http://nyti.

ms/1IqOOzE
Health
MNDING HARTS

BuildingaBetterValve
A new approach to replacing narrowed heart valve allow older and icker
patient to urvive treatment.

ByGINAKOLATA

JUNE20,2015

Withhissmooth,fleshyfaceandtwinklyeyes,HerbertAuspitz,93,hadanair
ofvigor,buthewasfadingfast.Hehadafataldiseasewithaprognosisworse
thanthatofmostcancers:severeaorticvalvestenosis.Itisanarrowingofthe
valvethatcontrolsbloodflowfromtheheart.Thereisnowaytopreventitand
therearenodrugstotreatit.
Untilrecently,hisfatewouldhavebeensealed.Hisdoctorsthoughthe
wastoolikelytodieiftheycrackedopenhisribsandstoppedhisheartwhile
theycutouthisoldvalveandsewedinanewone.
Thistime,theyhadanewoption.Theywereabletoreplacehisvalveusing
amethodrecentlyapprovedbyfederalregulatorsforpeoplewhoare
inoperableorathighriskfromopenheartsurgery.Hiscardiologists,ledby
Dr.HowardC.Herrmann,insertedanewvalvemadefromtheliningofacows
heartthroughacatheter,thenopeneditlikeanumbrella.
LyingonastretcherafterthehourlongprocedureattheHospitalofthe
UniversityofPennsylvaniainPhiladelphia,asmilingMr.Auspitzsaid,Im
veryveryverygrateful.
Thenewvalveprocedureispartofthechangingfaceofcardiaccareinthe

UnitedStates.Butevenasspeediertreatmenthashelpedslashthedeathtoll
fromheartattacksoverallinthepastdecade,thenumberofdeathsfromheart
failurecausedbyaorticvalvediseasehasrisen35percent,inlargepart
becausemorepeoplearelivinglongenoughtodevelopit.Morethan8,000
Americansdiefromthediseaseannually.Itisanillnessofagingandan
estimated100,000AmericansareinMr.Auspitzsposition,toooldorsickfor
surgeryandwithaseriouslynarrowedvalve.Butrecentstudiesinverysick
patientshavefoundthenewprocedureprolongedlives,offeringnewhopethat
thedeathtollfromnarrowingvalvescanbereduced.
Theprocedure,calledTAVR,fortranscatheteraorticvalvereplacement,is
nowbeingtestedonamuchlargerpoolofgenerallyyoungerpatientsat
intermediaterisk.Somecardiologistssaytheyworryitwillbeusedinsuch
casesbeforetheevidenceisin.Otherssayitwilleventuallyreplacesurgeryfor
almosteveryonewhoneedsanaorticvalve,notjustforthemostfragile.
TheTAVRstoryisawonderfulexampleofatransformativetechnology
thatbeganwithanideamanydismissed,Dr.PatrickT.OGara,theimmediate
pastpresidentoftheAmericanCollegeofCardiology,wroteinJAMA,the
JournaloftheAmericanMedicalAssociation.
Withtheprocedure,anewvalveisfoldedupandslippedintoacatheter
athin,flexibletubewhichisthenputintoabloodvesselinthegroin.When
thecatheterreachesthebaseoftheaortathelargebloodvesselthatcarries
bloodfromthehearttotherestofthebodythedoctoropensaballoonthat
inflatesthevalve.Theoldvalveremains,pushedasidebythenew.Patientsare
awakeandonlylightlyanesthetized.
Youareputtingavalverightabovetheheart,saidDr.LawrenceH.
Cohn,aHarvardheartsurgeon.Ifyouarenotcareful,youcouldobstructone
ofthecoronaryarteries,causingabigheartattack.Thisisnotchildsplay.Itis
notforthefainthearted.
HenryKissinger,92,aformersecretaryofstate,hashadtheprocedure.I
wasgettingoutofbreathmoreeasily,andmycardiologistsaidsomethinghad
tohappen,hesaidinatelephoneinterview.HesaidIwouldbeina
wheelchairifIdidnthaveitandmysurvivalrateinayearwouldbeonly50

50.
Dr.MartinLeonofColumbiaUniversityMedicalCenterreplacedMr.
Kissingersvalvealmostayearago.
Iammoreenergetic,peopletellmeIlookbetter,andIfeelmuchless
tired,Mr.Kissingersaid.Hedescribedtheprocedureaseasierandless
debilitatingthantheopenheartbypasssurgeryhehadpreviously.Theresno
comparison.
Fornow,evidenceoftheprocedureseffectivenessexistsonlyforthe
sickestpatientsandthereareonlyfiveyearsofdataonhowlongthevalves
last.Mosthighriskpatientsareolderthan80withalifeexpectancyoffiveto
sevenyears,butthedurabilityofthevalvesismorecrucialforintermediate
riskpatients,whoaremorelikelytobeintheir70swithalifeexpectancyof15
years.
Thereissomequestionaboutwhethertheprocessofinsertingthenew
valvesloosensdebristhatcancausestrokes.Onelargestudyfoundahigher
strokerateinpatientsreceivingvalveswithoutsurgerycomparedwiththose
receivingvalveswithsurgery.Anotherlargestudydidnotfindthiseffect.The
valvesalsotendtoleakslightlyaroundtheedges.Newdesignsare
amelioratingthisproblem,butnotsolvingit.
Andtheprocedureiscostly.Dr.ReginaldBlaber,whorunsthe
cardiovasculardiseaseprogramatOurLadyofLourdesMedicalCenterin
Camden,N.J.,saidthehospitallostmoneywhenitusedthevalves,althoughit
offerstheproceduresoitcangivepatientsthebesttreatment.
Itsahardpropositionwhen$32,500goesrightoutthedoorto
Edwards,thevalvemanufacturer,hesaid.Thehospitalgetsabout$40,000
fromMedicare,whichisfineiftherearenocomplications.Butolderpatients,
intheirlate80sand90s,oftenendupwithfour,fiveorevensevenday
hospitalstays.Wecouldlose$25,000,hesaid.
Nonetheless,excitementisgrowing.
Ithinkthefutureisthateveryonewhoneedsavalvewillgeta
transcathetervalve,saidDr.CatherineM.Otto,anechocardiologistatthe
UniversityofWashingtonwhodoesnotdotheprocedure.Itsgoingto

becomethestandard.

ItStartedWithaPig
Ittookabrainstormand20yearstoproducethisbreakthrough.
TheideasprangtolifewhenaDanishcardiologistheardtalksonopening
arterieswithballoonsandstentstinywirecagesataconferencein1989.
Ithought,ifyoucanputastentinacoronaryartery,youprobablycan
alsoputavalvein,saidthecardiologist,HenningRudAndersenofAarhus
UniversityinJutland.IdecidedIwantedtobethefirstintheworldtoputina
heartvalvewithoutsurgery.
Heboughtpigheartsfromaslaughterhouseandcarefullycutoutthe
aorticvalve,mountingitbyhandinsideahandmademetalstent.Heputa
deflatedballooninsidethevalveandcrimpeddownthevalvewithhisfingers.
Hemadehisowncatheterandputthecompressedvalveontheend.Thenhe
inserteditintoapig.
Iwasluckyitworkedontheveryfirstpig,Dr.Andersensaid.After
operatingon40pigs,heobtainedapatentonhisdeviceandtriedtogeta
companytodevelopit.
Nobodywasinterested,hesaid.
Aroundthattime,inFrance,Dr.AlainCribier,acardiologistatHpital
CharlesNicolle,inRouen,wasthinkingalongthesamelines.Hewasahighly
regarded,successfulinnovator,sohethoughtitwouldbeeasytofinda
company.
Istartedlookingforcompaniestohelpme,butitwasacompletefailure,
hesaid.AllthecompaniesintheUnitedStatesandEuropeandJapan,they
haveexperts,andtheexpertsaresurgeonsandtheysaiditisabsolutelynot
possible.Wewouldkillthepatientsonthetable.
HejoinedforceswithaformerJohnson&Johnsonexecutive,Stanton
Rowe,whobeganmakingtheroundsofventurecapitalists.But,Mr.Rowe
said,theirresponsewasalwaysthesame:Wewilllookintoit.Andwhodo
theycall?Thesurgeons.Theytoldthemallthereasonswhyitwontwork.

Dr.Cohn,theHarvardheartsurgeon,saidheandhiscolleagueshadgood
reasonstolookaskance.Theythoughtitwasstrangethattheoldvalvewould
justremainintheheart.Theywonderedwhythenewonewouldnotflyoffinto
therushofbloodbeingpumpedintotheaortaafterall,itwasnotbeing
sewnin.Andpushingavalveintoanatheroscleroticartery?Piecesofplaque
couldbreakoffandcausebloodclotsandstrokes.Finally,headded,itwould
takepatientsawayfromsurgeons.
Wewereskeptical,hesaid.
Twoandahalfyearslater,afterDr.Cribierhadpracticedinsertingvalves
insheep,a57yearoldmanarrivedathishospitalneedinganaorticvalve,on
thebrinkofdeath,withalmostnoheartbeat.Hehadsomanymedical
problemsseverecoronaryarterydisease,chronicpancreatitisthatsurgery
wasnotanoption.Thenagain,nohumanhadeverhadavalveputinwithout
surgery.
Ihadtoaskthepatienthiswish,Dr.Cribiersaid.Hisresponsewas,
Please,pleasedoit.
Itwasthemoststressfuldayforme,hesaid.Sheep,heexplained,donot
developaorticstenosis,andtheiranatomyisverydifferent.Wewerenotsure
wecouldtranslateitintoman,hesaid.
Assoonasitwasimplanted,Icouldseebloodcomingbacktohisface.
Twohourslater,weweredrinkingChampagneinhisroom.
FrenchregulatorseventuallygaveDr.Cribierpermissiontotrythe
procedureonpatientswhoselifeexpectancywasjusttwoweeks.Heandhis
colleaguesoperatedon45mostlyolderadultpatients,andsuccessfullytreated
38.Onepatientsurvivedaslongassixandahalfyears.
Buttheprocedurewasrisky.Itrequiredthreadingacatheterupthrougha
veininthegroin,goingacrosstheheartfromtherighttoleftside,passingthe
catheterthroughthemitralvalvebetweentheupperandlowerleftchambers
oftheheart,turningacornerinthelowerleftchamberandthenheadinginto
theaorticvalve.Itwasalltooeasytodamagetheheartwiththatstiffcatheter.
NobodybesidesCribiercoulddoit,saidDr.MichaelMack,asurgeonat
BaylorHealthCareSystem.

SuccessinAmerica
Nonetheless,in2004,EdwardsLifesciencesboughtPVT,thecompany
startedbyDr.Cribierandhiscolleaguesforabout$125million,mostofwhich
wenttoinvestors.
In2005,theresearcherstookthemethodtotheUnitedStates.Expertsat
fivemedicalcenterstrieditonfivepatients,thesickestofthesick.The
procedurewassotechnicallydifficultandthepatientssosickthatonlytwo
survived.
Theresalotofthingsinlifethatyouseeandsay,Shoot,whydidntI
thinkofthis?Dr.Macksaid.ImakenoapologiesfornotthinkingofTAVR.
Ineverthoughtitwouldwork.
Theresearchersbeganrethinkingtheprocedure.ThattorturousrouteDr.
Cribierhaddevised,goingthroughthegroinvein,wasnotworking.So
Edwardsmadenewcathetersthatcouldgostraighttotheheartthroughthe
groinartery.Thedisadvantagewasthatbypushingacatheterupstream
againstthedownwardrushofbloodthroughanartery,therewasagreater
chanceofbleedingordamagetotheartery.
BeforethemethodcouldbeapprovedintheUnitedStates,theFoodand
DrugAdministrationrequiredalargeclinicaltrial.Itbeganin2007,sponsored
byEdwards,andresultedinanapprovalforpatientswhocouldnothave
surgery.
Theresults,publishedinTheNewEnglandJournalofMedicinein2010,
showedthatforthesewhocouldhavesurgery,TAVRwasatleastasgood.For
thosewhocouldnothavesurgery,avalvereplacementwithTAVRreducedthe
deathrateby20percentinthefirstyear.
That,saidDr.LeonofColumbia,whowasthetrialsprincipalinvestigator,
wasremarkable.Ifwetreatfivepatients,wewouldsavealifeinthefirst
year,hesaid.Thereareveryfewtreatmentsinallofcardiovascularmedicine
thatcouldclaimthatIcanthinkofhearttransplant,andthatsit.
Theresultswereevenmorenotable,hesaid,becausetheearlyversionsof
thedeviceswereclunky,stiffanddifficulttouse.

TheF.D.A.approvedthemethodwiththeEdwardsdeviceforpatientsat
extremelyhighriskin2011.
Thatyear,Dr.Mack,whowasthenthepresidentofthethoracicsurgeons
society,andotherleadersmetwiththeF.D.A.andMedicaretodeviseaplanto
restrictthedevicesspreadtoplaceswheredoctorshadsufficientskillto
implantthemsafely.Theresultwasarequirementthatahospitalshouldbe
doingatleast50surgicalaorticvalvereplacementsayeartohaveaccesstothe
technology.ItwaswrittenintotheMedicarecoveragedecision,afirstfora
medicaldevice.
Thistechnologyisexpensiveandhighrisk,Dr.Macksaid.The
consensusofthegroup,hesaid,wasthatnoteveryoneofthe1,150cardiac
surgeryprogramsorthe1,600cathlabsintheU.S.shouldbeabletodoit.
InJune2014,afteranothercompany,Medtronic,didsimilarstudies,its
devicewasapproved,too,forhighriskpatients.
FormerskepticslikeDr.Cohnnowrecommendtheprocedureforhigh
riskpatients.
Morerecent2015datafromMedtronicindicatethatitsvalveisactually
betterthansurgeryforhighriskpatients,resultinginfewerdeaths,atleastin
thefirsttwoyears.AndnewdatafromanotherlargestudybyEdwardsfound
thatpatientsatintermediateriskdidbetterwiththenewestversionofitsvalve
thanwouldbeexpectedwithsurgeryinthefirst30days,whenmostdeaths
occur.Trulyphenomenalearlyresults,Dr.Herrmannsaid.
LastWednesday,theF.D.A.approvedthenewEdwardsvalveforhighrisk
patientsithadbeenavailableonlyinclinicaltrials.Medtronicalsohasanew
versionofitsvalvethatcardiologistsexpectwillsoonbeapproved.
Dr.Herrmann,aclinicaltrialinvestigatorforbothcompanies,saidthe
Edwardsvalveresultsweresoimpressivethatcardiologistsmightchangethe
waytheyevaluatepatients.Insteadofaskingifapatientistoosickforopen
heartsurgery,andthusacandidateforTAVR,theyshouldstartassumingthat
mostpatientswithsevereaorticvalvediseasewouldgetTAVR,evenifthey
couldsurvivesurgery.
Nowbothcompaniesarestudyinglowerriskpatientsinlargeclinical

trials.
Mr.Auspitz,the93yearoldmanwhosevalvewasreplacedin
Philadelphia,hadnotheardoftheprocedureuntilhisdoctorsuggesteditlast
year.Mr.Auspitzhadbeeninarehabilitationcenterforamonth,recovering
fromahospitalstayforheartfailure.Likemanywithaorticvalveproblems,he
hadblamedoldageforhisfatigue,shortnessofbreath,lackofstaminaandthe
fluidaccumulationinhislegsandfeet.
Afewdaysaftertheprocedure,Mr.Auspitzwassmilingandhappy,and
abouttogohome.
Afewmonthslater,hissonPaulwashelpinghimexerciseeverydayusing
bandsandlightweights.And,Mr.Auspitzsaid,forthefirsttimeinyearshe
wantedtopaintagain.HeplanstostartwithaportraitofPaul.

2015TheNewYorkTimesCompany