after Isolated Rapid Deployment Aortic Valve Replacement Comparison of Procedural Outcomes and Early Safety by Surgical Approach after Isolated Rapid Deployment Aortic Valve Replacement Thorsten C.W. Wahlers, M.D., Ph.D.,1 Axel Haverich, M.D.,2 Michael A. Borger, M.D., Ph.D.3 Malakh Shrestha, M.B.B.S, Ph.D.,2 Alfred A. Kocher, M.D.,4 Thomas Walther, M.D., Ph.D.,5 Matthias Roth, M.D.,5 Martin Misfeld, M.D.,3 Friedrich W. Mohr, M.D., Ph.D.,3 Joerg Kempfert, M.D.,5 Pascal M. Dohmen, M.D., Ph.D.,6 Christoph Schmitz, M.D.,7 Parwis Rahmanian, M.D.,1 Dominik Wiedemann, M.D.,4 Francis G Duhay, M.D.,8 Günther Laufer, M.D.4   1Medical University of Cologne, Cologne, Germany, 2Medical University of Hannover, Hannover, Germany, 3Heart Center Leipzig, Leipzig, Germany, 4Medical University of Vienna, Vienna, Austria, 5Kerckhoff Klinik, Bad Nauheim, Germany, 6University of Leipzig, Leipzig, Germany, 7University of Munich, Munich, Germany, 8Edwards Lifesciences LLC, Irvine, CA, USA

Background Aortic valve replacement through a minimal access approach is associated with favorable clinical outcomes1-3 However, several meta-analyses have reported significantly longer cross-clamp times compared to a full sternotomy1, 4 References 1. Brown et al., J Thorac Cardiovasc Surg. 2009;137:670-679 e5. 2. Machler et al. Ann Thorac Surg. 1999;67:1001-5. 3. Albacker et al. J Thorac Cardiovasc Surg. 2014;147:355-361.e5. 4. Phan K, et al., Ann Thorac Surg. 2014;98:1499-511.

Purpose In patients enrolled in the TRITON trial, we examined procedural and early (<30 days) safety outcomes after isolated rapid deployment aortic valve replacement through Full Sternotomy Upper Hemisternotomy Right Anterior Thoracotomy

Methods Prospective, multicenter single arm study (Hannover, Cologne, Leipzig, Vienna, Bad Nauheim, Munich) 287 patients with symptomatic, severe aortic stenosis underwent RDAVR using the EDWARDS INTUITY Valve System Inclusion criteria: age ≥ 18 yrs; AS ± AR; elective AVR ± concomitant procedure(s); informed consent; agree to f/u for 5 yrs Exclusion criteria: Pure AR; concomitant valve disease, or aneurysm of aortic root or ascending aorta requiring surgery; life-expectancy < 12 mos Patients were operated between January 2010 & October 2012 For the purposes of this study, patients were evaluated for: Perioperatively, for procedural times and technical success rates At discharge, for hospital length of stay At 30 days, for early adverse events

EDWARDS INTUITY Overview A rapid deployment technique that incorporates a subannular, balloon-expandable stent frame that mechanically widens the LVOT to ensure a larger EOA compared to conventional surgical valves

Triton Study Overview Technical Success 96.1% 98.6% 97.3% Enrollment Gen I Valve n=149 Gen II Valve n=138 Combined n=287 Technical Success (Deployment of the study valve within two attempts) 96.1% (149/155) 98.6% (138/140) 97.3% (287/295)

Surgical Approach Overview Number of Cases by Surgical Approach Enrollment n=295 158 (55%) Isolated AVR 71 (45%) Full Sternotomy 87 (55%) Minimal Access Incision 77 (89%) Upper Hemisternotomy 10 (11%) Right Anterior Thoracotomy

Results: Baseline Characteristics Enrollment n=295 Technical Success FS - 97.2% (71/73) UHS - 97.4% (77/79) RAT -100% (10/10) Isolated RDAVR n=158 Delivery and deployment of the study valve within two attempts Parameter Full Sternotomy (n=71) Upper Hemisternotomy (n=77) Right Anterior Thoracatomy (n=10) Age,yrs 75.7 ± 6.8 75.6 ± 6.6 75.3 ± 13.5 FEMALE 49.3 % (35/71) 50.6 % (39/77) 60.0 % (6/10) Logistic EuroSCORE, % 8.0 ± 6.4 7.9 ± 4.9 12.0 ± 14.8 Body Mass Index, kg/m2 28.7 ± 4.2 27.8 ± 4.4 25.7 ± 3.4 Body Surface Area, m2 2.0 ± 0.2 1.9 ± 0.2 LVEF, % 63 ± 11 58 ± 13 59 ± 8 TRITON Database as of 17-June-2014

Results: Distribution of Valve Sizes mean 23.3 mm mean 23.6 mm TRITON Database as of 17-June-2014

Results: Early Safety Outcomes Parameter Full Sternotomy Upper Hemisternotomy Right Anterior Thoracatomy All Cause Mortality 1.4% (1/71) 1.3% (1/77) 0.0% (0/10) Study Valve Related Mortality Reoperation for Bleeding 7.0% (5/71) 7.8% (6/77) Renal Failure/Dysfunction 2.8% (2/71) 9.1% (7/77) Thromboembolic Event Deep Sternal Wound Infection Respiratory Dysfunction 3.9% (3/77) Major Bleeding Events 11.3% (8/71) 6.5% (5/77) Study Valve Related Explant PVL Requiring Surgical Intervention 0.0% (0/71) Pacemaker Implants,Total 5.6% (4/71) 5.2% (4/77) Valve Related Pacemaker Implants 4.2% (3/71) 2.6% (2/77) TRITON Database as of 17-June-2014

Results: Procedural Times Parameter FS (n=71) UHS (n=77) RAT (n=10) p-value FS vs. UHS p-value FS vs. RAT Cardiopulmonary by-pass time (min) 71.6±41.8 69.6±19.1 122.2±22.1 0.2639 <.0001 Cross-clamp time (min) 43.5±32.5 43.1±13.1 88.3±18.6 0.1306 FS, full sternotomy; UHS, upper hemisternotomy; RAT, right anterior thoracatomy TRITON Database as of 17-June-2014

Results: Procedural Times II Comparison of Cross-clamp times to the Literature EDWARDS INTUITY Upper Hemisternotomy REFERENCE CROSS-CLAMP TIME (MIN) TRITON 43 Borger1 41 Schlomicher2 26 Overall 26 – 43 min Surgical Valves Upper Hemisternotomy REFERENCE CROSS-CLAMP TIME (MIN) Tabata1 72 Bakir2 62 Brinkmann3 75 Overall 62 – 75 min Borger et al. Ann Thorac Surg. 2015;99:17-25. Schlomicher et al. J Thorac Cardiovasc Surg. 2015 Feb;149(2):434-40. Tabata et al. Asian cardiovascular & thoracic annals. 2007;15:225-8. Bakir et al. Ann Thorac Surg. 2006 May;81(5):1599-604. Brinkman et al. Ann Thorac Surg. 2010;90:131-5. TRITON Database as of 17-June-2014

Results: Discharge Outcomes Parameter FS (n=69) mean ± sd (min, max) median UHS (n=76) RAT (n=10) P-value FS vs. UHS FS vs. RAT Hospital LOS (days) 11.7±6.3 (6.0, 50.0)10.0 13.1±10.6 (5.0, 89.0)10.0 9.5±6.7 (5.0, 28.0)7.0 0.8189 0.0116 ICU LOS (hours) 61.7±115.4 (0.0, 664.0)24.0 59.1±102.9 (0.0, 625.0)23.0 33.6±12.4 (24.0, 48.0)24.0 0.0936 0.5658 Intermediate Care LOS (hours) 22.3±45.1 (0.0, 192.0)0.0 43.7±92.8 (0.0, 504.0)0.0 19.2±42.0 (0.0, 120.0)0.0 0.1258 0.5940 In-hospital mortality 2.8% (2/71) 1.3% (1/77) 0.0% (0/10) 0.6076* 0.9999* P-values based on Wilcoxon * indicates use of Fisher's Exact test to calculate the P-values LOS, length of stay; FS, full sternotomy; UHS, upper hemisternotomy; RAT, right anterior thoracatomy TRITON Database as of 17-June-2014

Reoperation 19 mm Valve degenerated 21 mm Intuity Valve, 44 Min Reoperation 19 mm Valve degenerated 21 mm Intuity Valve, 44 Min. Clamptime

Conclusions Isolated RDAVR through an upper hemisternotomy can lead to shorter cross-clamp times than than have been historically reported in the surgical literature This benefit may facilitate minimally invasive AVR by lessening the concern over prolonged cross-clamp times Regardless of surgical approach, isolated RDAVR with EDWARDS INTUITY may lead to… Low in-hospital mortality rate Low early (<30 days) mortality rate Low new permanent pacemaker implant rate

Limitations TRITON represents initial experience using EDWARDS INTUITY Valve System; hence, incorporates learning curve Lack of active comparator group

Thank you for the attention. thorsten.wahlers@uk-koeln.de