1. CoreValve ® System Procedural Best Practices for: May 2013 CoreValve ® to Stented Bioprostheses Valve-in-Valve These best practices were created with detailed input, review and approval from practicing physicians. The information in this document is intended for educational purposes and is not meant as a substitute for the protocol, Instructions for Use or product training. Practice may vary based on clinical judgment. UC201304471a EE Innovating for life.

2. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. CoreValve ® Valve-in-Valve The following presentation outlines best practices and procedural considerations for the implantation for the CoreValve ® System in failed stented aortic bioprostheses.

3. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. CoreValve to Stented SAV Content: Nomenclature & Indications Pre-procedure Procedure Post-procedure

4. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. CoreValve Valve-in-Valve Stented Bioprostheses Nomenclature: Transcatheter Aortic Valve (TAV) Surgical Aortic Valve (SAV) Stented SAV (valve composed of xenograft material suspended on a man made stent or frame) Stentless SAV (valve composed of xenograft material without a stent or frame, includes homografts) Generally, references in this document to “annulus” or “annular contact” apply to the inner diameter of the surgical aortic bioprosthesis for TAV in SAV procedures. Stented SAV Stentless SAV

5. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. Valve-in-Valve Indications The Indications for the Medtronic CoreValve System have been updated: The Medtronic CoreValve system is indicated for patients with symptomatic native aortic valve stenosis or stenosed, insufficient, or combined surgical bioprosthetic valve failure necessitating valve replacement and presenting with femoral or subclavian/axillary access vessels with diameters ≥6 mm, or ascending aortic (direct aortic) access site ≥60 mm from the basal plane, and anatomical dimensions as described in the instructions for use. 1 Bold italics added for emphasis

6. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. Individualization of Treatment Failed SAV Additional instructions specific for TAV in SAV procedure: 1 Implanting a CoreValve or CoreValve Evolut™ percutaneous aortic valve in a degenerated surgical aortic bioprosthesis (valve in valve) should generally be avoided in patients with any of the following conditions: –The degenerated surgical bioprosthesis presents with a significant concomitant perivalvular leak (between prosthesis and native annulus), is not securely fixed in the native annulus, or is not structurally intact (e.g., wireform frame fracture). –The degenerated surgical bioprosthesis presents with a partially detached leaflet that in the aortic position may obstruct a coronary ostium.

7. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. CoreValve to Stentless SAV Nomenclature & Indications Pre-procedure Procedure Post-procedure

8. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. Pre-procedure Pre-procedure Steps for CoreValve Sizing and Orientation Considerations: 1.Identify SAV. 2.Determine annulus (inside) diameter of SAV. –Use the CoreValve Valve-in-Valve Sizing Guide. –Use CT and other imaging to measure annulus diameter. 3. Use CoreValve Annulus Size Ranges chart to select CoreValve size. 4. Image to consider orientation of SAV to coronary ostia.

9. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. Identify the Failed SAV Obtain the operative report from the patient’s SAV surgery (including implant technique) and other relevant details regarding the patient’s medical history. Secure manufacturer, model and size information for the patient’s SAV –Information may be in: The operative notes and/or Valve identification card supplied to patient by manufacturer Failed stented SAVs may also be identified by radiopaque structures unique to a given device (see sections on Radiographic/Fluoroscopic Identification). Lack of radiopaque structures likely indicate a stentless SAV

10. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. Identification of Failed SAVs Radiographic/Fluoroscopic Identification of SAVs Refer to the CoreValve Valve-in-Valve Sizing Guide

11. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. Determine Annulus Diameter of SAV Best Practice: Determine the annulus (internal diameter) of the SAV: Cross reference valve model and size to the CoreValve Valve-in- Valve Sizing Guide Image the failed SAV to measure its annulus diameter Compare internal diameter specification to measured diameter to confirm the annulus diameter Considerations: For pre-procedural screening: It is possible that the recorded size or even model of the failed prosthesis is incorrect so this should be verified. Pannus, etc., may have restricted the inflow orifice of the failed valve.

12. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. Determine Annulus Diameter of SAV Best Practice Imaging techniques consistent with native valve transcatheter replacement implant methodology should be used. Computed tomography (CT) is required. Instead of measuring the native annulus measure the: Inside diameter of SAV inflow (at the annulus) Distance between coronary ostia take off and the SAV valve annulus Echocardiographic measurement of the aortic root. CT of the aortic root and bioprosthesis.

13. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. Determine Annulus Diameter of SAV Consideration: When using the bioprosthesis manufacturer’s stated inside diameter it is important to know that “inside diameter” is only the space within the valve’s stent or frame.* Thus, “inside diameter” does not consider the space taken by the bioprosthetic tissue. See figure below. = valve inside diameter *Exceptions are the Sorin Mitroflow and St. Jude Medical Trifecta valves as these have the bioprosthetic tissue mounted outside of the frame.

14. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. Determine Annulus Diameter of SAV. Surgical Stented SAV Specifications Refer to the CoreValve Valve-in-Valve Sizing Guide

15. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. CoreValve Sizing: Best Practice Refer to Annulus Size Ranges for the CoreValve device (below) and: –If the measured internal diameter dimension of the SAV is smaller than the manufacturer’s stated internal diameter then use the measured size to determine the CoreValve device size. –If measurements are “in between” choose the smaller CoreValve device. CoreValve Size Aortic Annulus Diameter Ascending Aorta Diameter Perimeter Ranges Evolut 23 18 mm – 20 mm≤ 34 mm56.5 mm - 62.8 mm 2620 mm – 23 mm≤ 40 mm62.8 mm - 72.3mm 2923 mm – 27 mm≤ 43 mm72.3 mm - 84.8 mm 3126 mm – 29 mm≤ 43 mm81.6 mm – 91.1 Annulus Size Ranges for CoreValve & CoreValve Evolut

16. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. Pre-procedure Planning for Stented SAVs Considerations: Compare and contrast imaging measurements to: –Identify coronary ostia in relation to the failed prosthesis, especially stent posts. –Measure distance from basal plane to right and left coronary ostia takeoffs. It is common and recommended surgical practice to implant surgical valve commissure posts in alignment with the native aortic commissures. In consideration of the failed prosthesis stent posts observe that some models have 120°apposition (Fig. 1) while some may not (Fig. 2). Fig. 1 Examples include Carpentier- Edwards Perimount Valves. Stent posts are 120° apart. Sinus sizes are equal. Fig. 2 Examples include Hancock ® M.O., Hancock ® II and Mosaic ® valves. Stent posts are, clockwise from the largest sinus: 120°, 135° and 105°

17. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. CoreValve to Stentless SAV Nomenclature & Indications Pre-procedure Procedure Post-procedure

18. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. Procedural Considerations Sedation: Normal institutional TAV sedation protocols should be followed. –If patient is under general anesthetic then TEE should be utilized. –If conscious sedation is used then TTE should be on stand-by. Imaging: Simultaneous TEE, Angiography and Fluoroscopy is recommended. Access Routes: Most appropriate access route selected by clinician based on patient anatomical characteristics.

19. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. Procedural Considerations (cont.) Predilatation of Implant Site In most cases predilatation is not necessary. Balloon predilatation of a stenotic surgical aortic bioprostheses has not been evaluated. In cases where there is severe stenosis, pre-dilatation of the surgical aortic bioprosthesis may be done and the steps used are identical to native valve predilatation. 1 Insert the valvuloplasty balloon through the 18-Fr introducer sheath and advance it to the ascending aorta. 1 Reposition the angiographic equipment to the ideal viewing plane. Position the valvuloplasty balloon across the native or surgical valve, while maintaining strict fluoroscopic surveillance of the distal tip of the guidewire in the LV. 1 Perform balloon valvuloplasty per hospital protocol and remove the valvuloplasty balloon while maintaining guidewire position across the native or surgical aortic valve. 1

20. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. Deployment Considerations: Stented SAVs versus native valves: Present a stiffer non-expandable landing zone. Have less ellipticity than native anatomy. Have less consistent friction on the CoreValve System components compared to native calcification — anticipate movement toward the ventricle.

21. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. Deployment Best Practice: Advance the device through the native or surgical valve. Perform an angiogram to confirm that the pigtail catheter is in position within the noncoronary cusp of the aortic root. Fluoroscopically identify the appropriate landmarks. 1 To maintain maximum stability and mitigate forward movement of the CoreValve the guidewire should be shaped and well positioned in the apex of the left ventricle. Align the CoreValve coaxially. Control pace during deployment to reduce cardiac output and provide stabilization of the CoreValve during deployment.

22. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. Deployment Best Practice: Deployment Depth Within the aortic annulus (approximately 4 mm to 6 mm below the annulus) The annulus is defined as the angiographic floor of the aortic root in native anatomy, certain stented bioprosthetic valves without radiopaque markers at the inflow, and stentless bioprosthetic valves. In certain stented bioprosthetic valves, the radiopaque marker of the stent or sewing ring at the inflow of the valve can be used as the annulus for optimal placement. 1

23. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. Deployment Considerations: With an SAV there is less consistent retrograde friction on the CoreValve System components compared to native calcification. Anticipate movement of the CoreValve bioprosthesis toward the ventricle during deployment and adjust starting depth &/or reposition before annular engagement accordingly. Target a 4 mm implant depth. Avoid oversizing the CoreValve bioprosthesis Avoid placing bioprosthesis too deeply in the annulus. Conversely, once the CoreValve begins to deploy and contacts the SAV, antegrade friction is higher than with native valves making pull back difficult.

24. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. Consideration: If the CoreValve is positioned too deeply into the left ventricular outflow tract do not attempt to reposition. Refer to Complications Management materials for the CoreValve bioprosthesis for considerations to mitigate this issue. Deployment

25. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. CoreValve to Stentless SAV Nomenclature & Indications Pre-procedure Procedure Post-procedure

26. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. Post-Deployment Best Practice: Confirm gradient across the valve with invasive measurement.

27. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. References 1. CoreValve System Instructions for Use

28. Academia Medical Education INTERNATIONAL. CAUTION: For distribution only in markets where CoreValve® is approved. Not for distribution in U.S. or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français. The information in this document is intended for educational purposes and is not meant as a substitute for Instructions for Use or product training. Practice may vary based on clinical judgment. CoreValve is a registered trademark of Medtronic CV Luxembourg S.a.r.l. All other marks are registered by their respective owners. For more information and a complete list of adverse events, warning and contraindications reference CoreValve IFU.