Cardiolucca Heart Celebration. Seconda generazione delle valvole e miglioramento degli outcome nel trattamento percutaneo della stenosi aortica

Transcription

1 Cardiolucca 2014 Heart Celebration Seconda generazione delle valvole e miglioramento degli outcome nel trattamento percutaneo della stenosi aortica Sergio Berti Ospedale del Cuore Fondazione C.N.R. Reg. Toscana G. Monasterio

2 Second Generation TAVI

3 Patient Selection TAVI Procedure Team Performance Outcomes Device Technology

4 ADVANCE Survival by EuroSCORE EHJ (2014) 35,

5 High risk inaccuracy All AV surgery: Observed and predicted mortality rates according to the Logistic EuroSCORE; financial years (n= ) Observed Observed Predicted Predicted Testo Mortality rate Logistic EuroSCORE grouping

6 Problems with risk models High risk groups on whom data may not be collected - Immunosuppression, frailty Patients who previously had not been offered surgery due to severe comorbidity will not be represented - Liver failure, home oxygen Variables whose predictive power has been lost (reduced) - COAD, renal impairment

7 Frailty is a Phenotype Comorbidity (>2 conditions) 66% 25% Disability (>1 ADL) Frailty Weakness Muscle Wasting Physical Function Fatigue Cognition Depression Nutrition Weight Loss Limited Life Space Isolation Adapted from K. Alexander, Duke University

8 UK TAVI data N= Observed mortality Predicted mortality STS Score ,6% 6,9% LES ,6% 22,3%

9 How to monitor the TAVI team performance

10 How to monitor the TAVI team performance The CUSUM Chart

11 FTGM TAVI program: Procedural Success

12 Absence of Procedural Complications

13 Procedural Success and Absence of PAR

14 TAVI literature background Paul Gauguin: D'ou venons nous? Que sommes nous? D'ou allons nous? (Where do we come from? What are we? Where are we going?) Oil on sackcloth. Museum of Fine Art. Boston.

15 PARTNER Study Design (years ) 2009) Symptomatic Severe Aortic Stenosis ASSESSMENT: High-Risk AVR Candidate 3,105 Total Patients Screened n = 699 High-Risk Total = 1,057 patients 2 Parallel Trials: Individually Powered Inoperable n = 358 ASSESSMENT: Transfemoral Access ASSESSMENT: Transfemoral Access High-Risk TF High-Risk TA 1:1 Randomization 1:1 Randomization 1:1 Randomization TF TAVR VS AVR TA TAVR VS AVR TF TAVR n = 179 VS Standard Therapy n = 179 Primary Endpoint: All-Cause Mortality (1 yr) (Non-inferiority) Primary Endpoint: All-Cause Mortality Over Length of Trial (Superiority) 15

16 Pivotal Trial Design (years ) TCT 2013 LBCT Extreme Risk Study Iliofemoral Pivotal

17 TAVR should be the standard of care in inoperable patients because it saves lives

18 All Cause Mortality (ITT) Crossover Patients Censored at Crossover All Cause Mortality (%) 100% 80% 60% 40% 20% Standard Rx TAVR 50.8% 30.7% 20.1% NNT = 5.0 pts HR [95% CI] = 0.53 [0.41, 0.68] p (log rank) < % 43.0% 25.0% NNT = 4.0 pts 80.9% 54.1% 26.8% NNT = 3.7 pts 0% Months Numbers at Risk Standard Rx TAVR

19 Cardiovascular Mortality (ITT) Crossover Patients Censored at Crossover Cardiovascular Mortality (%) 100% 80% 60% 40% 20% 0% Standard Rx TAVR 44.6% 20.5% 24.1% NNT = 4.1 pts HR [95% CI] = 0.41 [0.30, 0.56] p (log rank) < % 30.7% 74.5% 41.4% Months 31.7% NNT = 3.2 pts 33.1% NNT = 3.0 pts Numbers at Risk Standard Rx TAVR

20 All 316 Cardiac 66(20.9%) Non Cardiac 163 (51.6%) Unknow 87 (27.5%) Heart failure 37 (56.1%) Pulmonary 38 (23.3%) Sudden death 31 (35.6%) MI 6 (9.1%) Renal failure 12 (7.4%) Unknow 22 (25.3%) Endocarditis 5 (7.6%) Stroke 19 (11.7%) Missing 17 (19.5%) other 18 (27.3%) Cancer 18 (11.0%) Other 17 (19.5%) Causes of Death 30 Days to 1 Year Cohort I and II (n=316) GI 12 (7.4%) Other 64 (39.3%) SOURCE Registry

21 In patients with high surgical risk, TAVR is an acceptable alternative

22 All-Cause Mortality (ITT) Mean Logistic Euro Score 29,3 HR [95% CI] = 0.93 [0.74, 1.15] p (log rank) = % 44.8% 44.2% 26.8% 33.7% 24.3% No. at Risk TAVR AVR

23 Mean Logistic Euro Score 17,7 D.H. Adams et al. for the CoreValve Clinical Investigator NEW ENGLAND JOURNAL of MEDICINE 29 March 2014

24 Clinical Outcomes at 30 Days Clinical Outcome Primary Endpoint TF (N = 96) TF (N = 95) EVENT RATE IN THE AT POPULATION # PATIENTS (KM %) TAA (N = 54) EVENT RATE IN THE VI POPULATION # PATIENTS (KM %) TAA (N = 54) Overall (N = 150) All-Cause Mortality 2 (2.1%) 6 (11.1%) 8 (5.3%) Cardiac Mortality 2 (2.1%) 5 (9.3%) 7 (4.7%) All-Stroke* 1 (1.0%) 3 (5.6%) 4 (2.7%) Disabling Stroke 0 (0.0%) 0 (0.0%) 0 (0.0%) Major Vascular Complication 5 (5.2%) 4 (7.4%) 9 (6.0%) Major Bleeding 19 (19.8%) 11 (20.4%) 30 (20.0%) Life-Threatening Bleeding 2 (2.1%) 3 (5.6%) 5 (3.3%) Rehospitalization 0 (0.0%) 0 (0.0%) 0 (0.0%) Overall (N = 149) All-Cause Mortality 1 (1.1%) 6 (11.1%) 7 (4.7%) VI, valve implant = all enrolled patients who received a SAPIEN 3 implant, and retain the valve upon leaving the cath lab * Severity of the one TF stroke unknown. Rehospitalization for for valve-related symptom or worsening of congestive heart failure.

25 Porcine Sealing Cuff Calcific nodules Conforms to native anatomy: optimal sealing in noncircular and calcified annulus Designed for intra-annular placement of 1-9 mm (23 and 25 mm valves) and 1-10 mm (27 and 29 mm valves)

26

27 TAVR is associated with early stroke hazard

28 Strokes (ITT) HR [95% CI] = 1.09 [0.62, 1.91] p (log rank) = % 3.2% 7.7% 4.9% 9.3% 8.2% Months Post Randomization No. at Risk TAVR AVR

29 All Strokes at 1 year 30 days stoke TAVR 4.9% Surgery 6.2% p 0.46 NEW ENGLAND JOURNAL of MEDICINE 29 March 2014

30 Vascular complications matter, they can affect survival and newer systems are better

31 Mortality vs. Major Vasc Complics TAVI patients Major Vascular Complication (n=31) No Major Vascular Complication (n=148) P (log rank) = Mortality (%) 47.2% 27.7% Months

32 Learning Curve Major Vascular Complications

33 Vascular Complication Categories SOURCE XT: At 30 Days (AT) SAPIEN (n=271) SAPIEN XT (n=282) Events n % n % p-value Perforation Dissection Hematoma

34 Reduction in sheath profile Lower vascular complication rates Vascular complications evolution* p = Min access vessel diameter 1 N=271 N=284 N=96 7/8mm 6/6.5mm 5.5/6mm 1 * Major vascular complications as defined by VARC M. Leon et al. A Randomized Evaluation of the SAPIEN XT Transcatheter Valve System in Patients with Aortic Stenosis Who Are Not Candidates for Surgery: PARTNER II, Inoperable Cohort. ACC 2013 San Francisco March 10, J. Webb et al. 30-Day Outcomes From the SAPIEN 3 CE mark trial PCR Paris May 2014.

35 Edwards Commander Delivery System Partial flex Ultra-low profile 14F esheath compatible* Distal flex Reduced minimum access vessel diameters SAPIEN 3 Valve Size 23 mm 26 mm 29 mm Edwards esheath Introducer Set 14F 14F 16F Minimum Access Vessel Diameter 5.5 mm 5.5 mm 6.0 mm *14F esheath compatible for 23 mm and 26 mm SAPIEN 3 valves. 16F esheath compatible for 29 mm SAPIEN 3 valve. 35

36 Paravalvular AR affects survival and should be reduced

37 Impact of Total AR on Mortality (AT) TAVR Patients 60.8% 38.2% 26.0% 53.7% 32.5% 25.6% 44.6% 35.3% 12.3% No. at Risk None-Tr Mild Mod-Sev

38 Impact of PVL on Late Mortality TCT 2013 LBCT Extreme Risk Study Iliofemoral Pivotal

39 ADVANCE Survival by Aortic Regurgitation * *At discharge EHJ (2014) 35,

40 Paravalvular Aortic Regurgitation (AT) p < p < p < p < p < No. of Echos

41 Echocardiographic Data at 30 Days TOTAL AR (N=149) PARAVALVULAR AR (N=149) N = 78 N = 39 N = 117 N = 77 N = 39 N = 116

42 The SAPIEN 3 Valve Builds Upon the Proven Benefits of the SAPIEN Platform Frame Design Enhanced frame geometry for ultralow delivery profile High radial strength for circularity and optimal hemodynamics Low Frame Height Respects the cardiac anatomy Bovine Pericardial Tissue Optimized leaflet shape Carpentier-Edwards ThermaFix* process for anti-calcification Outer Skirt Designed to minimize paravalvular leak *No clinical data are available which evaluate the long-term impact of the Carpentier-Edwards ThermaFix process in patients 42

43 Dati clinici a confronto: PVL Nello studio REPRISE II, il rigurgito paravalvolare moderato è stato osservato nell 1.0% dei pazienti con valvola Lotus a 30 giorni Pazienti con rigurgito paravalvolare a 30 giorni (%) Lotus 14 (n= 103) Sapien 15 (n= 225) Sapien XT 15 (n= 236) CoreValve 16 (n= 418) Severa Moderata Leggera Traccia Nessuna In CoreValve le categorie nessuna e traccia sono combinate % di pazienti con rigurgito paravalvolare moderato e severo REPRISE II Lotus 14 PARTNER II Sapien 15 PARTNER II Sapien XT 15 US Pivotal Trial CoreValve % 16.9% 24.2% 11.5% I risultati di studi clinici differenti non sono direttamente confrontabili. Questa informazione è fornita solo a scopi educazionali. 14 Meredith et al., TCT 2013, San Francisco; 15 Leon ACC 2013, San Francisco; 16 Popma TCT 2013, San Francisco 2014 Boston Scientific Corporation or its affiliates. All rights reserved.

44 The hemodynamics of TAVR and durability at 3 years are good and reassuring

45 Echocardiographic Findings (AT) Aortic Valve Area p = NS p = p = p = p = NS p = NS p = NS No. of Echos TAVR AVR

46 TAVR categories (risk is a continuum) Operable AS patients Low-intermediate risk Too sick Inoperable High risk 90% 10%

47 TAVR categories (risk is a continuum) Operable AS patients Low-intermediate risk Too sick Inoperable High risk A B C 90% 10%

48 TAVR categories (risk is a continuum) Operable AS patients? Low-intermediate risk Too sick Inoperable High risk IIA A B C 90% 10%

49 SURTAVI : Preliminary Design Severe AS Indication for AVR FEV 1 = forced expiratory volume in 1 second Heart Team Discussion N = 1100 Log EuroSCORE 6 or < 6 plus 1 risk factor (frailty, porcelain aorta, liver cirrhosis, radiation dermatitis, prior stroke, FEV 1 < 1 L) Yes 1:1 Randomization No Nonrandomized Registries TAVI VS AVR Control Primary Endpoint: All-Cause Mortality and Stroke N = 220 TAVI VS Medical Management AVR Endpoint: All-Cause Mortality N = 1760 N = 220 Serruys P, et al. TCT 2010.

50 Valve Implantation - Capodanno ESC in Saudi Arabia 2014, Jfebruary 5, 2014 Slide 50 Ferrarotto Hospital University of Catania

51 Conclusions In inoperable patients TAVI is a standard care In high risk patients TAVI results are comparable/superior to surgical aortic replacement Patient selection remains a learning curve. Team performance is an integral part of procedural success This is a breakthrough technology...what, where, why and when remain the questions!!

52 Cardiolucca 2014 Heart Celebration Seconda generazione delle valvole e miglioramento degli outcome nel trattamento percutaneo della stenosi aortica Sergio Berti Ospedale del Cuore Fondazione C.N.R. Reg. Toscana G. Monasterio