk factors for Stroke:

Risk Factor Stroke Association

Agee96-98 Increased age was significantly related to a higher number of new infarcts (r =0.37, pFairbairn et al.

BMIe96,e99 BMI ≤20 kg/m2 was a predictor of stroke and death. (HR 4.11, 95% CI 1.33-12.70)-Pilgrim et al.

History of Stroke e96-e100 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.

New onset Atrial Fibrillatione100-103 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.

Procedure Specific Predictors of Stroke

Procedural Step Theories for stroke Supportive Evidence

Pre implantation Instrumentation – Vessel puncture to Valvuloplastye97,e98,e104-

e107

Thrombo embolism from catheters, Air embolization from repeated flushing and multiple exchanges of wires and catheters.

1. Prolonged procedural time increases the risk of stroke.

2. Total HITS load comparable to valve deployment.

Rapid Ventricular Pacing (Testing /BAV)e108-e110

Temporary tachycardic cardiac arrest – cerebral hypoperfusion

1. Hyper intense signals on DW MRI without neurological or neurocognitive impairment.

Balloon Valvuloplasty of the Aortic Valvee109,e111

Disruption of endothelial layer and subsequent embolization of calcific material from the aortic valve.

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.

Trafficking of the delivery catheter with mounted prosthetic valve across the aortic arche97,e109.

Large caliber less flexible delivery catheters are more traumatic and prone to dislodge atheromatous debris.

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).

Valve positioning and Implantatione104,e107,e111,e112

Embolization of calcific and atheromatous debris from valve manipulation and crushing.

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%).

Valve Dislodgement/Embolizatione100 Mechanical friction between prosthesis frame and aortic wall.

1. More common with self expanding CoreValve.

Balloon Post Dilation (BPD)e100,e113 Additional dislodgement and embolization of calcific debris from the native aortic

Smaller valve area and higher degree of calcification are associated with an increased risk of BPD and hence stroke.

valve.

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.