Transcatheter aortic valve implantation for failed surgical aortic bioprostheses using a self-

expanding device: early results from the prospective VIVA post-market study

Prof. Ran Kornowski, Rabin Medical Center, Petah Tikva, Israel

Dr. Didier Tchétché, Clinique Pasteur, Toulouse, France

Prof. Jean-Philippe Verhoye, CHU Rennes, Rennes, France

Dr. Bernard Chevalier, Institut Cardio-vasculaire Paris-Sud, Massy, France

and on behalf of the VIVA Investigators

Speaker's name: Prof. Ran Kornowski

I do not have any potential conflict of interest

X I have the following potential conflicts of interest to report:

• Other(s): Proctor for Medtronic for TAVI cases using the CoreValve/EvolutR devices

Background

• Surgical aortic valve replacement has been the standard of care in symptomatic patients with aortic valve disease.

• However, bioprosthetic valves degenerate over time, requiring re-do surgery to replace them.

• As many patients are not candidates for reoperation, a less invasive valve-in-valve (ViV) procedure using transcatheteraortic valve implantation (TAVI) is an emerging alternative.

• The VIVA trial was designed to create a large prospective dataset among ViV patients treated in clinical practice.

Aims

• The objective of the Valve In VAlve trial (VIVA) is to systematically and prospectively collect data regarding use of TAVI with the CoreValve and Evolut R devices in patients with failing surgical aortic bioprostheses at high risk for re-do open-heart surgery.

Methods

• VIVA is an observational, single-arm, post-market multi-center study conducted at 23 sites in France, Germany, Israel, and Italy, which enrolled 202 patients.

• Adults with symptomatic degeneration of an aortic bioprosthesis(stenosis and/or regurgitation) who were acceptable candidates for elective treatment with a self-expanding transcatheter aortic valve were eligible for inclusion.

• Patients were required to have a logistic EuroSCORE >20% or STS score >10%, or presence of comorbidities that contraindicated redo surgery as assessed by the cardiologist and at least one cardiac surgeon OR deemed at high-risk for redo surgery by the heart team.

Trial Organisation

Executive

Committee/PIs:R. Kornowski, D. Tchétché, JP Verhoye

Publication

Committee:R. Kornowski, D. Tchétché, JP Verhoye, B. Chevalier

CRO:

CERC, Massy, France

1) CEC: P. Ménasché (Chair), G. Sardella, N. Löffelhardt

2) Echo Corelab: M. Poupineau

3) Site management

Sponsor: Medtronic

Endpoints and Compliance

Primary Safety Endpoint:

Primary Efficacy Endpoint:

Cardiovascular death at 30 days post procedure; expected to be below 10%.

Lack of significant aortic stenosis (mean gradient > 40mmHg) or insufficiency (> moderate severity) at 1 year post

procedure using clinical evaluation and echocardiography

Secondary Endpoints:

VARC-II endpoints: Access site complications, major bleeding, stroke, AKI stage III, new pacemaker implantation, and post-

implantation aortic gradient

30-day Compliance:

98.5%(191/194)

Baseline Characteristics

CharacteristicAll

(N=202)

Age (yrs) 79.9 ± 7.2

Men 47.0

Height (cm) 164.3 ± 9.1

Weight (kg) 73.7 ± 16.3

BMI (kg/m2) 27.2 ± 5.4

BSA (m2) 1.8 ± 0.2

LogEuroSCORE (%) 25.0 ± 14.3

STS score (%) 6.6 ± 5.1

Diabetes mellitus 26.2

Peripheral vascular disease 13.9

Chronic renal replacement therapy 1.5

Previous stroke 5.0

NYHA III/IV 70.7

LVEF %(n)

61.0 ± 12.0(157)

Values are mean ± SD or %.

Devices Utilized

CoreValveEnrolled: n=19

Evolut REnrolled: n=183

Mode of Bioprosthetic Failure

Failure Mode

Pre-procedure hemodynamicsAll

(N=202)Stenosis(N=114)

Regurgitation(N=46)

Combined(N=42)

AV max gradient, mmHg (mean ± SD)*(n)

56.0 ± 30.5

(115)

67.0 ± 28.8

(71)

32.9 ± 25.1

(28)

47.4 ± 20.8

(16)

AV mean gradient, mmHg (mean ± SD)(n)

31.6 ± 15.2

(162)

35.2 ± 14.0

(99)

19.9 ± 11.5

(32)

31.8 ± 16.5

(31)

AV regurgitation ≥ +2 (%)*(n)

52.1(142)

22.4(76)

88.6(35)

83.9(31)

*site-reported data; core lab data pending

Surgical Valve Types

Surgical Valve Characteristics

CharacteristicAll

(N=202)

Time since last SAVR, yrs (mean ± SD)

(median)

9.3 ± 4.4

8.8

Surgical valve type (%)

Stented

Stentless

93.1

6.9

Label size (%)

≤ 21 mm

> 21 mm and < 25 mm

≥ 25 mm

41.3

32.8

25.9

Internal diameter (%)

< 20 mm

≥ 20 mm and < 23 mm

≥ 23 mm

40.9

35.1

24.0

Procedural Characteristics

Characteristic

All(N=202)

Procedural success (%) * 98.5Device size (%)

23-mm

26-mm

29-mm

31-mm

63.7

26.9

9.5

0.0

Access (%)

Ilio-femoral

Subclavian/Axillary

Transcarotid

Direct aortic

96.5

2.0

1.0

0.5

Anesthesia (%)

Local

General

Sedation

41.6

23.3

35.1

*CoreValve/Evolut R device successfully deployed into surgical aortic bioprosthesis

Procedural Characteristics

CharacteristicAll

(N=202)

Pre-implantation valvuloplasty (%) 13.9

Device retrieved (%) 2.0

Post-implantation valvuloplasty (%) 20.8

Second device implantation (%) 2.5

Coronary obstruction (%)* 2.0

Converted to surgical AVR (%) 0.5

* 3 cases intra-procedural and 1 additional obstruction occurred soon after the procedure. All 4 cases occurred in Mitroflow SAVs.

Primary Endpoint: Cardiovascular Mortality at 30 Days

No. at risk:

202 180

2.5%2.0%

0%

1%

2%

3%

4%

5%

6%

7%

8%

9%

10%

0 5 10 15 20 25 30

Mo

rtal

ity

Days After Procedure

All-cause Mortality

Cardiovascular Mortality

Other Clinical Outcomes at 30 Days

EndpointAll

(N=202)

Duration of hospital stay, days (mean ± SD) 7.4 ± 6.1

All stroke (%) 3.0

Disabling (%) 0.0

Major vascular complication (%)* 6.5

Bleeding (%)*

Life-threatening

Major

Minor

14.9

0.0

7.0

7.9

Acute kidney injury (%)*

Stage I

Stage II or III

0.5

0.5

0.0

Permanent pacemaker implantation (%) £ 7.0

Kaplan-Meier event rates.*According to the Valve Academic Research Consortium 2 (VARC-2) definition£Baseline pacemaker included

Mortality by logEuroSCORE

Mortality by Failure Mode

Mortality by Surgical Valve Type

Paravalvular Regurgitation

Echocardiographic Findings by Failure Mode

NYHA Classification

• The VIVA trial confirmed the feasibility, safety and effectiveness of the TAVI ViV intervention using the CoreValve/Evolut R devices in high-risk patients with failing surgical aortic bioprostheses.

• 30-day mortality/CV mortality was 2.5%/2.0% among patients who had average LogEuroSCORE 25% and mean STS 6.6%. In this respect, the study met its primary safety endpoint at 30-days (which was pre-defined as 30-day CV mortality rate <10%).

• Complications were mostly minor (i.e. not life threatening) and at a relatively low rate.

• Echocardiography data at discharge and NYHA functional class after 30-days are favorable, which indicates the short-term effectiveness of this mode of treatment.

• The one-year clinical and echocardiographic efficacy data are awaited and will be reported in the near-future.

Conclusions

Participating Centers

FranceClinique Pasteur; Toulouse - Dr. Didier TchétchéHopital Jacques Cartier; Massy – Dr. Bernard ChevalierCHU Mondor; Créteil - Prof. Emmanuel TeigerCHU de Nantes - Dr. Thibaut ManigoldCHU Lille – Dr. Thomas Modine CHU Clermont; Clermont-Ferrand – Dr. Geraud SouteyrandTonkin Clinic; Villeurbanne – Dr. Didier ChampagnacCHU Rennes - Prof. Jean Philippe VerhoyeCHU Bordeaux; Pessac - Dr Lionel LerouxCHU Brest - Prof. Martine GilardCHU Rangueil; Toulouse - Dr. Bertrand MarcheixClinique Parly 2; Le Chesnay - Dr. Gregoire DambrinCHU La Timone; Marseille - Dr. Dominique Grisoli

GermanyHerzzentrum Leipzig - Dr. David HolzheySana-Herzzentrum Cottbus - Dr. Axel HarnathUK Hamburg Eppendorf - Prof. Ulrich SchäferHerz-und Diabeteszentrum NRW;

Bad Oeynhausen - Dr. Werner ScholtzKerckhoff Klinik; Bad Nauheim - Dr. Won-Keun Kim

IsraelRabin Medical Center; Petah Tikva - Prof. Ran KornowskiSheba Medical Center; Tel Hashomer - Prof. Victor Guetta

ItalyBrescia Hospital - Dr. Federica EttoriPisa Hospital - Prof. Anna Sonia PetronioSan Donato; Milano - Prof. Francesco Bedogni