top 10 advances in transcatheter valve therapy 2018 · the future of transcatheter heart valves...
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Samin K Sharma, MD, FACC, FSCAI
Senior VP for Operation & Quality, Mount Sinai Heart
Director Interventional Cardiology, Mount Sinai Health System
Anandi Lal Sharma Professor of Medicine in Cardiology
President Mount Sinai Heart Network
Mount Sinai Hospital, NY
COI: Speaker bureau for Abbott, BSC, CSI, Abiomed,
Top 10 Advances in Transcatheter Valve Therapy 2018
The Future of Transcatheter Heart Valves Aortic Valve
Medtronic CoreValve
Mitral Valve
Edwards Sapien XT
Tricuspid Valve
Edwards Perimount Magna
Pulmonic Valve
Medtronic Melody Valve
The Andersen Stent-Valve (1989)
Father of Transcatheter Valve Therapy
Percutaneous Valve Technologies (PVT)
Aortic Heart Valve
Bovine pericardium / Stainless steel stent
Polyurethane
23mm max diameter
24F
Alain Cribier
15 min post-TAVR
April 16, 2002; FIM-TAVR; Rouen, FR
Alain Cribier
Reasons for selection of the study
Revolutionary / significant observation
Widespread acceptance
Change in clinical practice
Top 10 Advances in Transcatheter Valve Therapy 2018
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10. Tricuspid Valve Intervention: TRILUMINATE
Top 10 Advances in Transcatheter Valve Therapy 2018
Trends in U.S. In-Hospital Mortality After
Isolated Tricuspid Valve Surgery, 2003 to 2014
Asmarats et al., J Am Coll Cardiol 2018;71:2935
Transcatheter Tricuspid Landscape
Asmarats et al., J Am Coll Cardiol 2018;71:2935
Coaptation Devices Suture Annuloplasty
Ring Annuloplasty
Transcatheter Tricuspid Valve Replacement
Heterotopic Caval Valve Implant
TriValve Registry: Patient Stratification According to
Procedural Success
Besler et al., J Am Coll Cardiol Intv 2018;11:1119
Assessment of tricuspid valve coaptation gap
n=117
Coaptation gap <7.2 mm
n=95
Coaptation gap >7.2 mm
n=22
Main TR jet
central/anteroseptal
n=78
Main TR jet
central/anteroseptal
n=78
Main TR jet
central/anteroseptal
n=78
Main TR jet
central/anteroseptal
n=78
Main TR jet
central/anteroseptal
n=78
Main TR jet
central/anteroseptal
n=78
Main TR jet
central/anteroseptal
n=78
Main TR jet
central/anteroseptal
n=78
TRILUMINATE Trial: TriClip System
TRILUMINATE TriClip Study
▪ Prospective, single-arm, multicenter feasibility study
▪ At least 85 patients in 15 centers (4 in US 35 patients:
Mount Sinai, Henry Ford, Abbott Northwestern, Cedar Sinai)
▪ Moderate or greater TR in NYHA II, III, ambulatory IV
▪ Follow-up to 3 years
Primary Endpoint: TR reduction > 1 grade at 30d
Secondary Endpoint: Cardiac mortality at 30d
Summary of Ongoing and Future Studies on
Transcatheter Therapies for Tricuspid Regurgitation
Proposed Algorithm for Transcatheter Tricuspid Valve Device
Selection Based on Mechanism & Patho-anatomy of TR
Asmarats et al., J Am Coll Cardiol 2018;71:2935
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9. Sentinel Cerebral Protection Device during TAVR
10. Tricuspid Valve Intervention: TRILUMINATE
Top 10 Advances in Transcatheter Valve Therapy 2018
Sources of Debris During TAVR: Strokes
TAVR DEVICES
Foreign
material
NATIVE HEART
Myocardium
TRANSVERSE ARCH
Arterial wall, calcific
and atherosclerotic
material
ASCENDING ARCH
Arterial wall, calcific
and atherosclerotic
material
STENOTIC VALVE
Leaflet tissue and
calcific deposits
TAVR & Stroke: Often Underreported
~4% Average Stroke RateContemporary TAVR studies have shown an average
of 4% stroke rate
>9% with Routine Neurologist
AssessmentStudies using routine discharge exams by
neurologists show higher clinical stroke rates
TM
TM T
M
TM
TM
TM
TM
Findings from the SENTINEL IDE Trial Together with Real World Outcomes
from Ulm, Erasmus and Cedars Sinai Medical Centers Demonstrate Consistent
Reductions in Stroke Among Nearly 2,400 Patients
1Kapadia S, et al. J Am Coll Cardiol 2017;69:367–77; 2Seeger J et al. 2017. JACC Cardiovasc Interv. 10(22)2297-2303; 3van Mieghem N. presented at
TVT 2018; 4Chakarvarty T. presented at TVT 2018
Histopathology of the Proximal Filter
Seeger et al., J Am Coll Cardiol Intv 2018;11:1683
Histopathology of the Distal Filter
Particle Size by Histomorphometry in the
Proximal and Distal Filter in Relation to Valve Type
Seeger et al., J Am Coll Cardiol Intv 2018;11:1683
Histomorphometry – Particle Size –
Proximal FilterHistomorphometry – Particle Size –
Distal Filter
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2.
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4.
5.
6.
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8. Antithrombotic Therapy post TAVR
9. Sentinel Cerebral Protection Device during TAVR
10. Tricuspid Valve Intervention: TRILUMINATE
Top 10 Advances in Transcatheter Valve Therapy 2018
What Antithrombotic Treatment After TAVR/TAVI?
Thrombo-embolic
Risk
Bleeding
RiskOAC-based
strategy(VKA or NOAC)
SAPT (ASA or Clopidogrel alone)
DAPT (ASA+Clopidogrel)
Mortality Structural Valve
Deterioration
AT+ AT-
Bioprosthetic Valve Dysfunction• in mean gradient (MG) ≥ 10 mmHg or new MG ≥ 20mmHg
• Prevalence of 4.5% post-TAVR
Makkar et al., N Engl J Med
2015;373:2015
Del Trigo et al, J Am Coll
Cardiol 2016;67:644
Anti-Thrombotic Treatment After TAVR:
Insights from the
FRANCE-TAVI Registry
FRANCE-TAVI Registry: Flow Chart
Collet JP, ESC 2018
France-TAVI Registry: KM Curves According
to Anticoagulation
Overtchouck et al., J AM Coll Cardiol Aug 22, 2018 Epub
France-TAVI Registry: Correlates to
Bioprosthetic Valve Dysfunction (BVD)
Overtchouck et al., J AM Coll Cardiol Aug 22, 2018 Epub
N=2555m=20
P-valueAdj. OR 95% CI upper 95% CI lower
BMI 0.002 1.05 1.02 1.09
Prior TAVR 0.025 2.96 1.15 7.64
Moderate/severe renal failure 0.034 1.46 1.03 2.08
Non-femoral access 0.049 0.53 0.28 1.02
Prosthesis ≤23 mm <0.001 3.43 2.41 4.89
OAC at discharge 0.005 0.54 0.35 0.82
France-TAVI Registry: Post-TAVR Antithrombotic
Strategy Flowchart
Overtchouck et al., J AM Coll Cardiol Aug 22, 2018 Epub
Major Ongoing Trials of Anti-thrombotics in TAVR/TAVI
Treatment Comparison Number of
Patients
NVAF Status
GALILEO RIVA vs DAPT/SAPT 1520 Excluded Enrolment
completed
ATLANTIS VKA vs Apixaban
DAPT/SAPT vs Apixaban
1510 Included
(stratified)
Enrolment almost
done
ENVISAGE EDOXABAN 1400 only Ongoing
POPULAR VKA vs VKA+clopi
DAPT vs ASA
1510 Included and
stratified
Ongoing
AVATAR VKA vs VKA+APT 170 Included
(stratified)
Ongoing
AUREA VKA vs DAPT 124 Excluded Ongoing
Trial completed enrollment as of April 2018
August 2018, DSMB recommended
to halt the study follow-up due to
safety concerns; Higher mortality?
What Do Guidelines Recommend?
• 2017 AHA/ACC Focused Update Guidelines for the management
of valvular heart disease
\\
• 2017 ESC/EACTS Guidelines for the management of valvular
heart disease
New!
New!
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4.
5.
6.
7. TAVR for Pure Aortic Regurgitation
8. Antithrombotic Therapy post TAVR
9. Sentinel Cerebral Protection Device during TAVR
10. Tricuspid Valve Intervention: TRILUMINATE
Top 10 Advances in Transcatheter Valve Therapy 2018
Pure Aortic Regurgitation Current Challenges for TAVR
Franzone et al., J Am Coll Cardiol Intv 2016;9:2308
This Pathology Presents Unique Technical Challenges for Current TAVI Systems
Procedural Data
Yoon et al., J Am Coll Cardiol 2017;70:2752
Procedural and Clinical Outcomes
Yoon et al., J Am Coll Cardiol 2017;70:2752
TAVR for Native Aortic Valve Regurgitation
Yoon et al., J Am Coll Cardiol 2017;70:2752
Outcomes According to DevicesMortality and Post-Procedural Aortic
Regurgitation
Self-Expabdable
ACURATE TA
Bioprosthesis
JenaValve™ Prosthesis
Kemfert et al., Eur J Cardiothoracic 2011;40:761
Engager™ Aortic
Transcatheter Valve
Sündermann et al., Eur J
Cardiothoracic 2012;42:e48Wendt et al., J Am Coll
Cardiol Intv 2014;7:1159
Transcatheter Aortic Valves for Pure AI
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6. Emerging TAVR Indications: LFLG, ViV, BAV, EARLY, UNLOAD
7. TAVR for Pure Aortic Regurgitation
8. Antithrombotic Therapy post TAVR
9. Sentinel Cerebral Protection Device during TAVR
10. Tricuspid Valve Intervention: TRILUMINATE
Top 10 Advances in Transcatheter Valve Therapy 2018
Emerging Indications of TAVR
Pt with moderate to severe AS
Bicuspid ASViV Bioprosthetic
Degenration
Alternate Access:
Axillary
Venacaval
Carotid
Moderate AS with
CHF
LFLG AS
Early TAVR in
asymptomatic
severe AS
Proposed Decision Tree Algorithm for Patients Presenting with
Classic
(EF <50%) Low-Flow, Low-Gradient AS
Généreux P, J Am Coll Cardiol 2018;71:1309
FAVOR TAVR if AS
deemed severe
By MDCT Ca2+
♀ ≥1,200, ♂ ≥2,000
EOA <1 cm2, MG <40 mmHg, and LVEF <50%
Dobutamine stress echocardiogram
Increase SV ≥20%
MG ≥40 mmHg
EOA ≤1.0 cm2
Increase SV ≥20%
MG <40 mmHg
EOA >1.0 cm2
Increase SV <20%
(no contractile
Reserve)
Ture severe ASPseudo severe AS
Heart team risk
assessment
Medical therapy vs.
consider enrollment in
TAVR-unload trial
Intermediate, high, or
extreme risk
TAVR
Low risk for SAVR
TAVR vs. SAVR pending low-risk trials results
Favor TAVR if noninferior
TOPAS-TAVI: Mortality Rates (N=287)
Ribeiro et al., J Am Coll Cardiol 2018;71:1297
0
10
20
30
40
30 Days 1 Year 2 Years
3.8
20.1
32.3
%
• Mean LVEF - 30 ± 10 mmHg
• Transvalvular gradient - 25 ± 7 mmHg
• Median STS Risk Score – 7.7%
• Multivariable analysis for death:
o COPD – p=0.02
o Lower hemoglobin values – p<0.001
o Moderate-severe AR post-TAVR
Cumulative Late Outcomes at 2 Yrs Follow-Up
(N=287)
Ribeiro et al., J Am Coll Cardiol 2018;71:1297
0
10
20
30
40
50
3.8 4.2
0.7
9.8
3.5
24.7
18.8
39.0
MI Stroke Endocarditis PPM PPM-defib Rehosp Cardiac Global
for HF death death
%
Clinical Outcomes and LV Changes Following TAVR in
Patients with LFLG-AS
Ribeiro et al., J Am Coll Cardiol 2018;71:1297
Ribeiro et al., Eur Heart J 2018;39:687
Predictors of Coronary
Obstruction
Clinical Presentation and
Management
Distribution of Distance Between Virtual
Tanscatheter Ring at a Size of the
Implanted Device
K-M Survival Curve at 1-Year Follow-Up
of Pts Undergoing TAVI for Degenerated
Bioprostesis Valve
Kaplan-Meier Curves for All-Cause Mortality
According to Early- and New-Generation Devices
Yoon et al., J Am Coll Cardiol 2017;69:2579
Early-Generation Device New-Generation Device
Procedural Outcomes in Bicuspid and Tricuspid
AS with Early- and New-Generation Devices
Yoon et al., J Am Coll Cardiol 2017;69:2579
0
5
10
15
20
25
Conversionto surgery
SecondValve
Implantation
Paravalvularleak
Absence ofdevice
success
NewPacemaker
2.5
7.2
15.9
21.6
14.7
0.32.2
10.3
13.1 13.7
%
p=0.02
p=0.72
p=0.005
p=0.03
p=0.003
Early-Generation Device
Sapien XT CoreValve
0
5
10
15
20
25
Conversionto surgery
SecondValve
Implantation
Paravalvularleak
Absence ofdevice
success
NewPacemaker
1.3 1.32.7
4.9
16.4
0.0 0.41.8 2.2
17.8
%
p=0.25
p=0.69
p=0.13p=0.53
p=0.62
New-Generation Device
Sapien 3 Lotus Evolut R
Bicuspid AS Tricuspid AS
EARLY TAVR Trial: ACC/AHA and ESC/EACTS Guidelines
Nishimura et al., J Am Coll Cardiol 2017;70:252; Baumgartner et al., Eur Heart J (2017) 00, 1-53
Asymptomatic Severe AS
MG ≥40 mmHg, AVA ≤1.0 cm2 and EF >50%
Exercise Testing (ACC/AHA Class lla)
PV ≥5 m/s (ACC/AHA) or ≥5.5 m/s (ESC):
Class lla
PV progression ≥0.3 m/s/year: ACC/AHA llb
and ESC Class lla
Severe SPH >60: ESC Class lla
Repeatedly markedly elevated BNP:
ESC Class lla
Exercise Imaging (ACC/AHA Class lla)
Increase in MG with exercise by >20 mmHg
ESC Class llb
Limiting Symptoms
Angina
Syncope
Dyspnea
Decrease exercise
tolerance
Abnormal SBP
response (drop or
<20 mmHg rise)
ACC/AHA Class l
ESC Class l
ACC/AHA Class lla
ESC Class lla
If Stress Test and Stress Echo Normal:
Clinical and Echo Follow-Up 6 months (ESC) and 6-12 months ACC/AHA Class l
+ -+
EARLY TAVR Trial: Flow Chart
AsymptomaticNegative stress test OR medical history
1:1 Randomization
Transfemoral
TAVR
Clinical
Surveillance
Primary Endpoint2 yr composite of all-cause mortality, all stroke,
and unplanned cardiovascular hospitalization
Asymptomatic, Severe Aortic Stenosis
Screening/Stress TestInclusion/exclusion criteria, treadmill stress test
SymptomaticPositive stress test
RegistryCommercial AVR (TAVR or
SAVR), Clinical Trial (e.g.
PARTNER 3 Trial), etc.
PI: Philippe Généreux, MD
Chair: Martin B. Leon, MD
NCT03042104
TAVR UNLOAD Trial Design
Steiner et al., J Am Coll Cardiol 2017;70:3026
TAVR UNLOAD (n=600)
LVEF <50%, NYHA 2-4, optima HF therapy (OHFT),
Moderate AS, NT-proBNP >1500 pg/ml
1:1 Randomization
OHFT OHFT and TAVR
Follow-up at 1, 6, and 12 months
Primary endpoints include death, disabling stroke,
hospitalization for HF, aortic disease, or stroke,
Quality of Life
Key inclusion Criteria:
• NYHA class ≥2
• NT-proBNP >1500 pg/ml or hospitalization for HF within the
last year
• Appropriate guideline-directed HF medical therapy (as
tolerated) for ≥3 months
• LVEF <50%, but >20%
• Anatomically suitable for SAPIEN 3
Moderate AS confirmed by the echo core lab and defined as:
• Mean transaortic gradient (MG) ≥20 mmHg and <40 mmHg and
aortic valve area (AVA) >1.0 cm2 and ≤1.5 cm2 at rest
OR
• MG ≥20 mmHg and <40 mmHg and AVA >1.0 cm2 at rest AND
MG <40 mmHg and AVA >1.0 cm2 with low dose dobutamine
stress echo
• MG <20 mmHg, if other parameters consistent with mod AS
according to echo core lab
Key Exclusion Criteria:
• LVEF <20% or inotropic support
• Recent CRT, revascularization, or in need of revascularization
• Prosthetic valve stenosis, bicuspid valve, associated severe
MR
• Severe RV dysfunction, COPD, or CKD, liver cirrhosis, GI
bleeding
Vascular Access of the Future?
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4.
5. TMVR Trials: MITRAL, GLOBAL Registry, APOLLO, TENDYNE
6. Emerging TAVR Indications: ViV, LFLG, BAV, EARLY, UNLOAD
7. TAVR for Pure Aortic Regurgitation
8. Antithrombotic Therapy post TAVR
9. Sentinel Cerebral Protection Device during TAVR
10. Tricuspid Valve Intervention: TRILUMINATE
Top 10 Advances in Transcatheter Valve Therapy 2018
Mitral Valve Replacement Devices Landscape
In Trials
FIM CasesIn Development
TMVR: Early Clinical Experience
Human Experience 52 cases 12 cases 23 cases 38 cases 20 cases
First Implant October-2013 June-2012 February-2014 September-2014 January-2014
Longest Patient F/U 2 year+ 1 year+ 2 years+ 2 years+ 2 years+
Patient Population Clinically Significant Severe MR and High Risk Surgical Candidates, NYHA II-IV
FMR Etiology 86% (n=22) 64% (n=11) 100% (n=13) 73% (n=15) 54% (n=11)
Successful Deployment 21/23 9/11 10/13 14/15 9/11
30-Day Mortality 1/23 5/11 5/13 2/15 3/11
30-Day Rehosp 3/23 Data not available Data not available 1/14 Data not available
MR Grade 0 at F/U 19/19 Data not available 8/9 13/14 Data not available
Abbott
Tendyne
Edwards
CardiAQ
Edwards
Fortis
Medtronic
TwelveNeovasc
CE approval study
CE approval study
Intrepid Twelve Valve: APOLLO Trial • Circular inner stent to house the valve plus a outer fixation ring to engage the mitral
annular anatomy.
• The outer fixation ring is designed to accommodate the dynamic variability of the native
mitral annulus while isolating the inner valve assembly throughout the cardiac cycle.
• A flexible brim is attached to the atrial end of the fixation ring which facilitates imaging
during the procedure.Valve Characteristics
Implant Shape Circular
Construction
Self-expanding nitinol
Frame, outer and inner polyester fabric skirt
Inner valve structure of 27 mm (orifice area 2.4
cm2
Outer diameter 43, 46 or 50 mm
Leaflet Trileaflet Bovine Pericardium
Catheter Size OD 35 Fr
Access Site T-Apical
MITRAL Trial
90 patients extremely high surgical risk (STS PROM >15% or M&M >50%)
SAPIEN XT SAPIEN 3Inclusion Criteria
NYHA II or greater
Native MV (MAC)n=30
Valve-in-Ringn=30
Valve-in-Valven=30
Severe MS (MVA ≤1.5 cm2)
Severe MR + Moderate MS
Severe MS (MVA ≤1.5 cm2)
At least Moderate-Severe MR
Severe MS (MVA ≤1.5 cm2)
At least Moderate-Severe MR
Results of MViV at AHA
Nov 13, 2017
Guerrero M, TCT 2017
Guerrero M, TCT 2017
MITRAL Trial: ViR Procedural Outcomes
100% Transseptal Access
OutcomesIn-Hospital
n=30
30 Days
n=29*
All-Cause Mortality 6% 6.8%
Cardiovascular death 3% 3.4%
Non-Cardiac death 3% 3.4%
* Last implant 10-3-17 (POD # 28 at time of this presentation)Data not yet adjudicated, may be subject to change.
MITRAL Trial: MAC Procedural Outcomes
Guerrero M, TCT 2017
50% Transseptal or TA(TS=14, TA=1)
Difficult anatomy for TS=1
50% Transatrial (n=15)Risk of LVOTO=3
Risk of embolization=6
Both=6
OutcomesIn-Hospital
n=30
30 Days
n=26*
All-Cause Mortality
16.7%Transeptal=1
Transapical=1
Transatrial=3
19.2%
Cardiovascular death 3.3% 3.8%
Non-Cardiac death13.3% MOF=4
15.3%
* 3 patients treated in October 2017 (POD # 13, 21 and 27 at time of this presentation)
1 patient withdrew consent while being discharged after successful transatrial TMVR
Objective
• We aimed to evaluate and compare the procedural and clinical outcomes of patients
undergoing TMVR for degenerated bioprostheses (valve-in-valve [ViV]),
failed annuloplasty rings (valve-in-rings [ViR]) and severe MAC (valve-in-MAC [ViMAC])
Outcomes of TMVR for Degenerated
Biprostheses, Failed Annuloplasty Rings
and Mitral Annular Calcification
Yoon SH, ESC 2018
Procedural Outcomes
Overall
(n = 521)
ViV
(n = 322)
ViR
(n = 141)
ViMAC
(n = 58)P value
Conversion to surgery, % 2.3 0.9 2.8 8.6 0.004
Valve embolization, % 1.7 0.9 1.4 6.9 0.01
LV perforation, % 0.8 1.2 0.0 0.0 0.58
Need for second valve, % 5.4 2.5 12.1 5.2 < 0.001
LVOT obstruction, % 7.1 2.2 5.0 39.7 < 0.001
Technical Success *, % 87.1 94.4 80.9 62.1 < 0.001
* Absence of procedural mortality; successful access, delivery; and retrieval of the device delivery
system; successful deployment and correct positioning of the first intended device; freedom from
emergent surgery or reintervention
Yoon SH, ESC 2018
Clinical Outcomes at 30-Days
0
20
40
60
80
Proceduralsuccess
Death at 30Days
Stroke Bleeding Major vasccompl
AKI (Stage 2or 3)
73.6
6.22.2 2.2 1.6
4.3
58.2
9.9
0.0
6.43.5
9.2
41.4
34.5
3.4 3.46.9
12.1
%
p<0.001
p=0.03
p=0.05p=0.07
p=0.15
p<0.001
ViV (n=322)
ViR (n=141)
ViMAC (n=58)
Yoon SH, ESC 2018
All-Cause Mortality According to TMVR
Yoon SH, ESC 2018
Landmark Analysis of All-Cause Mortality
1.
2.
3.
4. TAVR Valve Choice Trials: CHOICE, SOLVE-TAVI
5. TMVR Trials: MITRAL, MAC Registry, APOLLO, TENDYNE
6. Emerging TAVR Indications: ViV, LFLG, BAV, EARLY, UNLOAD
7. TAVR for Pure Aortic Regurgitation
8. Antithrombotic Therapy post TAVR
9. Sentinel Cerebral Protection Device during TAVR
10. Tricuspid Valve Intervention: TRILUMINATE
Top 10 Advances in Transcatheter Valve Therapy 2018
CHOICE Trial: Study Flowchart241 Transfemoral TAVR patients enrolled and randomized
Balloon-expandable valve
(Edwards Sapien XT, n=121)
Self-expandable valve
(Medtronic CoreValve, n=120)
Alive = 116
Dead = 5
LTFU = 0
Withdrawal = 0
Alive = 111
Dead = 6
LTUF = 1
Withdrawal = 2
30 Days
1 Year
Alive = 100
Dead = 21
LTFU = 0
Withdrawal = 0
Alive = 102
Dead = 15
LTUF = 0
Withdrawal = 3
100% Clinical follow-up 97% Clinical follow-up
CHOICE Trial: Clinical Outcomes at 1 Year
Abdel-Wahab et al., J Am Coll Cardiol 2015;66:791
0
20
40
60
17.4
5.8 7.4
1411.6
3.4
23.4
10.712.8
3.4
12.8 14.5 12.0
0.0
27.9
6.8
%
Death Stroke HF repeat Bleeding Major vasc Valve New PPM MACCE
hosp life threatening compl thrombosis
p=0.37
p=0.36
p=0.22
p=0.12
p=1.00p=0.85
p=0.19
p=0.54
Balloon-Expandable Valve (n=121)
Self-Expandable Valve (n=117)
A 2x2 Randomized Trial of Self-Expandable vs Balloon-Expandable Valves
and General vs Local Anesthesia in Patients Undergoing Transcatheter Aortic Valve Implantation
SOLVE-TAV
SOLVE-TAVI Program
Thiele H, TCT 2018
Primary Endpoint – Valve Strategy
Thiele H, TCT 2018
All-cause mortality, stroke, moderate or severe prosthetic valve regurgitation,
permanent pacemaker implantation at 30 days
0
10
20
30
40
50
Evolut R Sapien 3
Rate difference -1.14
90%CI -8.15 – 5.87
Pequivalence=0.02
Psuperiority=0.83
27.2%26.1%
%
Endpoints – Valve Strategy
Individual Components Primary Endpoint
Thiele H, TCT 2018
Secondary Endpoints – Valve Strategy
Evolut R
(n=219)
Sapien 3
(n=219)
Rate difference Pequivalence Psuperiority
Device time, min 63 ± 32 64 ± 43 0.80
Total procedural time, min 118 ± 48 117 ± 52 0.40
Cardiovascular mortality, n (%) 1/216 (0.5) 4/218 (1.8) 1.37 (-2.27 ─ 5.01) <0.001 0.37
Hospital stay, days 9 ± 7 9 ± 7 0.97
VARC-2 criteria:
Device success, n (%) 203/216 (94.0) 200/218 (91.7) -2.24 (-6.91 ─ 2.43) 0.002 0.46
Early safety, n (%) 24/217 (11.1) 33/219 (15.1) 4.01 (-1.57 ─ 9.59) 0.03 0.26
Clinical efficacy, n (%) 74/216 (34.3) 80/217 (36.9) 2.61 (-4.94 ─ 10.15) 0.05 0.61
Time-related safety, n (%) 41/217 (18.9) 58/219 (26.5) 7.59 (0.91-14.27) 0.27 0.07
Primary Endpoint – Anesthesia Strategy
All-cause mortality, stroke, myocardial infarction,
infection requiring antibiotic treatment, acute kidney injury at 30 days
2725.5
0
10
20
30
40
50
Local anesthesia General anesthesia
Rate difference -1.52
90%CI -8.47 – 5.42
Pequivalence=0.02
Psuperiority=0.74
27.0%25.5%
%
Thiele H, TCT 2018
Situations Where You Favor One Valve Over Another?A Clinicians Perspective: Most of AS are suitable for either valve
Evolut R
• Dense sub-annular calcium
• Intolerant to rapid pacing (↓↓EF)
• TAVR in SAVR (ViV)
• Ileo-femorals 5-6mm size
• Hypertrophied septum (HOCM)
• Subclavian approach
Sapien 3
• Ante-grade approaches
• Very large annulus >31-33mm
• Horizontal Aorta >60 degrees
• Concerns about PPM
• Pt with extensive CAD or prior PCIs
• Low coronary heights/ small SOV
1.
2.
3. Coronary Angiography post TAVR
4. TAVR Valve Choice Trials: CHOICE, SOLVE-TAVI
5. TMVR Trials: MITRAL, MAC Registry, APOLLO, TENDYNE
6. Emerging TAVR Indications: ViV, LFLG, BAV, EARLY, UNLOAD
7. TAVR for Pure Aortic Regurgitation
8. Antithrombotic Therapy post TAVR
9. Sentinel Cerebral Protection Device during TAVR
10. Tricuspid Valve Intervention: TRILUMINATE
Top 10 Advances in Transcatheter Valve Therapy 2018
• There is a high prevalence of CAD in patients with severe aortic
stenosis who undergo TAVR
• As TAVR expands to lower risk patients, progressive CAD will
necessitate future coronary angiography & PCI
• Few data describing the feasibility of coronary re-access post TAVR
have been reported
Background
Published Overview of CAG/PCI after TAVR ProceduresZivelonghi C, et al. Am J Cardiol 2017;120:625–31.
Htun WW, et al. Catheter Cardiovasc Interv 2017; Oct 8 [Epub ahead of print]
Allali A, et al. Cardiovasc Revasc Med 2016;17:391–8.
Boukantar M, et al. J Interv Cardiol 2017;30:56–62.
Chakravarty T, et al. J Am Coll Cardiol 2016;67:951–60.
Greenberg G, et al. J Invasive Cardiol 2013;25:361–3.
Murarka S, et al. Indian Heart J 2015;67:476–9.
Jackson M, et al. Cardiovasc Revasc Med 2017 Jul 31 [E-pub ahead of print]
Harhash A, et al. STEMI after TAVR: procedural challenge and
catastrophic outcome. J Am Coll Cardiol Intv 2016;9:1412–3.
Khan A, et al. Percutaneous coronary intervention after transcatheter aortic valve replacement:
approach and challenges. J Am Coll
Cardiol 2016;68:432–3.
Methods and Objectives
• A systematic review identified all published
peer reviewed articles describing coronary
angiography and PCI post TAVR
• We assessed proportion of patients who
had selective coronary angiography and
successful PCI, grouped by self-expanding
valve and balloon-expandable valve
devices
• We aim to propose a practical algorithm for
Self-Expanding Valve
Yudi, Sharma and Kini et al., J Am Coll Cardiol 2018;71:1360
Various Dimensions of Self-Expanding
Valves
Self-Expanding Valves and Coronary
Access
Location of the coronary ostium in relation to valve frame
Depicts closest diamonds that can be used to access the
coronary ostium
Annular plane
An optimally positioned self-expanding valve (A)
would make coronary access potentially easier
than one with a higher implant (B)
Yudi, Sharma and Kini et al., J Am Coll Cardiol 2018;71:1360
Self-Expanding Valve and Coronary Access if Ostia
Lines Up with Commissural Post
Annular planeLocation of the coronary ostium in relation to valve frame
Depicts closest diamonds that can be used to access the coronary ostium
(A)The commissural post
of a self-expandable valve
is 26 mm in height.
(B)Depending on the
height of coronary ostia, a
different catheter and
approach is necessary for
coronary reaccess, when
the ostium faces the side
of the commissural post.
Yudi, Sharma and Kini et al., J Am Coll Cardiol 2018;71:1360
Balloon-Expandable Valves
Features and Dimensions Balloon-Expandable Valve and Coronary
Ostia Based on Depth of Implant
Location of the coronary ostium in relation to valve frame
Annular plane
(A) Would make coronary access potentially easier than
one with a higher implant (B), where the coronary ostium
will be located below the seal skirt. Tall native leaflet or
bulky calcium at the leaflet tip may further increase
difficulty of coronary access in a high valve implant.
Yudi, Sharma and Kini et al., J Am Coll Cardiol 2018;71:1360
Summary of Factors Impacting Coronary Access
and Imaging Evaluation After TAVR
Algorithm for Coronary Angiogram Post-TAVR
with a Self-Expanding Valve
Yudi, Sharma and Kini et al., J Am Coll Cardiol 2018.71:1360
Algorithm for PCI Post-TAVR with a Self-Expanding Valve
Yudi, Sharma and Kini et al., J Am Coll Cardiol 2018;71:1360
Algorithm for Coronary Angiogram Post-TAVR with a
Balloon-Expandable Valve
Yudi, Sharma and Kini et al., J Am Coll Cardiol 2018;71:1360
Algorithm for PCI Post-TAVR with a Balloon-Expandable
Valve
Yudi, Sharma and Kini et al., J Am Coll Cardiol 2018;71:1360
1.
2. TAVR for Low Surgical Risk AS
3. Coronary Angiography post TAVR
4. TAVR Valve Choice Trials: CHOICE, SOLVE-TAVI
5. TMVR Trials: MITRAL, MAC Registry, APOLLO, TENDYNE
6. Emerging TAVR Indications: ViV, LFLG, BAV, EARLY, UNLOAD
7. TAVR for Pure Aortic Regurgitation
8. Antithrombotic Therapy post TAVR
9. Sentinel Cerebral Protection Device during TAVR
10. Tricuspid Valve Intervention: TRILUMINATE
Top 10 Advances in Transcatheter Valve Therapy 2018
PARTNER Trial Cohort B:
Inoperable Extreme Risk
Makkar et al., NEJM 2012;366:1696
Rate of Death (N=358)
20%
CoreValve Extreme Risk:
No Randomization1 Year Mortality (N=487)
Popma et al, JACC 2014;63:1972
PARTNER Trial Cohort A:
Primary Endpoints at 3-Yr
Kodali et al., NEJM 2012;366:1686
Death from Any Cause
Major drawback:
ES TAVR had 2x the
Stroke rates vs. SAVR
TAVR SAVR
Death from Any Cause
CoreValve Trial High Risk:
Primary Endpoints at 3-Yr
Deeb et al., JACC 2016;67:2565
SURTAVI Trial: Primary Endpoint at 2 Years
Reardon et al., NEJM 2017;376:1321
PARTNER 2A Trial: Primary Endpoint at 2 Years
Leon M et al. NEJM 2016;374:1609
Serruys et al., EuroIntervention 2018;14:877
SURTAVI Trial: Outcomes of Patients in the SAVR and
TAVI Groups Among the Three Strata of STS PROM
0
5
10
15
1.5
5.5
11.1
3.8 4.2
7.8
Death Stroke
STS <3% STS ≥3% - <5% STS ≥5%
(n=131) (n=480) (n=253)
%
TAVI
0
5
10
15
5.7 5.3
9.18.2
6.8 6.5
Death Stroke
STS <3% STS ≥3% - <5% STS ≥5%
(n=123) (n=405) (n=268)
%
SAVR
Study Design
Waksman et al., J Am Coll Cardiol 2018;72:2095
Prospective TAVR Cohort Historical Control SAVR Cohort
In-Hospital Procedural-Related Complications
Waksman et al., J Am Coll Cardiol 2018;72:2095
TAVR in Low-Risk Patients: Clinical Outcomes
Waksman et al., J Am Coll Cardiol 2018;72:2095
The PARTNER 3 Trial:
Study Design
1:1 Randomization
(n=1228)
TF - TAVR
(SAPIEN 3)
Surgery
(Bioprosthetic Valve)
Follow-up: 30 days, 6 mos, 1 year and annually through 10 years
CT Imaging Sub-Study (n=200)
Low Risk ASSESSMENT by Heart Team(STS < 3%, TF only)
Symptomatic Severe Calcific Aortic Stenosis
PRIMARY ENDPOINT:
Composite of all-cause mortality, all strokes, or
re-hospitalization at 1 year post-procedure
Bicuspid Valves
(n=100)
ViV (AV and MV)
(n=100)
PARTNER 3
Registries
Alternative Access (n=100)
(TA/TAo/Subclavian)
Actigraphy/QoL Sub-Study (n=100)
CT Imaging Sub-Study (n=200)
Actigraphy/QoL Sub-Study (n=100)
Results in ACC 2019
Medtronic TAVR in Low Risk PatientsTrial Design & leaflet Sub-study
▪ Patient Population: Low Risk Cohort
▪ Determined by Heart Team to be low surgical risk
▪ Primary Endpoint:
▪ Safety: Death, all stroke, life-threatening bleed, major vascular
complications or AKI at 30 days
▪ Efficacy: Death or major stroke at 2 yrs
▪ Sample Size: ~1200 Subjects
▪ Follow-up Evaluations:
▪ 30-days, 6-month , 18-month, and
1 through for 5 years
▪ Number of Sites: Up to 80 sites
Results in ACC 2019
Choice of TAVR vs Surgical AVR in Patients with
Severe Symptomatic AS
Nishimura et al., J Am Coll Cardiol 2017;70:252
TAVR
(Class I)
1. MitraClip for FMR: MITRA-FR, COAPT2. TAVR for Low Surgical Risk AS
3. Coronary Angiography post TAVR
4. TAVR Valve Choice Trials: CHOICE, SOLVE-TAVI
5. TMVR Trials: MITRAL, MAC Registry, APOLLO, TENDYNE
6. Emerging TAVR Indications: ViV, LFLG, BAV, EARLY, UNLOAD
7. TAVR for Pure Aortic Regurgitation
8. Antithrombotic Therapy post TAVR
9. Sentinel Cerebral Protection Device during TAVR
10. Tricuspid Valve Intervention: TRILUMINATE
Top 10 Advances in Transcatheter Valve Therapy 2018
General Principles of Therapy for MR
Primary
No Medical Therapy(Diuretics pallative)
Surgery for symptoms
or LV dysfunction(Repair > Replacement)
Consider prophylactic repair for
low risk with long term survival
Secondary
Medical Therapy first(BB,ACE/ARB, Aldactone, Diuretics)
CRT(Repair > Replacement)
Surgery only in highly selected pts
with CHF(Class 3/4 symptomatic and
acceptable surgical risk)
FMR
MitraClip is approved for
prohibitive surgical risk
Primary MR
?
DMRDMR
MITRA FR Study Design
Objective: To evaluate the clinical efficacy of
percutaneous mitral valve repair in addition to medical
treatment in patients with heart failure and severe
functional/secondary mitral regurgitation versus
medical treatment alone.
Primary Endpoint “Composite”: All-cause Deaths or
Unplanned rehospitalization for heart failure at 12
months
MITRA FR: Enrollment, Randomization, and Follow-Up
Obadia et al., N Engl J Med Aug. 27, 2018 Epub
MITRA FR: Prespecified Secondary Endpoints
Obadia et al., N Engl J Med Aug. 27, 2018 Epub
MITRA-FR: Clinical Outcomes at 12 Months
Obadia et al., N Engl J Med Aug. 27, 2018 Epub
0
20
40
60
80
PrimaryEndpoint
Death Unplanned HFhosp
MACE
54.6
24.3
48.756.6
51.3
22.4
47.451.3
p=0.53
p=NS
%
Intervention group (n=152) Control group (n=152)
MITRA FR: Kaplan-Meier Estimates of Survival
Without a Primary Outcomes Event
Obadia et al., N Engl J Med Aug. 27, 2018 Epub
Primary Composite Endpoint: All-cause Death and
Unplanned HF Hospitalization
The COAPT Trial
Cardiovascular Outcomes Assessment of the MitraClip Percutaneous
Therapy for Heart Failure Patients with Functional Mitral Regurgitation
A parallel-controlled, open-label, multicenter trial in ~610 patients with
heart failure and moderate-to-severe (3+) or severe (4+) secondary MR
who remained symptomatic despite maximally-tolerated GDMT
Randomize 1:1*
GDMT aloneN=305
MitraClip + GDMTN=305
*Stratified by cardiomyopathy etiology
(ischemic vs. non-ischemic) and site
Stone GW, TCT 2018
Primary endpoint: Rate of HF re-hospitalization at 24months
Secondary endpoints: Device related comp, mortality, need for
LVAD/transplant, QOL, NYHA Class
Primary Effectiveness EndpointAll Hospitalizations for HF within 24 months
HR (95% CI] = 0.53 [0.40-0.70]
P<0.001
0
50
100
150
200
250
300
0
MitraClip + GDMT (n=160)
GDMT alone (n=283)
35.8
67.9
Cu
mu
lati
ve
HF
Ho
sp
italizati
on
s (
n)
Time After Randomization (Months)
3 6 9 12 15 18 21 24
Stone et al., N Engl J Med Sept. 23, 2018 Epub
NNT (24 mo) = 3.1 [95% CI 1.9, 8.2]
Primary Safety EndpointFreedom from Device-Related Complications within 12 Months
MitraClip procedure attempted N=293
Device-related complications 9 (3.4%)
- Single leaflet device attachment 2 (0.7%)
- Device embolization 1 (0.3%)
- Endocarditis requiring surgery 0 (0.0%)
- Mitral stenosis requiring surgery 0 (0.0%)
- Left ventricular assist device implant 3 (1.2%)
- Heart transplant 2 (0.8%)
- Any device-related complication requiring
non-elective CV surgery1 (0.3%)
*KM estimate; **Calculated from Z test with Greenwood’s method of estimated variance against a pre-
specified objective performance goal of 88%
50%
60%
70%
80%
90%
100%
88% OPC
94.8% [95% LCL]
P<0.001
Stone et al., N Engl J Med Sept. 23, 2018 Epub
96.6%*
All-Cause MortalityA
ll-C
au
se M
ort
ality
(%
)
0%
20%
40%
60%
80%
100%
Time After Randomization (Months)
0 3 6 9 12 15 18 21 24
46.1%
29.1%
HR [95% CI] =
0.62 [0.46-0.82]
P<0.001
MitraClip + GDMT (n=302)
GDMT alone (n=312)
NNT (24 mo) =
5.9 [95% CI 3.9, 11.7]
Stone et al., N Engl J Med Sept. 23, 2018 Epub
Death or HF Hospitalization
Stone et al., N Engl J Med Sept. 23, 2018 Epub
MitraClip + GDMT
GDMT alone
All-c
au
se M
ort
ality
or
HF
Ho
sp
ita
liza
tio
n (
%)
0%
20%
40%
60%
80%
100%
Time After Randomization (Months)
0 3 6 9 12 15 18 21 24
67.9%
45.7%
HR [95% CI] = 0.57 [0.45-0.71]
P<0.001
NNT (24 mo) =
4.5 [95% CI 3.3, 7.2]
0
20
40
60
80
29.1
45.7
2.8 4.4 4.7 2.9 4.4 3.0 1.4
46.1
67.9
4.3 5.1 6.53.3
9.57.1
3.6
Adverse Events Within 24-Months
Stone et al., N Engl J Med Sept. 23, 2018 Epub
All-cause Death or HF PCI or Stroke MI New CRT LVAD or LVAD Heart
death hosp CABG implant heart transplant transplant
MitraClip + GDMT (n=302) GDMT alone (n=312)
p<0.001
p=0.12
p=0.02p=0.01
p=0.75
p=0.62p=0.93
p=0.32
p<0.001
Why are the COAPT Results so Different from
MITRA-FR? Possible ReasonsMITRA-FR (n=304) COAPT (n=614)
Severe MR entry criteria
Severe FMR by EU guidelines:
EROA >20 mm2 or RV >30
mL/beat
Severe FMR by US guidelines:
EROA >30 mm2 or RV >45
mL/beat
EROA (mean ± SD) 31 ± 10 mm2 41 ± 15 mm2
LVEDV (mean ± SD) 135 ± 35 mL/m2 101 ± 34 mL/m2
GDMT at baseline and FU
Receiving HF meds at baseline
– allowed variable adjustment
in each group during follow-up
per “real-world” practice
CEC confirmed pts were failing
maximally-tolerated GDMT at
baseline – few major changes
during follow-up
Acute results: No clip/≥3+ MR 9% / 9% 5% / 5%
Procedural complications* 14.6% 8.5%
12-mo MitraClip ≥3+ MR 17% 5%
Conclusions• In pts with HF and moderate-to-severe or severe secondary
MR who remained symptomatic despite maximally-tolerated
GDMT, transcatheter mitral leaflet approximation with the
MitraClip was safe, provided durable reduction in MR,
reduced the rate of HF hospitalizations, and improved
survival, quality-of-life and functional capacity during 24-
month follow-up
• As such, the MitraClip is the first therapy shown to improve
the prognosis of patients with HF by reducing secondary
MR due to LV dysfunction
WE expect MitraClip soon to become ACC Class I
indication for FMR after GDMT (just like CRT)
1. MitraClip for FMR: MITRA-FR, COAPT
2. TAVR for Low Surgical Risk AS
3. Coronary Angiography post TAVR
4. TAVR Valve Choice Trials: CHOICE, SOLVE-TAVI
5. TMVR Trials: MITRAL, MAC Registry, APOLLO, TENDYNE
6. Emerging TAVR Indications: ViV, LFLG, BAV, EARLY, UNLOAD
7. TAVR for Pure Aortic Regurgitation
8. Antithrombotic Therapy post TAVR
9. Sentinel Cerebral Protection Device during TAVR
10. Tricuspid Valve Intervention: TRILUMINATE
Top 10 Advances in Transcatheter Valve Therapy 2018
Reasons for selection of the articles Revolutionary / significant observation
Widespread acceptance
Change in clinical practice
Final result → BETTER INTERVENTION & PT’s SURVIVAL
TMVR for MAC, AC for TAVR, MITRA-FR:
TMVR, TTVR, BAV, ViV, TOPAS, SOLVE-TAVI:
Sentinel CPS, AR TAVR, CAG postTAVR :
COAPT in FMR, TAVR Low risk:
Top 10 Advances in Transcatheter Valve Therapy 2018
Cumulative TAVR Procedures: TVT Registry 2012 to 2014
TAVR in USAProcedural Performance and Outcome of TAVR since FDA Approval
65% 35%
2018: ≈5000 TAVR per month in USA
There is a Range of TAVR Mortality in US
Practice
Risk Adjustment:
Using variables from
the previously
developed TVT in-
hospital mortality
model.
Edwards et al., JAMA, Epub March 9, 2016
TAVR Complications: Transfemoral Population
JD Carroll, ACC 2016
In-Hospital Outcomes - Volume
P Value for Association
Unadjusted = <0.0001
Adjusted = 0.1494
P Value for Association
Unadjusted = <0.0001
Adjusted = <0.0001
P Value for Association
Unadjusted = <0.0001
Adjusted = <0.0001
Unadjusted
Adjusted
Unadjusted
Adjusted
Unadjusted
Adjusted
Mortality Vascular complications Bleeding Complications
CVA complications
Growth in TAVR Procedures at MSH
2013 to 2017Major complication: N = 4 7 12 10 8
10 %
N
Length of Stay in Days: 7.8 7.4 6.3 4.9 4.7
O/E Mortality Ratio: 1.32 1.96 1.64 0.69 0.74
Excellent TAVR Volume & Outcomes 2017N=306 (55% Evolut-R CoreValve, 45% SAPIEN 3)
78% Conscious Sedation; 22% GA
82% Perc Femoral; 11% Cutdown Iliac, 6% Subclavian, 1% Direct Aortic
%
MSH DataTVT Registry
Excellent Growth in MitraClip Procedures at MSH
2013 to 2017In-Hospital Death: N = - 0 1 2 4
N FDA approval
in Oct 25, 2013
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