Long-term experience with porcine
`aortic valve xenografts
`
`Betw en I 71 and 197 . glutoraldeh.\d •-pn-sen·ed 1 nrcine aortic 1•a/ve x •nogrqfts 11 •er e elllflloycd {or
`isolated replace/li e/If l~{ rh e lllitrall·ah ·e (M I R) i11 _43 1 utient ·, repl1c me111 r~( thr• 1 mic l'ah·c ( 1 R) ;11
`J 7 1 c1fi 111s, 111d cloulle I'(J/l'e rcplaa111 111 ( R 111d M R) in 1 fJCilienr ·. Po ·toe •rativdy, 1 111 ~ - r em1
`IIR, M R, and double Falre
`anricoa 'llla!ion 11as 11U r mtine/y gil •e1t.
`peratil· morwlity rates {or
`groups 11 ere 7.R , 6 .0. a lid II .r per ·enf, resp 'f'fi1 ·e!y: th ' 111ajority o.f early po ·rojJerativc deutlls ll'ere
`t.'iso iated with concolltila/11 ·orm1wy artery di cus '.
`o deatlr ll'as artrihuwh/ · to · ·1wgrq{t dy.Jimction .
`1/oi\'-IIP q{ (1/1 p 1/ienf,\ ' I' 1\' olltlil!f!d. Tile tr. ra! duratio11 <d'fol/nw-up for tht MIIR
`)m11p \I'CJS 3.47
`IIR group 1-18 patienl-yc 1rs, and .for de uhl ' 1'a/1·e r epltl'CIIIent 37 putient-rr tc;
`patienl-yC'ars, for rhe
`nwximum fo //o\1'-ttf' for the. e three gmu1 s II'O S -1.-1. -1.0, and - .-I )'l1ar , respccti,· 'ly . ctuari(/1 o;ralvsis of'
`postvpemril•e Slll'l'il•a/ rar •s ot o C0 /11111011 int n ·al q{ 3 y • II'S sho11 1ecl 78 per ·ent for MIIR fJoliem . . 9! pc;r
`R patients. al/(18 p •r ent (projected) .for patients with dr 11hl ' I ' llr ' r •placement (l'i5, 96,
`cent f er
`and 9 1 per cen t./( r operwil c Sllrl'il'ors, r '.\'fl l'Ctil·e/y.
`I t/Jis Yom intcn •al 92 f er cc/11 of 1VR p uimrs,
`99 p r ce111 (~{
`R pctlienl.\ , and 96 per cent (projected) r~f pmi '111
`ll'it!J lottble 1 all·e rt pla('('menr ll'ere
`Fe of !ltr nnbneml olic episvdr•s. Altogether, / _ t~f' the total 5 1 mh• , implanted exhibitc I sm1u el'idence
`of dy.~{uncticm durin'S the eotirl' period of'.jiJ//oll'- llf1 C'I 1CIIIIation, l11t in only _ inswnces (horh ntifra/) ll'fiS
`intrin ·ic I' tllwlogica/ im ·oll 'l!/JI ' Ill r~( th xenc~rqfr tis.vue dommented. Actuarial ana!_vsi · q(xe11ogrr!/l
`dv.~/itnctiun at a ·on1111011 inten•al of 3 years a.fi r Ofleration sho11 l!d 9'i per (' 1111 r?f' MVR patients, 9H per
`·c·11t of' A IIR pcaient. , C/1/(1 97 f' el' cent (prnjer'fl>d) nf patienls with do11hle l'(l/l •e replal' 'TIIellf to l • fre · r~/'
`this ·nmplil'ation . These dat 1 • upport the use ~/' glurarahlehyde-pre en·ed porcil/fJ . no )rq(r. o ~ super;or
`that flO. e a low ri. k r~f tllrmnboembnlism "'it/Jour anti ·o t ~ ularian . Them· r~a!l durability(~/'
`biopro. t/Jesr•.
`such \'(//1•e . ll'ithin rh rcstrinirm c~( a nwx inutm currenr fo/loll'·llfJ inten•a/ q{' 4.4 y •ar, , oppear
`·omparohl<' to that r~{' currently n•ailab/e IIIC'c/l(lnica/ pr ,,,·tit •ses and just~'[ifs ('()llfinued clinical use.
`
`dward
`Philip
`Stanford,
`
`tin n M.
`y r, M.D. (b
`
`invitati n) Ran all 8.
`invitati n and Norman ~
`
`ri pp, M.
`humwa ' M.
`
`by invitation)
`
`m nl of h art valv with bi pr sth . • on-
`f "fr sh" aortic allograft was initial d at
`slru ted
`nt r in l 7
`tanf rd Univ r ity Mcdi al
`caw;;
`f
`dis atisfaction with th
`throm o mboli compli ations
`f m · 'hani al valv
`ubstitut
`th n urr ~ ntJy avail-
`a I . 1 • 2 u
`quent analysis has docum nt d that u h
`allografls arc associated with an ace ptably low rate of
`thr m o mboli ' m without I ng-t rm anti ·o gulati n,a
`but th
`. tability ol all graft ti . ue for
`ith r mitr::tl
`r
`replac mcnt ha. not 1 r v d sati ·fa t r .
`aortic valv
`
`y ars postop ra l i v
`rgoing ITlitral val
`
`nl of 1 ati nts
`ly only 40 p r
`r pia· m nl (MVR) and 49
`val
`r pia
`lini al and/or
`
`hibit
`
`r . Stanford ni ersit
`
`From th D ·partm ~ ntof an.liovascular ur
`M ·<.Ji ·al
`l:lllc r. Stanford , alif. 94 0 .
`Addrc. s for r•prints: dward B.
`tinson , M.D.,
`·partm nl of ar-
`dio ascular Surgcr , Ianford nivcr ity M Ji al
`cnt r, SIHn-
`ford, ulif. 4305.
`*Establish 'd Investigator. American Heart As
`
`ialion.
`
`vnlv
`
`*Hancock aboraluric ·, Inc..
`
`naheim
`
`nlif.
`
`54
`
`STJUDE1043
`IPR of Patent No. 6,821,297
`
`

`

`Volume 73
`Number 1
`January, 1977
`
`~1Ydrllulic fun ti( 11 w r ' sati. fact r 1.5 uring th ensu-
`ars porci n x n grafL ,.~,~ r employ d for re-
`Ing 4
`rla em nt r mitral and/ or aorti val v s in 4 I pati nt.
`at th'
`·
`nt r port r
`nt r. Th purp s
`f th pr
`t
`IS
`r ostop r, tive r suiL and tn fo u
`· ummari
`th
`I at
`Parti ularl
`ng-t rm durabilit
`f thi
`iopr -
`lh si ·.
`
`I
`.
`F.d\i "''d L b
`1,
`.... ~ a < rarnncs , m:., an,,
`
`n·•
`"•
`
`alif.
`
`Porcine aortic 1 a!l'e eno rafts
`
`55
`
`Table I.
`finical characteri rics of parients
`undergoing xenograft va!l·e replacement
`
`e
`\ omen
`M~;;n
`g (yr.)
`A emg
`Rang
`N.Y.H.A .
`
`150
`93
`
`54
`7-74
`
`3
`I
`159
`50
`
`42
`125
`
`58
`15-8-4
`
`6
`s_
`90
`18
`
`fi!R
`+AVR
`
`51
`
`_7
`24
`
`6
`20-77
`
`10
`34
`7
`
`Table II. ombined procedures durin' xenngrafi
`
`Procedure
`
`M R
`
`AVR
`
`J
`0
`I
`10
`
`..J 3
`18
`4
`0
`
`MIR
`+AVR
`
`7
`5
`0
`0
`0
`3
`0
`I
`0
`
`D. Ventricu lar
`
`f r
`dard dosage ' was prescrib d earl p stop rati vel
`ith r
`approximate! on
`third of the patient ha ing
`MYR or double valve r placem nt and forth sc A VR
`pati nt
`in whom c ncomitant aorta-cor nar bypass
`graftin g had b en performed. Sub. quently, antic agu-
`lati n was discontinu d 6 to 8 we ks po toperati
`I .
`c pt at th di
`retion of th
`rf'ferring physician nr in
`ca s f int rcurr nt throm o mboli ' Ill . On thi s ba 'i .
`34 pati nts ' hound rwent MVR r main on a regim n
`or long-1 rm anticoagulation (-5 in atrial fibrill.ation).
`a. w 11 as 7 patients with V Rand 4 pati nts with doubt
`val e r pia em nt.
`Postoperative evaluation. Curr nt evaluation of all
`. urviving patients wa obtain d during a 4 m nth cl s-
`ing int rval (Jul
`t 0
`t b r. l975) by examination at
`thi center orb
`onta ·t
`ilh the 1 aticnt' s ph sician.
`unctional cia ·sification was assigned on the ba~ is of
`·un· nt symptoms a ordino to New York H art A -
`so iation crit ria ( 1964) .
`
`STJUDE1043
`IPR of Patent No. 6,821,297
`
`

`

`The Journal of
`Thoracic and Cardiovascular
`Surgery
`
`100
`
`\_
`I
`I
`I
`!-!-- - - - -- -- - ---
`
`I
`
`- - - -
`
`80 -
`
`60 r-
`
`(i)
`
`1-z w
`~ 0..
`
`_J
`;.J
`~
`
`{/)
`
`_J < > > ~ 40-
`..... z w
`(.) a:
`w
`0..
`
`20-
`
`- - - -
`
`I
`
`I
`
`I
`
`,_,
`........... , ____ !
`----!-------
`
`5
`
`Stinson et a/.
`
`100i\
`
`I
`
`80-
`
`(i)
`
`1-z w
`i=
`<d:
`0..
`_J 60-
`_J
`~
`_J
`
`<d: > > ~ 40 f-
`1-z w
`0 a: w
`
`11)
`
`0..
`
`I
`
`I
`I
`3
`2
`YEARS POSTOP
`
`l
`4
`
`5
`
`I
`I
`I
`1
`00~----~------~2------~3~-----+4------~5
`
`YEARS POSTOP
`
`Fig. I. Postoperative ' Urvival, calculat -d by th actuarial
`method . for all patients undergoi ng mitral valv
`r placcm nt
`with <:1 xenograft.
`rate is included. The
`p rati ve mortiJlit
`terminal, da. hed portion of lh
`urvi al curve repr s nts an
`inl rval during which no vent (i .e., death) occurr d.
`
`Xenograft dysfunction was di agnosed on the basi of
`everal criteria: (I) c nfirm d hydrau lie dy fun tion
`toperative
`uffi ient to r quire reoperati n (2) th p
`d v lopm nt of a new murmur haract ristic of va lvu-
`lar r gurgitation (a rtic or mitral) , unl ss proved by
`angiocardiography to r-pr -s-nt sol ly n 1 ripr sth ti
`leak with ut any
`entral
`m nent
`inv lvin' th
`xen graft leaflet , or (3) endocarditis re ulting in
`ath
`or r op rati n. The s
`nd criterion is consid rc
`ne essary ina much as a n wly ev lop d regur itant
`murmur aft r ti sue valve repla -m nt cannot reliabl
`linically as repr senting perivalvular
`b di stinguished
`versus transvalvular insuffi ien y, in contrast to ex-
`p ri enc with most mechani. al valve substitut s.
`Thromboemboli
`event w r
`categori cally didg-
`no ed on the ba i of any n w n urologic d ficit,
`whether transient or permanent. or other peripheral
`arterial mbolic episode. Only c rebrovascular ac i-
`dents pr ved by postmortem xamination n t to have
`re ulted from emboli were excluded from classification
`as emboli. Patients were on idered at ri sk for throm-
`boemboli m throughout th curT nt peri
`I of follow-up
`or until death or reoperation.
`The total durati.on of r; II w-up for pati nts with
`MVR was 347 patient-year ( ummation of all incli-
`vidllal foil w-up interval s, whether to d ath or curr nt
`evaluation); the average follow-up interval for surviv-
`
`Fig. 2. Poslop ~rat i v survival for all pill ients undergoing aor-
`tic va lve replacement with a x nogntft. h
`t rm inul, dash c1
`portion of the survival urve re1 res nts an inL rval clurinn
`whkh n v nl (i ... d alh)
`~.: urr d.
`
`lmonthto4.4 y ar ).
`l.6 years (rang
`ing pati nt wa
`For patient with A VR the total foil w-up analy i in-
`clud d 148 pati.ent-y at (av rage for urviving patient
`I. y ar, ranJ
`J month t 4 .0 y ar ), and for patients
`with MVR and A V R th
`total duration of follow-up
`7 pari · nt-y nrs (av rag
`wa
`follow-u for survivin :r
`pati nt 0.9 y ar, rang
`I month t 2.4 y ars).
`t tal durati n of follow-up in pati nt-y ar
`h
`for
`a h of th
`thr
`groups was u. d as a d n minat r for
`f lineari ed rat
`calculation
`ific ventn such as
`f SJ
`thromb emboli m or x n graft dy fun tion. h
`t tal
`numb r of such vents was divid d by the total num
`r
`of patient-y ars of foil w-up and multipli "d by 10
`to
`xpr ss av rag
`ri k as
`r
`nl p r pati nt-y ar. Alt r-
`nat ly, this cal u lation ma ' b
`pr ss d as nllmb r of
`ev nt per I 00 patient-y ar . Alth ueh th.i method of
`ri sk calculation pr v ides a r ali ti approximation of
`stati stical pr bability for som cv nts. it may ov resti-
`mat
`individual ri k f r om complicati ns, uch as
`thromboemb li m, either becau e
`f multipl
`vents
`ustained by a ingle patient orb cause of "clustering"
`during th early postoperati v period in a patient group
`with limited duration of foll ow-up. Rat of complica-
`ti n and survival th refore were also calculated y
`the actuarial method that pr vides nn e timatc of the
`per cent of the total pati nt group fl'e of or aff cted by
`c: n event ov r time. This implies withdrawal of a pa-
`
`STJUDE1043
`IPR of Patent No. 6,821,297
`
`

`

`Volume 73
`Number 1
`January, 1977
`
`P rcine aorti
`
`1 all·e xeno rafts
`
`57
`
`ignihcanc
`-tailed
`ariu I .
`as ign d L
`th 1 values thus btained.
`
`Results
`
`mitt d
`
`UIT d aft r
`
`us c ronary
`
`STJUDE1043
`IPR of Patent No. 6,821,297
`
`

`

`5
`
`Stinson eta!.
`
`Table Ill . m1su c?f dia no ed x '110 raft dysjimction
`
`(lft Sl'
`
`MIR
`( 11 = _./ )
`
`II R
`(11 = 167)
`
`lnsuftk ien murmur
`arly
`La!
`ndocurdi1is
`al
`
`4
`
`T lui.
`
`I
`0
`
`I
`0
`
`MIIN
`+AVR
`(11 = 51 J
`
`0
`
`b pa. s crrafting to a · · th
`
`influ n of this mbined
`
`n graft
`f
`of the total 5 I_
`i ht in th MYR
`
`The Journal of
`Thoracic and Cardiovascular
`Surgery
`
`tio · w ·rc p rf m11 d b au · of intri n i ~
`al
`d . fun ·t i n.
`
`r in f ·tiv
`
`riph raJ a ular
`lin ari d th rombo m
`
`ati
`d l rmin
`
`· aminali on. The oth er lettfl et ·of thi
`had no abnormalili ·.
`ln 2 pati nt. , cl
`·urn nl I
`fi i ntl
`
`thi s int rval.
`
`n 0 raft lea fl t
`
`im-
`
`raft dy functi n
`n mitral on a rtic). B th
`pati nt und rw nt reo eration th at was unsuc ssful.
`tohl 12 va lv s ·at "P: ri d as dys-
`two of th
`Thu
`functi naJ it
`thi annyl is hav b en d cum nt d a
`in v lv m nt of x n -
`f primar
`featur s
`on fl ti ·u (
`thin th mitral lo ali n). In th
`remain-
`der , the cause of dy function r mains unkn wn r wa
`s
`ndary to infec ti v I sions. A t tal of five reop ra-
`
`fa stan-
`ha rt at
`
`d i n 2 at i , n ts
`oth within Lh
`v nt yi ld a
`nt p r
`lu ·-fr
`
`STJUDE1043
`IPR of Patent No. 6,821,297
`
`

`

`Volume 73
`Number 1
`January, 197?
`
`sur iving pati nt r tain un ti nal
`'lbi lity.
`
`Ia ·~ lJ I r IV dj -
`
`for fabri ali n of heart valve
`u
`in
`stigat r
`valuat d b ' man
`
`Porcine aortic 1 alve ·eno raft
`
`59
`
`ta-
`
`caus of
`fa rtic
`
`t n-
`·on-
`is rrc . nll
`
`tribut
`unknown.
`ur2::! arl cxperienc with this typ of biopro ·th si.
`for MVR pr du d sati fa tor
`linicaJ r" ull. in t rm.
`f r"storati n of phy ical apa ity and an a · ptabl
`1 w rat of thromboemboli ' JTI with ut long- term an-
`ti oaguJation . T h pr
`nt anal
`is of th
`f
`r suit.
`both MVR and A VR, incorporating longer r rinds of
`postop rative valuati n e ·tending to n arly 4.5
`ars
`aft r mitral alve sub. titution. c nfirm. th
`arlier
`intervaL of f Jlnw-up
`hr ughout th
`observation .
`a ailabl , 92 p r · nt of MVR pati nts 99 p r c nt of
`A VR 1 ·:~.ti nts, and 96 per cent of 1 ati nt · un I rg
`ing
`doubl valve r pia ement remain fr
`of thrombo m-
`boli cpis des. Only a small minority of pati nts hav
`b n maintained on a r gi m n of oral anti ·oagulation
`for indi iuual r asons at th dis r ti n of th 1 aticnt'
`privat
`hysi ian. In th ca. of MVR cal ulatiun
`f
`th
`tim -r lat d incid nc of thrombo mbulism slight!
`xc ds
`th t rep rt d by 8 n h 'k ·:tnd StcuT''
`f r
`
`STJUDE1043
`IPR of Patent No. 6,821,297
`
`

`

`The Journal of
`Thoracic and Cardiovascular
`Surgery
`
`i .: H mt Lral'l
`X Bar att-Bo c ·. B.
`nrlit..: ln~.:n mp·t • nc· :.u1tl
`I. I . I<JM.
`
`1 rti · al · Rcp lan·-
`t ·no~b. Tho a · JY:
`
`. , und anglois,
`. . 'arpenti ·r,
`al
`'T <111splantation , Lane t 2:
`
`r-
`
`n or
`
`II
`
`rinson et a/.
`
`loth-
`
`int
`
`. t nosi
`In nl
`
`epla em 3 nt. London, I Y7 .. , Bull n orth and
`p. 5 15.
`14 B m c h ' ~ , L . 1. , an I
`turr,
`pprai~ul of Lat R
`urrent
`R4., 1975 .
`
`..
`
`Prost h e!-.·~:
`nrdiol. 35:
`
`., R i ~, R.
`
`into account.
`tak n
`n of
`n graft al
`and , within th
`s app ar uffi
`warrant th eir continu I clinical u ·
`
`Ma imum
`t nd
`
`~ R - N
`R ·
`ng II. W. W. , Wuerll ·in , R.
`Mi tra l
`
`..
`;..~ l vc
`ppli il-
`
`Valve:-.
`
`15
`
`ll
`
`17
`
`hum-
`Mitral Val
`
`l'nr
`
`'alves, J.
`und
`Ill
`R ·. 65: 64, 197 . .
`I ~ Hud · n,
`
`IY mith , J.
`
`anu R ~ i s, R. L. :
`al
`·~ I mplantcd
`AIW IOV K.
`
`orti
`
`al c
`
`ortic
`
`al
`
`s~. [ . N . , R os , K . J . , a ntl
`Emanuel , R.: Mitral al · R ·pia· Ill ·nt With Pr s ·rvcd
`ada
`rli Homo~ ralh , J. TIIORAC.
`' f'i
`IWIO AS ·.
`URG. 65:71 2 , 1973 .
`2 1 Buch, W .. Kos k, J.
`
`., anti An ''II , W. W .:
`
`6
`
`humway, N. : .:
`
`IW JOV c.
`
`lorrow, A .
`.. and
`onccpt in th e Fabricuti
`lh •scs, J. TIIORAC .
`ricr1, R. B. , StinstJti , L.
`Profound Local Hypothermia for M
`p n-1-lcart urgcry , J .
`. 66: 73 1, 197 ..
`R
`7 Ross,
`.: Homograft R pi a ~ m nt of th
`i.tl.v . an ct 2l 4 7, I ~6
`
`. orti
`
`pr ~s.
`ohn, L. H., amber! , .1 . 1.. a. tan ·du .
`
`. R., anti ol -
`
`STJUDE1043
`IPR of Patent No. 6,821,297
`
`

`

`Volume 73
`Number 1
`January, 1977
`
`Porcine aortic 1 a/r x '110f?,ra.fi
`
`61
`
`lin~ .. J. J .:
`th ~
`ardiac Valv · Replacc mt:nl With
`tal ili z ·d
`al v ·: Indica-
`lutarald ' hyde Por ·in · orli ·
`ti on • p ·rnti ve R ·suit • and rnllnw- up . he. t 68: 162.
`I 75.
`
`Discussion
`R .
`LB ~ R T
`Pvrtlrmd. Ore .
`
`RR
`
`·nough to ' rit e
`
`111 nt . the r suits an: th~.: same : 96 p ct: nt
`rsus 97 1 r · nl.
`rai l.! ;u 3 car · as 99 1 r c ·nt e rs u~ 97
`The
`rnbolism -frc
`
`f thi s information. \ C COnti llll
`tO U.' both
`11 liP bas il>
`the clutlH: cr -'d al
`· in the track nnfi ll tJrati on an<.J
`th
`~: l·"d al
`. W ·us th • hctcrw~raft prosthesi~ in
`non- doth-c
`cases in which antic agulation is not poss ible. \ e all w ill
`ith great interest. th • longer t ' 1'111 rt:sLdts in
`surel y follow ,
`ti nson' . s•ri" · of pa ti ent:-. tel se~ , hat the tru ly late:
`Dr.
`ompli ·at ion rate " ill be.
`
`I N
`
`r r
`t 6 v •ars
`th r · i no informati on on ·ern in,
`cov r 'd va lv,.
`) w ca survi al with the non- clo th-co er~.:d
`the CllOf:;rall
`th
`ball- al v pro ·th '"'si s \ as 78 p ·r
`·nt, an I
`ith til '
`·loth-
`red val ~.:. 7 _ JK:r c~.:nt.
`1 10 years, , e have informatiL)n
`co
`for th e n ln- cloth-c v ·red alvt.:. th actu:.tri:.tl sur ivai
`onl
`rat b i ng
`I per ce nt.
`thrombo mblll i~m rat ', the · •noe.raft
`If one con. iders th
`actually pro iu s no significant impro
`cloth-co t:r d alv • <tnd it is not quite as athrombo~ ni · U!'>
`th cloth-e vcr ·d valv · for mitral val
`' r pi a cmcnt in an-
`I patient s. The im:idcnc> of thrnmbo rnl oli sm
`ti coag.ul at
`nogrart , as 31 prox.imat ~ 1 y 5 per cent per yca.r,
`with the
`versus 6 perc •nt per yt.::.:tr for the.: n(Hl- ·loth-co ed al · In
`th ' mitral position and 3 I er c ·nt per y ·ar r r th cloth-
`(~over 'd alv
`in th mitral 1 osition . Pai n, I .str 's. that pa-
`11 ' Ill :\ with th ·se ball val ws ha
`had long-t ·nn anti ouc.u lant
`tr 'atn1 ·nt .
`r ·1laccm 111. th · cmbnl ic ral ' i:- 2 P r
`l·or ·•ortic al
`·nt
`· no~ra!'t and l .ft p •rcntp ' r ycarfo d oth-
`P r ' ar forth ·
`.. ~vi th anti "ongulant s. Thcr~ i!-> no st<llistt-
`covered aort ic al
`~
`·all 1 sig nifl ant diffcr·nc.
`fair ,
`. Ad111i11 dl y . thi s comparison will not b· c<. mpl t ·l
`~Inc:
`tit ~ follmv-up i ~ so ~hort rnr th ' X ·nografl. Th rc m:.t
`h . clust ring nr 'aJ ly cmbnlk
`·omplil.'ations i n the lirst l('ilf
`, hi .1~ , oulu t .111J to skc'
`ol foll ow-u1 ,
`th
`information
`aga i~.· t th
`' nogral't prosth ·sis.
`. W11h til" track v al s, hnw •v ·r. the lon!:!.CSI and rn~an
`follow- up is th . sam as v ith the , cm>graft , and rhb series i:
`mur comparable. W
`.. ,11 sec no significant diiTL:rcn ·' in the
`results in t rms or survi al :.111d ·mbLlli · iocid"nce at til · ~nd
`oj' ) Y •ar. \ ith anti ·oa •ulunl therap . . rnr ' ampk , tllC 3
`y ar sur i v~tl rat · , ith tit · mitral xcnol!,raft is XS perc nl anLI
`Wit h the Ira ·k valv •. in th
`rnitrHI rnsi tion . 89 p r Cl! lll.
`~inet
`'-l wo p 'r ·ent nf patients wi th th · rnilrnl xcnn"rafl "~'1..!1''
`' rsus HY p r . ·ntnf thos· ' ith the mttral
`free of emh li ·m,
`track valve ( ligures d t rmin ·d ucwariall y).
`With regard to . ur ivai. r llowin J aoni · alvc r pine -
`
`RP --
`
`T I E R
`
`L
`R .
`Pwis. Fn111 c
`I would li ke to congratul ate I r .
`ell nt
`r. hum\ ay·~ group at
`anu \ ·II dm:ulll ntcd prcs' ntation.
`tanfonJ ha .. -. h ~· n pion. rin o inti ·su ' a l ve~ ror a lonr. tim
`and an staiem ·nt from thi s group d ~er : parli ·ula; all ·n~
`ti on.
`I shall l im it m ' comm ' Ills t
`th major pwbkm rais o b
`~ no graf't val e. w hi ·h is its durabilit ·.
`incc w
`intro-
`the
`uu ·ed the LI S of gllllara ldch d• for ' 11 oraft pr 'S'I'Va tiun in
`at g
`ar fn llo' -up . In a first p rind of
`196 ', \- · nm ha
`used t' o metho . 0 f
`clini cal in C'\ti gation ( 1968 to 1970 . ,
`glutaraldl.!hytle preservation: buff r ·d glut ara lu hyck 1 p r
`. p r c •nt
`fi rst I I patients an I glutara ldeh '0 •
`·cnt in th
`pl us :odium metal ·rioclate in a fnllm ing . cries or
`1 pa-
`ti ents. Because the incidence or al c fai lur"' was hieh r in
`l!.lutarald ~ h yde group. w · subsequ ntl
`th metaperiuclat '
`use I buff r •d glutnrald hyde ' ith ut m ·taperiodatc .
`al c
`failur . in both groups were or tlli' "C tyr · : inf · ·tinn . cal-
`~ iti ca ti o n, and ti ssue r ·rftm:ll inn or ll::ars . he third ·ompli ·a-
`tion was the r suit of
`ith r In alit.etl inllammator
`rca ·tion
`r fatig ue lesions.
`-
`·ample or alcif1carion o ne
`[
`lid·] Thi: slid shm . an
`. ar afta in'l plant<.~tion in th ~ pulmonary po. iti<lll .
`[
`lic.lc] Thi~ slide s h ow~ a al
`perforati on d u ~ to fati gue
`k ' i ns at
`years .
`It shou ld be e mpha~i;.ed th at n1o~> t nf thes
`failures oc-
`curred in val ·s pr ' J areu in our res •arch lahoratory befor~
`' became com mercially availabl •. T he incij nee of
`th
`al
`vul e f:.:tilur has b . n rctluccd in th
`JTtst -1 y ·ars by usin ,
`val es pr ·parco nn a lar~c ~ca l
`b) bcu ·r rnan11fa ·turin '
`facilities ' itll superior qualit) control.
`Th' main on· rn remains th ' ti ssu • fttti!!,U • lesions. On a
`·pec im n n:mov ·I at years, d'spitc '>.ell cnt henwd numic
`fun ·ti on. w· found ur ~a · of' ollag n d "t:ll •ration an I ·lasti c
`fib r rrn •111el1(3(iOn . he ti SSUe WaS SliP h(J
`thif11l ' f than he-
`n the oth r hand. th cusp surra ,, wa~
`for· implantati on.
`cov r·J by host fibrou s ti ssue. Thi ~ 1 ro · ·s. or n ·ap tllation
`is diff·r· nt from th at of hos t ''II ingrm th seen in valvular
`grafts, since th •r • is nn ce ll penetra ti on into th e tissue. Tlti ~>
`pro· ' !'>S
`·oulu be of -riti al
`imp rl an ·
`for th , lon!.!-l ·rm
`dttrabi li( I Of' (hCS" b iOj1fOS (h C~el> aS the \I:JIVC <; (J'LJ \.:I llfC is it sdf'
`rei nfnrc d .
`Thu s at I ~ a s t four factors ma play a rok in Lht.: long-I rm
`durability of 'I bioprosthes is:
`l iSS ll pr 'SCf ctti on, USe uf' a
`n xihlc stcnt. al c s ·I ctinn and mountinl!., and th proc · .
`
`STJUDE1043
`IPR of Patent No. 6,821,297
`
`

`

`2
`
`Iinson eta/.
`
`The Journal ol
`Thoracic and Cardiovascular
`Surgery
`
`R .
`Padua, /tal '
`diL:al chool , 55 1 ati nts
`nivcrsit
`At the
`hu
`had on or mor cardiac vnlv s r"pla oed with the Han-
`c ·k x nograft b nc
`f t o surgi al group . . Thi!-i
`~ nngrart
`was ria ··d in the mitral
`r aortic position. or both , in ° m
`pati nt-; and in the tri u pid position in oth r ·. I want to ~ i v
`m cr, 1975,a th
`ar
`o bricfr pcrlon urr sults upto
`a bit dif~ r nt from rhos dcscrib d by
`arp nti r with
`r.
`
`·ami nation of the alv _. that \1 as r mov d r cui d th at
`·usp. w r stiff: th r
`,, ere ur , of alcifi ation on
`ull th
`th th ... atrial unu v ·ntriculm surfaces . Histologi s ction!l
`w r r vi wed b Dr. Willium Robt:rl !-1 at lh National In ti·
`tut • · of H alth und b
`of
`ho
`a~>r d that thcr
`
`uni
`
`ur two surgi oul groups implant d glutarald hyd ·-pru-
`c ·ss ·d Hanco k xcnugrafts in -lA I 1 ali nts up to th
`~ n I of
`1975.
`r lid ] Th is slid sho s an a oluariul sur ivai curv · fol'
`mitral al
`repl acem ·nt, w hi ·h als comprises the hospital
`rat 0 It s em
`t 1 m v r signilkanl that
`morwlit
`from th
`first ' ar on, th cur c is on a straight hori zo ntal lin
`forth
`nc t SY1 y~a rs.
`I at complit:ation ·. In
`th
`[ lid ·] Thi s tabl , summariz
`387 pati nt!oi tl ' re \
`r 6 ·pi ·od S of thr01 b mbo li ~lll , 2
`·as s of' prosth si. failure, _ of ndo ar liti., and on
`·as of'
`miirul va lv rcstenosis.
`long-term
`is a functi lllal classifi ·ution of th
`[ lidc) Her
`survi or · with Hanco k
`nografts in th mitral position.
`Their pr s nt . tat us s' ms tn b quit good, as on 1rrn ~d by
`several hemodynamic controls. Most of th pati nt. hang d
`from N. Y.H.A.
`lasses ll1 and IV to
`Ia s s I and II .
`[n t: nclu ion , 2 years ag , in dis us. in Dr. Carp ntier' ·
`pap ·rat the Ass ·iation 111" tin 1 , [ stated thai our policy wa~
`
`acl: llllUiato mnt'
`ru le rath r tllilll
`prnhl ·m ma b th
`
`c ·ption.
`N ·v ·rthelc •s, with the pr s nl stat • of th art of pr . th ' tic
`the Han ·nl'k pnrcin ' valv prostiPsis ur·
`vulv pru<.lu tion
`r·ntly r mains our first-lin vn l
`
`R . T I N S N ( los in ')
`l ar and d tailed col11·
`Lurr' '
`I apprl! ·iut very rnu ·I
`m nt ' . I nt r-in. titutional ·omp·tri. ons ar dang r us, at
`-t,
`but n v rth less must I bas~d up nat least similar tati ·ti al
`tlcscrib d basicall y no
`ig·
`m ·Lhods of alcul tion . H ha
`nifi ant diff"rcnc s within th - c nstnlint of th
`f ll ow-up
`ri sk or throm·
`int rvals avui labl, for sur ivnl an I for th
`·c ption beinP" thal th m ·hanical pros-
`bn ·mholism
`th
`th si · uo s r ·quir
`long-t rm anti · agulation . Thi s fa tor
`must be tak ·n into ac ount in any loncr-tcrm omparaliVC
`'i.'
`f ·linical utilit .
`anul
`orin. tanc ,in ur valuati nof th ln,1-t rmre: ultswith
`
`STJUDE1043
`IPR of Patent No. 6,821,297
`
`

`

`Volume 73
`Number 1
`January, 1977
`
`pali ·nts . ontributing n arl. 5,0 0 patiGnt-
`ar ·
`' ho had und rg ne rcpla · ·mcnt ' ith th e
`for anal _. i.
`tarr-
`d\ ards Model 61 2 , 1200. or L60 val t:
`, I anal ,ud mor-
`bidity and monalit r rat s for antjcoa ulati n. The a eracr
`rate wa · 5.3 p r cent p r pati nt-y ar; that i~. for
`m rbidit
`any hem rrhagic epi sode. he mortality rat averaged 0. 8 per
`~ nt P r pati nt-y ar. Thi s consid rati n n ust b
`tak n into
`a -count in ompan.11i v 3 analy ·is.
`lu ·t"'r-
`tin mphasizing thatth
`r. 'hr was~d so corr
`ing r vents durin' un "arl y po11ion of th
`follow-up inter al
`is a r strictivc fact or in utili in • lin ari z d rates of thr m-
`boemboli sm , or an other su h e nt. in patient with a
`limit d durati on off llow-up .
`Dr. arp nti r i, recognized t
`
`a ion "r in thi
`
`fi eld . rt
`
`Porcine aorti
`
`'ah e xenografts
`
`6 3
`
`wa • quill: appropriat e for him to mphasize differences in th
`t p •s of h miL:al tr ·atm •nt of ti · ~ uc for long- term i mpl<.~nta­
`ti on. Bi che mi cally. there is a uross djffer n e bd\ ccn a
`proc S!)
`that
`inc rp ratt: n pr~.::viou s o ·idati n ·tep with
`. dium m tap "riodat and on which does not ,
`t:f r
`trt:at-
`ment with glutaraldehyd . Hi word of aution re arding th
`I ng-term utlo k is appr priat . I ann l respond to hi
`· mmcnt on th b:r is of our data. iw ·much a. t\ o al
`p ri n
`failures in a total
`or '532 ratient- car · simply do
`not pro ide a meaningful data bas
`for long- term c, trapola-
`
`ur on lu ·i n, I w uld sub-
`con(; pt that th
`ption
`
`STJUDE1043
`IPR of Patent No. 6,821,297
`
`