Edwards Lifesciences Corporation, et al. Exhibit 1141, Page 1 of 8
`
`

`

`
`
`()lliuial Journal of lho Anmricem Society for Arliiitini lnlornal Organs
`
`
`I O URNAL
`
`E D I TC.) R
`
`Eii A. Friedman
`
`Brooklyn, NY
`
`DEPUTY EDlTOR
`
`Monica M. Beyer
`Brooklyn, NY
`
`EDl‘l‘ORlAL ASSISTANT
`
`Barbara Erler
`
`Brooklyn, NY
`
`W
`
`SECTION EDITORS
`
`Gas Exchange
`Ruben H. Bartlett
`Ann Arbor, MI
`
`New Technology
`T. M. 5, Chang
`Montreal, Canada
`
`Biomalerials
`Robert ('3. Guicloin
`(Quebec, Canada
`
`Medical Instrumentation
`Paul S. Malchosky
`Mentor, OH
`
`Dialysis and Kinetics
`john K. Leypcfldi
`.JT
`Salt Lake City, l
`
`Implantable Pumps
`Henry Buchwald
`Minneapolis, MN
`
`Nephrology
`Karl l3. Nolph
`Colmnbla, MO
`
`Cardiac Assist
`Don 8, Olsen
`
`Salt Lake (filly, UT
`
`Tissue Engineering
`Jeffrey A. Hubbell
`Austin, TX
`
`Bioengineering
`Winfred M. Phillips
`Cainesville, FL
`
`Transplantation
`lamos W. Long
`Salt Lake City, UT
`
`Clinical Cardiovascular
`Robert Kormos
`
`Pillslaurgl'), PA
`
`EDITORIAL BOARD
`
`Christopher R. Blazigg
`Robert L. 130th
`Anatole Begaml‘)
`Henry Binghwaid
`George W. Bulfaloe
`Mi‘ii‘ml Dasgupm
`lohn l’. Daugirflas
`Thomas‘ A. Depnm
`
`Mrinzll K. lIIDCwanieo
`Eugene (1L. [Ectkgtein
`Hiroaki Haras‘aki
`Kevin lii. l~|ealy
`Neal H. (:3. Hwang
`Michael lesson
`Marcia L. Keen
`lames A. Magovem
`
`Lyle F, Mockros
`Syocl F. Mohammad
`Tofy Mussivand
`Steven J, Phillips
`Beth Marie l’lmino
`Elisaku Sasnki
`Richard Sherman
`
`Ronald G. 'l'ompkins
`Carol ‘loninnto
`Steven N. Vaslel
`David M. Ward
`
`Victor C. Yang
`105mm BY Zwischenborgor
`
`EDITOR EMERITUS
`
`George E. Schreiner
`
`IW
`
`Edwards Lifesciences Corporation, et al. Exhibit 1141, Page 2 of 8
`
`Edwards Lifesciences Corporation, et al. Exhibit 1141, Page 2 of 8
`
`

`

`
`
`
`
`
`
`M368 Advance in Mitral Valve Repair Using 3 Device Flexible in Three Dimensions; The. St judo Medical»
`Séguin Annuloplasty Ring
`1, R1 563nm, R. Drama/la, Rt Raglan; and l’. A. (filmplal
`
`M372 The inflexible Mitral Annulus After Valve Prosthesis: Inherent Risk of Dynamic Left Ventricular Outflow
`Tract Obstruction
`'
`
`Tokay/7i Kornoda, Roland Helzor, lollzmn Clo/linger, lvlenrylr .S‘lniawyltl, lrn‘epll l loll’nulstnr, Mlclnwl I Nib/(‘1‘,
`Roland llollx, Chi/«.10 L/yama, and I"li'lilITtt? Maeln
`M375 Complement Activation is involved in the Structural Deterioration of Bovine l’ericardial Bioprosthetic
`‘
`Heart Valves
`Mt Moczar, L. lecerl, M. (final, and II), 1.1‘)l$élln(,’0
`
`M381
`
`Translnminal Aortic Valve Placement: A Feasibility Study With a Newly Designed Collapsilflo Aortic
`Valve
`
`Nader Moazami, Marc BEES/6?", Michael Argcmziano, Asim I'-'. (form/Inf, .‘ii’lnlUS if, {mortar/m, lolm U. /. dl/“Itdllril
`[Eric A. Rose, and Molnnnl C. 01
`
`SLIDE FORUM #3WACCESS AND VASCULAR Pl{(i)Sl"l"lESlS
`
`M386 A Self~Expanding Bifurcated Endovascular Graft for Abdominal Aortic Aneurysm Repair: An Initial
`Study in a Canine Model
`Gregory 1. Wilson, Petr Klomonl, YEIS‘US/ll l’. Kato, lohn l3. Marlln, I. [aim Khan, RyderA/clrrm, lmn-l’ierm Utfil’t-‘lllllt‘.
`David (I. MacCJregor, and Loona rd l’lflC/‘ltlk
`
`M394 lmpregnafion of Basic Fibroblast Growth Factor on a Microporous Small Caliber Graft Enhances
`Vascularization
`
`Kiyoshi Doi, Sl'iinlchi Salon, Takah/‘ro CID/<11, and ‘l‘akolrlsa Mat'suda
`
`M398 Penetrating Micropores Increase Patency and Achieve Extensive Endothelialization in Small Diameter
`v
`Polymer Skin Coated Vascular Grafts
`Takalumi Okoshi, Giorgio Soldzml, Moses Goddard, and Pierre M. (Sal/old
`
`POSTER SESSION #3—«PERFUSlON AND CIRCULATORY ASSISTANCE "l'ECl-lNlCQUliS
`
`M402 Ferromagnetic Artificial Cells for Artificial Circulation
`Yoshlnori lvlitamura, Tatsulllko War/a, and [El/'1‘ Okan‘mto
`
`Pem‘issm” ‘0 Phillmrupy articles: This; publication l5 protected by copyright. Pt-vmlsslon to photocopy must bu *wtjnmtl in writing from?
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`69 Text printed on acid~free paper.
`
`Edwards Lifesciences Corporation, et al. Exhibit 1141, Page 3 of 8
`
`Edwards Lifesciences Corporation, et al. Exhibit 1141, Page 3 of 8
`
`

`

`
`
`DETElllORATION 0F lllOl’ROS'l‘HETlC HEART VALVES
`
`M381
`
`to.
`
`l7.
`
`luminak D, l’r‘nl.)hnkar(.21,About-tum HY,
`I highest 1, ‘lipton l
`tjturnn tfjtvtt’ji: ("llulat'nldtrhyllo “,1 curhoxyglutmnir: acid and
`t’alt‘ltttt] in unplanlml hioprmtluatir, hmrt Vithtffi. I l Ivan Vii/w
`Dis 3:
`l ll
`Ito, win,
`ltw Ml, lionghnm’ Hit: 'i'iasuo inmrlmniw oi tinnimrr pericardium
`
`in different total onviromnont: nvidenrgo for limo dependent
`(1cmmmodation, absence: oi pletrliclty and now rolea for only
`lagon and elastin. (Tire Rue: 4‘): 533:3»344, 1981,
`Hi. Scott M, Vusoly I: Aortic valve cusp microstructurn: the role oi
`elastin. Ann Thorac Sun: on: $39] ~S3‘1’4, tours.
`
`
`
`Transluminal Aortic Valve Placement
`
`A Feasibility Study With a Newly Designed Collapsible Aortic Valve
`
`NAUliR MOAZAMI, MARC? Bmstrn, Minn/xiii. ARGENZIANC), ASIM F. Cirourmm, $ANTO5
`tor-m [3.
`t3.
`/\l.l..t?|\ll)()ltl~’, Elthi A. ROSE, AND Mtil-rtMtE’l'
`(3. Oz
`
`Cmmrmm,
`
`percmaneous stunts are used in vascular applications in com
`junction with angioplasty and in combination with graft man
`terial for repair of abdominal anonrysmr. The authors have
`designed a collapsible bioprosthetic aortic valve for place«
`menl by a transiuminal catheter technique. This trileaflet
`stunt valve is composed of stainless steel and bovine peri~
`cardium. Stont valves, 23 and 2‘) mm, were tested in a pulse
`duplicator system with rigid rings trom 21 to 31 mm in 2
`mm increments. At a mean flow of 3.1 L/min (110.7), normal
`systemic aortic pressure was generated with a transvalvular
`gradient of 14.9 :t:. 7 mmHg (mean
`SD). Regurgitation frac»
`tion ranged from it) to 18% (mean 13.8 :t; 3%) in the best
`ring size. Valves with the best hemodynamir: profiln were
`used for implantation in three 70 kg pigs in an open chest
`model. The valve was collapsed in a ’14 Fr catheter designed
`to allow slow, controlled release. Alter resection of the ow
`live leaflets, the new valve was placed in the suhcoronary
`position. No additional sutures were used for securing the
`valve. Two animals were successfully weaned from cardity
`pulmonary bypass; and maintained systemic pregsures of
`100/45 ($10) and 116/70 (25:15) mmHg, respectively. lntra»
`Operative color echocardiography revealed minimal regun
`gitation, central flow, lull opposition of all leaflets, and no
`interference with coronary blood flow. lloth animals were
`sacrificed after being off bypasa for 2 hr. Postmortem exam—
`ination revealed the valves to be securely anchored. The
`third animal was weaned from cardiopulmonary bypass hut
`developed refractory ventricular fibrillation because of
`valve dislodgment due to structural failure. Although long
`term wrvival data are needed, development of a hemody»
`namically acceptable prosthetic aortic valve for translumi~
`nal placement is feasible. ASAIO Ioumal 1996;42:M381»-
`M385.
`
`lntrnvasmlar stunts; have grnilimlly runninecl occuplnrtce for
`
`From the [mom‘tnwnt ol Stirgury, Loin
`livntor, New York, Now York,
`Rl‘l’lint “Kit-Wits: Nnrlnr Monxmni, Ml), (Ittlumhin~l’rr-ahytorlmt
`Mmliml (Center, [’0 tiox 383, (730 W ‘1 (>23 St, New York, NY 100 32,
`
`mbimProsthytoriun Medical
`
`portrmeral and coronary vascular occlusive disease.“ ‘ Cour
`hinntions of stems with grafts have allowed for intralumlrml
`bypass of aneurysms and long segment atl‘terosclorott(; |o~
`sionsf‘ Transienli percutaneous aortic valve replacement
`it; an extended 21;:)[:>lic:ation oi this new technology that offers
`several new challenges. Firgl, tho valve needs to be atztttn
`mtnly pliwilionod without the benefit of direct opt-3n visual-
`ization. Second, the valve must remain iirmly in the annulus
`under physiologic conclitlonts. Finally, in the absence ol su~
`turns, the vulva ll'lUSl provide a sufficient steal to minimize
`pt‘arlvalvular mgurgitation.
`We have (involution a novel sutureless bovine rmricarclial
`bioprosthetic aortic valve mounted on a collapsible stunt.
`This prosthetic valve can be collapsed in a 2.4 Pr catheter for
`rlolivury. This report represents our initial clmraclorizalion oi
`this valve in a pulse duplicator system and in an open chest
`porcine modol.
`
`Methods
`
`Stunt Valve Cm‘n‘truction
`
`Stainless; steel wire, size 0.020”, was used to construct all
`stems, and size 0.022” was st,)l<l(2rod on the ring to serve as
`the anchoring fixation point in the aortic: annulus. For con
`structing the stem valvro at different sizes, luvnuse of the
`collapsible nature of the design, all valves were: placed in a
`ring ol prodetorrninocl size. Subsequently, htwine pnrittar»
`dium stabilized by a photooxidation prmzt-ésss" was sewn on
`the stunt from a single sheet to titlltSlrttCl trileallot valves cow
`Strained to (.lillorent sizes.
`
`In Vitro Measurements
`
`/\ total of it) sit-mt valves were constructet‘l‘ The low“ that
`were accroptnlzilo in terms of overall symmetry were sol»
`jetted to further studies. A pulse duplicator similar to a pit“
`viously described mock circulatory syestom" was constructed
`
`Edwards Lifesciences Corporation, et al. Exhibit 1141, Page 4 of 8
`
`
`
`Edwards Lifesciences Corporation, et al. Exhibit 1141, Page 4 of 8
`
`

`

`
`
`M882
`
`MOAZAMI ET AL.
`
`
`
`
`
`Aortic l’rcs
`'l‘mnxdm-w
`
`
`
`Lui‘t‘lmtirivulnr
`P19551110 ‘i'I 1mm]ticyr
`
`'
`
`I
`
`Dual Chamber
`I’ulsatiio Pump
`
`Figure 1. Diagram of the mock circulatory loop used for in‘virro
`testing of valves. The chamber allows for adjustment of compliance
`and resistance.
`
`(Figure i). This system uses an Abiomed [WES 5000 dual
`gchamhor (Abiomed, lnc:., Danvors, MA) to generate pulsatilo
`Iiloi/v. [Each stroke. ejects {to-85 ml of saline into the circuit.
`The system possesses an open reservoir to simulate the vow
`nous and atrial systems. in addition, a pistorr~~cylinrlor~spring
`arrangement functions as an adjustable compliance (:hamw
`her. Peripheral vascular resistance could be adjusted by ap-
`plication of a clamp to the circuit partially to impede forward
`flow. The valve was placed on it ring in a rigid Chamber made
`0i Plexiglas. The ring size in tho chamber could be changed
`toadiarnetor ranging from 2‘! to 31 mm in 2 mm increments.
`A 5 Fr Millar catheter (Millar lnstrun'mnts, Houstom TX) was
`placed on the ventricular side and the aortic side of the valve
`to measure transvalvular pressures gradients. An ultrasonic
`flow probe (‘i‘rartsonic25, ltharxi, NY) was placed on the out»
`{low tubing to monitor forward and backward flow. All data
`were digitized at 200 Hz using a 12 bit: ND board (A!) instru-
`
`merits, Milford, MA) recorded with the Mad Al) system mid
`stored on the hard drive for subgequont analyst). Regurgitant
`fraction was calculated by the ratio of the integral of barrio
`ward flow to the integral of total flow (forward and backward)
`using Customized wavo analygis goltwaro (leitLJR; Wax/1;»
`metrics, inc, Lake Oswogo, OR).
`
`Animal Carr-3
`
`Animals received humann care in compliance with the
`Principles; of Laboratory Animal Care itnmulati-zd by the insti—
`tute of Laboratory Animal Resources; and lhe (Cit/idle for the
`Care and Use of Laboratory Animals published by the Na-
`tional institutes of Health (NIH Publication No. 86—23, re»
`vised 1985).
`
`Experimental Procedure
`
`Pigs woighing ouw7o kg were anusthotizetl with ketamino
`(2t) trig/kg) and thiamylal sodium (4,8 trig/kg). After endolrzt»
`shoal intuhation, anesthogia was maintained with isrfiluranu
`(l.5~2.5"/0) mixed with 100% oxygen. Lidocaino 2 trig/kg
`and brotyllium 5 mg/kg were givmt as a loading dose, and
`a continuous drip of l mg/kg/hr for each was; maintained
`througl‘mut
`tho extxirrimont. Standard concentrations of
`phenylonhrino (N(~>()«Syrtt~)|')ririno; Winthrop Pliarmatmtith
`calls, New York, NY), noropinophrino liilartrato (ltevophctl;
`Winthrop Pharmaceuticnls), and epirieplrrino drips wore
`used as needed to maintain a mean blood pressure of ()l.)
`whiio on cardiopulmonary bypass (Cl’i‘i).
`lntorrml paddles
`charged up to 50 V were used for defibrillalion {IS riot-adieu].
`
`Surgical Procedure
`
`Stornotomy was performed, and tho pericardium was
`opened.
`i-lopnrin (2300 rig/kg) Was administered and adt»
`quote anticoagulntion was verified by an activated clotting
`time,) of greater than 400 set; A 14 Fr cannula was; inserted in
`the aorta and a 36 Fr dual slngo venous cannula was inserted
`in lite. right atrium for Cli’li. The aorta was dissuctorl proxi»
`
`
` Table 1. Hemodynamic Characterization of the Stem Valves in the Mock Circulatory System
`
`
`
`
`
` Valve Size (mm) Ring Size (mm) VP (mmHg) AoP (mmHg) Rogurgitant Fx (9/0) Ftow (L/min)
`
`
`
`
`
`
`
`
`
`
`
`Empty chamber (no valve)
`
`8.8
`100
`167
`177
`25
`3‘8
`100
`149
`158
`27
`3.5
`100
`156
`165
`29
`3.3
`100
`152
`157
`31
`2.7
`10
`163/70
`173/20
`21
`3.2
`14
`178/70
`188/23
`23
`2.2
`26
`150/33
`1 60/25
`25
`2,1
`50
`184/36
`1 93/35
`27
`2
`14
`120/60
`130/15
`21
`2.1
`18
`169/52
`174/9
`23
`2.1
`27
`145/37
`1 53/25
`25
`8.71
`13
`146/63
`161/10
`27
`3.67
`15
`149/52
`163/12
`29
`4.5
`20
`147/46
`1 69/1 8
`:51
`3.24
`10
`122/60
`137/9
`27
`3.46
`17
`120/42
`145/18
`29
`
`
`
`
`144/25 114/30 2731 3.28
`
`23
`
`28
`
`29
`
`29
`
`VP, ventricular pressure; AoP. aortic pressure; Fx. traction.
`
`Edwards Lifesciences Corporation, et al. Exhibit 1141, Page 5 of 8
`
`Edwards Lifesciences Corporation, et al. Exhibit 1141, Page 5 of 8
`
`

`

`
`
`PERCUTANEOUS AORTlC VALVE
`
`M883
`
`
`
`
`
`not;
`B»
`
`Figure 3. (A) Short axis echocardiogram demonstrates the three
`leaflets to be fully apposed during diastole. One of the leaflets is
`Slightly redundant (B) Long axis view demonstrates opening of the
`leaflets. The lower. redundant leaflet does not open completely.
`
`Results
`
`In Vitro Studies
`
`Table 1 shows the results obtained from studying valves of
`different sizes in our pulse duplicator system. Flow gener—
`ated ranged from 2.0 to 4.5 L/min with a mean of 3.l l./min
`($07). The lowest regurgitation fractions were obtained by
`placing the valves in rings 2 mm smaller than the stent valve.
`Placing the valve in smaller chambers caused too much
`leaflet redundancy and interference with proporvalve open»
`ing. The valves were considered adequate for animal implanv
`tation ilthe regurgitant fraction was less than “30/0 at a given
`annulus size and a diastolic pressure of (>0 mmHg could be
`maintained. Calibration of the pulse duplicator in absence 0i
`any valve shows that the system has a transvalvular gradient
`of 540 mmHg. The stem valves had at mean transvalvular
`gradient of 14-9 ($7.4) mini-lg In Figure 2, representative
`pressure and flow curves generated in our mock circulatory
`loop are. shown.
`
`
`
`l 0
`
`
`Aorta
`
`r
`:33
`
`Ventricle
`
`0:34
`0:35
`
`161)
`
`Q) N
`120
`L4
`131)
`80
`g me;
`L.
`m E 40
`
`0
`
`Time (secs)
`
`Figure 2. Representative in vitro aortic and ventricular pressure
`tracing for a 28 mm stern valve in a 21 mm ring.
`
`malty until the origin of the trait main coronary artery could
`be visualized. Subsizrquently, the animal was placed on CPB
`and cooled to 32 “(3. Alter placement oi a left ventricular vent
`mmugh the apex of the heart, the proxirrml aorta was cross»
`crammed. Ono liter of 4°C standard crystalloid czardioplegia
`SOtut-ion was delivered to tho aortic root to arrest the heart. A
`partial transveer aortotomy was; rmriormed as close to the
`Coronary artery as technically feasible. The deep aorth root
`in this animal n’todel nowgsitzttod the use of three ll‘adion
`Mumgrtlattecl at each commlssuro to pull the native leaflets
`into View. Alter sizing the annulus with standard sizors, the
`ameriztte stent valve, collapsed in a 24 Ft catheter, was
`delivered under direct vision and secured in placed. No su-t
`tures were used for fixation oi the stern valvor All traction
`‘StilLll‘l‘PS were removed and the aortotomy was closed with
`a double layer of running 4~0 polypropylene suture. Alter
`rorrioving tho cross~clnrnp, doairing tho loll ventricle, and lt3~
`warming, the animal was slowly weaned from CPB.
`
`Hommiymrmic NiCi.l..‘il.l/‘t?ll'len(§,
`
`Pressure was measured with a .‘3 Fr Millnr mlcromanometor
`placed in the left ventricle through the apex, and a second
`tzatltotor guided to the proximal aorta through the loft carotid
`artery. All hemodynamic data were recorded oil CPB on the
`Mzt(:l.,;th system, All data are reported £15 mean : standard
`deviation.
`
`tic/locordiogrztp/iy
`
`TWO dimensional and nt~mode ochocardiograms were ob»
`tained using a hand held 5 MHz ultrasound transsducer
`(Vingnted CFM 750; Vingmod Sound, Inc:., Salt Lake City,
`UT). Color llow Doppler was obtained to assess valvular
`gurgitation.
`t'l
`
`Table 2. Size 0! the Aortic Annulus After Cardiac Arrest
`Relative to the Size of the Stent Valve Implanted
`
`Annulus Size
`Valve Size
`
`Animal
`(mm)
`(mm)
`
`23
`18
`‘1
`29
`25
`2
`
`
`3 23 20
`
`Edwards Lifesciences Corporation, et al. Exhibit 1141, Page 6 of 8
`
`Edwards Lifesciences Corporation, et al. Exhibit 1141, Page 6 of 8
`
`

`

`
`
`MOAZAM! ET AL
`
`
`
`
`
`'i‘imc (501:9)
`
`Figure 4. Representative in viva aortic and ventricular pressure
`tracings. Mean aortic root pressure was 116/70 rnran. with mainte-
`nance; of a diastolic gradient of 66 mnng between the aorta and left
`ventricle,
`
`In Vii/o Studies
`
`Table 2 rlr-nntzmstrntos the size of tho porcine atl‘ttttlltt‘; anti
`the most appropriately sized valve that was available for im-
`iz>lanttiti0ii Erigagrzn‘itznt of the valve required approximately
`5 min, Crt.)55~t3litlti}) limo was amiroxitnately 20 min in aniu
`mats i and 3 and 40 min in animal 2 l}(.>(.IEtUSQ of inadvertent
`dislodgrnont oi the aortic: cannula. All animula wort? succtassw
`fully weaned from (le’li.
`Anier i malltli’illttztd a systemic pressurr-z ol IOU/45 (iz'lii')
`mini-lg over it period of 2 hr. ll‘ilt’i,t0[')(1?l’Z)ti\/G ochotzttrtliogrti»
`phy rewarded (goinplteto openingof two leaflets, with the third
`ll}i,tll()l redundant and relatively li‘t‘tmti)l)llti?. All leaflets wort-e
`hilly apposed during; diastole (Figure ’3). The. stont vulva was
`in the sol’tcxrronury position without any ohstrurztinn to «or»
`nnziry blond llow. Color limppler studios Sl‘tOWtEBt'l milrl regur-
`gitation at the level of the non mobile posterior leaflet. Post»
`mortem oxamii’mtion revealed corntzilote fixation of the valve
`til the annulus without any tiiriplattoi‘nont. Becauw oi the
`small size. of the illil'ltllllfi, one of llttzi‘ leaflets lei)l2)t;}iili(3(l rerlun~
`(Slant, as; had been nhservocl (luring otrhntzardiogmphy.
`
`Animal 2 was suttcessiully wounori from hynttas, lint within
`5 min refractory ventricular fibrillation (lif‘v’i’lOlli-‘(L il’ogtmmv
`tem examination rovoalorl (lislorlgnwnt till this Vilth.‘ St?£‘(>lttl"
`ztry to Structural failure.
`Animal ’3 had an annulus; giant iii 2t] mm anti rtmrivtztl it
`23 mm stem valve. This animal tnztintziinoii .t .«zystrii‘nit' lthlitl
`pressure of '|
`'1 6/70 (it 5) intuit}; I‘m-matrix) rtéttiitlinitr (it lllt‘
`aortic; root and loft ventritxlo revealt-rrl an é‘tiSYfiliillt.’ gradient of
`2 (:tz’i) mml'lg. "l'lw moan (litiqtnlirx gt‘éttllt‘itl Win;
`{it} (~ '
`
`mmHg with the left ventricular diastolic [)l'tfféfitli't? at 4.9
`mmI-rlg, suggesting ttlfi)$€ntit:} oi Signiiimnt i'vituriiitzitintt (Pity
`one 4). Two tlit'ittai'txiional t?(.fl‘t<)ii.’.£tl’tillt)gritltl‘ty i‘t-‘Vt‘t'tlttil iii) tur-
`biilorit'o (luring sygtolo, with lttuilllQliéti‘itft‘ oi (:oittml tluw.
`Color ll')t.3i')[:)lt3r llriw showutl tram (:tznlml “willtitllilllitlll No
`[Titerivetlvulzir lonk could in: itlti‘t‘tilllt-ft’l. ttt-lvlutlt“ lf‘t'il"it)('£ii'tll(ii§"
`mphy faltth/(‘tfil lull opening; oi tho inallnts; with riiriiplotn (in,
`position ('lLllli'ig (.lliitfilt)li;? (Figure, 5).
`
`[iiswssion
`
`It porchinrvmtisdy llli|.)ldl'll<ll)l(.l aortii’
`lLJtivoltminoni of
`valve poses many trlmllmiging (‘1.)ltSllet‘itllol'tS. l’wn investigatv
`tori» have t’t;lii.’t?itll‘y’ (rltlfiifl‘llitifll arrrilt: stont veilvret. int noi'rsutrv
`
`neotis aortic valve roplzttrnn‘tnnt: it
`lmll
`(.‘iigitt Llit(l n balloon
`trxrmndablt} porcine valvof'“ This study pit-mint}; it now do»
`gign lot it (:(Ltlllthill‘flH, guttiroltaxs l)lt)l)l‘0islltttl it: vgtlvo t’nr ll‘ifll'lh"
`ltttt‘titiz‘tl atitilltxitiorr 'l'ht-v acute aturly was; tlliilt‘l‘lrllfl’li to oval-I
`
`unto SLlVCl'iill feature» of this (it. tight
`First, the stability Olit Stiltil‘()lt)€3‘5 stout in tho ,iurtit‘ annulus
`noteclml in ht) (l(.?l()l'l't'lll‘l('3(lt
`ltt
`till
`in vim; shining, the vath‘
`rvmztirtod iii'nily anchored in (hr-r ring with no (llfil)lrltit-tl'lttklil.
`This was criiitirintrtl in ll'lifl animal {stutliom Willi tho t‘X"‘t?])lll)ll
`nl’ nnii'nttl 2‘ in this animal, valvu (liSlt)(ltJ,lttt?i'll rir'r'urrotl sore
`ontlury to structural lailuro oi lltt.‘ filtétil i'tl thrt thltl point, This;
`was pt'nlizilfly amused by £:.’X(,I(L‘?;fith;l lttitltllwlitl ion and wear (ll
`the stunt (luring the multiple in vitro stutlios that were not
`l(')iill(:!(l. l’mviouz; progthotit‘ valves; have also l)l..‘t‘|t plagued
`with this prohimri, and design changes have lt'ttfltttlvtl making;
`the girut from a single shoot
`(it
`li’tt-,‘.l'<il
`in (flllilll'titlt-Z‘ wolil
`Siti:3.""”
`
`
`
`
`
`Ewi-
`'
`m, tic: artiya
`
`‘
`
`Figure 5. (A) m‘MOde echocardiogram demonstrates tutt opening and closing of the leaflets. (8) Long axis view with trace regurgitation
`during diastole reprosented by the mosaic pattern at the center of the valve. No perivalvular treak is observed
`
`Edwards Lifesciences Corporation, et al. Exhibit 1141, Page 7 of 8
`
`Edwards Lifesciences Corporation, et al. Exhibit 1141, Page 7 of 8
`
`

`

`
`
`
`
`i‘ERCUTAHEOUS AORTIC VALVE
`
`M385
`
`Acknowledgments
`‘l'ltoauthois timnk (.L'arlxmiaariiiti, inc. (Armin, TX) for preparation
`of bovine i'ntZ‘riCitl‘diLtltt and assiutunm with {Ollbltuciltnt of the valvm
`on tho stout?”
`
`References
`
`Second, .tn eilocrtivt? watertight Mml to provont porivitlvulzir
`lt-uilmgr- iii of pm‘a-imoiti’it ii'iip<.,)rliti‘i(,o. Our studies; have (loin
`ormtmtori
`that tho att-mt valvo mechanism effectively prev
`vents; regurgitation when the valve i5 anchororl t'irooerly. the
`rlynzimic nature of the aortic: root (luring tho cardiac cycle
`ti'iiit {Amigos this? aorta to (marriage? in aim” is; probably another
`l'r-igitilm in lavor ol'
`t.3llti’(fli\/(3 sealing, We [bostiilato that this
`(lyl'ttll't'llt’ intercititiori l)t“th‘(‘t’t tl'm «toot valve and aorta is‘ the
`rmisoi‘i that minimal to trait" regurgitation was observed in
`tho animal studio's, as opposacr’l to the.
`in vitro data, which
`Wore (i(.)ll(.*(.‘.ltz'(l in a riggicl 5ystom and msultorl in i()~~ 18% r<z~
`gurgitntion.
`Finally, we have shown that when on apprimriately sizocl
`valve it; iinpianttzét‘l in the Sltlitjot‘tmttl‘y position, flow is unidi»
`roct'ional, with no l't)l’l.)Lll('?itf.I‘(-’ and minimal transvalvular gm~
`
`(liunt not] control flow. Tl
`i'actors; are imi'mrtizint
`it) the
`)
`(liiqign of a pini-illtvilt; valve with good iiemoiiyntimi(: i‘iorfor»
`,
`1.,
`ii'idi'lt 0‘
`
`Conclusion
`
`.Wo ltc‘lVC‘ (:lvvolopod a (collnmililo l:)ir;)i>ro5tliotir.t aortic:
`valve for in‘iplamtzition in tho subizt)rormry DQSitltilt at
`the
`[ct/nljiil the aortit: .‘mnulusi This; report summarizes; tlw prev:
`liniirtt’n‘y @vflltmllttl’t of this stunt valve in terms of merino art--
`mining, prevontim’i ol
`rogiirgittitioii, and adequate" flow
`prowmiiwr "Tho smirly is;
`limitet‘l
`in that
`long tiarm analyses
`Wmc not {fit’tl’lt)t’ih(‘[l, and many ('tLtossliorw re guiding), ('ll.ll'i:tl)ll«
`itv of tlw sitarnt zintl lonl’lots ron’min optm, in addition, chronic
`Militias; are nievrlod to 85540853 valve tltromlit>gm‘iirsity, tiiron'r-
`l")0t..‘l‘til)()ll$lh, anti abatentrij oi stont migration. 'l'his’ proliml»
`“my sturl‘y (:“Sliftlillfil‘tt‘s that it Sittitlt’t-tltj‘fifi ifiroSthotit; stool vulvv
`in ltll'i(illt)lti‘ll in tho aortic position, and is a Non toward Liv-«-
`Vt,‘l(,)i.)l‘it(¥l’ti of a porr‘utmmoms; {'t[)l'il‘()ii(‘,l't in the lt,.)l‘(;‘5(3t§ill)lt-’
`to t tirr‘.
`
`2.
`
`7,
`
`t'iiiilovz’iscular ropuir of abdominal aortic: aneurvgirts
`1. Powell ltlf:
`and other arterial lt?‘»ioi'ts, I VIML fiuri; 2 l: 54W 357‘, 1005,
`l"ist::liman t.l)t,. I eon Mil, Baim DS, or a]: A mi'iiloiniyorl (‘0tiipxit'l~
`ion of coronary stunt t)li‘t(.'f:‘ntt?i‘tl and balloon angioplasty in
`the troz'itnwnt ol (,m‘orml’y artvrv (list-Ago. N log] 1 Mod Til:
`4‘JG-r‘15til, 199:1.
`ii. Sorruyt‘i PW! lnogure P, Kimnonoii l5, (at til: A ('Ulilimi‘l‘xt)“ oi l’ml-
`looiwxin‘tnrlnblte stunt implantation with lmllonn .‘ingioplzmty
`in plilltz’l‘tK with coronary nrtvry (“543.190, N log] I Mud 3'5 l:
`Mitt-49".“), 1094,
`44 Clutter TAM, Greer: RM, Ouriol it, 1:! a]: ‘Trmisimnornl enchwzw
`<tulgirziorticiirgit'tplnwn‘mnr / Vim: Sui-g; l8: tttfs 19?, 1991
`2). Moore MA, limitatliizvslzv iii. (.Ilwunig UT, of a]: Stabilization of
`plzfl’itii'ti'dlril tissue by (lyounitxclinttrtl pliutoozirlation. / Ifiiomml
`Mali-2r Rec 28: ()l t. (118, I99rti
`ti, Rmenlxarg (Ii, Phillips WM. landis UL, Piorw WS: mom” Ml
`ovaliiatioi‘i of “it? Pennsylvania State lull'tin-ll'filly Moria (Zircon
`lntory SyztorrmS/UO/4(2):4t
`:W,
`l‘léi‘i.
`l’tivmile L), Wright KC, \anlm‘o ,8»:
`t.)i~>ve:lr.>pimmi and initial
`[Jifi’liTil‘ttlitl mutilation of u [)rmtl‘ietir aortii’ valve for tinnw
`tidtlmtt‘l‘ i,>l2tii;r;:rrii3nt. lilac/foli'ngy 1813; iiit r
`l‘S‘t,
`l‘iE-lLZ.
`(5. Anderson HR, Knuclairn it, l'lnwnlmrn lM: 't'mmltimiiizil in‘li)l£tll'
`tattoo of .ii'tit’iiiul limit valvoes: description of it now ("Xiliiil'itl-
`ethlw g‘iortirr valve anrl initial maulta with implantation liy t‘iilli"
`DIGI’ torrl'iniquo in closurl Ll'lt‘éil pity-2. iz'zir i-lwrl I
`lit: 7(1):} 1 708.
`l‘léll
`it. Bjork V0: The tilt.»rl<~$ltilr.ry lilting, (limb valve: past, prownt éll'itl
`l'uturol (Tit/(liar Surgery: Stain of tlio Art Rt.‘\’lt"lt’$ 1987, it“
`000
`‘itarok l’lK, l3::’ri-tt.itlt.‘t RL, l’ldll KV: 'l'lio lvtvtltronitvt tail valve: (lo
`volopnwnt and tilinitiztl t”
`l.)(.‘t’lt‘l‘il§‘t3. ( unlit.” .‘itirgt'ly: fitiitu oi
`
`[lib/tr! Itrrvl'ow‘i W87, 231,;-
`int).
`'t'intlalte W15, tilztck MM, Martin iii: in vitro Wellimtinn of Work
`tlwtir: heart valvvss: anoinnliim and lii‘i'iit;‘itioiv;.t
`tin NW“ l’l‘iyv
`fol Meat; «3:
`l
`lfiw 1'30, 1982,
`iii. Arom KV: Choice Ul liil;t(,’li;'ttiit..t‘tl Aortic prominent: valvv, in [:nr
`ory RW, Arum l<\/ (orifil/ ‘li’io Aorllz' Valve, Philatlolpliizi, Han--
`ltf‘y &‘ livllum 1091, pp 187’ am.
`
`it),
`
`l l.
`
`Edwards Lifesciences Corporation, et al. Exhibit 1141, Page 8 of 8
`
`Edwards Lifesciences Corporation, et al. Exhibit 1141, Page 8 of 8
`
`