The Lotus Valve, The Latest Developments and Future Aspects. Professor Jan Harnek MD PhD FESC Lund University Sweden

Transcription

1 The Lotus Valve, The Latest Developments and Future Aspects Professor Jan Harnek MD PhD FESC Lund University Sweden

2 Potential Conflicts of Interest Speaker s name: Jan Harnek MD PhD jan.harnek@gmail.com DISCLOSURE INFORMATION: Consulting within the last 24 months Full-time Lotus Proctor for Boston Scientific

3 Aortic Stenosis Pathology Normal Degenerative Calcified Bicuspid Rheumatic SH AO Oct2016 Page 3

4 Aortic Stenosis: Changing Epidemiology Degenerative Calcified Bicuspid Normal X Rheumatic SH AO Oct2016 Page 4

5 Prevalence of mod or severe VHD (%) Increasing Prevalence of Valvular Heart Disease in the Elderly Population-based Studies All valve disease Mitral valve disease Aortic valve disease Olmsted County, MN < > < >75 Nkomo VT at al. Lancet 2006;368: SH AO Oct2016 Page 5

6 Incidence of Aortic Stenosis

7 Natural History of Aortic Stenosis

8 AO-Heart Valves History Concept: M. Edwards engineer and A. Starr MD Sept 1960 first surgical implant Univ. of Oregon Numerous valves biological and mechanical Numerous annuloplasty devices H. Rud-Andersen MD 1989 First percutaneous valve A. Cribier MD 1992 First TAVR 2002 by Cribier Edwards and Strarr Henning Rud Andersen SH AO Oct2016 Page 8

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10 Lotus Valve Timeline 23mm & 27mm 25mm SAFARI 2 SAFARI FIM Direct aortic REPRISE I REPRISE II Transfemoral 1 st Lotus Implant REPRISE III 2016 Boston Scientific Corporation or its affiliates. All rights reserved. SH AA MAY 2016

11 Depth Guard LOTUS Edge * Valve System Design Goals Bovine Pericardium Proven long-term material To minimize LVOT interaction to reduce PPM Braided Nitinol Frame Designed for strength, flexibility, and ability to retrieve, reposition, and redeploy Adaptive Seal** Minimizes paravalvular leak by conforming to irregular anatomical surfaces *This device is pending CE Mark and is not available for sale. **Meredith, I. REPRISE II. TCT Boston Scientific Corporation or its affiliates. All rights reserved. One View Locking Additional radiopaque markers enable operator to confirm locking in 1 view Flexible Catheter Reduced proximal profile and more flexibility to improve trackability New to LOTUS Edge * SH AA SEPT16

12 Designed for Simplified Delivery Improved vessel access with more flexible catheter and a smaller proximal profile 3 4F reduction in profile of proximal catheter compared to Lotus 1 > 30% more trackable with a minimized preshaped curve 1 LOTUS Edge * Lotus 1. In bench test comparing Lotus Valve System versus Lotus Edge Valve System Profile: Edge OS Print and Trackability: ER11346 LOTUS Edge n=4, Lotus n=2. *This device is pending CE Mark and is not available for sale Boston Scientific Corporation or its affiliates. All rights reserved. SH AA SEPT16

13 Next Generation TAVI Design Goals 14Fr isleeve * Expandable Sheath 14Fr design Improved vessel access BOLT Direct Access Sheath Reduced length Uncoated with multiple markers LOTUS Edge * Valve System Enhanced flexibility Optimizing valve deployment Simplified locking 21mm Five Valve Sizes 29mm 18mm 29mm Annulus Size *This device is pending CE Mark and is not available for sale Boston Scientific Corporation or its affiliates. All rights reserved. SH AA MAY 2016

14 LOTUS Edge Valve System Design Features Compared to Current Lotus Valve Lotus LOTUS Edge * Delivery System Pre-shaped Flexible Sheath 18 / 20F 14F / 15F* Q Locking Verification Multiple views 1 view Valve Sizes 23mm, 25mm, 27mm 23mm, 25mm, 27mm, 21mm*, 29mm* (*late 2017) Deployment Controlled Mechanical Controlled Mechanical with Depth Guard Product Box Long/Tall Flatter/Rectangular *This device is pending CE Mark and is not available for sale Boston Scientific Corporation or its affiliates. All rights reserved. SH AA SEPT16

15 Designed for Simplified Deployment One View Locking Additional radiopaque markers allow one view locking intended to: Minimize contrast and radiation Reduce procedure time One View Locking *This device is pending CE Mark and is not available for sale Boston Scientific Corporation or its affiliates. All rights reserved. SH AA SEPT16

16 Designed for Simplified Deployment Depth Guard Deployment Technology Depth Guard Technology designed to reduce LVOT interaction and lower PPM rates Lotus Valve Annulus Lotus Edge * Valve Annulus Funnel shape deployment Bell shape deployment Anchors early during deployment Minimizes depth of valve frame Enables more predictable placement *This device is pending CE Mark and is not available for sale Boston Scientific Corporation or its affiliates. All rights reserved. SH AA SEPT16

17 Goal for Depth Guard Technology and PPM Rate LOTUS Edge * Valve System Depth Guard Technology New Deployment Technique + + = Lower PPM rate Designed to reduce LVOT interaction Posts aligned to the annulus *This device is pending CE Mark and is not available for sale Boston Scientific Corporation or its affiliates. All rights reserved. SH AA SEPT16

18 Lotus Valve System Unmatched Freedom From PVL* Adaptive Seal : Conforms to the anatomy to create a secure seal Adaptive Seal Functioning valve with no PVL after deployment *As published to date. Results from different studies are not directly comparable. Information provided for educational purpose only. 1) I. Meredith, REPRISE II, TCT ) I. Meredith, RESPRISE II, TCT )I. Meredith, REPRISE II EXT., PCR LV ) PARTNER II S3: Thourani, V H, et. al. Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis. The Lancet, April 3, ) S. Brecker, Core Valve ADVANCE, europcr ) G. Manoharan, Core Valve Evolut R CE Study, TCT ) G. Manoharan, Portico CE Study, TCT Boston Scientific Corporation or its affiliates. All rights reserved. SH AA SEPT16

19 Designed for Complete Repositionability With complete repositioning prior to release, even after full deployment, LOTUS Edge * allows unprecedented control, ensuring precise placement 100% R e p o s i t i o n a b l e at Valve functions immediately during deployment Precise placement for every patient 100% D e p l o y m e n t with 0% M a l p o s i t i o n i n g i n R E P R I S E T r i a l s 1-3 Ɨ Repositionability for managing complexities *This device is pending CE Mark and is not available for sale. TAV-in-TAV, ectopic placement, valve migration or embolization: 1) I. Meredith, REPRISE I. TCT 2015.; 2) I. Meredith, REPRISE II. TCT 2015; 3) I. Meredith, REPRISE II EXT. PCR LV Ɨ LOTUS Transaortic Valve studied in REPRISE trials Boston Scientific Corporation or its affiliates. All rights reserved. SH AA SEPT16

20 LOTUS Edge * Valve System Planned Valve Sizes & Treatment Range 23 mm LOTUS Edge * Valve 25 mm LOTUS Edge * Valve 27 mm LOTUS Edge * Valve Native Annulus Diameter 20 mm and 23 mm 23 mm and 25 mm 25 mm and 27 mm Deployed Lotus Valve OD** 23 mm 25 mm 27 mm Deployed Valve Height 19 mm 19 mm 19 mm *This device is pending CE Mark and is not available for sale. **As measured by baseline diagnostic imaging 2016 Boston Scientific Corporation or its affiliates. All rights reserved. SH AA SEPT16

21 isleeve * Introducer Design Goals for Expanding Access isleeve * Features Ultra-thin walled expandable sheath design Low Profile (14F/15F) introduction and removal Novel Tri-Fold Seam is designed to minimize vessel trauma Easier expansion versus existing expandable sheaths Transient expansion can improve vascular closure Designed specifically for LOTUS Edge * *This device is pending CE Mark and is not available for sale. *This device is pending CE Mark and is not available for sale Boston Scientific Corporation or its affiliates. All rights reserved. SH AA SEPT16

22 Lotus Clinical Program REPRISE I REPRISE II REPRISE II Extension RESPOND Feasibility Study; Acute Safety & Performance (Extreme/High Risk) N=11; single arm; 23mm valve size Primary Endpoint: Device success (VARC-1) without MACCE Meredith et al, EuroIntervention 2014 Mar 20;9(11): CE Mark Study; Safety & Performance (Extreme/High Risk) N=120; single arm; 23 & 27mm valve sizes Primary Device Performance Endpoint: Mean pressure gradient at 30d Meredith et al, JACC 2014; In Review Safety & Performance Study (Extreme/High Risk) N=130; single arm; 23 & 27mm valve sizes Primary Safety Endpoint: All-cause mortality at 30d Post Market Safety & Performance Study (Real World) N=1000; single arm; 23, 25 & 27mm valve sizes Primary Endpoint: All-cause mortality at 30d & 1y REPRISE III FDA Approval Study; Safety & Efficacy (Extreme/High Risk) N~1000; Global RCT vs. comparator; 23, 25 & 27mm valve sizes Enrollment Complete REPRISE Edge Safety & Performance Study N~60; Single Arm; 23, 25 & 27mm valve sizes Primary Endpoint: Mean aortic pressure gradient at discharge REPRISE IV and REPRISE V trials in development 2016 Boston Scientific Corporation or its affiliates. All rights reserved. SH AA SEPT16

23 Implant example of the Lotus Edge SH AO Oct2016 Page 24

24 Crossing arch 18mm BAV 23mm Edge valve Low position due to 9mm LM Top-post technique planned Very low resistance crossing arch

25 Initial unsheathing a) Create a small funnel b) Seat valve in annulus Slight backwards tension applied c) Maintain top-post at annulus Catheter angle changes more on Edge when pulling/pushing Top-post probably facilitated by BAV

26 Locking process Centralize catheter Very easy to observe gaps closing NC buckle-post last to close

27 Final result Good final result No partial resheath Good coronary access Trace PVL 4.5 min catheter time

28 Exchangeable 23mm Lotus Valve retrieval and exchange for 25mm Lotus Valve 23mm 25mm Borderline 23mm had moderate PVL despite repositioning Valve was exchanged for a 25mm, final result no PVL SH AO Oct2016 Page 29

29 Repositionable Partial: as many time as needed Complete: only once SH AO Oct2016 Page 30

30 Hemodynamic Stability Fluoro top view of Lotus Valve Boroscopic LVOT view of Lotus Valve Lotus Valve Deployment in Benchtop Flow Model SH AO Oct2016 Page 31

31 PARTNER Trial 1-Year Outcomes Stratified by PVL PVL is a Significant Predictor of Mortality Overall Log-Rank P< Multivariate Analysis Predictors of One-Year Mortality Variable Hazard Ratio P Value PVL (Mild vs. None/Trace) HR=1.37 [1.14, 1.90] P<0.001 PVL (Mod/Severe vs. None/Trace) HR=2.18 [1.57, 3.02] P< Kodali, et al. Eur Heart J 36 (2015): SH AO Oct2016 Page 32

32 PARTNER Trial 3-Year Outcomes Stratified by PVL PVL is a Significant Predictor of Mortality Multivariate Analysis Predictors of Three-Year Mortality Variable Hazard Ratio P Value PVL (None/Trace vs. Mild to Severe) HR=2.11 [ ] P<0.001 Kodali, et al. N Engl J Med (2012): SH AO Oct2016 Page 33

33 % Patients with Mod/Severe PVL 12-Month Moderate & Severe PVL TAVI Clinical Trials 80 11,8 Mod/Severe PVL 12-Month Mild PVL ,7 Portico CE Study 1 20,9 40,9 SAPIEN PARTNER II 2 29,2 9,4 30,8 SAPIEN XT PARTNER II 2 39,3 CoreValve ADVANCE 3 4,3 29,1 25,8 CoreValve Ext Risk 4 CoreValve High Risk ,2 DirectFlow DISCOVER ,7 LOTUS REPRISE II/II EXT 7 STS Score: N: Results from different studies are not directly comparable. Information provided for educational purpose only. 1 Manoharan G, TCT Leon M, ACC Linke A, Eur Heart J Popma J, JACC Adams D, N Engl J Med Lefevre T, JACC:CI Meredith I, PCR LV Information not intended for use in France. Lotus is an investigational device and not for sale or distribution in the US. CE mark received Information for the Lotus Valve System is for use in countries with applicable product registrations. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. SH AO Oct2016 Page 34

34 Safari 2 Guidewire Design Goals Fluoroscopic image of the Safari Guidewire in-situ Graphic of Safari Guidewire positioned in the left ventricle 3 Curve Sizes: Extra Small Small Large One Length (275cm) Enhanced wire predictability, with superior shape retention Streamlined device delivery through optimized rail support Widest guidewire choice with three curve sizes SH AO Oct2016 Page 35

35 Lotus Ongoing and Upcoming Core Trials and Investigator- Sponsored Research for the Lotus Valve Int./Low Risk NOTION II Lotus vs Other TAVI* Monash Exp. MRI Study LV Mechanics Hemodynamic Eval. Wohrle Registry Real World Wohrle Registry LEAR (LOTUS Edge) BSC Core Trials REPRISE I REPRISE II REPRISE II EXT REPRISE III REPRISE JAPAN RESPOND REPRISE CAS REPRISE IV & V TAVR vs SAVR MRI Study 4D MRI assessment Combined Procedures LAAC & TAVR Pilot *TAVR includes: CoreValve, Evolut-R, S3, and SAPIEN XT Boston Scientific is not responsible for the collection, analysis or reporting of the investigator-sponsored research output which is the sole responsibility of the investigators. Boston Scientific s involvement in investigator-sponsored research is limited to providing financial support for research that advances medical and scientific knowledge about our products. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. SH AO Oct2016 Page 36

36 Bicuspids Horizontals LVOT calcifications Septal bulge No need for BAV or Rapid pacing Subclavian and Trans Aortic LOTUS Probably Today the Best Valve in the World Lotus in failed surgical aortic valves Compassionate use and off label in the Mitral position: MAC; failed rings and surgical mitral valves SH AO Oct2016 Page 37

37 Bicuspid Anatomy Verification & Lotus Valve Sizing Bicuspid aortic valve anatomy Preliminary identification was site-reported Validation performed by echocardiography core laboratory * and via systematic review of CT angiograms at Erasmus Medical Centre Type 0 0 raphe Type 1 1 raphe L-R R-N N-L Type 2 2 raphes L-R / R-N Valve sizing was determined using valve matrix Final decision was at the discretion of the operator * Echo Core Laboratory: Cardialysis Core Laboratory, Rotterdam, the Netherlands; Core Lab Chief: Osama I.I. Soliman, MD, PhD, FACC, FESC Valve classification schematic modified from: Sievers HH, Schnidtke C. J Thorac Cardiovasc Surg 2007;133: SH AO Oct2016 Page 38

38 RESPOND Bicuspid Analysis: Patient Disposition Intent-To-Treat Analysis N=1014 No Lotus valve implanted n=18 As-Treated Analysis n=996 Non-bicuspid Aortic Valve n=965 (96.9%) Bicuspid Aortic Valve n=31 (3.1%) Bicuspid valve type Type % Type % Type 2 3.7% Presented by Blackman, PCR SH AO Oct2016 Page 39

39 RESPOND Bicuspid Analysis: Principal Safety Results As-treated population (N=996) 30-Day Outcomes Bicuspid N=31 Non-bicuspid N=965 Correct positioning of a single prosthetic valve in the proper anatomical location 100.0% 99.8% Repositioning success (if attempted) 90.0% (9/10) 96.0% (287/299) P-value All-cause mortality and disabling stroke 6.5% 4.0% All-cause mortality 3.2% 2.2% Cardiovascular mortality 3.2% 2.0% All stroke 3.2% 3.0% Disabling stroke 3.2% 2.2% Major vascular complications 6.5% 2.8% Life-threatening or disabling bleeding 6.5% 2.1% Myocardial infarction (>72h post-procedure) 0.0% 0.6% Acute kidney injury (Stage 2 or 3) 3.2% 2.5% Newly implanted permanent pacemaker 19.4% 30.4% P-value obtained by Fisher Exact test or Chi Square test, as appropriate. Presented by Blackman, PCR SH AO Oct2016 Page 40

40 Percentage of Evaluable Echocardiograms RESPOND Bicuspid Analysis: PVL at Discharge As-treated population (N=996) Core lab adjudicated data Bicuspid P=NS Non-bicuspid Severe Moderate Mild Trace None N=29 N=905 Presented by Blackman, PCR SH AO Oct2016 Page 41

41 LOTUS In Bicuspids None or trace PVL s!

42 Lotus in Horizontals > 60 degrees None or trace of PVL! SH AO Oct2016 Page 43

43 LOTUS when Calcium into the LVOT Annular rupture never seen! In ~ 7000 implants worldwide. None or trace of PVL!

44 Lotus if Septal Bulge No embolization's!

45 RESPOND Balloon Valvuloplasty Analysis (N=500) Evaluation of 30-d outcomes with or without BAV; BAV at discretion of the operator No significant difference between groups in device success/performance Variable Absence of procedural mortality Correct positioning of a single valve in proper location Repositioning success, if attempted Valve retrieval success, if attempted Mean aortic gradient <20mmHg BAV (N=283) No BAV (N=201) P value 0.4% (1/283) 0% (0/201) 1.00 * 99.6% (278/279) 99.5% (196/197) 1.00 * 100.0% (61/61) 97.1% (68/70) 0.50 * 90.9% (10/11) 100.0% (8/8) 1.00 * 96.1% (249/259) 97.9% (186/190) 0.29 Peak velocity <3 m/s 95.8% (248/259) 97.9% (186/190) 0.21 No moderate/severe PVL 99.2% (260/262) 100.0% (192/192) 0.51 * Values are percent (n/n) or mean ± standard deviation (n). Site-reported data. *P value from 2-sided Fisher s test; otherwise from Chi-square test for categorical values and t test for continuous variables. Presented by Van Mieghem ACC Information not intended for use in France. Lotus is an investigational device and not for sale or distribution in the US. CE mark received Information for the Lotus Valve System is for use in countries with applicable product registrations. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. SH AO Oct2016 Page 46

46 Percent of Evaluable Echocardiograms RESPOND Balloon Valvuloplasty Analysis (N=500) Evaluation of 30-d outcomes with or without BAV; BAV at discretion of the operator Significantly more PVL in the BAV group at hospital discharge P= ,5 79,8 BAV (N=262) Core lab adjudicated data. Presented by Van Mieghem ACC ,3 88,0 No BAV (N=192) Severe Moderate Mild Trace None SH AO Oct2016 Page 47

47 Lotus Subclavian Access Study Mean gradient, mmhg Patients, % 29 Patients with severe aortic stenosis, increased operative risk, and considered unsuitable for TF access 79 ± 7.5 years, 82.8% male Baseline STS score: 7.7 ± 8.7 Clinical Outcomes % (n/29) All-cause mortality 0% Cardiovascular Mortality 0% All Stroke 3.4% (1) Disabling Stroke 0% LT/Disabling bleeding 0% Major Vascular Complications 3.4% (1) AKIN (Stage 2/3) 3.4% (1) New PPM 17.2% (5) Bailout valve-in-valve 0% 100% successful valve deployment P< ± ± ± 5.2 Baseline 21% 79% Post procedure PVL 52% 27mm P< ± 0.6 Post procedure Mild None 14% 23mm 2 1,6 1,2 0,8 0,4 0 34% 25mm 100% none/mild PVL post-procedure EOA, cm 2 Severe Mod Presented by Petronio, PCR SH AO Oct2016 Page 48

48 Lotus Subclavian Access Study Mean gradient, mmhg Patients, % 29 Patients with severe aortic stenosis, increased operative risk, and considered unsuitable for TF access 79 ± 7.5 years, 82.8% male Baseline STS score: 7.7 ± 8.7 Clinical Outcomes % (n/29) All-cause mortality 0% Cardiovascular Mortality 0% All Stroke 3.4% (1) Disabling Stroke 0% LT/Disabling bleeding 0% Major Vascular Complications 3.4% (1) AKIN (Stage 2/3) 3.4% (1) New PPM 17.2% (5) Bailout valve-in-valve 0% 100% successful valve deployment P< ± ± ± 5.2 Baseline 21% 79% Post procedure PVL 52% 27mm P< ± 0.6 Post procedure Mild None 14% 23mm 2 1,6 1,2 0,8 0,4 0 34% 25mm 100% none/mild PVL post-procedure EOA, cm 2 Severe Mod Presented by Petronio, PCR SH AO Oct2016 Page 49

49 Lotus - Trans Aortic Access Direct Aortic / Trans Aortic

50 Lotus in Failed Surgical Aortic Valves 21 Mitroflow ID 17.3 mm, 25 Mitroflow; ID 21 mm; CT ID 24.5 mm Distance to LCA and RCA 6 and 8 mm 23 Lotus 25 Lotus In Hancock II, 23mm; ID 20.5mm 23 Lotus

51 Lotus Valve in Mitral Position Remarkable Safety Compassionate use and off label In MAC In failed surgical rings In failed surgical valves

52 Where current Lotus is not recommended Tortuosity, fatal dissection Tortuosity, could not get marker in outer curvature reaching the arch. SH AO Oct2016 Page 53

53 Summary The Lotus System is truly fully repositionable and retrievable. You should expect a surgical result Ease of use and safety: No Rapid pacing No BAV - pre or post implant Local anesthesia No TEE Early function offers hemodynamic stability You control the procedure, not the procedure that controls you Unique safety profile: Lotus in failed surgical Valves /rings Superior in horizontals Superior in bicuspids Superior in LVOT calcifications Superior if septal bulge Todays high PPM and delivery-system sizes are anticipated solved with the LOTUS Edge, available Q SH AO Oct2016 Page 54

54 What Next Predictions are difficult. Especially about the future. Shorter frame height 15/16 mm Further system reduction 3-4 F Build in cerebral protection Dedicated Mitral/Tricuspid replacement valves and repair devices SH AO Oct2016 Page 55

55 Logic will take you from A to B. Imagination will take you everywhere. Thank you! SH AO Oct2016 Page 56