Multicentre clinical study evaluating a novel resheatable self-expanding transcatheter aortic valve system

Transcription

1 Multicentre clinical study evaluating a novel resheatable self-expanding transcatheter aortic valve system Preliminary Results: Acute and 1-year Outcomes Ganesh Manoharan, MBBCh, MD, FRCP Consultant Cardiologist Royal Victoria Hospital Belfast, UK On behalf of the Portico Valve CE Mark Investigators CAUTION Investigational device. Limited by Federal (US) law to investigational use Product referenced is approved for CE Mark.

2 Challenges and limitations of TAVR devices Control and placement accuracy Critical in minimizing PVL and conduction disturbances Adequate Sealing Minimize paravalvular aortic regurgitation Heart block requiring pacemaker post-implantation 2 Delivery System Profiles (OD) Reduce vascular complications

3 Portico Valve Unique Nitinol properties allows valve to be fully repositioned * and retrieved * in situ Large cell geometry to minimize PV Leak Bovine pericardium leaflets with porcine pericardium sealing cuff Nonflared annulus section of stent frame and optimal valve height Targeted placement in annulus *Until fully deployed. Transfemoral low profile delivery system Minimal protrusion of valve into LVOT 3

4 Portico Valve Overview Portico 23 mm and 25 mm valves study completed Portico 27 mm and 29 mm valves study ongoing Transfemoral delivery system compatible with 18 F introducer sheath Leaflet functionality after partial deployment, allowing controlled deployment without rapid pacing Intuitive, ergonomic handle Portico 23 mm: mm Portico 25 mm: mm Release Lever Deployment / Resheath Wheel Functioning Leaflets During Deployment 4

5 Portico Valve TF EU 23/25 mm Study Design Objective To assess the safety and performance of the St. Jude Medical Portico heart valve and the St. Jude Medical transfemoral transcatheter delivery system in subjects with severe symptomatic aortic stenosis. Design Prospective; non-randomized; multi-center trial Max 50 subjects for each valve size Study included 23 mm and 25 mm valves Enrolled 23 mm: Dec 2011 through Nov 2013 Enrolled 25 mm: Jan 2013 with patient follow-up ongoing 18 F Transfemoral Delivery System F/U at discharge, 30 d, 3 mo., 6 mo., 12 mo. Primary Endpoint All-cause mortality at 30 days Lead Investigators Ganesh Manoharan, MBBCh, MD, FRCP Thomas Walther, MD, PhD 5

6 Subject Selection Criteria Key Inclusion Criteria Senile degenerative aortic stenosis with mean gradient > 40 mmhg, jet velocity > 4.0 m/s, or initial valve area < 1.0 cm 2 or aortic valve area index 0.6 cm 2 /m 2 High operable risk and suitable for TAVI per Subject Selection Committee 30-day predicted operative mortality/irreversible morbidity risk < 50% Suitable peripheral vessels and aorta to allow 18 F access 6

7 Secondary Endpoints Safety: Adverse Event Rates (VARC Definitions) Cardiovascular mortality Myocardial infarction (MI) Disabling stroke (Major Stroke) Efficacy: Functional improvement from baseline as compared to 30 days NYHA Functional Classification Six Minute Walk Test Effective Orifice Area (EOA) Non-disabling stroke (Minor Stroke) Acute kidney injury (AKI) Vascular access site and access-related complications Bleeding Composite of periprocedural encephalopathy, all stroke, all TIA All events adjudicated by an independent Clinical Events Committee 7

8 Study Clinical Centers Heart Team Center Total n (%) David Holzhey, MD* Axel Linke, MD Ganesh Manoharan, MD* Mark Spence, MD Thomas Walther, MD, PhD* Helge Möllmann, MD Martyn Thomas, MD* Simon Redwood, MD Jan Kovac, MD* Raj Rajendra, MD / Amerjeet Banning, MD Karl-Heinz Kuck, MD, PhD* Ulrich Schäfer MD, PhD Universität Leipzig Herzzentrum Leipzig, DE Royal Victoria Hospital Belfast, UK Kerckhoff-Klinik GmbH Bad Nauheim, DE St. Thomas Hospital London, UK Glenfield Hospital Leicester, UK Asklepios Klinik St. Georg Hamburg, DE** 37 (35.9) 25 (24.3) 14 (13.6) 9 (8.7) 9 (8.7) 9 (8.7) Total 103 * Principal Investigator ** Asklepios Klinik St. Georg only participated in 25mm study 8

9 Baseline Characteristics Characteristic All Subjects (mean values) Age, yrs 83.9 ± 4.9 Gender % Female 97.1% NYHA class II NYHA class III/IV 20.8% 79.4% STS score (mortality) 6.2 ± 3.5 Logistic EuroSCORE 16.7 ± 7.5 Aortic valve area (cm 2 ) 0.6 ± 0.2 Mean gradient (mmhg) 45.5 ± 13.0 Left ventricular ejection fraction (%) 65.8 ± minute walk (meters) 174 ± 107 9

10 Baseline Risk Factors Risk Factor Incidence (n = 103) Coronary artery disease 46.6% (48) Renal failure/insufficiency 34.0% (35) Pulmonary hypertension 24.3%) (25) PTCA with stent 18.4% (19) Carotid artery disease 15.5% (16) Risk Factor Incidence (n = 103) Cardiac arrhythmia 52.4% (54) Atrial fibrillation 29.1% (30) Left bundle branch block 4.9% (5) Other arrhythmia 16.5% (17) Myocardial infarction 9.7% (10) Transient Ischemic Attack 9.7% (10) Cerebral Vascular Accident 8.7% (9) Permanent pacemaker 6.8% (7) Peripheral vascular disease 5.8% (6) Coronary artery bypass 5.8% (6) Cerebral vascular disease 3.9% (4) Porcelain Aorta 4.9% (5) 10

11 Procedural Information Anaesthesia type Local Conscious sedation General Parameter All Subjects 55.3% 35.9% 34% Procedure Time* (mins) 40.4 ± 18.5 Implant Time** (mins) 13.3 ± 12.0 Valve in Valve 3.9% (n = 4) Valve Re-sheathed Re-sheath successful 23.8% 100% Depth of implant into LVOT (mm) 6.5 ± 5.0 * Vascular access to delivery system removal ** Insertion of delivery system to removal 11

12 Clinical Safety Results All events adjudicated by an independent clinical events committee Event Death Cardiovascular Death Disabling (Major) stroke Non-disabling (Minor) stroke 30 day Rate (%) n = % 2.9% 2.9% 1.0% 1 yr overall Rate (%) n = % 5.8% 3.9% 1.9% New pacemaker implantation 9.7% 10.7% Myocardial infarction 1.9% 1.9% Acute kidney injury Stage 3 AKI Major vascular complication Minor vascular complication 7.8% 1.9% 5.8% 3.9% 9.7% 2.9% 6.8% 3.9% Life threatening or disabling bleeding 3.9% 3.9% Coronary Obstruction 0.0% 0.0% 12

13 Average Mean Gradient (mmhg) Core Laboratory Echo Results Mean Gradient and Valve Area Mean Gradient Valve Area p = < P = < Average Ao Valve Area (cm 2 ) No. Patients Mean Gradient Valve Area Baseline 30 days 3 months 6 months 12 months

14 Paravalvular Aortic Regurgitation 100% 4.0% 1.5% 2.9% (n = 3) (n = 1) (n = 1) 8.8% (n = 3) 80% 60% 69.3% 68.5% (n = 52) (n = 37) 64.7% (n = 22) 40% 20% 0% 26.7% 29.6% (n = 20) (n = 16) 23.5% (n = 8) 30 Days 6 Months 1 Year n = 75 n = 54 n = 34 Severe Moderate Mild None/Trivial 14

15 NYHA Classification Changes Over Time 100% 7% 1% 0% 90% 13% 16% 20% 80% 70% 60% 50% 40% 73% 54% 35% 35% NYHA IV NYHA III NYHA II NYHA I 30% 20% 10% 21% 32% 49% 46% 0% Baseline 30 Days 6 Month 12 Month 15 N = 102 N = 82 N = 68 N = 46 75% of subjects improved at least one NYHA class at 30 days; only 2% worsened.

16 Conclusions TAVR with the St. Jude Medical Portico valve system produces clinically meaningful and sustained improvements in patient outcomes up to one year. The Portico 23 mm and 25 mm valves study demonstrate exceptional hemodynamic performance and improvements in NYHA class. The 18 F St. Jude Medical Portico system with resheathable technology allows for precise and reproducible valve placement. This study establishes an excellent safety profile with the 18 F Portico system depicted by low rates of pacemaker implantation, vascular complications, stroke and death. 16

17 Brief Summary: Prior to using these devices, please review the Instructions for Use for a complete listing of indications, contraindications, warnings, precautions, potential adverse events and directions for use. Devices depicted may not be available in all countries. Check with your St. Jude Medical representative for product availability in your country. Prior to use, appropriate Portico valve training must be completed by physician. Unless otherwise noted, indicates that the name is a trademark of, or licensed to, St. Jude Medical or one of its subsidiaries. ST. JUDE MEDICAL and the nine-squares symbol are trademarks and service marks of St. Jude Medical, Inc. and its related companies St. Jude Medical, Inc. All Rights Reserved. 17