howard c. herrmann, md, facc, mscaihoward c. herrmann, md, facc, mscai john bryfogle professor of...

Update on TAVR

Howard C. Herrmann, MD, FACC, MSCAI

John Bryfogle Professor of Cardiovascular Medicine and SurgeryHealth System Director for Interventional Cardiology

Director, Cardiac Cath Labs, Hospital of the Univ of PA

Perelman School of Medicine University of Pennsylvania

Philadelphia

Disclosure Statement of Financial InterestWithin the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.

Discussion may include unapproved and off-label devices, procedures, and indications

Equity

MicrointerventionalDevices

Consulting Fees/Honoraria

Edwards LifesciencesBayerWells FargoLeering

Grant/Research Support

Abbott Vascular Edwards LifesciencesSt. Jude MedicalMedtronicGoreSiemens

BayerBoston SciCorviaCardiokinetxUniv Laval

Status of TAVI by Surgical Risk LevelTrial Device Risk Outcome

PARTNER 1B SAPIEN Inoperable TAVR > Medical TherapyPARTNER 1A SAPIEN High Risk TAVR = SAVRPARTNER 2A SAPIEN XT Intermediate Risk TF TAVR > SAVRPARTNER S3i SAPIEN 3 Intermediate Risk TAVR > SAVR

PARTNER 3 SAPIEN 3 Low Risk Enrolling

ValveTechnology

SAPIEN SAPIEN XT SAPIEN 3

Sheath Compatibility 22-24F 16-20F 14-16F

Take-Home Messages:

1. In intermediate risk patients with severe symptomatic AS, TAVR is non-inferior to SAVR for death/disabling stroke at 2 years

2. Will likely change the guideline to class I from IIa

• Randomized comparison of TAVR and SAVR in severe symp AS at intermediate risk for surgery• 1660 patients• STS PROM 4.5%• SAVR: more AKI, AF, Transfusion• TAVR: more AR, PPM, lower grads

Reardon et al, NEJM 2017;378:1321-1331

6.3%5.2%

3.7%4.5%

3.5%2.2% 1.6% 1.1% 1.1%

0%

5%

10%

15%

20%

P1B (TF) P1A (All) P1A (TF) P2B (TF) P2B XT (TF) S3HR (All) S3HR (TF) S3i (All) S3i (TF)

All-Cause Mortality at 30 DaysEdwards SAPIEN Valves (As Treated)

175 344 240 271 282 583 491 1072 947

SAPIEN SXT SAPIEN 3

PARTNER 1 and 2 Trials(Overall and TF Patients)

Estimated Global TAVR Procedure Growth

SOURCE: Credit Suisse TAVI Comment –January 8, 2015. ASP assumption for 2024 and 2025 based on analyst model. Revenue split assumption in 2025 is 45% U.S., 35% EU, 10% Japan, 10% ROW

In the next 5 years, TAVR growth will doubleIn the next 10 years, TAVR will increase X4!

Penn TAVR Program: Growth in Procedures

~2000

Chart1

Total FY08

Total FY09

Total FY10

Total FY11

Total FY12

Total FY13

Total FY14

Total FY15

Total FY16

Total FY17

# Transcatheter cases

Penn Medicine Transcatheter Total Volume FY08-current

10

27

39

79

193

212

270

324

391

414

HUP

FY08Jul-07Aug-07Sep-07Oct-07Nov-07Dec-07Jan-08Feb-08Mar-08Apr-08May-08Jun-08commtrialn=10

Commercial0000000000000TF000Sapien 110

Trial00002111004110TA000Sapien XT0

Total00002111004110TAO000Sapien 30

Trial randomized SAVR01010CoreValve0

Aborted-not counted10






















Total99131078111316102521152TAO101Sapien 30






Total1918913141316144131313159TAO10212Sapien 30


Aborted-not counted2131 open TAVRAVR (Trial)13




Total1518715111014913232318173TAO628Sapien 348

Trial randomized SAVR33121000000010LSC112CoreValve28

Aborted-not counted119380173AVR (Trial)10




Total302112221219101712241321213TAO505Sapien 35

Trial randomized SAVR0000110000002LSC404CoreValve79

Aborted-not counted11001003158322076Lotus1

AVR (Trial)2

FY16Jul-15Aug-15Sep-15Oct-15Nov-15Dec-15Jan-16Feb-16Mar-16Apr-16May-16Jun-16commtrialn=253thru 6/30

Commercial132016231915182021161219212TF14231173Sapien XT8

Trial36332414536141TA101Sapien 3172

Total162619262119192426191820253(+40)TAO314CoreValve12

TMVRLSC808Evolut R50

Trial randomized SAVR0000000000000trans-septal202Lotus4

Aborted-not counted020000000000215632188Portico7

AVR (Trial)0253

FY17Jul-16Aug-16Sep-16Oct-16Nov-16Dec-16Jan-17Feb-17Mar-17Apr-17May-17Jun-17Totalscommtrialn=241thru 5/31

Commercial1112221422202428231727220(+27)TF19517212Sapien XT7

Trial5530111301121(-19)TA213Sapien 3168


Mitraspan100000000001SCA15015Evolut R50

CardiaQ100000000001trans-septal617Evolut-Pro6

Compassion00000000010122120241Lotus1

TMVR (off label v-in-v)000100111015AVR (Trial)01Portico6

Trial randomized SAVR000010001002Mitraspan1

Aborted-not counted000000000224CardiAQ1

Compassion1

241

Calendar 2013Jan-13Feb-13Mar-13Apr-13May-13Jun-13Jul-13Aug-13Sep-13Oct-13Nov-13Dec-13n=149

Commercial131341046785124086Sapien 1862013 & 2014

Trial3103978102371063Sapien XT47n=365

Total1614413131315187151110149Sapien 314Sapien 1120

Trial randomized SAVR11203133121018CoreValve2Sapien XT115

Aborted-not counted0Sapien 364

CoreValve66

Calendar 2014Jan-14Feb-14Mar-14Apr-14May-14Jun-14Jul-14Aug-14Sep-14Oct-14Nov-14Dec-14n=216

Commercial471191610211411191017149Sapien 134

Trial1012146797132264Sapien XT68

Total14913232318302112221219216Sapien 350



n=76

Calendar 2015Jan-15Feb-15Mar-15Apr-15May-15Jun-15Jul-15Aug-15Sep-15Oct-15Nov-15Dec-15TotalSapien XT33

Commercial10171219915132016231915188Sapien 339

Trial00054636332436CoreValve34

Total101712241321162619262119224(+8)

Trial randomized SAVR0000000000000


JulyAugSeptOctNovDecJanFebMarAprilMayJuneTotal

Commercial FY1200000018167111760check

Commercial FY131417812119131341046121

Commercial FY14785124047119171195

Commercial FY1521141119101710171219915174

Commercial FY16132016231915182021161219212(+ 38)

Commercial FY171112221422202428231727220(+27)


Trial FY0800002111004110

Trial FY0921321232441227

Trial FY1060342332215334

Trial FY1135855476685668

Trial FY12991310781050314492

Trial FY1351224631039743

Trial FY14810237101022146781

Trial FY1597132200054639

Trial FY1636332414536141

Trial FY175530111301121(-19)


Total FY0800002111004110

Total FY0921321232441227

Total FY1060342332215334

Total FY1135855476685668

Total FY1299131078111316102521152

Total FY1319181014151516144131313164

Total FY141518715111014913232318176

Total FY15302112221219101712241321213

Total FY16162619262119192426191820253

Total FY171617251423212531231828241(-9)

Total FY0810

Total FY0927

Total FY1034

Total FY1168

Total FY12152

Total FY13164

Total FY14176

Total FY15213

Total FY16253

Total FY17241

Trial FY0810

Trial FY0927

Trial FY1034

Trial FY1168

Trial FY1292

Trial FY1343

Trial FY1481

Trial FY1539

Trial FY1641

Trial FY1721

Commercial FY1260

Commercial FY13121

Commercial FY1495

Commercial FY15174

Commercial FY16212

Commercial FY17220

TrialCommercialTotal

Total FY0810010

Total FY0927027

Total FY1034034

Total FY1168068

Total FY129260152

Total FY1343121164

Total FY148195176

Total FY1539174213

Total FY1641212253

Total FY1721220241

4568821338

FY13FY14FY15FY16FY17

Transfemoral101138193233212

Transapical46251123

Transaortic128554

Transaxillary0241215

Trans-Septal00017

Total159173213253241

*TAVR/TMVR

n=159

Sapien 1127(FY2013)

Sapien XT32

Sapien 30

CoreValve0

Total159

n=173

Sapien 167(FY 2014)

Sapien XT30

Sapien 348

CoreValve28

Total173

n=213(FY 2015)

Sapien XT103

Sapien 330

CoreValve79

Lotus1

Total213

n=253(FY 2016)30-Jun

Sapien XT8

Sapien 3172

CoreValve12

Evolut R50

Lotus4

Portico7

AVR (Trial)0

Total253

n=241(FY 2017)31-May

Sapien XT7

Sapien 3168

CoreValve0

Evolut R50

Evolut-Pro6

Lotus1

Portico6

Mitraspan1

CardiAQ1

Compassion1

Total241

AVR (Trial)1


Commercial FY131417812119131341046121

Commercial FY14785124047119171195(-26)

Commercial FY1521141119101710171219915174(+79)

Commercial FY16132016231915182021161219212(+38)

Commercial FY171112221422202428231727220(+27)

Trial FY1351224631039743

Trial FY14810237101022146781(+38)

Trial FY1597132200054639(-42)

Trial FY1636332414536141(+2)

Trial FY175530111301121(-19)

Total FY1319181014151516144131313164

Total FY141518715111014913232318176(+12)7%

Total FY15302112221219101712241321213(+37)17%

Total FY16162619262119192426191820253(+40)16%

Total FY171617251423212531231828241(+8)


Total FY15302112221219101712241321213

Total FY16162619262119192426191820253

Total FY171617251423212531231828241(+8)

HUP

2013 & 2014 TAVR Model Distribution

TAVR Valve Model # Utilization

HUP 2013 & 2014 TAVR Model Distribution

PPMC

2013-2015 (bottom-top)

HUP Calendar Year 2013-2015 TAVR Model Distribution

HUP-PPMC

HUP FY14 Valve Model Distribution

Physician %


For Herrmann


HUP-PPMC MAC-GA


HUP TAVR Cath Data

Transfemoral

Transapical

Transaortic

Transaxillary

Trans-Septal

Access Totals

Transcatheter Volume

Transcatheter Valve Replacements by Access (FY13-FY17 current)

Sheet1

Trial

Commercial

# Commercial vs Trial

HUP Transcatheter Distribution 2007-current

Sheet2

FY Transcatheter Growth


HUP Overall Transcatheter Volume FY07-current

Sheet3

FY10Jul-09Aug-09Sep-09Oct-09Nov-09Dec-09Jan-10Feb-10Mar-10Apr-10May-10Jun-10commtrialtotaln=5




Trial randomized SAVRCoreValve0























Total85610989441311794TAO257Sapien 338

Trial randomized SAVRLSC101CoreValve8





Total996118799912157111TAO404Sapien 325

Trial randomized SAVRLSC606CoreValve33



Commercial1161081251199111111114TF8720107Sapien XT7

Trial22231421031324TA303Sapien 377


Trial randomized SAVRLSC909Evolut R27


124

FY17Jul-16Aug-16Sep-16Oct-16Nov-16Dec-16Jan-17Feb-17Mar-17Apr-17May-17Jun-17commtrialn=1735/31/17

Commercial2111141412131112181716159(+56)TF14814162Sapien XT3

Trial4302210101014(-7)TA202Sapien 3110


TMVR010010000002LSC505Evolut R46

Trial randomized SAVRseptal202Evolut-Pro8


173

Calendar 2010Jan-10Feb-10Mar-10Apr-10May-10Jun-10Jul-10Aug-10Sep-10Oct-10Nov-10Dec-1010/30/15

Commercial000000000000

Trial0011011012119S3i CAP39Lotus5

Total0011011012119S3 interm22TF Lotus5

Trial randomized SAVRS3 HR23TA Lotus0

Aborted-not countedTotal S376TAO Lotus0

SC Lotus0

Calendar 2011Jan-11Feb-11Mar-11Apr-11May-11Jun-11Jul-11Aug-11Sep-11Oct-11Nov-11Dec-11S3i CAP39TF Evolut1

Commercial000000000000TF33TA Evolut0

Trial20111033231421TA4TAO Evolut0

Total20111033231421(+12)TAO2SC Evolut0

Trial randomized SAVR

Aborted-not countedS3 interm22

TF18

Calendar 2012Jan-12Feb-12Mar-12Apr-12May-12Jun-12Jul-12Aug-12Sep-12Oct-12Nov-12Dec-12TA4

Commercial10339326322337TAO0

Trial20121001101110

Total304510327423447(+26)S3 HR23

Trial randomized SAVRTF12

Aborted-not countedTA8

TAO3

Calendar 2013Jan-13Feb-13Mar-13Apr-13May-13Jun-13Jul-13Aug-13Sep-13Oct-13Nov-13Dec-13

Commercial45421143461035Total S376

Trial01004442248837TF56

Total564255856109873(+26)TA16

Trial randomized SAVRTAO4

Aborted-not counted

P2B30

Calendar 2014Jan-14Feb-14Mar-14Apr-14May-14Jun-14Jul-14Aug-14Sep-14Oct-14Nov-14Dec-14TF24

Commercial114393846108764TA4

Trial830102415010034TAO2

Total94413117996118798(+25)

Trial randomized SAVRP2A10

Aborted-not countedTF6

TA4

Calendar 2015Jan-15Feb-15Mar-15Apr-15May-15Jun-15Jul-15Aug-15Sep-15Oct-15Nov-15Dec-15TAO0

Commercial99757611610812595

Trial00278122231432P127

Total999121571381211139127(+29)TF14

Trial randomized SAVRTA13

Aborted-not countedTAO0

Calendar 2016Jan-16Feb-16Mar-16Apr-16May-16Jun-16Jul-16Aug-16Sep-16Oct-16Nov-16Dec-16P31

Commercial1199111111211114141211145TF1

Trial21031343022122TA0

Total13109141214251414161412167(+40)TAO0

Trial randomized SAVRSAVR0

Aborted-not counted

Calendar 2017Jan-17Feb-17Mar-17Apr-17May-17Jun-17Jul-17Aug-17Sep-17Oct-17Nov-17Dec-17P31

Commercial111218171674(+13)TF1

Trial010102(-5)TA0

Total111318181676(+18)TAO0

Trial randomized SAVR00000SAVR0

Aborted-not counted

JulyAugSeptOctNovDecJanFebMarAprilMayJune

Commercial FY1200000010339319




Commercial FY161161081251199111111114

Commercial FY172111141412131112181716159(+56)


Trial FY080000000000000

Trial FY090000000000000

Trial FY100000110011015

Trial FY1110121120111011

Trial FY1233231420121022

Trial FY1301101101004413

Trial FY14422488830102455

Trial FY1515010000278125

Trial FY1622231421031324

Trial FY174302210101014(-7)


Total FY08

Total FY09

Total FY100000110011015

Total FY1110121120111011

Total FY12332314304510341

Total FY1327423446425548

Total FY1485610989441311794

Total FY15996118799912157111

Total FY16138121113913109141214138

Total FY172514141614141113181816173(+49)

Total FY080

Total FY090

Total FY105

Total FY1111

Total FY1241

Total FY1348

Total FY1494

Total FY15111

Total FY16138

Total FY17173

Trial FY080

Trial FY090

Trial FY105

Trial FY1111

Trial FY1222

Trial FY1313

Trial FY1455

Trial FY1525

Trial FY1624

Trial FY1714

Commercial FY1219

Commercial FY1335

Commercial FY1439

Commercial FY1586

Commercial FY16114

Commercial FY17159

TrialCommercial

Total FY0800

Total FY0900

Total FY1050

Total FY11110

Total FY122219

Total FY131335

Total FY145539

Total FY152586

Total FY1624114

Total FY1714159

169452605

includes off-label TMVRFY10FY11FY12FY13FY14FY15FY16FY1731-May

Transfemoral5821276081121162

Transapical031921261232

Transaortic00107252


Transseptal00000052

Total511414894101143173



Commercial FY1326322345421135(+16)

Commercial FY1443461011439339(+4)

Commercial FY15846108799757686(+47)

Commercial FY161161081251199111111114(+28)

Commercial FY172111141412131112181716159(+56)

Trial FY1233231420121022

Trial FY1301101101004413(-9)

Trial FY14422488830102455(+42)

Trial FY1515010000278125(-30)

Trial FY1622231421031324(-1)

Trial FY174302210101014(-7)

Total FY12332314304510341

Total FY1327423446425548(+7)15%

Total FY1485610989441311794(+46)49%

Total FY15996118799912157111(+17)15%

Total FY16138121113913109141214138(+27)20%

Total FY172514141614141113181816173(+49)


Total FY15996118799912157111

Total FY16138121113913109141214138

Total FY172514141614141113181816173(+49)

FY16 PPMC

n=124

Sapien XT7

Sapien 389

CoreValve9

Evolut R29

Lotus4

138

FY17 PPMC

n=173

Sapien XT3

Sapien 3110

CoreValve0

Evolut R48

Evolut PRO6

Lotus6

Mitraspan0

CardiAQ0

173

Sheet3

PPMC FY16 Valve Model Distribution

FY Transcatheter Valve Growth

# Transcatheter Cases

PPMC Overall Transcatheter Growth FY07-current

Trial

Commercial

# Trial vs commercial

PPMC Transcatheter % Distributation FY07-current

Transfemoral

Transapical

Transaortic

Transaxillary

Transseptal

Access by FY

# of cases by access

PPMC Transcatheter Access FY07-current

PPMC FY17 Valve Distribution

FY13FY14FY15FY16FY17AS OF 5-31-17

Transfemoral128198285351374includes mitral v-in-v

Transapical67512055

Transaortic12159106


Trans-Septal00059

total207267324391414

PPMCHUPTotal

Total FY0801010

Total FY0810Total FY0902727




Total FY12193Total FY13481642129%




Total FY16391Total FY17173241414(+40)

Total FY1741462113381959

thru 5-31-2017

Trial FY0801010

Trial FY0902727

Trial FY1053439

Trial FY11116879

Trial FY122292114

Trial FY13134356

HUPJulyAugSeptOctNovDecJanFebMarAprilMayJuneTotalTrial FY145581136

Total FY15302112221219101712241321213Trial FY15253964

Total FY16162619262119192426191820253(+40)Trial FY16244165

Total FY171617251423212531231828241(-2)Trial FY17142135(-26)

PPMCJulyAugSeptOctNovDecJanFebMarAprilMayJuneTotal

Total FY15996118799912157111Commercial FY12196079

Total FY16138121113913109141214138(+27)Commercial FY1335121156

Total FY172514141614141113181816173(+51)Commercial FY143995134


Commercial FY16114212326(+66)

Commercial FY17159220379(+83)

n=391(FY 2016)30-Jun

Sapien XT15

Sapien 3263

CoreValve21

Evolut R77

Lotus8

Portico7

n=414(FY 2017)31-May

Sapien XT10

Sapien 3279

CoreValve0

Evolut R94

Evolut-Pro14

Lotus7

Portico7

Mitraspan1

CardiAQ1

Compassion1

414

*double valve case

TrialCommercial

Total FY1179079

Total FY1211479193

Total FY1346156202

Total FY14136134270

Total FY1564260324

Total FY1665326391

Total FY1735379414

53913341873

PPMCHUPTotal

62113381959

Penn Medicine FY16 Valve Distribution

Transfemoral

Transapical

Transaortic

Transaxillary

Trans-Septal

FY Transcatheter Access Volume

# Transcatheter Cases

Penn Medicine Transcatheter Access FY13-current


Penn Medicine Transcatheter Total Volume FY08-current

Penn Medicine FY17 Valve Distribution

Trial

Commercial

Total volume

Penn Medicine % Distribution FY11-current

FY15Jul-14Aug-14Sep-14Oct-14Nov-14Dec-14Jan-15Feb-15Mar-15Apr-15May-15Jun-15Total%FY15%

Bavaria142123121200199Bavaria9

Szeto6547343315244722Szeto22

Desai151069512585991210548Desai48

Vallabhajosyula9624543569256028Vallabhajosyula28

Atluri01010001011052Atluri2

21719 JEB1009 JEB100

FY15Jul-14Aug-14Sep-14Oct-14Nov-14Dec-14Jan-15Feb-15Mar-15Apr-15May-15Jun-15FY15%

Herrmann1284941026514388539Herrmann39

Anwaruddin12105998697771110046Anwaruddin46

Giri6433023203423215Giri15

217100100


Bavaria010120120120104Bavaria4

Szeto2434563244134116Szeto16

Desai6141013119111112581012048Desai48

Vallabhajosyula68583351089667730Vallabhajosyula30

Atluri211021012131156Atluri6

2539 JEB1004 JEB100

FY16Jul-15Aug-15Sep-15Oct-15Nov-15Dec-15Jan-16Feb-16Mar-16Apr-16May-16Jun-16FY16%

Herrmann8461099691010769437Herrmann37

Anwaruddin5189118512121166911244Anwaruddin44

Giri3545451353554819Giri19

254100100


Bavaria10301012113135.3Bavaria5.3

Szeto41120242121208.3Szeto8.3

Desai1011167121112218131914058.1Desai58.1

Vallabhajosyula15751078613387330.3Vallabhajosyula30.3

Atluri1010111210083.3Atluri3.3

24113 JEB1004.7 JEB100

FY17Jul-16Aug-16Sep-16Oct-16Nov-16Dec-16Jan-17Feb-17Mar-17Apr-17May-17Jun-17FY17

Herrmann6584871013111068836.6Herrmann36.6

Anwaruddin91011101181014671411045.6Anwaruddin45.6

Giri126046546184317.8Giri17.8

241100100

%

FY15 TAVR DISTRIBUTION

%


%


%


%


FY17Jul-16Aug-16Sep-16Oct-16Nov-16Dec-16Jan-17Feb-17Mar-17Apr-17May-17Jun-17

Herrmann6584871013111082

Anwaruddin910111011810146796

Giri126046546135

Li25141416141411131818157

Raza000000000000

370

HUPJulyAugSeptOctNovDecJanFebMarAprilMayJuneTotal

Total FY171617251423212531231828241

PPMCJulyAugSeptOctNovDecJanFebMarAprilMayJuneTotal

Total FY172514141614141113181816173

AccessFY17AS OF 5-31-17

Transfemoral334includes mitral v-in-v

Transapical5*includes 1 combined TAVR/v-in-v TMVR, therefore Access total is +1 from HUP/PPMC total

Transaortic5

Transaxillary18

Trans-Septal8

Total370

n=370(FY 2017)31-May

Sapien XT9*double valve case

Sapien 3247

CoreValve0

Evolut-R90

Evolut-Pro8

Lotus7

Portico6

Mitraspan1

CardiAQ1

Compassion1

370


2014201520162017thru 2/3/17201420152016

MAC4013619124MAC87188

GA17689496GA230118

MAC-GA CONV110

2014 accurate

add 2015 HUP

2016 accurate

20142015

MAC4771

GA5134

add nov-dec 2015 data

add 2016 data

48% MAC

68% MAC

MAC

GA

PPMC MAC vs GA 2014-2015

MAC

GA

HUP/PPMC MAC vs GA 2014-2015

27% MAC

61% MAC

MAC

GA

HUP/PPMC MAC vs GA 2014-2015

19% MAC

60% MAC

80% MAC

MAC

GA

calendar Year (January-December)

# TAVR cases per calendar year

HUP MAC calendar year 2014-2016

TAVR casesHUP cathCCH cathPAH cathPPMC cathUPHS cathnon-UPHS cath

FY15218126611114474

FY16158871210010949

as of 2/11/16

HUP cathCCH cathPAH cathPPMC cathnon-UPHS cath

FY15126611174

FY16871210049

UPHS cathnon-UPHS cath

FY1514474

FY1610949

HUPPPMCthru 2/29

Commercial FY1260Commercial FY1219






Commercial FY1200000018167111760check

Commercial FY131417812119131341046121

Commercial FY14785124047119171195

Commercial FY1521141119101710171219915174

Commercial FY161320162319151820144(+25)

PPMCJulyAugSeptOctNovDecJanFebMarAprilMayJune





Commercial FY1611610812511972(+11)

PENN MEDICINEJulyAugSeptOctNovDecJanFebMarAprilMayJuneTotal

Commercial FY12000000281910202079

Commercial FY13162311141312171881257156

Commercial FY141111918505815122614134

Commercial FY15291817291824192619241621260

Commercial FY162426263131202929216(+36)

Penn Medicine Q1 13-16Total

FY120

FY1350

FY1431

FY1564

FY1676

Sapien 3 impact to TVT


Commercial FY1521141119101710171219915174

Sapien 3 Intermediate96000000054529

Total302011191017101712241320203




Total17241859

HUP/PPMC w/ HUP S3iJulyAugSeptOctNovDecJanFebMarAprilMayJuneTotal

Commercial FY15291817291824192619241621260


Total382417291824192619292026289

HUP/PPMC w/ HUP S3iJulyAugSeptOctNovDecJanFebMarAprilMayJune

Commercial FY12000000281910202079

Commercial FY13162311141312171881257156

Commercial FY141111918505815122614134

Commercial FY15382417291824192619292026289


HUP/PPMC w/ HUP S3iTotals

Commercial FY1279

Commercial FY13156

Commercial FY14134

Commercial FY15289

Commercial FY1683

PENN MEDICINETotal

Commercial FY1279

Commercial FY13156

Commercial FY14134

Commercial FY15260

Commercial FY16216

Commercial FY12

Commercial FY13

Commercial FY14

Commercial FY15

Penn Medicine Commercial TAVR Growth

Total

Quarter 1 Fiscal Volume Comparison

# commercial TAVR

Penn Medicine 1st Quarter Comparison Commercial TAVR

Commercial FY12

Commercial FY13

Commercial FY14

Commercial FY15

Penn Medicine Commercial + HUP S3i TVT Volume

Commercial FY12

Commercial FY13

Commercial FY14

Commercial FY15

Commercial FY16

Commercial FY12

Commercial FY13

Commercial FY14

Commercial FY15

Commercial FY16


Commercial471191610211411191017149

Trial1012146797132264

Total14913232318302112221219216




Commercial1017121991513201623154

Trial000546363330

Total10171224132116261926184(-1)





Trial830102415010034

Total94413117996118798


Aborted-not counted



Trial002781222327

Total999121571381211105(+22)


Aborted-not counted

HUPPPMCPAHCCH

Monthly Cardiac Cases0611018

HUPPPMCPAHCCH

FY16-current cases04381018

Jan-16HUPPPMCPAHCCH

CABG1857

Valve1144

Valve/ CABG502

TAVR1400

Aortic810

VAD100

ECMO400

Other005

Transplant000

FY16 to dateHUPPPMCPAHCCH

CABG11057

Valve12044

Valve/CABG3802

TAVR7900

Aortic4210

VAD600

ECMO3500

Other805

Transplant000

HUP

PPMC

PAH

CCH

January 2016 Case Breakdown

Monthly Cardiac Cases

Campuses

Monthly Volume

January 2016 Cardiac Cases

FY16-current cases

Campuses

FY16 to date volume

HUP

PPMC

PAH

CCH

FY16-current Case Breakdown

• Hybrid OR

• Heart team intact (Anesthesia, CV Surgery, Cardiology)

• MAC predominately (vs CS)

• Peripheral access (no PA catheter, no RIJ line)

• Percutaneous access

• Fast track to floor

• D/C home POD # 2-3

TAVR at Penn Today ≈ 500 Cases Annually

“It Takes a Village!”

• Lower the rate of complications to those of SAVR:

• Vascular complications

10

Lotus Deployment

Medtronic TAVR EnVeo R

Evolut Pro

New valves will likely provide trade-offs between vascular complications (size), sealing (PVL), and need for PPM.

Assuming all of these are undesirable, which do you consider to be the worst?

1. Vascular complications

2. Mild AR/PVL

3. PPM

14

Meredith, et al., presented at PCR London Valves 2014; Adams, et al., N Engl J Med 2014; 370: 1790-8; Leon, et. al. presented at ACC 2013; Lefevre et al., J Am Coll Cardiol 2016; 1:; Popma, et al., J Am Coll Cardiol 2014; 63: 1972-81; Linke, et. al. presented at London Valves 2015; Van Mieghem, et al., presented at EuroPCR 2015; Kodali, et al., presented at ACC 2015; Holmes, et al., JAMA 2015; 313: 1019-28; Meredith, et al., presented at ACC 2015, 1 Williams, et. al. presented at ACC 2016; Thourani, et al, presented at ACC 2016

4.0% 3.9%

5.5%

6.8% 7.0%

0.0%

3.3%

4.1%

2.5%

4.9%4.3%

1.5%

2.7%

5.5%

0%

1%

2%

3%

4%

5%

6%

7%

8%

CoreValveExtreme

RiskN=489

LOTUSRESPOND

N=500

PorticoCE StudyN=103

LOTUSREPRISE II

+ ExtN=249

Direct FlowDISCOVER

N=75

Evolut RCE Study

N=60

Evolut RIDE N=241*

SAPIENPARTNER

IIBN=276

SAPIENTVT HR

N=12182

CoreValveHigh Risk

N=390

SAPIEN XTPARTNER

IIBN=284

SAPIEN 3PARTNER II

HRN=583

SAPIEN 3PARTNER II

S3iN=1078

SAPIEN XTPARTNER

IIAN=1011

% P

atie

nts w

ith S

trke

at 3

0 Da

ys

Extreme Risk Extreme/High Risk High Risk Intermediate Risk

* Disabling Stroke

Incidence of CVA after TAVI remains clinically significant, particularly in high risk patients

15

• 68-100% of TAVI patients affected1-11

• Most patients have multiple infarcts• “Silent” infarcts associated with12-14

• 2-4-fold risk of future stroke• >3-fold risk of mortality• >2-fold risk of dementia• Cognitive decline• Dementia

New cerebral lesions are found in the vast majority of patients following TAVI

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Rod

es-C

abau

2011

Gha

nem

201

0

Arno

ld 2

010

Kahl

ert 2

010

Asta

rci 2

011

DEF

LEC

T III

cont

rol a

rm20

15

Biju

klic

201

5

CLE

AN-T

AVI

cont

rol a

rm

PRO

TAVI

-C

Neu

roTA

VR

MIS

TRAL

-C

% of TAVI patients with new cerebral lesions on DW-MRI

Ghanem, et. al, JACC 2010

1. Rodes-Cabau, et al., JACC 2011; 57(1):18-282. Ghanem, et al., JACC 2010; 55(14):1427-323. Arnold, et al., JACC:CVI 2010; 3(11):1126 –32

4. Kahlert, et al., Circulation. 2010;121:870-8785. Astarci, et al., EJCTS 2011; 40:475-96. Lansky, et al., EHJ 2015; May 19

7. Bijuklic, et al., JACC: CVI 20158. Linke, et al., TCT 20149. Vahanian, TCT 201410. Lansky, et al. London Valves 2015

11. van Mieghem N, et al. EuroIntervention2016;12:499-507 12. Sacco et al., Stroke 201313. Vermeer et al., Stroke 200314. Vermeer et al., New Engl J Med 2009

Background

• The Claret MontageTM dual-filter Cerebral Protection System was developed to protect the brain from injury caused by embolic debris.

• Randomized controlled trial data showing the efficacy of any embolic protection device in TAVR are missing.

SENTINAL TRIAL:Primary Efficacy Endpoint

42.2% reduction [95% CI: -3.2,67.6)

p = 0.33

New

Les

ion

Volu

mes

in

Prot

ecte

d Te

rrito

ries (

mm

3 )

350

300

250

200

150

100

50

0Control(N=98)

178

Median ± 95% Confidence Limit

Treatment(N=91)

102.8 0%10%20%30%40%50%60%70%80%90%

100%

Are small emboli that do not cause disabling or clinical strokes bad?

1. Very bad

2. Only a little bad and a reasonable trade-off for avoiding surgical recovery

3. Only a little bad, but would persuade me to have surgery if I was intermediate or low risk

4. Not bad at all

When an embolic protection device is avail in my hospital (cost ~1.5-3K), I will use it in…:

1. All patients

2. No patients

3. Selected patients based on device

4. Selected patients based on my assessment of stroke risk

Valve Leaflet Abnormalities

Diastole

Systole

Makkar, et al. 2015

New TAVR Pharmacology Trial

PIs: Dangas, G.Windecker, S.

US PI:Herrmann, H.

In 5 years all patients receiving bio AVR (TAVR and SAVR) will be treated for 3-6 months with:

1. Dual anti-platelet therapy (current standard of care)

2. Warfarin anticoagulation to INR 2-3

3. DOAC

4. Reduced dose warfarin (INR goal 1.5-2.5)

5. Reduced dose DOAC (rivaraxaban [10 mg] or apixaban [2.5 bid])

6. Echo (TEE) or CT guided therapy

Commercial AVR (TAVR or SAVR), Clinical Trial (P3), etc.

Symptomatic N=1,000 ptsPositive stress test

ScreeningNot eligible if 10

Asymptomatic Severe, Calcific AS

Asymptomatic N=1,109 ptsNegative stress test OR confirmation via med history*

TF- TAVR Clinical Surveillance

Registry

Primary Endpoint (superiority): 2-year composite of all-cause death, all stroke, and

unplanned cardiovascular hospitalization

Clinical and Echo Follow-up: 30 days (TAVR only), 1, 2, 3 and 5 years Telephone Follow-up:

1, 2, 3 and 5 years

Randomization 1:1Stratified by ability to perform stress test

Principal Investigator:Philippe Généreux, MD,

Chair: Martin B. Leon, MD

NCT03042104; 1st patient consented March 16th

InternationalMulticenter

Randomized

TAVR-UNLOAD Trial Design

Heart FailureLVEF < 50%

NYHA ≥ 2Optimal HF

therapy(OHFT)

Moderate AS

TAVR UNLOAD

Trial

R

TAVR + OHFT

OHFT Alone

Follow-up:1 month6 months

1 year

Clinical EndpointsSymptomsEcho QoL

Primary EndpointHierarchical occurrence of:

All-cause death Disabling stroke Hospitalizations for

HF, aortic valve disease, or non-disabling stroke

Change in KCCQ

Reduced AFTERLOADImproved LV systolic and diastolic function

New indications for TAVR. I recommend TAVR for which of these patients:

1. Asymptomatic AS only if very severe (mean gradient >50 mmHg)

2. Asymptomatic AS if severe (mean gradient >40 mmHg)

3. Moderate AS (AVA >1.0 cm2) if symptomatic with LV dysfunction

4. 1 and 3

5. 2 and 3

TAVR Durability IssuesSome of the problems associated

with this type of analysis…• 2 center experience, ultra-sick patients,

earliest versions of the Sapien THV• Incorrect statistical methods - THV

degeneration is a time-dependent “process”, not a clinical “event”

• Competing risks of frequent deaths in these patients with multiple co-morbidities creates censoring problems

• Echo data are incomplete - ascertainment and interpretation, and definitions used were spurious - creates significant biases

• No. at risk after 5 years drops precipitously - tail shape unreliable• “Clinical” SVD - freedom from re-intervention - never discussed

27

Longitudinal Hemodynamics in Partner 1

• All patients with evaluable echoes over time at core lab

N= 2482 TAVR patients

• Median F/U 3.1 years (Max 5 years)

• Main findings:

• Stable hemodynamics

• Only 5 patients had re-intervention for SVD (0.8%)

• Mod/severe AR 3.7% (slight increase over time)

Douglas et al, JAMA Cardiology 2017 (in press)

Regarding durability, pick the statement you most agree with:

1. TAVR valves will not be as durable as surgical prostheses, but the

difference will be small and won’t influence procedure selection

2. TAVR valves will be less durable and will make surgery preferable in

patients

Low Risk TAVR Trials

* Source: Clinicaltrials.gov

Sponsor Edwards (NCTO2675114)* Medtronic (NCTO2701283)*

Device Sapien 3 Evolut R / EnVeo R

Design Prospective, randomized Prospective, randomized

Comparator 1:1 to SAVR 1:1 to SAVR

Analysis Non-inferiority Non-inferiority

N 1228 1250

Inclusion Heart team risk

Regarding low risk patients, pick the statement you most agree with:

1. TAVR will eventually replace surgery in most patients, including those

at low risk due to the procedural advantages and patient preference

to avoid surgery

2. Despite likely non-inferiority in the low risk trials, surgery should still

be preferred due to lack of even mild PVL and known durability.

3. Risk is less important to me than age. Eg., a low risk 78 yo should get

TAVR and an intermediate risk 70 yo should get SAVR.

Update on TAVRDisclosure Statement of Financial Interest�Status of TAVI by Surgical Risk LevelTake-Home Messages:�� 1. In intermediate risk patients with severe symptomatic AS, TAVR is non-inferior to SAVR for death/disabling stroke at 2 years� 2. Will likely change the guideline to class I from IIaAll-Cause Mortality at 30 Days�Edwards SAPIEN Valves (As Treated) Slide Number 6Penn TAVR Program: Growth in ProceduresTAVR at Penn Today ≈ 500 Cases Annually What additional evidence is required to make �TAVR suitable for everyone?Lotus DeploymentSlide Number 11Slide Number 12Slide Number 13Incidence of CVA after TAVI remains clinically significant, �particularly in high risk patientsNew cerebral lesions are found in the vast majority of patients following TAVIBackgroundSENTINAL TRIAL:�Primary Efficacy EndpointSlide Number 18Slide Number 19Valve Leaflet Abnormalities Slide Number 21Slide Number 22Slide Number 23TAVR-UNLOAD Trial Design Slide Number 25Slide Number 26Longitudinal Hemodynamics in Partner 1Slide Number 28Low Risk TAVR TrialsSlide Number 30

howard c. herrmann, md, facc, mscaihoward c. herrmann, md, facc, mscai john bryfogle professor of...

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