1. INTERNATIONAL. CAUTION—For distribution only in markets where CoreValve has been approved. Not approved in the USA or Japan. Non destiné au marché français. ©Medtronic, Inc. 2013. All Rights Reserved. Transcatheter Aortic Valve Implantation Aortic Root Rupture UC201403230 EE

2. INTERNATIONAL. CAUTION—For distribution only in markets where CoreValve has been approved. Not approved in the USA or Japan. Non destiné au marché français. ©Medtronic, Inc. 2013. All Rights Reserved. Background | Definition The aortic root extends from the basal plane of the valve leaflets to the sinotubular junction, and includes the annular plane. Aortic rupture occurs when a portion of aorta is torn, allowing blood to exit the aortic lumen. This may lead to a lack of blood flow to other organs, and hemodynamic collapse. Any portion of the root, including the annulus, may be ruptured during TAVR procedures. Piazza et. al; Circ Cardiovasc Interv. 2008; 1: 74-81

3. INTERNATIONAL. CAUTION—For distribution only in markets where CoreValve has been approved. Not approved in the USA or Japan. Non destiné au marché français. ©Medtronic, Inc. 2013. All Rights Reserved. Background | Definition Aortic Root Rupture: Rare (0.5-1.0%) 1,2,3, but potentially catastrophic TAVR complication. Often leads to uncontrollable bleeding/tamponade, hemodynamic collapse, and may lead to death if not controlled. –Mortality for patients that experience aortic root rupture is nearly 50% 4. –Patients must often be converted to open surgery immediately after controlling bleeding and stabilizing hemodynamics. Less severe ruptures may be controlled by packing and sutures, or a second balloon dilatation 5 or valve-in-valve 6 may be performed to seal the leak. Haldenwang, Thorac Cardiovasc Surg; 2013; 61(5):425-7 Autopsy study showing a subannular transmural tear with a prosthetic Sapien valve in the aortic position (A), and left ventricular rupture (B) after TAVI. Transmural tears are marked with a white vessel loop. Calcification is noted by (1) in each image. 1 Pasic et. al, Ann Thorac Surg 2010; 90: 1463-70; 2 Lange et. al, Eur J Cardio-Thorac Surg 2011; 40: 1105-1113; 3 Eltchaninoff et. al, Eur Heart J 2011; 32: 191-197; 4 Barbanti et. al, Circ 2013; 128: 244-253; 5 Mylotte et. al, Eurointervention 2013; 8: 1103-1109; 6 Moat et. al, Eurointervention 2013; 8: 1103-1109.

4. INTERNATIONAL. CAUTION—For distribution only in markets where CoreValve has been approved. Not approved in the USA or Japan. Non destiné au marché français. ©Medtronic, Inc. 2013. All Rights Reserved. Contained and Uncontained Rupture Severity Subban et. al, JACC Cardiovasc Int 2013; 6(6): e33-34 UncontainedContained Pseudoaneurysm of LVOT, Periaortic HematomaCardiac Tamponade, Death Pasic et. al, Circ Cardiovasc Interv. 2012; 5:424-432

5. INTERNATIONAL. CAUTION—For distribution only in markets where CoreValve has been approved. Not approved in the USA or Japan. Non destiné au marché français. ©Medtronic, Inc. 2013. All Rights Reserved. Background | Valve Sizing Sizing goal: Transcatheter valve must be larger than annulus to establish a proper seal, reduce PVL, and ensure anchoring, but not large enough to cause annular injury/rupture. For balloon-expandable valves, 5-15% area based oversizing is recommended 1-3. However, oversizing is also associated with increased risk of annular rupture. –If extensive oversizing is necessary, underfilling the balloon is suggested 1. –Presence of root calcification or other anatomic modifiers may also influence sizing choice. For self-expandable valves, greater oversizing (perimeter or mean diameter) may be needed to ensure adequate radial force 1. –Multimodality imaging, including CT, is highly recommended 4, but there are not specific oversizing guidelines for self-expandable valves. 1 Willson et. al, J Cardiovasc Computed Tomography 2012; 6: 406-414 2 Blanke et. al, Circ Cardiovasc Interv 2012;5:540-548. 3 Binder et. al, JACC 2013; 62 (5):431–8 4 CoreValve Best Practices Handbook; June 2013

6. INTERNATIONAL. CAUTION—For distribution only in markets where CoreValve has been approved. Not approved in the USA or Japan. Non destiné au marché français. ©Medtronic, Inc. 2013. All Rights Reserved. Multislice Computed Tomography (MSCT) Imaging MSCT can provide a more accurate, 3D assessment of the noncircular aortic annulus than 2D forms of imaging, such as transesophageal echocardiography (TEE) for sizing. –The only method available for proper calcification assessment. MSCT is the preferred imaging modality – provides the ability to make multiple measures of the annulus, including perimeter, area, and diameter. This is important for sizing non-circular annuli. –A retrospective analysis of 157 patients treated with CoreValve revealed that using MSCT perimeter guidelines resulted in significantly reduced PVL, compared with TEE-sizing 1 Double-oblique transverse MSCT projections of LVOT showing calcification degree NoneMildModerateSevere Barbanti et. al, Circ 2013; 128: 244-253 1 Mylotte et. al, JACC 2013; 62(18)SB: B227. Poster abstract, TCT 2013.

7. INTERNATIONAL. CAUTION—For distribution only in markets where CoreValve has been approved. Not approved in the USA or Japan. Non destiné au marché français. ©Medtronic, Inc. 2013. All Rights Reserved. Clinical Experience | Type and Site of Rupture In a survey of 31 consecutive patients who received Sapien (n=27) or Sapien XT (n=4) transcatheter valves, and experienced aortic root/annular/LVOT rupture, approximately 2/3 were uncontained ruptures, and 1/3 were contained periaortic ruptures/hematomas 1. Site of rupture: –annulus (67.7%) –sinus of valsalva (16.1%) –LVOT (9.7%) –sinotubular junction (6.4%) Predictors of Rupture: Moderate/severe subannular or LVOT calcification and prosthesis oversizing (> 20%). White arrow: periaortic contrast extravasation from aortic root rupture Colli et. al, Eur J Cardiothoracic Surg 2011; 39:788 1 Barbanti et. al, Circ 2013; 128: 244-253

8. INTERNATIONAL. CAUTION—For distribution only in markets where CoreValve has been approved. Not approved in the USA or Japan. Non destiné au marché français. ©Medtronic, Inc. 2013. All Rights Reserved. Increased Number of Aortic Root Rupture Cases Since 2010, there have been only 13 published case reports specifically on annular/aortic root rupture 1-13. The number of yearly case reports has increased in 2013, and may be due to: Increased numbers of TAVR procedures performed Heightened awareness/increased publication on aortic root rupture 1 2 2 8 1 Aminian et. al, Cath and Cardiovasc Interventions 2013; 81:E72-E75; 2 Bouabdallaoui et. al, Int. J Cardiol 2013; 16963; 3 Colli et. al, Eur J Cardiothoracic Surg 2011; 39:788; 4 Dahdouh et. al, JACC Cardiovasc Int 2013; 6(4): 416-417; 5 Debonnaire et. al, Eurointervention 2013; 8:1103-1109; 6 Haldenwang et. al, Thorac and Cardiovasc Surg 2013; 61(5): 425-427; 7 Hayashida et. al, JACC Cardiovasc Int 2013; 6(1): 90-91; 8 Himbert et. al, Eur Heart J 2010; 31(24): 2995; 9 Kim et. al, Cath Cardiovasc Int 2013; epub; 10 Lee et. al, Cath Cardiovasc Int 2012; epub; 11 Negi et. al, Gen Thorac Cardiovasc Surg 2013; epub; 12 Subban et. al, JACC Cardiovasc Int 2013; 6(6): e33-34; 13 Yu et. al, J Invasive Cardiol 2013; 25(8): 409-410

9. INTERNATIONAL. CAUTION—For distribution only in markets where CoreValve has been approved. Not approved in the USA or Japan. Non destiné au marché français. ©Medtronic, Inc. 2013. All Rights Reserved. Aortic Root Rupture Case Outcomes While aortic root rupture is potentially fatal, approximately half of patients still survive the event. –After stabilization of hemodynamics and hemorrhaging, most patients are converted to open chest surgery for repair of the rupture and surgical replacement of the valve 14,15. –Transcatheter valve-in-valve is also performed to stabilize these patients 16. 1 2 1 1 3 5 1 Aminian et. al, Cath and Cardiovasc Interventions 2013; 81:E72-E75; 2 Bouabdallaoui et. al, Int. J Cardiol 2013; 16963; 3 Colli et. al, Eur J Cardiothoracic Surg 2011; 39:788; 4 Dahdouh et. al, JACC Cardiovasc Int 2013; 6(4): 416-417; 5 Debonnaire et. al, Eurointervention 2013; 8:1103-1109; 6 Haldenwang et. al, Thorac and Cardiovasc Surg 2013; 61(5): 425-427; 7 Hayashida et. al, JACC Cardiovasc Int 2013; 6(1): 90-91; 8 Himbert et. al, Eur Heart J 2010; 31(24): 2995; 9 Kim et. al, Cath Cardiovasc Int 2013; epub; 10 Lee et. al, Cath Cardiovasc Int 2012; epub; 11 Negi et. al, Gen Thorac Cardiovasc Surg 2013; epub; 12 Subban et. al, JACC Cardiovasc Int 2013; 6(6): e33-34; 13 Yu et. al, J Invasive Cardiol 2013; 25(8): 409-410; 14 Barbanti et. al, Circ 2013; 128: 244-253; 15 Pasic et. al, Ann Thorac Surg 2010; 90: 1463-70; 16 Yu et. al, J Invasive Cardiol 2013; 25(8): 409-410

10. INTERNATIONAL. CAUTION—For distribution only in markets where CoreValve has been approved. Not approved in the USA or Japan. Non destiné au marché français. ©Medtronic, Inc. 2013. All Rights Reserved. Pre- and Intra-Procedural Contributors to Rupture Pre-ProceduralIntra-Procedural Small AnnulusOver- or post-dilatation of prosthesis Calcified Annulus/LVOT/Root Enhanced oval shape of annulus in the presence of calcification

11. INTERNATIONAL. CAUTION—For distribution only in markets where CoreValve has been approved. Not approved in the USA or Japan. Non destiné au marché français. ©Medtronic, Inc. 2013. All Rights Reserved. Conclusions Rupture of the aortic root is a rare but potentially catastrophic complication of TAVR. There has been an increase in published cases recently. Predictors of rupture include moderate or severe calcification of the LVOT, root, or annulus, as well as prosthesis oversizing. –Accurate pre-procedural sizing and caution with balloon post-dilatation may help in reducing the frequency of these events. Pasic et. al, Ann Thorac Surg 2010; 90: 1463-70