Late breaking news in heart valve disease C. Bouleti

Primary endpoint Device success (VARC definition) Successful vascular access, delivery and deployment of the device Correct position of the device Aortic valve area > 1.2 cm2, mean aortic gradient < 20 mmHG or V max < 3 m/s, AR<3 Only 1 valve implanted in the proper anatomical location

Baseline patient characteristics

Baseline TTE

Procedural factors: valve size

Procedural details

Immediate results: AR

Primary endpoint: device success

Clinical outcome at 30 days

Clinical outcome at 30 days

JAMA

CoreValve US Pivotal Trial High Risk Results

CoreValve US Pivotal Trial Primary Endpoint: All-cause mortality at 1 year 24 (Adams et al. N Engl J Med 2014 online March 29)

Study Device and Access Routes 4 valve sizes (18-29 mm annular range) Transfemoral Subclavian Direct Aortic 18Fr delivery system 25 25 25 25

Primary Endpoint: All-cause mortality at 1 year Non-inferiority Testing: TAVR with the CoreValve prosthesis was non-inferior to SAVR for 1 year all-cause mortality with a 7.5% non-inferiority margin Superiority Testing: If the primary endpoint was met at the one-sided 0.05 level, a subsequent test for superiority was performed at the one-sided 0.05 level 26

Hierarchical Testing of Secondary Endpoints Δ mean gradient baseline to 1 year (non-inferior) Δ effective orifice area baseline to 1 year (non-inferior) Δ NYHA class baseline to 1 year (non-inferior) Δ KCCQ baseline to 1 year (non-inferior) Difference in MACCE* rate at hospital discharge or 30 days, whichever is later (superiority) Δ SF-12 baseline to 30 days (inequality) * Major adverse cardiovascular and cerebrovascular events, defined as a composite of all-cause mortality, myocardial infarction, all stroke, or aortic-valve reintervention 27

Participating Sites 28

Inclusion Criteria NYHA functional class II or greater Severe aortic stenosis: AVA ≤ 0.8 cm2 or AVAI ≤ 0.5 cm2/m2 AND mean gradient > 40 mm Hg or peak velocity > 4 m/sec at rest or with dobutamine stress echocardiogram Risk of death at 30 days after surgery was ≥ 15% and the risk of death or irreversible complications within 30 days was < 50% Surgical risk assessment included consideration of STS Predicted Risk of Mortality estimate and other risk factors not captured in the STS risk model 29

Exclusion Criteria Recent active GI bleed (< 3 mos), stroke (< 6 mos), or MI (≤ 30 days) Any interventional procedure with bare metal stents (< 30 days) and drug eluting stents (< 6 months) Creatinine clearance < 20 mL/min Significant untreated coronary artery disease LVEF < 20% Life expectancy < 1 year due to co-morbidities 30

Study Disposition

Baseline Demographics 32

Baseline Demographics 33

Primary Endpoint: 1 Year All-cause Mortality ACC 2014 19.1% 4.5% Surgical 14.2% P = 0.04 for superiority 3.3% Transcatheter 34

All Stroke 35

Hierarchical Testing of Secondary Endpoints Δ mean gradient baseline to 1 year (non-inferior; P<0.001) Δ effective orifice area baseline to 1 year (non-inferior; P<0.001) Δ NYHA class baseline to 1 year (non-inferior; P<0.001) Δ KCCQ baseline to 1 year (non-inferior; P=0.006) Difference in MACCE rate at hospital discharge or 30 days, whichever is later (superiority; P=0.103) Δ SF-12 baseline to 30 days (inequality; nominal P<0.001) 36

1 Year MACCE 37

Other Endpoints 38

NYHA Class Survivors 39

Paravalvular Regurgitation 40

Subgroup Analysis for 1 Year Mortality 41

Subgroup Analysis for 1 Year Mortality 42

Conclusion We assessed the safety and effectiveness of TAVR with the CoreValve prosthesis compared to surgical valve replacement in symptomatic patients with severe aortic stenosis at increased surgical risk One-year survival was superior in patients that underwent transcatheter replacement with CoreValve as compared with surgical AVR 43

DONC… Si SAPIEN XT > COREVALVE (CHOICE) ET QUE COREVALVE > CHIRURGIE (COREVALVE US PIVOTAL TRIAL) ALORS ….

DONC… …. SAPIEN > CHIRURGIE

DONC… ... SAPIEN > CHIRURGIE

All Cause Mortality in PARTNER A TAVI vs AVR The primary analysis reveals no difference in mortality between TAVR and AVR with a hazard ratio of 0.88. The two year KM estimates of mortality are 35% for AVR and 33.9% for TAVR. (Kodali et al. NEJM 2012;366:1686-95) Months 47

PARTNER-A: population Mêmes critères d’inclusion (surface Ao, NYHA≥ 2, mortalité estimée à 30 jours >15%) Mais STS 12% versus 7% ES logistic 29% versus 18% pop à plus haut risque dans PARTNER

PARTNER-A: procedure Voie d’abord: 30% de transapical Valve ancienne génération (Sapien)

PARTNER-A: stroke Recueil retrospectif des stroke Vs Prospectif pour CoreValve trial Plus de stroke retrouvés (TAVI 6% et chir 3% dans PARTNER Vs 9% et 13% dans CoreValve Trial ) “When you look harder you find more”

Conclusion La place importante du TAVI est confirmée par des études randomisées avec niveaux de preuve élevés En passe de donner de meilleurs résultats que la chirurgie ? Interprétation des études doit être prudente et attention aux comparaisons