Review of Available Medtronic Core Valve Transcatheter Aortic

Review of Available Medtronic Core. Valve Transcatheter Aortic Valve Implantation Clinical Results Learning Curve and Clinical Outcomes CRT Washington February 21, 2010 Time: 15: 40 -15: 50 On behalf of Patrick W. Serruys – Nicolo Piazza, MD, FRCPC CRT 2010 Erasmus MC, Thoraxcenter

DISCLOSURES Nicolo Piazza, MD Medtronic consultant.

Core. Valve Clinical Data Source First-in-Man COR 2004 -01 (India/Venezuela) 1 st G 25 F CRS bovine pericardium n=4 (Inoperable) Feasibility COR 2005 -01 (7 sites in Europe and Canada) 2 nd G 21 F porcine pericardium n=52 (Inoperable + high risk) 21 F Safety and Feasibility Study COR 2004 -02 (Germany) COR 2004 -03 (Canada) 1 st G 25 F bovine and 2 nd G 21 F porcine pericardium n=20 (Inoperable) COR 2006 -02 (9 sites in Europe and Canada) 3 rd G 18 F porcine pericardium n=126 18 F Safety and Feasibility Study

Core. Valve Clinical Data Source Post-marketing surveillance Published Observational Series Expanded Evaluation Registry (151 sites) Grube et al. JACC 2007; 50: 69 -76 (n=86) - Clinical outcomes 3 rd G 18 F porcine pericardium Grube et al. Circ Cardiovasc Intervent 2008; 1: 167 -175 (n=136) - Clinical outcomes n=1500 Piazza et al. Euro. Intervention 2008; 4: 242 -249 (n=646) Subclavian Expanded Evaluation Registry 3 rd G 18 F porcine pericardium n= 79 Laborde JC. Euro. PCR 2009, Barcelona. Piazza et al. JACC Interv 2008; 1: 310 -316 (n=40) - Conduction abnormalities Jilaihawi et al. Am Heart J 2009; 157: 160169 (n=34) - Conduction abnormalities Calvi et al. PACE 2009; 32: S 126 -S 130 (n=30) - Conduction abnormalities Ussia et al. EHJ 2009; 30: 1790 -1796 (n=30) - Quality of Life Piazza et al. Eurointervention 2009 (in press) (n=1122) - Matching

Objectives • Review results of • 18 F safety and feasibility study • 18 F Expanded Evaluation Registry (EER) • Published observational studies • Grube et al. Clinical outcomes study • Ussia et al. Quality of life outcomes • Piazza et al. Matching study

The Past and Present The Future Core. Valve Device Scalloped inflow Reduce turbulence 1 st G 25 F delivery catheter Self-expanding nitinol frame + treated Anti. Ca Porcine pericardium tissue 2 nd G 21 F delivery catheter Bovine pericardium 23 -, 26 mm 26 -, and 29 -29 mm and 31 -mm device (annuli 20 -27 mm) FIM studies 2004 (n~20) 21 F safety and feasibility study (n~52) Skirt and leaflets cut into 3 independent sections 3 rd G 18 F delivery catheter Partially Fully retrievable andand repositionable CE Mark - March 2007

Baseline Characteristics High risk patients with severe aortic stenosis

Procedural and 30 -day Outcomes Need for standardization of endpoint definitions (VARC)

Quality of Life SF 12 Questionnaire 5 -month follow-up (n=30) PF=physical functioning; RP=role physical; BP=bodily pain; GH=general health; VT=vitality; SF=social functioning; RE=role emotional; MH=mental health Following Core. Valve implantation, there was a marked improvement in all 8 domains of the SF 12 QOL questionnaire Ussia et al. EHJ 2009; 30: 1790 -1796

1 -year Survival Outcomes 18 F Safety and Efficacy 18 F (n=126) - 70. 9 % Grube et al. Circ Cardiovasc Intervent 2008 25 F (n=10) - 60% 21 F (n=24) - 80% 18 F (n=102) - 84% The improved 1 -year mortality outcomes across generations is likely related to improvements in the device, patient selection, and technical learning curve

Is TAVI associated with less morbidity and mortality in high risk patients compared to conventional valve surgery? Between Jan 2006 and Dec 2008 we prospectively enrolled 1633 consecutive patients who underwent TAVI and SAVR at 2 institutions (Rotterdam -Bern) 508 patients EXCLUDED (primary diagnosis of aortic regurgitation, multiple valve surgery, or concomitant aortic root surgery) 1122 patients INCLUDED TAVI group - 114 patients (Core. Valve) SAVR group - 1008 patients ( CABG) Piazza et al. Euro. Interventions 2009; 5: 580 -8

Baseline Characteristics 55% Class I/II 86% Class III/IV Piazza et al. Euro. Interventions 2009; 5: 580 -8

Baseline Characteristics Piazza et al. Euro. Interventions 2009; 5: 580 -8

Distribution of Age Patients undergoing TAVI were significantly older

Distribution of Logistic Euro. SCORE Virtually all patients undergoing TAVI had high logistic Euro. SCORES A small proportion of patients undergoing SAVR had high logistic Euro. SCORES

Distribution of Propensity Scores Overlapping region of propensity Selective and minimal overlap in the score distributions indicates SAVR ranges propensity score - extremely higher of propensity scores patients from the TAVI and SAVR Two important right skewed questions: group with similar baseline 1. How much overlap? characteristics who are-elligible for TAVI propensity score uniformly comparison distributed 2. Who are the overlapping patients?

30 -day Mortality and its associated Predictors Age Logistic Euro. SCORE NYHA Class 1. 46 (1. 01 -2. 11) p=0. 043 1. 65 (1. 20 -2. 25) 1. 61 (1. 35 -1. 91) p<0. 001 p=0. 02 P=0. 005 (for trend) MI within 90 days 4. 13 (1. 38 -12. 39) p=0. 011 Multivariable Univariable Analysis Diabetes Mellitus 2. 01 (0. 99 to 4. 07) P=0. 052 Creatinine 200 mol/L Atrial fibrillation 4. 13 (1. 38 -12. 39) p=0. 011 4. 75 4. 03(2. 10 (1. 87 to to 11. 26) 8. 66) p<0. 001

Various Techniques for Risk Adjustment of 30 -day Mortality Odds Ratio (95% CI) Crude Multivariable Propensity score (PS) adjusted PS adjusted, multivariable PS matched IPT* weighted IPT weighted, multivariable * IPT - Inverse probability of treatment weighted * Kurth T et al. American journal of epidemiology 2006; 163(3): 262 -270)

Conclusion Based on these results and the currently available data, there is a need for a randomized controlled trial Furthermore, if the practice does not become evidenced-based and taking into account health economic factors, TAVI will not be considered legitimate or justified in the eyes of the health authorities and therefore not reimbursed.