therelentlessdrivetolowrisk: obstacles and …€¦ · salus national surgical pi surtavi reprise...
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THE RELENTLESS DRIVE TOLOW RISK: OBSTACLESAND OPPORTUNITIES
Michael J. Reardon, M.D.
Professor of Cardiothoracic Surgery
Allison Family Distinguish Chair of Cardiovascular
Research
Houston Methodist DeBakey Heart & Vascular Center
COI
Steering committeesCoreValveEvolut RSurTAVI
Reprise IIISalus
National Surgical PISurTAVI
Reprise IIIEvolut R low risk trial
EXTREMERISK
DONE
DONE
HIGH RISK
DONE
DONE
HIGH RISK CLINICALOUTCOMES
Events TAVR SAVRP
Value
Life threateningor disablingbleeding
19.1 41.3 <0.001
Acute kidney injury 6.2 15.1 <0.001
Atrial fibrillation 19.8 36.3 <0.001
Reintervention 2.5 0.4 0.020
Major vascular complications 7.1 2.0 0.001
Pacemaker implant 28.0 14.5 <0.001
Aortic valve hospitalization 27.6 21.9 0.087
Endocarditis 0.9 1.7 0.346
6
Subgroup
All-cause Deathat 3 YearsKM
RatesHazard Ratios
(95%CI)
Interaction PValue
TAVR SAVRAge 0.35
>85 38.8 41.9 0.89 (0.63, 1.24)≤85 27.5 36.8 0.70 (0.49, 1.00)
Gender 0.65Male 34.8 40.7 0.84 (0.60, 1.16)Female 30.7 37.1 0.75 (0.52, 1.08)
BMI 0.82≤30 35.4 41.3 0.80 (0.60, 1.06)>30 26.5 34.2 0.75 (0.46, 1.23)
LVEF 0.24≤60 35.7 38.7 0.89 (0.66, 1.21)>60 28.3 38.8 0.65 (0.43, 1.00)
Diabetes 0.70No 34.7 43.0 0.74 (0.55, 1.01)Yes 29.6 34.5 0.82 (0.55, 1.25)
1.00 2.000.500.250 125
ACC2016 7
Subgroup
All-cause Deathat 3 YearsKM
RatesHazard Ratios
(95%CI)
InteractionP
ValueTAVR SAVR
Prior CABG 0.90No 34.8 42.2 0.78 (0.59, 1.04)Yes 28.3 32.5 0.81 (0.50, 1.32)
PVD 0.56No 34.4 38.6 0.84 (0.61, 1.16)Yes 30.0 38.8 0.73 (0.49, 1.07)
Hypertension
0.46
No 50.4 59.8 0.56 (0.21, 1.44)Yes 32.1 38.2 0.80 (0.62, 1.03)
STSScore 0.14≤7% 27.1 38.5 0.66 (0.46, 0.95)>7% 39.3 39.8 0.95 (0.68, 1.32)
1.00 2.000.500.250 125
ACC2016 8
0
0.001
0.002
0.003
0.004
0.005
0.006
0.007
0 30 60 90 120 150 180 210 240 270 300 330 360
Est
imat
ed
Haza
rdR
ate
Days Post Procedure
HRPivotal TAVR
HRPivotal SAVR
Perip ocedural ElevatedHazard
Constant Hazard
Delayed Recovery
TAVR vs. AVR must showequivalent or better
mortalityhemodynamics
morbidityquality of life
durabilitypatient acceptance
PVL/ Pace
maker
?
What do randomized trial tellus?
TAVR is the treatment ofchoice in anatomically TAVR
suitable high-risk patients
How About Lower Risk Data?
Evolution in Patient Selection inU.S. TAVR Clinical Trials
11 2% 11 0%11.8%
0%
2%
4%
6%
8%
10%
12%
14%
PARTNERBTAVR
PARTNERIIB
SAPIEN
PARTNERIIB
SAPIEN XT
CoreValveER
Iliofemoral
CoreValveER
ContinuedAccess
TVTRegistry
SAPIENTF
PARTNERATAVR
PARTNERTF
ContinuedAccess
CoreValveHR
TVTRegistry
SAPIENTF
STS
Score
Inoperable (extreme risk) High-Risk
Partner IIA
SurTAVI
SurTAVI data will bepresented in 2017
TAVR vs. AVR must showequivalent or better
mortalityhemodynamics
morbidityquality of life
durabilitypatient acceptance
PVL/ Pace
maker
?
Intermediate risk
Low Risk Randomized Trials
UK “ALL-COMERS”TRIAL
Severe symptomatic aortic stenosis
Age ≥80 years (ie all comers in this age group)
Or Age ≥70 years + >/= 1 co-morbid state
Both AVR and TAVI deemed to be acceptable
options (Eligibility determined by the MDT)
Randomised to TAVI or surgical AVR (1:1)
– with any CE marked device
N = 808 patients
Primary end point - All-cause mortality at one year
6.2%
13.9%
79.9%
FDAApproved
FDA Approved
Trials
PVL?
CURRENTHMH VALVES
Nitinol wire frame,bovine tissue
valve; outer PUskirt; mechanical
expansion andlocking
Evolut RSelf-expanding,Nitinol frame, 3
sizes, Recapture,Reposition andRedeployment
balloon exp(4 sizes),
cobalt frame;bovine tissuevalve; outerskirt; precisepositioning
CURRENTHMH VALVES
Polyester fabric cuff withtwo inflatable rings;positioning wires for
placement; bovine tissuevalve
Portico:Nitinol frame, Bovine
and Porcinepericardial valve.
Reposition, redeployand recapture
Open cell and intraannular
68.8%79.5%
72.4%
28.6%15.4%
24.1%
2.6% 5.1% 3.4%100%
TF TAA Overall
None/Trace Mild Moderate Severe
SAPIEN 3 TAVR (CE Study)
Femoral TA All
0.1%
S3PVL at 30
days (n
=1500)
Moderate/severe PVL at 30days is 3.4%
Evolut 2.0
REPRISEII TRIAL
Direct Flow TAVR (DISCOVERY)
24.2
16.9
14.2
11.49.0
4.0 3.41.4 0.6
0
5
10
15
20
25
30
%Pat
ients
wit
hM
od/S
eve
rePV
L
SAPIENXT
PARTNER
II, Inop1
SAPIENPARTNERII Inop1
CoreValveADVANCE2
CoreValveExtreme
Risk3
CoreValve HighRisk4
Portico
CEStudy5
SAPIEN36
DirectFlow
DISCOVER7
LOTUSREPRISE
II &EXT8
N=236 N=225 N=639 N=412 N=356 N=75 N=116 N=74 N=1771Leon M, ACC2013, 2LinkeA, PCR2014. 3PopmaJ, JACC2014; 63(19): 1972-81, 4AdamsD, N Engl JMed 2014; 370: 1790-98. 5Manoharan, et al. TCT2014. 6Webb J, EuroPCR2014. 7Schofer, JACC2013. 8Ian Meredith, London Valves2014. Resultsfrom different studiesnot directlycomparable. Informationprovided for educational purposeonly
1 Month Moderate & Severe PVLTAVI Clinical Trials
29.2
20.9
119.4
6.8 6.14.3
00
5
10
15
20
25
30
3512-mo Mod/ Severe PVLrate
Adverse Clinical OutcomesTAVI Clinical Trials
PARTNERII SAPIEN
XT5
PARTNERII SAPIEN5
PARTNERB
SAPIEN6
CoreValve
ADVANCE1
PARTNERA SAPIEN7
CoreValveHigh Risk3
CoreValveExt Risk4
LOTUSREPRISE
II2
N: 284 276 179 996 348 390 489 120
%o
fPat
ients
1LinkeA, PCR2014., 2Ian Meredith, TCT2014 3AdamsD, N En179gl JMed 2014, 4PopmaJ, JACC2014, 5Leon M, ACC2013., 6Leon, NEJM 2010., 7Smith, NEJM2011.Resultsfrom different studiesnot directly comparable. Information provided for educational purpose only
PREDICTIONS FOR2020
PVL will be largely solvedand similar to SAVR with
engineering designimprovements
78.176.06
78.71 80.07 80.53
77.4
63.89
68.44
74.4976.32
40
50
60
70
80
90
Baseline Discharge 30 days 6 months 12 mo
TAVR
SAVR P=0.023
P=0.19
Volu
me
(mL)
0
20
40
60
80
100
P=0.1288
Seve
rePPM
(%)
TAVR SAVR TAVR SAVR TAVR SAVR
baseline Discharge 12 mo
None Mild Moderate Severe
Prosthesis-Patient Mismatch
• Severe PPM occurssignificantly more afterSAVR than TAVR
Zorn AATS2015
PREDICTIONS FOR2020
SAVR hurts the heart for atleast 6 months and this isunlikely to change by 2020
Durability
DVIR DATA
PREDICTIONS FOR2020
We will not get an answer ondurability until intermediate andlow risk trials reach 10 years
PREDICTIONS FOR2020
SAVR is a mature techniquewhile
TAVR is young and likely tounder go substantial
improvements
Technical disasters have alreadydecreased and will decrease
0
0.001
0.002
0.003
0.004
0.005
0.006
0.007
0 30 60 90 120 150 180 210 240 270 300 330 360
Est
imat
ed
Haza
rdR
ate
Days Post Procedure
HRPivotal TAVR
HRPivotal SAVR
Pe procedural ElevatedHazard
Constant Hazard
DelayedRecovery
PREDICTIONS FOR2020
SAVR is technique drivenTAVR is technology driven
TAVR will enjoy a wideradoption than SAVR
PREDICTIONS FOR2020
We used to ask “Which casesare bad for SAVR” and do
TAVR
We will ask “Which cases arebad for TAVR” and consider
SAVR
PREDICTIONS FOR2020
Surg
icalR
isk
Low Risk Intermediate Risk High Risk Extreme Risk
Both dividing linesmoving to the leftbut how far?Durablity
PREDICTIONS FOR2020
Surg
icalR
isk
Low Risk Intermediate Risk High Risk Extreme Risk
Both dividing linesmoving to the leftbut how far?
If proven durablity found
All risk categories will be TAVR candidates
Thank You
0.0
10.0
20.0
30.0
40.0
50.0
60.0
Baseline Discharge 1 Month 1 Year 2 Years 3 Years
TAVR SAVR
AV
Mean
Gra
die
nt,
mm
Hg
In 18 TAVR(9.5%) and 17 SAVR(12.6%) with a >50%increase in AV mean gradient:
72*Site-reported
Structural Hemodynamic Deterioration*ACC2016
6.2%
13.9%
79.9%
FDAApproved
FDA Approved
Trials