1. Structural Heart Live Cases
Supported by:
Edwards Lifesciences
Terumo Medical Corp

2. Disclosures
Samin K. Sharma, MD, FACC Speaker’s Bureau – Boston Scientific Corp., Abbott Vascular Inc, ABIOMED, CSI Annapoorna S. Kini, MD, FACC Nothing to disclose Gilbert Tang, MD Physician proctor for Edwards Lifesciences George Dangas, MD

3. November 13, 2018- Structural Heart Live Case# 26: SP, 96 yo M
Presentation: Severe dyspnea on exertion NYHA Class III x 4 months
PMH: HTN, HLD, diabetes, AFib on anticoagulation & prostate cancer in remission
Medications: Atorvastatin, Warfarin, Furosemide, Nebivolol, Saxagliptin, KCL
Labs: Hgb 12.4, PLT 88K, K 3.6, Cr 0.9, INR 1.8
EKG (10/2/18): AF with RBBB
TTE (10/21/18): EF 53%, mild MR, moderate TR, mild to moderate AR, moderate pulmonary hypertension, RV dysfunction, severe AS (PG/MG/AVA/PV= 29/16/0.65/2.7m/s), SVI 27ml/m2
Cath (9/11/18): Non-obstructive coronaries

4. Severe AS (PG/MG/AVA = 29/16/0.65) Severe Aortic Stenosis
TTE
Severe AS (PG/MG/AVA = 29/16/0.65)
AV Peak velocity = 2.7 m/s
Severe Aortic Stenosis

5. CTA: Aortic Annulus Aortic Annulus Max: 33.5 mm Min: 27.5 mm
Mean: 30.5 mm
Perimeter = 95.5 mm
Area = mm2
Annular angle = 55°
Annulus: 27.5mmx33.5 mm
Area: mm2 Perimeter: 95.5 mm
Annulus Angle: 55°

6. CTA: SOV, STJ, Coronary Ostia
RCA: 17.7 mm
RCC: 40.4
Sinus of Valsalva
RCC = 40.4 mm
LCC = 39.0 mm
NCC = 37.6 mm
STJ height (above annulus) = 30.0 mm
STJ = 35.4 x 37.8 mm (mean 36.6 mm)
LVOT = 25.7 x 34.2 mm (mean 30 mm)
Ascending aorta = 35 x 36.7 mm
(mean 35.9 mm)
NCC: 37.6
LCC: 39.0
LM: 19.2 mm
STJ 35.4 x 37.8 mm

7. Femoral Arterial Access
13x13mm
10.5 x12 mm
10x10 mm
10x12mm
11x11mm
11x12mm
Longitudinal View
Right Iliac/Femoral
Longitudinal View
Left Iliac/Femoral
Access 3D

8. Great Vessel Anatomy for Cerebral Protection Device Consideration
Innominate 13.5 mm
Left common carotid 9 mm

9. Edwards Sapien-3 Patient Selection
Patient CTA Findings
Annulus:
Max: 33.5 mm
Min: 27.5 mm
Mean: 30.5 mm
Perimeter = 95.5 mm
Area = mm2
STJ= 35.4 x 37.8mm

10. Summary of Case
Presentation: 96 year old male with NYHA Class III DOE
TTE: EF 53%, mild to moderate AR, moderate pulmonary hypertension, RV dysfunction, low flow low gradient paradoxical severe AS (PG/MG/AVA/PV = 29/16/0.65/2.7m/s), SVI 27ml/mm2
STS risk mortality: %
EuroScore risk: %
Logistic Euroscore mortality: %
Course: Patient was considered to have LF-LG paradoxical severe AS and was evaluated by Heart Team. Due to his multiple co-morbidities and frailty status, the patient was determined to be Extreme Risk for SAVR
Plan: The patient is here for TAVR with a 29 mm (+2cc) SAPIEN-3 via transfemoral access (right percutaneous) with possible Sentinel cerebral protection.

11. Issues Related To The Case
Balloon Expandable (BE) vs Self Expanding
(SE) TAVR valve choice trials in severe AS

12. 5/22/2019

13. PRAGMATIC Plus: VARC Outcomes in the Propensity-Matched Population at 30 Days
5/22/2019
MCV (n=204)
ESV (n=204) %
Life-threatening
p=0.35
p=0.42
p=0.12
p=0.34
p=0.17
Chieffo et al., J AM Coll Cardiol 2013;61:830

14. PRAGMATIC Plus: VARC Outcomes in the Propensity-Matched Population at 1-Year
5/22/2019
MCV (n=204)
ESV (n=204)
p=0.14
p=0.27
p=0.20 %
p=0.14
p=0.30
Chieffo et al., J AM Coll Cardiol 2013;61:830

15. 5/22/2019

16. Balloon-Expandable THV
Cohort Selection
5/22/2019
1005 unique TAVI patients from in Ontario, Canada
723 unique patients
Final Cohort = 714 Patients
Self-Expanding THV
n=397 patients
Balloon-Expandable THV
n=317 patients
282 excluded who had non-transfemoral or had two different types of TAVI devices
9 excluded who had TAVI procedure status Emergency or Salvage, or Cardiogenic shock, or Cardiac Arrest, or missing TAVI device type
Wijeysundera et al., Am J Cardiol 2017;119:1094

17. Outcomes After Inverse Probability of Treatment Weighting
5/22/2019
Balloon-Expandable THV (n=317)
Self-Expandable THV (n=397)
Outcomes at 1-Year
Outcomes at Last Follow-Up
(Follow-up to March 31, 2015) %
p=0.57
p=0.24
p=0.18
p=0.53
Wijeysundera et al., Am J Cardiol 2017;119:1094

18. Procedural Complications After Inverse Probability
of Treatment Weighting
5/22/2019
Balloon-Expandable THV (n=317)
Self-Expandable THV (n=397)
p<0.05
p=0.02
p=0.13
p=0.01
p=0.45
p=0.002
p<0.0001 %
(Mean±SD)
Wijeysundera et al., Am J Cardiol 2017;119:1094

19. JAMA 2014;311:1503

20. CHOICE Trial Study Flow
Abdel-Wahab et al., JAMA 2014;311:1503

21. CHOICE Trial: Primary Endpoint – Device Success
Successful valve placement
with vascular access, 1 valve
in correct position & < mod AI

22. CHOICE Trial: Procedural Details
Balloon-Expandable valve (n=121)
Self-Expandable valve (n=117)
p=0.001 %
p=<0.001
p=0.78
p=0.35
p=0.38
p=0.03
p=0.77
p=0.33
Device Succ Echo Implant of Death Stroke Bleeding Vascular MACCE New PP
primary endpt mod AI ≥2 valves compl
Abdel-Wahab et al., JAMA 2014;311:1503

24. CHOICE Trial: Study Flowchart
241 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
Alive = 100
Dead = 21
LTFU = 0
Withdrawal = 0
Alive = 102
Dead = 15
LTUF = 0
Withdrawal = 3
1 Year
100% Clinical follow-up
97% Clinical follow-up
Abdel-Wahab et al., J Am Coll Cardiol 2015;66:791

25. CHOICE Trial: Clinical Outcomes at 1 Year
Balloon-Expandable Valve (n=121)
Self-Expandable Valve (n=117)
p=0.22 %
p=0.37
p=0.85
p=0.19
p=1.00
p=0.36
p=0.54
p=0.12
Death Stroke HF repeat Bleeding Major vasc Valve New PPM MACCE
hosp life threatening compl thrombosis
Abdel-Wahab et al., J Am Coll Cardiol 2015;66:791

26. CHOICE Trial: 1-Year Outcome After TAVR with
Balloon-Expandable vs Self-Expandable Valves
Abdel-Wahab et al., J Am Coll Cardiol 2015;66:791

27. SOLVE-TAV
A 2x2 Randomized Trial of Self-Expandable vs Balloon-Expandable Valves and General vs Local Anesthesia in Patients Undergoing Transcatheter Aortic Valve Implantation

28. Background I – Valve Strategy
TAVR is developing as standard strategy for symptomatic patients with severe aortic stenosis at high to intermediate risk.
TAVR device design led to relevant technical and clinical improvements (e.g. pacemaker rates, paravalvular leakage, vascular complications).
There is limited evidence for direct valve comparisons (CHOICE, REPRISE III) in particular for latest generation valve designs.

29. Background II – Anesthesia Strategy
In clinical routine TAVR is performed in ≈50% using general or local anesthesia with conscious sedation.
Registry data suggest
lower mortality
lower morbidity
shorter ICU and hospital stay
shorter procedure times with local anesthesia.
There is a lack of adequately powered randomized trials.
Villablanca et al., Catheter Cardiovasc Interv. 2017;1

30. SOLVE-TAVI Program
Thiele H, TCT 2018

31. Hypotheses
Self-expanding CoreValve Evolut R is equivalent to balloon-expandable Sapien 3 (Edwards) valve
Local anesthesia with conscious sedation is equivalent to general anesthesia
in symptomatic aortic stenosis patients undergoing transfemoral TAVR
Thiele H, TCT 2018

32. Study Flow Chart - Valve Strategy
Thiele H, TCT 2018

33. Baseline Characteristics – Valve Strategy
Evolut R
(n=219)
Sapien 3
Age (years); mean ±SD
81.7 ± 5.3
81.5 ± 5.7
Male sex; n/total (%)
105/219 (47.9)
109/219 (49.8)
Risk scores
STS score (%); mean ±SD
7.7 ± 7.2
7.6 ± 7.4
Log. EuroScore I (%), mean ±SD
18.4 ± 12.1
18.3 ± 13.1
EuroScore II (%), mean ±SD
6.1 ± 5.5
5.4 ± 4.9
Frailty; n/total (%)
93/216 (43.1)
80/217 (36.9)
Peripheral arterial disease; n/total (%)
28/219 (12.8)
27/219 (12.3)
Prior myocardial infarction; n/total (%)
Prior PCI; n/total (%) 
Prior CABG; n/total (%)
Atrial fibrillation; n/total (%)
Pacemaker/ICD; n/total (%)
19/219 (8.7)
84/219 (38.4)
26/219 (11.9)
103/219 (47.0)
24/218 (11.0)
22/219 (10.1)
79/219 (36.1)
18/219 (8.2)
93/219 (42.5)
23/219 (10.5)
Prior stroke; n/total (%)
25/219 (11.4)
26/218 (11.9)
Renal insufficiency; n/total (%)
177/216 (81.9)
184/214 (86.0)
Pulmonary hypertension; n/total (%)
106/216 (49.1)
105/218 (48.2)
COPD; n/total (%)
30/219 (13.7)
29/217 (13.4)
Cardiovascular risk factors
Diabetes; n/total (%)
Arterial hypertension; n/total (%)
HLP; n/total (%)
Current smoking; n/total (%)
79/218 (36.2) 
193/219 (88.1)
118/218 (54.1)
8/218 (3.7)
68/219 (31.1) 
204/219 (93.2)
10/219 (4.6)
Thiele H, TCT 2018

34. Treatment – Valve Strategy
Characteristic
Evolut R
(n=219)
Sapien 3 P
Pre echo data
AVA; cm2
AVA index; cm2/m2
Mean gradient; mmHg
Peak gradient; mmHg
TAPSE; mm
LVEF >55%; n/total (%)
LVEF 45-54%; n/total (%)
LVEF 35-44%; n/total (%)
LVEF <35%; n/total (%)
0.76 ± 0.19
0.41 ± 0.12
39.5 ± 14.4
63.9 ± 22.9
20.6 ± 4.6
114/203 (56.2)
56/203 (27.6)
21/203 (10.3)
12/203 (5.9)
0.77 ± 0.20
0.43 ± 0.12
64.2 ± 26.4
19.9 ± 5.7
114/201 (56.7)
52/201 (25.9)
16/201 (8.0)
19/201 (9.5)
0.60
0.39
0.52
0.37
0.49
Valve size
23 mm; n/total (%)
1/215 (0.5)
51/218 (23.4)
26 mm; n/total (%)
56/215 (26.2)
120/218 (55.1)
29 mm; n/total (%)
108/215 (50.2)
47/218 (21.6)
34 mm; n/total (%)
50/215 (23.3)
Pre dilatation; n/total (%)
83/219 (37.9)
86/216 (39.8)
0.68
Post dilatation; n/total (%)
77/219 (35.2)
50/218 (22.9)
0.006
Recapturing; n/total (%)
55/204 (27.0)
<0.001
Contrast agent, ml
119 ± 44
98 ± 33
Fluoroscopy time, min
14.2 ± 12.8
12.0 ± 6.1
0.02
Thiele H, TCT 2018

35. Primary Endpoint – Valve Strategy
All-cause mortality, stroke, moderate or severe prosthetic valve regurgitation,
permanent pacemaker implantation at 30 days
Rate difference -1.14
90%CI – 5.87
Pequivalence=0.02
Psuperiority=0.83
27.2%
26.1% %
Thiele H, TCT 2018

36. Endpoints – Valve Strategy Individual Components Primary Endpoint
Thiele H, TCT 2018

37. Secondary Endpoints – Valve Strategy
Evolut R
(n=219)
Sapien 3
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
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 ( )
0.27
0.07
Thiele H, TCT 2018

38. Study Flow Chart - Anesthesia Strategy
Thiele H, TCT 2018

39. Treatment – Anesthesia Strategy
Characteristic
Local Anesthesia
(n=218)
General Anesthesia
(n=220) P
O2 saturation at start of anesthesia; %
92.7 ± 25.0
91.6 ± 27.3
0.08
Minimal O2 saturation during anesthesia; %
88.0 ± 27.4
93.3 ± 21.8
<0.001
O2 saturation at end of anesthesia; %
83.2 ± 36.7
81.9 ± 38.2
0.42
Conversion to general anesthesia
Agitation; ; n/total (%)
Emergency surgery; n/total (%)
Respiratory insufficiency; n/total (%)
Hemodynamic reasons; n/total (%)
13/218 (5.9)
3/13 (23.1)
5/13 (38.5)
2/13 (15.4)
Transesophageal echocardiography; n/total (%)
8/210 (3.8)
73/217 (33.6)
Anesthesia medication
Remifentanyl; n/total (%)
Propofol; n/total (%)
Dexmedetomidine; n/total (%)
Sufentanyl; n/total (%)
Fentanyl; n/total (%)
Piritramide; n/total (%)
Other non-benzodiazepine drugs; n/total (%)
18/218 (8.3)
56/218 (25.7)
111/218 (50.9)
63/218 (28.9)
13/218 (6.0)
7/218 (3.2)
213/220 (96.8)
198/220 (90.0)
3/220 (1.4)
7/220 (3.2)
9/220 (4.1)
6/220 (2.7)
0.39
0.79
Thiele H, TCT 2018

40. Primary Endpoint – Anesthesia Strategy
All-cause mortality, stroke, myocardial infarction,
infection requiring antibiotic treatment, acute kidney injury at 30 days
Rate difference -1.52
90%CI – 5.42
Pequivalence=0.02
Psuperiority=0.74
27.0%
25.5% %
Thiele H, TCT 2018

41. Endpoints– Anesthesia Strategy Individual components primary endpoint
Thiele H, TCT 2018

42. Treatment – Anesthesia Strategy
Characteristic
Local Anesthesia
(n=218)
General Anesthesia
(n=220) P
O2 saturation at start of anesthesia; %
92.7 ± 25.0
91.6 ± 27.3
0.08
Minimal O2 saturation during anesthesia; %
88.0 ± 27.4
93.3 ± 21.8
<0.001
O2 saturation at end of anesthesia; %
83.2 ± 36.7
81.9 ± 38.2
0.42
Conversion to general anesthesia
Agitation; ; n/total (%)
Emergency surgery; n/total (%)
Respiratory insufficiency; n/total (%)
Hemodynamic reasons; n/total (%)
13/218 (5.9)
3/13 (23.1)
5/13 (38.5)
2/13 (15.4)
Transesophageal echocardiography; n/total (%)
8/210 (3.8)
73/217 (33.6)
Anesthesia medication
Remifentanyl; n/total (%)
Propofol; n/total (%)
Dexmedetomidine; n/total (%)
Sufentanyl; n/total (%)
Fentanyl; n/total (%)
Piritramide; n/total (%)
Other non-benzodiazepine drugs; n/total (%)
18/218 (8.3)
56/218 (25.7)
111/218 (50.9)
63/218 (28.9)
13/218 (6.0)
7/218 (3.2)
213/220 (96.8)
198/220 (90.0)
3/220 (1.4)
7/220 (3.2)
9/220 (4.1)
6/220 (2.7)
0.39
0.79
Thiele H, TCT 2018

43. Situations Where You Favor One Valve Over Another?
5/22/2019
Situations Where You Favor One Valve Over Another?
A Clinicians Perspective: Most of AV 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 and very small annulus
Horizontal Aorta >60 degrees
Concerns about PPM
Pt with extensive CAD or prior PCIs
Low coronary heights/ small SOV

44. Lotus
Valve
System
Radiopaque Marker
Adaptive Seal
Nitinol Frame
Bovine Pericardium

45. REPRISE III: RCT Study Algorithm
Heart Team assessment
Case Review Committee confirmation
Neurologist examination‡
DAPT ≥1m OR warfarin + ASA or clopidogrel ≥1m (if anticoagulation needed)
Clinical & echocardiographic follow-up: discharge or 7d, 30d, 6m, annually 1-5
Randomized 2:1 (Lotus : CoreValve)
N=912
Severe aortic stenosis; extreme or high operative risk
Annulus ≥20 mm and ≤27 mm; transfemoral access
Lotus Valve* (23, 25 & 27mm)
CoreValve† (26, 29 & 31mm)
‡ Performed by a neurologist, neurology fellow, neurology physician assistant, or neurology nurse practitioner
† CoreValve platform (includes CoreValve Classic and Evolut R)
* Centres with no Lotus experience enrolled 2 roll-in patients before commencing enrollment of the evaluable cohort
T Feldman EuroPCR 2017

46. REPRISE III: Primary Composite Safety Endpoint
1 Year − Intent-to-Treat
Primary Composite Safety Endpoint* (%) 40
30.7% 10 30 20
CoreValve (305)
Lotus Valve (607)
P = 0.83
30.2% 30 90
180
270
365
*All-cause mortality, stroke, life-threatening/major bleed, stage 2/3 AKI, major vascular complications
Feldman et al., JAMA 2017;319:27

47. REPRISE III: Kaplan-Meier Event Rate 1-Year – Intent-to-Treat
All-Cause Mortality
All-Cause Mortality/Disabling Stroke
Feldman et al., JAMA 2017;319:27

48. REPRISE III: Additional VARC Events at 1 Year
Intent-to-Treat
CoreValve (N=305)
Lotus (N=607)
P Value
Myocardial infarction, %
4.4
3.2
0.39
Life threatening bleeding, %
9.8
9.9
0.96
Major bleeding, %
8.4
8.3
0.97
New onset atrial fibrillation, %
4.7
6.6
0.25
Hospitalization*, %
13.8
11.2
0.27
Endocarditis, %
0.0
0.7
0.31
Valve thrombosis, %
1.5
0.03
Repeat procedure†, %
2.0
0.2
0.007
Feldman et al., JAMA 2017;319:27

49. REPRISE III: Paravalvular Leak at 1 Year
Core Lab Assessment – Intent-to-Treat
≥ Moderate PVL
Percent of Gradable Echocardiograms
Lotus
(N=442)†
CoreValve
(N=203)†
Mod-Sev
Paravalvular Leak*
39.9
11.3
36.9
10.8
1.0
81.7
5.9
10.4
All PVL
Superiority Testing
P <0.001
11.1%
Patients with Moderate or Greater PVL (%)
Moderate
Mild
Trace
None
2.0%
CoreValve
(N=216)
Lotus
(N=451)
Feldman et al., JAMA 2017;319:27

50. Take Home Message: Balloon Expandable (BE) vs Self Expanding (SE) TAVR Valve Choice in Severe AS
Two RCTs and 2 registries of BE vs SE TAVR valves have showed similar outcomes in majority of severe AS pts with some pro and con of each valve in specific clinical and anatomic scenarios. Small vascular access will favor SE while presence of extensive CAD will favor BE device
Future efforts need to focus on reducing the need of PPM, prosthetic regurgitation and leaflet deterioration after TAVR especially when this technology will be applied to younger and low risk pts. These are essential to really establish TAVR as the destination therapy in younger pts.

51. Question # 1 Correct answer: A
Following are the RCTs or registry data comparing of SE vs BE TAVR except:
A. NOTION
B. CHOICE
C. SOLVE-TAVI
D. PRAGMATIC PLUS
Correct answer: A

52. Correct answer: D Question # 2
Following are the true regarding the 30-day results of Choice trial comparing BE vs SE TAVR valve except:
Stroke incidence is similar between 2 groups
Mortality is higher in the SE group vs BE group
PPM is higher in SE vs BE group
Device success is similar between 2 groups
Correct answer: D

53. Correct answer: C Question # 3
Following are the true regarding the 1-Year results of Choice trial comparing BE vs SE TAVR valve except:
Stroke incidence is similar between 2 groups
Mortality is similar between 2 group
Vascular complication is higher in SE vs BE group
Bleeding complication is similar between 2 groups
Correct answer: C

54. Correct answer: A Question # 4
Following are the true regarding the results of Solve-TAVI trial comparing BE vs SE TAVR valve except:
Stroke incidence is similar between 2 groups
Mortality is similar between 2 groups
PPM is similar between 2 groups
Mod-severe AI is similar between 2 groups
Correct answer: A

55. Correct answer: D Question # 5
Following are the true regarding the results of Solve-TAVI trial comparing LA vs GA during TAVR procedure except:
Stroke incidence is similar between 2 groups
Mortality is similar between 2 groups
AKI is similar between 2 groups
Catecholamine meds use is similar in GA vs LA group
Correct answer: D