DETAILS OF EVIDENCE TAVI FROM ITS EXISTENCE IN INTERVENTIONAL CARDIOLOGY TO THE SURTAVI REGISTRY ..AS AN OPTION FROM HIGH RISK UNOPERABLE PATIENTS TO INTERMEDIATE AND LOW RISK PATIENTS

1.  
TRIAL EVIDENCE OF TAVI
Dr.Praveen Nagula

4.  April 16,2002 first case report.
 From 2003 -2004, single center registeries - for feasibility.
 I REVIVE – Initial Registry of Endovascular Implantation of Valves in
Europe
 RECAST – Registry of Endovascular Critical Aortic Stenosis Treatment.
o 23 mm bioprosthesis
o Equine pericardium mounted on a stainless steel balloon expandable stent
o Antegrade (trans septal ) approach.
o Procedural success – 75%.
o Aortic valve area increased consistently from 0.6 cm2 to 1.6 cm2.
o Fall in mean trans valvular gradient (37 mm Hg to 9 mm Hg).
o Increase in LVEF (45% +18% to 53% +14%)
o 30 day mortality rate was 23%.
o MACCEs – 26%.
o Patient survival was 63% by 6 months.
o Moderate to severe perivalvular AR (63%), valve embolization were limitations
of the procedure.

5.  To reduce the degree of the perivalvular aortic insufficiency – valves
were oversized in relation to the aortic annulus – 26 mm size
prosthesis became available.
 Appropriate valve sizing – transverse diameter of the aortic annulus
at the level of the aortic leaflet insertion.
 Retroflex catheter – atraumatic passage across the aortic arch,
facilitated passage through retrograde approach.
 Sheath length was increased to deliver the catheter-valve ensembly
directly into the descending aorta.
 Minimal arterial diameter, vessel tortuoisity and vessel calcification
were still the major limiting factors.

6.  REVIVAL II
 REVIVE
 Canada (Canadian Special Access)
 Valve area < 0.8 cm2
 High predictive operative mortality >20%.
 New valve modifications were included.
o Use of bovine pericardium
o Increase of the skirt to decrease the perivalvular insufficiency.
o Addition of the anticalcification treatment
 Webb et al – retrograde approach – 78% success – 96% after 25 cases.
 30 day mortality was 12%(expected was 28%).
 Moderate perivalvular leaks in 3 patients at 1 month.
 Led to valve approval and commercialization in Europe in 2007

7.  Most recently developed form of transcatheter AVR.
 First reported by Lichtenstein
 7 patients with severe AS.
 Valve implantation was successful in all of them.
 No Procedural deaths.
 Results were consistent with that of the retrograde approach.
 Observed 30 day mortality was 14%(expected 35%).
 Walther et al – 93.2% successful implantation.
 Conversion rate to conventional AVR -6.8%.
 Trace to mild AR - 23 patients.
 30 day mortality was 13.6%(26.8%)
 Use of extracorporeal life support was frequent(47%)

8.  Rate of 90% successful valve placements.
 Persistent improvement in symptoms,valve area,mean
gradient,aortic insufficiency and quality of life(Qol).
 Survival
 MACCEs were seen in 65%
1 month 81.8%
3 months 71.7%
6 months 58.7%
Stroke 5%
Emergent cardiac surgery 2.5%
Myocardial infarction 17.5%
Svensson LG,Kapadia S,et al. Ann Thorac Surg 86;46-55,2008.

9. No. of Patients 1123
Centers in Europe 32 centers
Procedural success 93.8%
30 day mortality was 6.3%
Mean survival was 74%
NYHA class improvement was 86% at 30 days (p<0.001)
Mean gradient decreased from 46.1 mm hg to 11.2 mm Hg
No valve deterioration structurally.
Vascular complications 8.3% transfemoral approach ,
hemodynamic support in 0.9%,
tamponade in 4%,
PPI in 4.4%,
infection in 2.4%,
stroke in 5.3%. AF 12%

10.  Trans apical approach is associated with high mortality not because of
procedure but because of increased comorbidities and age of the
patient.
 To date, transfemoral approach is the default one and transapical is
offered only to those who donot qualify for transfemoral approach.
 Comparison of SAVR and trans apical TAVR – similar operative
mortality,similar 1 yr survival,shorter ICU stay and shorter duration of
mechanical ventilation.
 Trans apical is complementary to trans femoral approach.

11.  2005-2009.
 339 patients(high risk)
 49.6% trans femoral ,50.4% - trans apical
 Procedural success was 93.3%.
 30day mortality was 10.4%.
 Mortality increased to 22% at mean follow up of 8 months –
COPD,CKD, Periprocedural sepsis – independent predictors.
 Patients with porcelain aorta had better survival at 1 yr follow
up.

12.  19 sites in France.
 Valve area <0.6cm2.
Edwards SAPIEN Core Valve
Trans femoral 39% 27%
Trans apical 29%
Sub clavian 5%
Results
Death at 30 days 13%
stroke 4%
Vascular complications 7%
Transfusions > 1 unit 21%
Need for PPI High in Core Valve group
Mean survival was 76.5%
Mean valvular gradients were 10 mmHg
NYHA Ior II 86%

13. Primary Safety end point Freedom from death from the index procedure to 30 days and 6
months.
Primary efficacy end point Hemodynamic status of the valve,QoL,NYHA class improvement at
12 months after implantation.
Inclusion criteria Logistic Euro SCORE >20%
STS score >10% if the earlier was less than 20%
Porcelain aorta or chest deformities
All patients had Senile degenerative aortic stenosis (<0.8cm2,PG >40mm
Hg,AJV>4m/sec)
Mean patient age was 82 yrs
Clinical status 84% of transfemoral ,85% of trans apical – NYHA III,IV
Post procedure Mean gradient fell to 10 mm Hg,valve are increased to 1.6cm2.
NYHA class improvement 60% had improved to NYHA I/II at 6 months,1yr.
Survival at 18 months Transfemoral 71%,transapical 44% (not comparable )

14.  Severe symptomatic AS patients.
 Cohort A – powered for noninferiority analysis
o traditional AVR vs TAVI
o 700 patients
 Cohort B – powered for superiority analysis
o 358 patients
o Optimal medical treatment(including BAV ) vs TAVI
 Cohort C – frail patients
o Who die with aortic stenosis but not because of aortic stenosis.

19. Results of Cohort A AVR TAVI P value
All cause mortality 50.7% 30.7% <0.001
CV mortality 41.9% 19.6% <0.001
Repeat hospitalization 44.1% 22.3% <0.001
Death or repeat
hospitalization
(composite end point)
72.6% 42.5% <0.001
Follow up No degeneration
No re stenosis
Less HF symptoms
Vascular complications 1.1% 16.2% <0.001
Major bleeding 11.2% 22.3% <0.001
Major strokes 1.1% 5.5% 0.06

22. N = 358Inoperable
Standard
Therapy
n = 179
ASSESSMENT:
Transfemoral
Access
TF TAVR
n = 179
Primary Endpoint: All-Cause Mortality
Over Length of Trial (Superiority)
1:1 Randomization
VS
Symptomatic Severe Aortic Stenosis
• Primary endpoint evaluated when all patients reached one year follow-up.
• After primary endpoint analysis reached, patients were allowed to cross-over to
TAVR.
Severe Symptomatic AS with
AVA< 0.8 cm2 (EOA index
< 0.5 cm2/m2), and mean
gradient > 40 mmHg
or jet velocity > 4.0 m/s
Inoperable defined as risk of death
or serious irreversible morbidity
of AVR as assessed by
cardiologist and two surgeons
exceeding 50%.

23. • All-Cause Mortality
• Cardiac Mortality
• Re-hospitalization
• Stroke
• NYHA functional class
• Echo-derived valve areas, transvalvular gradients,
and paravalvular leak.
• Mortality outcomes stratified by STS score, paravalvular leak and
age.

24. N = 358
Randomized Inoperable
N = 179
TAVR
N = 179
Standard Therapy
124 / 124 patients
100% followed at 1 Yr
85 / 85 patients
100% followed at 1 Yr
81 / 83 patients
97.6% followed at 3 Yrs
19 / 19 patients
100% followed at 3 Yrs
50 / 51 patients
98.0% followed at 5 Yrs*
6 / 6 patients
100% followed at 5 Yrs*
Cross Over
11 pts
Cross Over 9
pts
10 Patients Withdrew
* ± 2 months follow-up window

25. Characteristic TAVR
N = 179
Standard Rx
N = 179
p-value
Age – yr 83.1 ± 8.6 83.2 ± 8.3 0.95
Male sex (%) 45.8 46.9 0.92
STS Score 11.2 ± 5.8 12.1 ± 6.1 0.14
NYHA
I or II (%)
III or IV (%)
7.8
92.2
6.1
93.9
0.68
0.68
CAD (%) 67.6 74.3 0.20
COPD
Any (%)
O2 dependent (%)
41.3
21.2
52.5
25.7
0.04
0.38
Creatinine > 2 mg/dL (%) 5.6 9.6 0.23
Frailty (%) 18.1 28.0 0.09
Porcelain aorta (%) 19.0 11.2 0.05
Chest wall radiation (%) 8.9 8.4 1.00

29. • Mortality benefit was similar in elderly (>85 yr) patients
compared to those ≤85 years.
• Cardiovascular mortality and all-cause mortality benefit was
seen even in patients with high STS score.
• Patients with O2 dependent COPD may have less mortality
benefit.
• Beyond early procedural risk of stroke there was no persistent
risk over 5-year follow up.
• Moderate and severe paravalvular leak is associated with
higher cardiovascular mortality particularly in patients with
less comorbidities.

30. • At 5 years follow-up benefits of TAVR were sustained as measured
by:
– All-Cause Mortality
– Cardiovascular Mortality
– Repeat Hospitalization
– Functional Status
• Valve durability was demonstrated with no increase in
transvalvular gradient or attrition of valve area.

34.  

36.  Safety and efficacy of the CoreValve Revalving System in two cohorts of
patients.
 1 end point - 12 month all cause mortality or major stroke.
30 day risk of
mortality
No. of patients
First Cohort Extreme risk for
surgery (sAVR) or
Inoperable for sAVR
>50% 487 pts
Subclavian –axillary
Trans aortic access
100 pts
Second cohort High risk for surgery
(sAVR)
>15% 790 pts

37.  Safety and Efficacy Study of the Medtronic CoreValve®
System in the Treatment of Severe, Symptomatic Aortic
Stenosis in Intermediate Risk Subjects Who Need Aortic
Valve Replacement (SURTAVI).
 intermediate risk [ STS score of 3-8% ]

38.  Surgical Replacement and Transcatheter Aortic Valve
Implantation
 Multicenter randomized clinical study.
 Europe.
 Broader group of patients( intermediate risk for SAVR )
 Safety and efficacy of TAVI vs SAVR
 Heart team approach is used.

40.  Long term and real world impact of TAVI therapy.
 Prospective,observational international post market study to
evaluate clinical outcomes of patients with severe AS.
 1000 patients
 90 sites.
 Followed up for atleast 5 years after the implantation.
 1 end point - MACCEs at 30 days after the procedure.

41.  Enrollment of 100 patients in 7 to10 experienced CoreValve
European sites
 Characterize implantation procedures at best european sites.
 Intermediate term outcomes in high risk patients.
 Best practice event rates.
 30 day and 1 yr mortality
 Stroke
 Vascular complications
 AR
 Development of conduction disturbance requiring PPP.