1. Longevity of transcatheter and surgical bioprosthetic aortic valves in patients with severe aortic stenosis and lower surgical risk
Lars Sondergaard, MD, DMSc Professor of Cardiology Rigshospitalet
Copenhagen, Denmark
- On behalf of the NOTION trial investigators

2. Lars Sondergaard conflicts of interest
I do not have any potential conflict of interest
I have the following potential conflicts of interest to report:
Honorarium: Medtronic
Institutional grant/research support: Medtronic
Consultant: Medtronic
Employment in industry:
Owner of a healthcare company:
Stockholder of a healthcare company:
Other(s):

3. Nordic Aortic Valve Intervention Trial the NOTION trial
TAVI has become a standard treatment for patients with severe aortic stenosis and higher surgical risk
Ongoing controlled trials will help to define the role of TAVI in patients at lower surgical risk
The Nordic Aortic Valve Intervention (NOTION) trial was the first to randomise lower risk patients to either SAVR or TAVI (CoreValve)

4. The Notion Trial summary Objective:
To compare TAVI vs. SAVR in lower risk patients
>70 years eligible for surgery (all-comers population)
Primary
outcome:
Composite rate of all-cause mortality, stroke or
myocardial infarction at 1 year (VARC II-defined)
Secondary outcomes:
Safety and efficacy (NYHA), echocardiographic outcomes(VARC II-defined)
Design:
Prospective, multi-centre, non-blinded, randomised
trial (N=280)
Enrollment
period:
December April 2013

5. The NOTION Trial all-cause mortality
31.1%
29.4%
Number at risk:
138
135
130
119
100 52
125
123
118
110 92 58

6. The NOTION Trial aortic valve performance* * * * *
*p < TAVI vs. SAVR
TAVI SAVR * * * *

7. The NOTION Trial valve durability analysis
Analysis of the durability of TAVI is important as the therapy looks to expand to patients with longer life expectancy
A post-hoc analysis of prosthetic valve durability using expanded definitions for valve dysfunction and failure was undertaken
The implanted cohort of patients was analysed

8. The NOTION Trial durability analysis methods (I)
Bioprosthetic valve dysfunction (BVD) was defined as:
Structural valve deterioration (SVD) or
Non-structural valve deterioration (NSVD) or
Bioprosthetic valve thrombosis or
Endocarditis
– 2 major criteria according to modified Duke criteria
Capodanno et al. Eur Heart J, in press

9. The NOTION Trial durability analysis methods (II)
Structural valve deterioration (SVD)
Moderate or severe haemodynamic SVD
Mean gradient ≥20 mmHg or
Mean gradient ≥10 mmHg change from baseline or
Moderate/severe intra-prosthetic aortic regurgitation (AR) (new or worsening from baseline)
Non-structural valve deterioration (NSVD)
Moderate/severe patient-prosthesis mismatch at 3 months or
Moderate/severe paravalvular regurgitation (PVL)
Capodanno et al. Eur Heart J, in press

10. The NOTION Trial structural valve deterioration
TAVI
SAVR
n=139
n=135
SVD
Moderate haemodynamic SVD
2.9% (4/139)
20.7% (28/135)
Severe haemodynamic SVD
0.7% (1/139)
3.0% (4/135)
26.1%
3.9%
Number at risk:
139
134
130
124
112 94 50
135
118
101 92 74 41

11. The NOTION Trial structural valve dysfunction through 5 years
components
TAVI
SAVR
n=139*
n=135*
P-value
SVD
3.6%
(5/139)
21.5%
(29/135)
<0.0001
Moderate haemodynamic SVD
2.9%
20.7%
Mean gradient ≥20 mmHg
2.2%
19.3%
Mean gradient ≥10 and <20 mmHg change from 3mo
1.4%
8.1%
Moderate Central AR 0%
Severe haemodynamic SVD
0.7%
3.0%
Mean gradient ≥40 mmHg
1.5%
Mean gradient ≥20 mmHg change from 3mo
Severe Central AR
*Not all subjects have completed 5 year follow-up

12. The NOTION Trial non-structural valve dysfunction through 5 years
components
TAVI
SAVR
n=139*
n=135*
P-value
NSVD
54.0%
(75/139)
57.8%
(78/135)
0.52
Moderate/severe PPM at 3 months
43.2%
Moderate PPM at 3 Months
30.9%
29.6%
Severe PPM at 3 Months
12.3%
28.2%
Moderate/severe PVL
21.6%
1.5%
Moderate PVL
20.9%
Severe PVL
0.7% 0%
*Not all subjects have completed 5 year follow-up

13. The NOTION Trial bioprosthetic valve dysfunction through 5 years
components
TAVI
SAVR
n=139*
n=135*
P-value
BVD
55.4%
(77/139)
65.2%
(88/135)
0.10
SVD
3.6%
21.5%
<0.0001
NSVD
54.0%
57.8%
0.52
Thrombosis 0% NA
Endocarditis
4.3%
5.9%
0.55
*Not all subjects have completed 5 year follow-up Subjects could have more than 1 component of BVD

14. The NOTION Trial durability analysis methods (III)
Bioprosthetic valve failure defined as:
Valve-related death
Death caused by BVD or sudden unexplained death following diagnosis of BVD
Aortic valve re-intervention
TAVI or SAVR following diagnosis of BVD
Severe hemodynamic SVD
Mean gradient ≥40 mmHg or
Mean gradient ≥20 mmHg change from baseline or
Severe AR (new or worsening from baseline)
Capodanno et al. Eur Heart J, in press

15. The NOTION Trial bioprosthetic valve failure
TAVI
SAVR
P-value
n=139
n=135
BVF
Valve-related deaths
4.3% (6/139)
3.7% (5/135)
0.80
Re-intervention
2.2% (3/139)
0.0% (0/135)
0.25
Severe haemodynamic SVD
0.7% (1/139)
3.0% (4/135)
0.21
9.5%
8.5%
Number at risk:
139
135
132
126
115 96 51
124
117
109 91 54

16. The NOTION Trial limitations
NOTION enrolled patients from when echo-
based sizing was standard of care instead of CT sizing
No core lab was used for evaluation of
echocardiographic examinations

17. The NOTION Trial conclusions
Through 5 years follow-up of the NOTION trial:
Excellent haemodynamic valve performance was maintained
Bioprosthetic failure was low and similar for the self- expanding transcatheter (CoreValve) and the surgical valves implanted
Structural valve deterioration was significantly greater for SAVR compared with TAVI
There was no valve thrombosis and similar rates of endocarditis for both groups