(/us/index.htm)
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`Corevalve US
`
`TAVR Platform
`
`For Heallhcare Professionals - United States
`
`Important Safety Information
`
`lNDlCATlONS
`
`The Medtronic CoreValve‘"‘ system is indicated for relief of aortic stenosis in patients with symptomatic heart disease due to
`severe native calcific aortic stenosis (aortic valve area $0.8 cmz, a mean aortic valve gradient of >40 mm Hg, or a peak aortic—jet
`velocity of >4.0 m/s) and with native aortic annulus diameters between 18 and 29 mm who arejudged by a heart team, including
`a cardiac surgeon, to be at extreme risk or inoperable for open surgical therapy (predicted risk of operative mortality and/or
`serious irreversible morbidity 250% at 30 days).
`
`CONTRAINDICATIONS
`
`The CoreValve"‘ system is contraindicated for patients presenting with any ofthe following conditions:
`I known hypersex1siti\*ii_\' or contrainrlieation to aspirin. heparin (HIT/HITTS) and bi\'aliru(lin, ticlopidinc, clopidogrcl, Nitinol (Titanium or
`Nickel), or S€IlSlti\'lt_\/'
`to contrast media, which can not be adequately prcrne(liczitc_d
`
`I ongoing, sepsis, including active endocarditis
`
`- preexisting mechanical heart valve. in aortic position
`
`WARNINGS
`General
`
`-
`
`lm plantation of the Medtronie Co1'eV;1lvc system should he perforlned on ly by ph_\_ns‘icians who have ri‘—2ceivcd Mcdtronie CoreVal\'e training.
`
`- This procedure Sl1()1ll(l only he performed where emcrgenc_\f aortic Valve surgciy can he performed promptly.
`
`I Mechanical failure of the <ieli\—'c1y catheter .s_vstcn'i and /or accessories may result in patient complications.
`
`Tran5catheterAorric Valve (Bioprosthesis)
`-I Accelerated deterioration oltlie bioprostliesis may occur in patients presenting with an altered calcium metabolism.
`
`Precautions
`General
`
`I The safety and effectiveness of the Medtronie Corevalve system have not been evaluated in the pediatric population.
`
`I The salizty and GffCCtl\'(él1L‘,SS of the l)iop1'osthcsis for aortic valve replacement have not been evaluatetl in the following patient populations:
`I without Aortic Stenosis (AS)
`
`- who are at high, moderate, or low rsurgical risk (predicted periopcrative in(>i‘tzility risk of <50%)
`- with untreated, clinically significant co1‘onar_\~‘ artery disease requiring, rcvascularization
`
`- with a preexisting prosthetic heart valve. in any position
`
`2- with cardiogcnic shock manifested by low ca1'diac output, vasoprcssor dependence, or mechanical liernodyiiaiiiic support
`
`- The safety and efi'eeti\‘ciiess of a Co1'e\—"al\-'e“*“ hioprosilicsis implanted within a failed preexisting transcathctcr or silrgical l)l0pl'0Sll1€SiS have
`not been dcmonslmted.
`
`I The safety and effectiveness of the bioprosthesis for aortic valve I‘cpl£lCCIT1CI)il)21Ve not been e\'aluatc.d in patient populations presenting with
`the following:
`
`- hlood (l_v.sc1‘a.s‘iz1s as defined: leukopcnia (WBC <1000 cells/mm3), lhrombocytopcnin (platelet count <50,000 cells/nung), history
`of bleeding diathesis or coag1.ilopath)', or hypereoagulablc states
`
`- congenital bicuspid or unicuspid valve verified by eel1oea1‘tliograpl1y
`I mixed aortic valve disease (aortic stenosis and aortic rcgurgitatirin with pretlominant aortic 1'egurgitatio11 [3-4+])
`
`a moderate to (3—4+) or severe (4+) mitral or (4+) tricuspid rcgiirgitation
`
`NGRRED EXHlBIT 2228
`
`Medtronic Inc., Medtronic Vascular,
`
`Inc. & Medtronic Corevalve, LLC v.
`Troy R. Norred, MD.
`Case IPR2014-001 10/001 1 1
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`

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`I hypcrtrophic obstructive cardiomyopathy
`I new or untreated echocardiographic evidence of intracardiac mass, thrombus, or Vegetation
`I native aortic annulus size <18 mm or >29 mm per the baseline diagnostic imaging
`I
`transarterial access not al)le to accommodate an 18-Fr sheath
`
`sinus of valsalva anatomy that would pre\'ent adequate coronary perfusion
`I
`I moderate to severe mitral stenosis
`
`I
`
`severe ventricular dysfunction with left ventricular ejection fraction (LVEF) <20% as measured by resting echocardiogram
`
`I end-stage renal disease requiring chronic dialysis o1' creatinine clearance <20 cc/min
`I
`symptomatic ca1'otid or vertebral artery disease
`I
`severe basal septal hypertrophy with an outflow gradient
`
`Prior to Use
`
`Exposure to glutaraldehyde may cause irritation of the skin, eyes, nose, and throat. Avoid prolonged or repeated exposure to the vapors.
`Damage ma_y result from forceful handling of the catheter. Prevent kinking of the catheter when removing it from the packaging.
`This device was designed for single patient use only. Do not reuse, rcprocess, or resterilize this product. Reuse, reprocessing, or rcsterilization
`may compromise the structural integrity of the device and /or create a risk of contamination of the device, which could result in patient injury,
`illness, or death.
`
`The biop1'osthesis size must be appropriate to fit the patient’s anatomy. Proper sizing of the device is the responsibility of the physician. Refer
`to Instructions for Use for available sizes. Failure to implant a device within the sizing matrix could lead to adverse effects such as those listed
`in Section 5.0.
`
`Patients must present with femoral or subclavian/axillary access vessel diameters of 26 mm or an ascending aortic (direct aortic) access site
`260 mm from the basal plane.
`
`Implantation of the bioprosthesis should be avoided in patients with aortic root angulation (angle between plane of aortic valve annulus and
`horizontal plane/vertebrae) of >30" for 1'igl1t suhclavian/axillary access or >70" for femoral and left subelavian/axillary access.
`Use caution when using the subclavian/axillary approach in patients with a patent LIMA graft or patent RIMA graft.
`
`During Use
`
`Adequate rinsing of the bioprosthesis with sterile saline, as described in the Instructions for Use, is mandatory before implantation. During
`rinsing, do not touch the leaflets or squeeze the bioprosthesis.
`
`If a capsule becomes damaged during loading or the capsule fails to close, replace the entire system (bioprosthesis, catheter, and CLS). Do not
`use a catheter with a damaged capsule.
`
`After a bioprosthesis has been inserted into a patient, do 11ot attempt to reload that l)ioprosthesis on the same or any other catheter.
`
`During implantation, if resistance to deployment is encountered (e.g., the micro knob starts clicking or is tight or stuck), apply upward pressure
`to the macro slider while turning the micro knob. If the bioprosthesis still does not deploy, remove it from the patient and use another system.
`
`While the catheter is in the patient, ensure the gui(lcwire is extending from the tip. Do not remove the guidewire from the catheter while the
`catheter is inserted in the patient.
`
`Once deployment is initiated, retrieval of the bioprosthesis from the patient (e.g., use of the catheter) is not recommended. Retrieval of a
`paitially deployed valve using the catheter may cause mechanical failure of the delivery catheter system, aortic root damage, coronary artery
`damage, myocardial damage, vascular complications, prosthetic valve dysfunction (including device malposition), embolization, stroke, and/or
`emergent surgery.
`
`During deployment, the bioprosthesis can be advanced or withdrawn as long as annular contact has not been made. Once annular contact is
`made, the bioprosthesis cannot be advanced in the retrograde direction; if necessary, and the frame has only been deployed $2/3 of its length,
`the bioprosthesis can be withdrawn (repositioned) in the antegrade direction. However, use caution when moving the bioprosthesis in the
`antegrade direction.
`
`Use the handle of the delivery system to reposition the bioprosthesis. Do not use the outer catheter sheath.
`
`Once deployment is complete, repositioning of the bioprosthesis (e.g., use of a sna1'e and/or forceps) is not recommended. Repositioning of a
`deployed valve may cause aortic root damage, coronar_v arteiy damage, myocardial damage, vascular complications, prosthetic valve
`dysfunction (including device malposition), embolization, stroke, and/or emergent surgery.
`
`Do not attempt to retrieve a bioprostliesis if any one of the outflow struts is protruding from the capsule. If any one of the outllow struts has
`deployed from the capsule, the bioprosthesis must he released from the catheter before the catheter can be withdrawn.
`
`Ensure tl1c capsule is closed before catheter removal. If increased resistance is encountered when removing the catheter through the introducer
`NORRED EXHIBIT 2228 - Page 2
`sheath, do not fo1'ce passage. Increased resistance may indicate a problem and forced passage may result in damage to the device and/or harm
`to the patient. Ifthc cause of resistance cannot be determined or corrected, remove the catheter and introducer sheath as a single unit over the
`guidewire, and inspect the catheter and confirm that it is complete.
`Clinical long—term durability has not been established for the bioprosthesis. Evaluate bioprosthesis performance as needed during patient
`
`

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`Postprocedure, administer appropriate antibiotic prophylaxis as needed for patients at risk for prosthetic valve infection and endocarditis.
`
`Postprocedure, administer anticoagulation and/or antiplatelet therapy per hospital protocol.
`
`Excessive contrast media may cause renal failure. Preprocedure, measure the patient's c1'eatinine level. During the procedure, monitor contrast
`media usage.
`
`Conduct the procedure under fluoroscopy.
`
`The safety and efficacy of implanting a second CoreValve”‘ bioprosthesis within the initial CoreValve”' bioprosthesis have not been
`demonstrated. However, in the event that a second CoreValve“‘ bioprosthesis must be implanted within the initial CoreValve“‘ bioprosthesis
`to improve valve function, valve size and patient anatomy must be considered before implantation of the second CoreValve”‘ bioprosthesis to
`ensure patient safety (e.g., to avoid coronary obstruction).
`
`
`
`POTENTIAL ADVERSE EVENTS
`
`Potential risks associated with the implantation of the Medtronic Corevalve transcatheter aortic valve may include, but are not
`limited to, the following:
`death
`
`ca1'diac arrest
`
`coronary occlusion, obstruction, or vessel spasm (including acute coronary closure)
`emergent surgery (e.g., coronary artery bypass, heart valve replacement, valve explant)
`
`multi-organ failure
`heart failure
`
`myocardial infarction
`
`cardiogenic shock
`
`respiratoiy iusufficiency or respiratoiy failure
`
`cardiovascular injuiy (including rupture, perforation, or dissection of vessels, ventricle, myocardium, or valvular structures that may require
`intervention)
`
`perforation of the myocardium or a vessel
`
`ascending aorta trauma
`cardiac tamponade
`
`cardiac failure or low cardiac output
`
`prosthetic valve dysfunction including, but not limited to, fracture; bending (out-of-round configuration) of the valve frame; under-expansion
`of the valve frame; calcification; pannus; leaflet wear, tear, prolapse, or retraction; poor valve coaptation; suture breaks or disruption; leaks;
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` ‘ ~ ~ * ' ‘ * ‘ ' ' ' “" "' ~.~’ i: regurgitation; stenosis mal—sizing (prosthesis-patient mismatch); ‘
`‘
`thrombosis/embolus (including valve thrombosis)
`
`valve migration/valve embolization
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`ancillary device embolization
`emergent percutaneous coronary intervention (PCI)
`
`emergent balloon valmloplasty
`
`major or minor bleeding that may or may not require transfusion or intervention (including life—threatening or disabling bleeding)
`allergic reaction to antiplatelet agents, contrast medium, or anesthesia
`
`infection (including septicemia and endocarditis)
`
`stroke, TIA, or other neurological deficits
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`permanent disability
`
`renal insufficiency or renal failure (including acute kidney injiuy)
`
`mitral valve regurgitation or injury
`tissue erosion
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`vascular access related complications (e.g., dissection, perforation, pain, bleeding, hematoma, pseudoaneurysm, irreversible neive injury,
`NORRED EXHIBIT 2228 - Page 3
`compaitment syndrome, arte1'iovenous fistula, stenosis)
`conduction system disturbances (e.g., atrioventricular node block, left-bundle branch block, asystole), which may require a permanent
`pacemaker.
`
`

`
`Please reference the Corevalve Instructions for Use for more information regarding indications, warnings, precautions and
`potential adverse events.
`
`CAUTION: Federal law (USA) restricts this device to sale by or on the order of a physician.
`
`Corevalve is a registered trademark of Medtronic CV Luxembourg S.a.r.l.
`Confida and Brecker Curve are trademarks of Medtronic, Inc.
`
`Amplatz Super Stiff is a trademark of Boston Scientific.
`Lunderquist is a registered trademark of Cook Medical.
`©2014 Medtronic, Inc.
`
`All Rights Reserved
`
`© 2014 Medtronic, Inc. (http://www.medtronic.com)
`
`Terms of Use (http://www.medtronic.com/statements/terms/index.htm)
`
`Privacy Statement (http://www.medtronic.com/statements/privacy.htm)
`
`Corevalve Connect (http://coreva|ve.force.com/)
`
`NORRED EXHIBIT 2228 - Page 4