`Medtronic, Inc., Medtronic Vascular, Inc.,
`& Medtronic Corevalve, LLC
`v. Troy R. Norred, M.D.
`Case IPR2014-00111
`
`
`
`
`as
`(fig
`V W
`I
`~
`PERCUTANEOUS AORTIC p
`/fl'_ ‘(.1/yfj.»-.”Jr-»(r5’”
`VALVE
`REPLAcENi?Egi§/twig: g
`
`
`
`
`
`r
`
`.
`
`-r'....-fl/if
`
`5”‘
`
`
`
`The aortic valve undergoes a series of changes based upon the
`structure at birth and the dynamic stresses, which“-it+has-to~undergo~~daily.
`(:22
`The trileaflet aortic valve will not become stenotic usually until the 7”‘
`decade unless infectious processes are introduced sooner. The incidence of
`aortic stenosis can reach between 2 to 9 % in this age range. The average
`moitality rate at all ages is 9% /year which also increases as a population
`ages. Coupled with these facts is the likelihood that as a person ages and
`becomes symptomatic with aortic stenosis, he is less likely to be an
`operative candidate. The mortality of octogenarians has been reported as
`high as 20% for aortic valve replacement that can preclude a reasonable
`attempt at the therapy of choice, which is surgical replacement.
`
`_
`
`_ % (M
`V
`i
`if
`
`4
`
`i In an attempt to formulate an effective therapy for this class of patients, I
`have designed awseries of devicepgyvhich can be placed nonsurgically so as to
`minimize thegfiishl to the patient cl” ring the procedure. This procedure
`M,
`involves novel/as well as known e uipment and techniques.
`‘V ‘X ) /),,,i9:,.i—.»..« /
`A
`5/l’”"’ii/A
`if
`:/‘/26'/‘a’?//“H/i’ Wax‘
`675"‘ 7/"(V
`The first in ailine ofoptions involves the placement ofan aortic valve
`5,
`‘
`"/4‘ y f
`V (5 /1; 3?’ / '75 (‘fl
`incorporated within a stent. This device wouldWb_ey_ aigchored in theH_a§c_flending
`/.
`,5, p
`A aorta with further support supplied in br»aric'l:ii"'vesps§;l,‘s«or des'C§§:Qj_9_gM§9,rl§§1 as
`.7! a
`'
`/;%;l*‘f"/fit‘
`[A <3 K,»/T/7% seen necessary by the stress forces placedwuponwthe artificial valve and \\»~\
`I
`/
`("(1W
`.
`gr/or
`I N
`if M calculated before the procedure (please see appendixli. Theovalve would be
`[/3 ‘:;.;,/h C “
`connected to the stents by serially connected rods. This design would
`M
`er?
`displace the forces placed upon the artificial/biomechanicavbioprosthetic
`x/5‘ ‘J -,/26 \
`.24 valve across a large surface area. Placing the device nonsurgically
`t ’’/:,:,/l’
`eliminates the need for bypass pump or sternotomy for placement.
`art‘. [/7
`FIGURE 1. There are several variations to the valve design that can be
`/9’, M K
`utilized using these techniques and concepts. The first is the umbrella
`‘M g
`A
`gggflshapiednyalyegjivhich w9Mul;dW_b”eWy_pyla9Me;d% in a position above the native valve,
`MW
`and WhE{}.il.E.9lL%IZ$§S, Woui d seal the Opening between the aorta and left
`ventricle. Thi ~we=ald~al-sc ~ akeTeit~idealrfonthese-vpatierits~whepriinari*ly
`/flhavemacrtie-re
`rgitation.
`"he hinges can be of several types: (in order to
`//”' produce as mu h laminar ow characteristics as possible) 1. Stainless steel
`rods envelope within a r bet or plastic polymer that would withstand
`i
`""“:J4»4:v{//“')‘6'~~:’1»4i"‘"l£’~’“~L«*’1"’i’
`(:1/C..:T(fii.~‘i,/»L{l/y /
`/7x:f~c1~-«:’.’»i/‘i’"
`
`if
`
`r»71?f
`
`/
`
`AM
`'3
`:1, fiigifln/ii
`
`'
`
`1
`
`i
`
`U//«Mi/5 C)/'}/*1
`
`'
`
`_
`,
`V
`4.?-;(,.i»z»««,/{ /J.a»-vzwevc 4.
`.5;
`,
`.
`
`
`
`l
`_
`_
`/5921. z»uwt'I?W7-";i.3
`‘(:;7,7a.a:vr.'i
`
`4.;;,.«;%,.az».%
`
`55%»
`‘
`
`
`
`
`
`
` Z/1/Z’i(ZT /J A’ A
`.«:'.;../ice’ c;"..,.w £1/...,.... ML~z<3\~«.«_.ta..'ZZ7/legs)
`~~"
`y
`
`./W /j_{._,4_
`i.g\...;.::
`E
`and plastic polymer with
`/3 sheer stresses with opening and closing; 2.
`the thickest portion at the bases and the narrowest portions at the center so
`My 4_,_;\,§
`that it folds during systolic contraction of the left ventricle. The tip of the
`valve would be of a semicircular design to permit the much desjr.ed...la_m.inar~* AjlH,_.,..,.g{....M'v1 :7
`flow characte_ris_ties__..o£theiWa9urt”icvyal§/e. This would decrease the shear stress
`\/(5
`..
`placed upon the aortic root and ascending aorta. The design rngayykpa sow
`incorporate a semi circular configuration opposing the______M _al_ja>so
`as to disperse the stress upon the aortic valve along a larger surface a a and
`to maximize the flow characteristics to the coronary arteries. This valve
`
`would be placed within a catheter system. However a steering and
`placement mechanism, incorporating a connection of removable rods guide
`by a half ball configuration may be necessary. The femoral artery would
`aecessed»':aa1dbt§annulated. _:l:l;eMf_€2,111;Q1;al-3.1_e.i.:l;3?YQ14_ld be sa
`cannulatecl. g9;h.V,ag§fa§j\”ué7§rade andretrogrademappfroiaidlifwould be used to
`y » VMM_W/i3.laC§"tfi锧fEn’[/Va]Ve combinatiloniiiiwithiin the right ‘anatomical position. The
`.
`L ‘M visualization would utilize continuous roentgenogram and ultrasound
`ring.../_‘,. 531%:/:5;
`techniques, which are currently available. The most important visualization
`//""""/llW,,...a
`tool would be ICE (intracardiac echocardiography). In this valve model,
`/ direct connection of the valve to the aortic root would not be utilized unless
`the direction of the jet from the aortic valve made it necessary. The
`, procedure would involve inflation of balloons within the aortic valve and
`1 ascending aorta to deploy the stent/valve combination. If traditional
`valvuloplasty does not produce significant enough opening of the aortic
`valve and relieve the gradient between the left ventricle and aorta then a
`series of further steps may be required.
`Removal of the native aortic valve would not be necessary. The focus
`would instead be upon debulking of the native aortic valve. The central
`theme would hinge upon abolition of the resting gradient. The techniques
`employed would attempt to achieve a large effective aortic valve area
`regardless of the functioning of the native valve post-procedure because an
`artificial valve designed to prevent aortic regurgitation would be in place.
`The valves are designed not to hinder the ejection of blood from the left
`ventricle, and to minimize the aortic regurgitant volume. These techniques
`may include the positioning of an Er»-YSGG percutaneous laser to decalcify
`the valve and repeat balloon aortic valvuloplasty. If not effective then high
`frequency ultrasound percutaneously applied may be necessary. These
`techniques have been shown to be highly effective at producing debulking
`and preventing restenosis. However, they produce tremendous aortic
`regurgitation. This would not be a problem for the unattached valve which
`would work as stated previously for aortic regurgitation. if the desired
`‘
`L’.t,.«g..c..
`/...(.,<.~:»:’.—r.r/‘
`vb»
`4:1.
`,/9/Zv:*«.»~r./m~r*’
`
`a
`
`.,.._j,g:»/
`_//.mw,4{
`A
`
` . ».;.)_b
`
`c;I...»..//24/4»:/2/<«e8«»%:t2
`I
`,
`\i“».._
`i"’/i..%I:{..:<?t
`5:14 sf-rr’~/i71"z!»»~v-»;§
`
`,.,/9 6 ‘AC/is
`if
`
`.;,._,1..._.g
`
`/72¢’—-<«»;354'evfl“f‘"”39
`
` //
`
`j/Z.a>/ 4:}/{/LL-«ff?
`
`‘
`
`
`
`cg;;i4:.t»}./,1
`4.2" gwzi
`/ax/L at /.1»it«/T»-We
`(,//
`/L,,<f/////z-’(,,/1,/L.4».»«»,«“"l
`
`.
`
`(«cw-
`
`NORRED EXHIBIT 2153 - Page 2
`
`
`
` v
`
`«::>
`
`«‘
`
`,
`
`4&9“ Cgékéjars.)/L:;>4.Ae?~é‘} "(Z2 /;:¢—z’ 4;: 5»;
`,/
`,./.4“?/?««/.i':2r‘--‘~«~
`LA,
`
`'
`
`(::>'“{-.z7.,:l”lT7v(//i’V_¢)",‘c{/’’/‘L
`
`/3'\«’i?,<%‘;'f("'1:7
`(TM
`,.rfl>---»v<E7’?""‘f3
`(x¢.(f’(;“-‘Ci-»vz,
`CZ U/V99;
`,/
`'W..%..IL, x._
`g” »-:7,
`4 ”
`._
`§
`A
`..
`/“'«~€'—~‘5"‘5"’(
`Qwéj
`'fl/
`[W
`_/s4»..»¢:;‘€§’,.r2M/<.A«.,.A1i:2
`M
`‘fix *
`M
`I
`‘~L”/}
`I/1,.~z',,..zi«,),«d/Mwéfifi
`{ gtivua/’ 5/
`1 1/vvL.{J(3ZZ»»L,~.2?«é’:J
`fl/(fi""“”"‘iV:'$“”{d
`
`Z{:,;;,€;
`
`Q.
`
`“l;(Z/"‘~*(,"V‘*
`
`_ //,}4,A,é3i/C«;€..¢./37;
`V
`‘
`
`/1/\,u(22~/5 M
`
`I
`
`,
`
`:9 CAj%€V€P
`
`/)<t-rz / U’ 617’? ‘/
`
`§y§7§M
`
`JflPaev¢Md
`
`/2 1.2’ cf 7‘ (//Z 67
`
`NORRED EXHIBIT 2153 - Page 3
`NORRED EXHIBIT 2153 - Page 3
`
`
`
` /
`
`,</_)
`
`
`\,4,é::g,r
`C;
`'_“
`¢,..,;;%.»..«.i../4:2‘
`6”./"'1/"L L*“«~"1"L«//7
`
`,4f2ft<,.x;»(7-uai. <3
`
`‘A?
`
`..
`
`('7
`
`..
`
`/.
`
`I /£44,‘
`/)"‘ .
`,.e’
`i/‘”‘'’/''
`:3‘ Bi?
`(Xx!
`3/‘
`I /
`ii/—«’
`3
`,,r:‘»v*
`.
`(V)?/(.»z,r
`6 /V’
`\/kt/'
`, \.
`'
`»>.../»"'A/Y 2
`(MN
`,1.»
`
`U 1‘ M “Q
`¢x«<~' f
`__,t.-
`/"
`>>a.
`
`»
`
`..,
`_
`[L/.
`(u/(4.
`«r~m,,
`[:/‘IL/‘T’/Z»’1v()':f\L:j'”"L./':\.-’~/Xv‘
`results were not seen then a host of options are still available; for example,
`two rings could be guided onto both the aortic and Ventricular sides of the
`native aortic valve and pneumatically sealed together. Then expandable and
`gjczp’/é)/l/"5 ‘
`.‘\‘NrI\\f7lu"’
`A "’”"'”retra‘ctab'le’”bigtomes could be percutaneously placed for cont/rp/1,lgeMd_
`disseetign of the native aortic valve. Along this concept, the biotomes could
`.,/O /£146)
`be used for primary resection without stabilizing rings, but there would need
`to be a stabilization mechanism. Another such mechanism could employ the
`use of a micro screw into the native Valve, which would act as an anchor to
`guide a biotome onto the native valve. Then the biotomes would take small
`snips in a controlled fashion off of the native valve. This would gradually
`increase the effective orifice area.
`because the artificial valve is
`not anchored or dependent upon the native valve for its function, this_____W
`technique could be easily reapplied, if the native valve were toqif6st§pMc3s§;>»«
`without compromising the artificial valve. A tremendous advantage of this
`,, procedure would be its independence from a need for a percutaneous bypass
`‘
`.
`,
`‘
`,/ ’
`ix)"
`'
`/,/L.
`./""c>"“'*"" ~7*"-*"“"”€“"",
`
`
`
`The second valve design could be best desc ibed as a conical design. It
`would be composed of 16 to 32 individua rubber/plastic/metal plates, which
`would be interconnected by resistant_/.fal§fi:c2‘ Figure 2 shows how this valve
`would be connected tcget-her. It would be placed in direct opposition of the
`native aortic valve. It would expand during systole and collapse during
`diastole.
`It would also be anchored along the aortic root wall with
`connecting rods to the ascending aortic stents. The rods would be placed
`between the right and left coronary ostia tangentially along the Einus of
`Valsalva. In this design there would not be any intraluminal rods within the
`ascending aorta as with the umbrella design. The techniques described
`above to relieve the aortic stenosis would also be applicable to this valve.
`This valve however may not be the best valve for isolated aortic
`regurgitation given the direct placement of the valve over the native valve
`may impede opening and create an outflow obstruction. However, given the
`curved and redundant nature of this valve, and the fact that it centralizes the
`ejectionjet from the left ventricle, it may produce the most laminar flow
`characteristics and the le_a§_t,,hematplogie sequelae. The edges may need to
`have a loose rim ofglfiblé Ij[13_1§§_21fial, which act as a flap valve, to help reduce
`peri-valvular leaks (See aplpendix). To minimize components and to aid in
`miniaturizing the device f r delivery, the connecting cones can be reduced to
`2 -» 4 interconnecting rods, which are draped in a sheet of fibrous polymer
`(See appendix).
`
`NORRED EXHIBIT 2153 - Page 4
`NORRED EXHIBIT 2153 - Page 4 T
`
`
`
`Other valvular designs whichkmay prye valuable to this technique include
`the ‘usage of cadaver/porcine “ corp ated valves placed within a
`
`percutaneously stented system
`oulcl have the benefits of favorable flow
`and hematologic characteristics. T e initial designs are shown in the
`
`appendix. Also tilted disk/duo
`design could be hinged and compacted
`within a percutaneous system to p ovide reasonable partition between the
`
`left ventricle and aorta. Howeve , hese valves have been shown to have less
`favorable hematologic sequelae T e central themes involve increasing the
`effective aortic valve orifice ara iile minimizing the resultant aortic
`
`regurgitation. Thus, the goals “ red cing left Ventricular energy expenditure
`
`and its resultant long-term suelae f pressure overload would be met with
`this system of percutaneous‘ deliver id aortic valve/s.
`
`
`NORRED EXHIBIT 2153 - Page 5
`NORRED EXHIBIT 2153 - Page 5