The Impact of Live Case Transmission on Patient Outcomes during Transcatheter Aortic Valve Replacement: Results from the VERITAS Study Dr. Ron Waksman On behalf of the VERITAS Investigators

Disclosures FDA provided partial grant support

Ron Waksman, MD Consulting: Biotronik, Inc. Abbott Laboratories Boston Scientific Corporation Medtronic, Inc. Merck and Company, Inc. Honoraria: Abbott Laboratories,

Background Live case demonstrations presenting cutting-edge technology during interventional cardiology meetings have been performed for over 30 years and are considered a valuable educational resource. There is an ongoing discussion on whether patients who are treated during live case demonstrations are exposed to a higher risk. Currently there is no safety data on live TAVR cases and the Valve Devices under IDE are not allowed to be broadcast.

VERITAS Trial Objectives VERITAS: (Transcatheter Aortic Valve IntERvention-LIve Case TrAnsmiSsion) Objective: Assess the safety of patients treated with TAVR during a live case or video-taped transmission as compared to those treated with TAVR without live or recorded transmission. Hypothesis: The rate of major complication within the live case or video-taped transmission TAVR patients will be similar to those treated without a transmission.

VERITAS Study Safety Endpoints Safety assessed by the rates of major complication defined as the composite of: In-hospital death Stroke, post procedural Tamponade Valve embolization Coronary obstruction Renal failure requiring dialysis Need for pacemaker Infection VARC In-hospital Outcomes

VERITAS Study Procedural Safety Endpoints Procedure time Fluoroscopy time (minutes) Intubation time (if performed) Amount of contrast use (cc) Length of stay in intensive/coronary care units Length of hospital stay Development of myocardial infarction (MI) Respiratory or heart failure requiring mechanical ventilation Device migration, need for a second valve Need for open heart surgery Need for unplanned cardiopulmonary bypass Major vascular complications including Access site complication requiring open repair Distal embolization requiring surgery

VERITAS Trial Design Case-Control Study TAVR Matched Control : NOT Live transmission or taped TAVR 42 Enrolled Matched Case: Live transmission or taped TAVR 42 Enrolled Registry Case: Live transmission or taped TAVR 18 Enrolled Matching Criteria Site and operator STS Score ± 2 points Date of the TAVR procedure ± 4 weeks First attending for the TAVR procedure Access site/valve for TAVR Inclusion Criteria: Subject > 18 years of age Subject underwent TAVR procedure with: Edwards-Sapien transfemoral approach Edwards-Sapien transapical approach CoreValve transfemoral approach

Methodology Sites conducted a retrospective chart review to collect data for all Case and Control subjects as appropriate per Ethics Committee guidelines. Only de-identified information collected on these subjects. The sites matched the control subject to the case subject by the specified criteria. Site and operator First attending for the TAVR STS Score ± 2 points Access site/valve for TAVR Date of the TAVR (± 4 weeks)

Principal Investigator Case Registry Subjects VERITAS Study Sites Site Principal Investigator Matched Pairs Case Registry Subjects Guys and St Thomas' Hospital London, United Kingdom Martyn Thomas, MD 13 8 Bern University Hospital Bern, Switzerland Steffen Gloekler, MD 10 CardioVasculares Centrum Frankfurt Frankfurt, Germany Horst Sievert, MD 4 Saint Paul's Hospital Vancouver, Canada John Webb, MD 7 San Raffaele Hospital Milan, Italy Antonio Colombo, MD 6 MedStar Washington Hospital Center Washington, DC, USA Ron Waksman, MD 2 Total 42 18

Demographics & Medical History Case (n=42) Control P value Case Registry (n=18) Age 84.19 ± 6.77 82.21 ± 8.44 0.240 76.8 ± 10.7 Males 54.8% 38.1% 0.189 55.6% Caucasian Race 92.7% 88.1% 0.713 100% Diabetes 20.0% 16.7% 0.917 33.3% Hypertension 70.7% 66.7% 0.871 Hypercholesterolemia 56.1% 39.0% 0.185 61.1% Renal Insufficiency 32.5% 23.8% 0.529 22.2% COPD 19.5% 11.9% 0.515 11.1% Congestive Heart Failure 92.9% 97.6% 0.616 NYHA Class III or IV 67.6% 68.3% 0.862 72.2% Endocarditis 0% 2.4% 1.000 0.0% Current tobacco use 2.5% 14.3% Prior Balloon Aortic Valvuloplasty 9.5% 0.142 27.8% Logistic EuroScore 20.64 ± 11.88 20.57 ± 13.68 0.979 16.9 ± 11.7 STS Risk Score 6.54 ± 3.22 6.46 ± 3.20 0.911 4.9 ± 2.9

Risk Factors Case (n=42) Control P value Case Registry (n=18) Coronary Artery Disease 51.9% 40.0% 0.563 3 vessel CAD 25.9% 12.0% 0.296 20.0% Prior Revascularization 40.5% 26.2% 0.247 47.1% Prior Myocardial Infarction 11.9% 0.164 16.7% Peripheral Vascular Disease 7.3% 7.1% 1.000 22.2% Cerebrovascular Disease 2.4% 0.616 11.1% Stroke or TIA 21.4% 0.015 Surgical Candidate 38.1% 39.0% 0.810 70.6% Permanent Pacemaker 12.8% 15.0% 0.964 44.4% Current Arrhythmia 57.9% 45.9% 0.421 27.8% Atrial fibrillation 34.2% 35.1% LBBB 7.9% 10. 8% 0.711 5.6% RBBB 13.2% 0% 0.543 0.0% 1º AV Block 10.5% 10.8%

Baseline Echo Case (n=42) Control P value Case Registry (n=18) Mean Systolic PA Pressure (mmHg) 51.8 ± 22.3 35.0 ± 7.0 0.100 N/A Mean AV Gradient (mmHg) 42.4 ± 18.5 48.5 ± 18.0 0.140 49.0 ± 18.7 Peak AV Gradient (mmHg) 68.5 ± 28.9 73.7 ± 22.7 0.400 86.1 ± 32.4 AV Area (cm2) 0.7 ± 0.2 1.0 ± 1.6 0.390 0.7 ± 0.2 Aorta Diameter (cm) 3.0 ± 0.6 0.790 3.2 ± 0.6 Aortic Annulus Dilated 0.0% 2.4% 1.000 11.1% Calcified 63.2% 61.0% 0.974 66.7% Bioprosthesis 10.5% 9.8% Sessile or Mobile Aortic Atheroma (>5 mm) 33.3% 25.0% 0.696 Moderate or Severe Aortic Stenosis 92.5% 90.5% 100% Moderate or Severe Mitral Stenosis 2.7% 0.481 5.6% Aortic Regurgitation +1 35.0% 34.1% 22.2% +2 30.0% 26.8% 0.966 27.8% +3 5.0% +4 4.9% Left Ventricular Ejection Fraction 56.8 ± 12.3 52.1 ± 14.3 0.110 55.8 ± 19.0

Procedure Case (n=42) Control P value Case Registry (n=18) Femoral Access 90.0% 92.9% 0.834 72.2% Ventricular Apex Access 7.5% 7.1% 27.8% Adjunctive PCI 0.0% 4.8% 0.494 5.9% Valve Type Edwards 69.0% 73.8% 0.810 61.1% Core Valve 31.0% 28.2% 38.9% Rapid pacing used 78.6% 81.0% 1.000 Need for Second Valve 9.5% 2.4% 0.360 5.6% Initial Valve Retrieved Valve Deployment Success 100% --- Final Valve Correct Positioning 91.2% 97.0% 0.614 94.4% Delivery Catheter Retrieval Success Access Site Closure Surgical, Any 32.5% 35.0% 35.3% Surgical, Transfemoral 0.829 15.4% Closure Device, Transfemoral 71.8% 84.6%

Bioprosthetic Valve Types

Post Procedure Echo Case (n=42) Control P value Case Registry (n=18) Mean Systolic PA Pressure 53.2 ± 20.4 44.7 ± 14.0 0.420 46.0 ± 6.9 Delta Mean AV Gradient -30.6 ± 19.5 -34.9 ± 16.3 0.316 -37.4 ± 19.9 AV Area 1.6 ± 0.5 1.4 ± 0.4 0.141 1.4 ± 0.2 Delta AV Area +0.7 ± 0.5 +0.9 ± 0.6 0.325 +0.6 ± 0.2 Aorta Diameter (cm) 3.0 ± 0.5 3.0 ± 0.6 0.717 3.0 ± 0.4 Moderate or Severe Aortic Stenosis 0.0% --- Moderate or Severe Mitral Stenosis 5.9% 0.239 Aortic Regurgitation +1 43.5% 52.6% 52.9% +2 28.2% 7.9% 0.067 29.4% +3 5.1% 10.5% +4 0% Left Ventricular Ejection Fraction 54.1 ± 10.5 54.9 ± 9.7 0.697 50.4 ± 12.3

Intraprocedural Complications * Defined as +3 or +4

VARC Complications Death: p=1.000; Cardiac Death: p=1.000; Tamponade: p=0.494; AKI 3: p=1.000; Post MI: p=1.000; Conversion to Open Heart: p=1.000; Unplanned CPB: p=1.000; End organ failure: p=1.000

VARC Vascular Complications and Bleeding

Additional Post Procedural Outcomes All p = NS

Key Procedural Variables Case (n=42) Control P value Case-Registry (n=18) Number of Operators 3.2 ± 1.7 2.9 ± 1.4 0.443 2.3 ± 0.46 More than 3 Operators 21.4% 22.0% 0.835 0.0% General Anesthesia Usage 76.2% 54.8% 0.066 61.1% Intubation time (minutes) 4.7 ± 4.6 14.8 ± 40.7 0.200 5.6 ± 4.7 Procedure time (minutes) 130.2 ± 50.6 100.6 ± 43.7 0.006 98.8 ± 41.0 Fluoroscopy time (minutes) 21.0 ± 13.2 20.9 ± 16.5 0.986 16.9 ± 10.9 Amount of contrast use (cc) 180.4 ± 104.2 161.2 ± 76.3 0.358 156.3 ± 82.9 Length of stay in ICU (days) 3.6 ± 4.2 2.6 ± 2.2 0.177 1.3 ± 1.8 Length of hospital stay (days) 10.5 ± 5.7 10.4 ± 6.3 0.957 10.3 ± 8.1

Limitations Retrospective data collection Sample size is small 18 case were unable to be matched to controls Due to the study design, patient satisfaction was not attainable

Summary Although the STS and EuroScore assessments were similar between the case and control patients, there is a suggestions that the live- or taped-transmission patients were slightly more complicated, but statistical significance was not reached. These results suggest that broadcasting TAVR live case demonstrations in selected patients from selected centers is safe and associated with similar complication rates, fluoro times, contrast volume and length of stay.

Conclusions These data support that TAVR procedures when done by operators who perform high volumes of cases for both live case transmissions in general and TAVR procedures such procedures are safe and similar with respect to events as non-transmitted cases. Such transmissions, however, should be performed by experienced and high volume operators. Live- or taped-transmission of TAVR procedures should be utilized for the introduction of the technology and for initial training of the procedural techniques. To ensure the adequate exposure to new techniques and devices for the TAVR procedure, Live case transmission of investigational devices should be utilized more frequently within the IDE studies to ensure transparency of new device techniques.