ValvularHeartDisease

MarkJ.Pirwitz,M.D.,F.A.C.C.President/C.E.O.,SetonHeartInstitute

PhysicianExecutive,CardiovascularServiceLine,SetonHealthcareFamily

ChiefofDivisionofCardiology,AssistantProfessorDepartmentofMedicine,UniversityofTexasDellMedicalSchool

PrevalenceofValvularHeartDisease

•  PrevalenceinU.S.A=2.5%–  0.7%age18-44–  13.3%overage75

•  Epidemiologyhaschangedsignificantlyoverpast50years•  Declineinrheumaticheartdisease•  Steadyincreaseinlifeexpectancyresultinginmore

degenerativevalvedisease

RelativeDistributionofNativeHeartValveDisease

Heart,Lung,B.,Volume94,519–524,©2008

EtiologyofValvularHeartDisease

Iung,B.&Vahanian,ANat.Rev.Cardiol.10.1038/nrcardio.2010.202

AorticStenosis

RiskFactorsforDevelopmentofCalcificAorticStenosis

§  Increasingage§  Malegender

§  Hypertension§  Smoking

§  Elevatedlipoprotein(a)§  ElevatedLDLcholesterol

AorticStenosis-NaturalHistory

OttoCM.Timingofaorticvalvesurgery.Heart.2000;84:211-21.

•  Survivalafteronsetofsymptomsis50%at2yearswithoutintervention

5YearSurvivalRates

23

4

12

30 28

3 0

5

10

15

20

25

30

35

BreastCancer

LungCancer

ProstateCancer

OvarianCancer

SevereInoperableAS

ColorectalCancer

NationalInstitutesofHealth.NationalCancerInstitute.SurveillanceEpidemiologyandEndResults.CancerStatFactSheets.

Survival,%

ManagementofAsymptomaticAorticStenosis

•  AsymptomaticpatientswithAShaveoutcomessimilartoage-matchednormaladults.

•  Treatmentofconcomitanthypertensionandhyperlipidemia•  Nospecificmedicaltherapyhasbeenshowntoslowprogressionof

diseaseprocess•  PhysicalactivityisnotrestrictedinasymptomaticpatientswithmildAS;

thesepatientscanparticipateincompetitivesports.PatientswithmoderatetosevereASshouldavoidcompetitivesports.

•  BaseduponACCguidelines,echocardiographyisrecommendedfor:–  re-evaluationofpatientswithknownASandchangingsymptomsorsigns–  re-evaluationofasymptomaticpatients:everyyearforsevereAS;every1to2

yearsformoderateAS;andevery3to5yearsformildAS.

AorticStenosis–ProgressiontoSymptomaticDisease

Study,year #ofpatients SeverityofAS Event-freesurvivalwithoutsymptoms

Kelly,etal.1988 51 Vmax>3.6m/s 59%at15months

Rosenhek,etal.2000 128 Vmax>4.0m/s 67%at1year

Das,etal.2005 125 AVA<0.8cm2 46%at1year

Pellikka,etat.2005 622 Vmax>4.0m/s 82%at1y67%at2y33%at5y

SurgicalTreatmentforAorticStenosis

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Sur

viva

l, %

AVR, Sx

No AVR, Sx

BrownML,PellikkaPA,SchaffHV,etal.JThoracCardiovascSurg.2008;2:308-315.

•  InsymptomaticpatientswithAS,AVRimprovessymptomsandimprovessurvival.•  Intheabsenceofseriouscomorbidconditions,AVRisindicatedinvirtuallyallsymptomaticpatients

withsevereAS.•  AverageperioperativemortalityintheSTSdatabaseis3.0%to4.0%forisolatedAVRand5.5%to6.8%

forAVRplusCABG

TypesofValveProstheses

•  Mechanical–  Ballandcage(Starr-Edwards);singletiltingdisc(Medtronic-Hall);bileaflet(St.

Jude,Carbomedics)–  Durablewithlowratesofmechanicalfailure–  Generallyhemodynamicallyefficientexceptinsmallsizes–  Requireslong-termantithrombotictherapy(INR2.5-3.5x3months,then2-3

thereafter)•  StentedHeterograft

–  Bovinepericardialorporcineaorticvalvetissue–  Imperfecthemodynamicefficiency–  Lowriskofthromboembolismwithoutcoumadin(<0.7%/yr)

•  StentlessHeterograft–  Stentlessporcinevalvetissue–  Enhancedhemodynamicefficiency–  Lowthromboembolicrisk

StructuralDeteriorationofBioprostheticValvesAuthor,Yr ValveType TimeofSVD PatientAge,Yr FreedomfromSVD,

%

Jamieson,1988 Porcine 10 30-59 81

Burr,1992 Porcine 13-15 <65 62

65-69 98

70-79 95

Pelletier,1995 Pericardial 10 <60 86

60-69 95

>70 100

Banbury,2001 Pericardial 15 55 70

65 82

75 91

ProportionofPatientswithSevereAorticStenosisTreatedwithAVR

Only26-57%ofpatientswithsevereASultimatelyundergoAVR

TAVR–TranscatheterAorticValveReplacement

•  Forpatientswhoareeitherathigh/prohibitiveorintermediateriskforopen-heartsurgery,TAVRmaybeanalternative

•  Thislessinvasiveprocedureallowstheaorticvalvetobereplacedwithanewvalvewhiletheheartisstillbeatingusingcatheter-basedtechniques

EdwardsSAPIENTranscatheterHeartValve

Bovinepericardialtissue

PETskirtStainlesssteelframe

TAVRAccessTechniques

Additional:Subclavian,Innominate,Carotid,Transcaval

PARTNERRESULTS:TAVRvs.StandardMedicalTreatment(Mortality)

PARTNERRESULTS:TAVRvs.StandardMedicalTreatment(FunctionalClass)

PARTNERRESULTS:TAVRvs.SurgicalAVR(Mortality)

TAVRinIntermediateRiskAorticStenosisPatients

•  PARTNER2ATrialrandomized2032intermediateriskpatientstoTAVRorSAVR

•  TAVRnon-inferiortoSAVRwithregardtomortalityordisablingCVAat2years(19.3%vs.21.1%)

•  LowerratesofAKI,Afib;largerAVA;shorterlengthofstaywithTAVRvsSAVR

MBLeon,etal;NEJM4/2/16

SetonHeartInstituteValveProgramYear Volume

2014 11

2015 29

2016 47

2017 79

24

InHospitalMortality 1.3%(1.5%)

MajorBleeding 1.3%(1.7%)

LOS 1.9d(1.9)(6din2015)

CVAat30d 1.3%(2.0%)

>mildPVLat30d 0%(1.2%)

30dReadmission 11.4%(7.7%)

Rolling4QuarterClinicalOutcomes

AorticInsufficiency-Etiology

•  idiopathicdilatationoftheaorta•  congenitalabnormalitiesoftheaorticvalve(mostnotablybicuspidvalves)•  calcificdegeneration•  rheumaticdisease•  infectiveendocarditis•  systemichypertension•  myxomatousdegeneration•  dissectionoftheascendingaorta•  Marfansyndrome•  traumaticinjuriestotheaorticvalve•  ankylosingspondylitis•  syphiliticaortitis•  rheumatoidarthritis

AcuteAorticInsufficiency

•  Diagnosis–  Newdiastolicmurmur,tachycardia,rales–  Pulsepressuremaynotbeincreasedbecausesystolicpressureis

reducedandtheaorticdiastolicpressureequilibrateswiththeelevatedLVdiastolicpressure

–  LVsizeisusuallynormalonexam,CXR,echo–  Echocardiographyisindispensableinconfirmingthepresenceand

severityofthevalvularregurgitationanddeterminingitscause–  Ifdissectionissuspected,TEE/CT/MRIisindicated

SuddenLargeRegurgitantVolume

Tachycardia,Hypotension,PulmonaryEdema

AbruptIncreaseinLVEDPwithDecreased

ForwardStrokeVolume

AcuteAorticInsufficiency-Treatment

•  Deathduetopulmonaryedema,ventriculararrhythmias,electromechanicaldissociation,orcirculatorycollapseiscommoninacutesevereAI

•  Urgentsurgicalintervention•  Nitroprussideforacuteafterloadreduction•  Dopamine,dobutaminetoaugmentforwardflow•  IABPiscontraindicated•  CareshouldbetakenifB-blockersusedinthesettingof

dissectionasthismayblockcompensatorytachycardia

ChronicAorticInsufficiency

•  Diagnosis–  Diastolicmurmur,displaceLVimpulse,widepulsepressure,S3–  LVsizeisusuallyenlargedonexam,CXR,echo–  Echocardiographytoconfirmthepresenceanddeterminetheseverity

ofthevalvularregurgitation,assessaorticrootsize,andevaluateLVfunction

SlowIncreaseinRegurgitantVolume

Initially,MaintenanceofForward

StrokeVolumeandLVEDP

IncreaseinEnd-DiastolicVolumeand

LVCompliance

IncreasedAfterloadResults

inImpairedContractility,

ElevatedLVEDP

ChronicAorticInsufficiency-NaturalHistory

Asymptomatic/NormalLVfunction ProgressiontoSxand/orLVdysfunction=6%/yr

ProgressiontoLVdysfunction=3.5%/yr

Suddendeath=0.2%/yr

Asymptomatic/LVDysfunction ProgressiontoSx=>25%/yr

Symptomatic Mortality>10%/year

ChronicAorticInsufficiency-MedicalTherapy

•  VasodilatortherapyisindicatedforchronictherapyinpatientswithsevereARwhohavesymptomsorLVdysfunctionwhensurgeryisnotrecommendedbecauseofadditionalcardiacornoncardiacfactors.

•  Vasodilatortherapyisreasonableforshort-termtherapytoimprovethehemodynamicprofileofpatientswithsevereheartfailuresymptomsandsevereLVdysfunctionbeforeproceedingwithAVR

•  Maybeconsideredforlong-termtherapyinasymptomaticpatientswithsevereARwhohaveLVdilatationbutnormalsystolicfunction–  2smallstudies(Nifedipinevs.Digoxin;Nifedipinevs.Enalaprilvs.placebo)

•  Vasodilatortherapyisnotindicatedfor:–  asymptomaticpatientswithmildtomoderateARandnormalLVsystolic

function–  asymptomaticpatientswithLVsystolicdysfunctionwhoareotherwise

candidatesforAVR–  SymptomaticpatientswitheithernormalLVfunctionormildtomoderateLV

systolicdysfunctionwhoareotherwisecandidatesforAVR

MitralStenosis

•  Etiology–  Predominatelyduetorheumaticcarditis.Lesscommonlycongenitaloraquired(LAmyxoma,severeannularcalcification)

•  2:1female:male

MitralStenosis•  Pathophysiology

–  ReductioninvalveareacausesincreasedtransmitralgradientresultinginelevatedLApressure,pulmonaryedema,diminishedcardiacoutput.

–  Valveareas>1.5cm2usuallydonotcausesymptoms,butdecreasesindiastolicfillingtimefromtachycardia(infection,Afib,pregnancy,etc.)increasesMVgradientandmayprovokesymptoms.

–  Progressive,indolentprocesswithlonglatentperiod(20-40years)•  Diagnosis

–  Maypresentwithnosymptoms,fatigue,ordyspnea/pulmonaryedema.–  AccentuatedS1,openingsnap,diastolicrumble–  EchocardiographyshouldbeperformedtodeterminethediagnosisofMS,

assesshemodynamicseverity(meangradient,MVarea,andpulmonaryarterypressure),assessforconcomitantvalvularlesions,andassessvalvemorphology.

MitralStenosis-NaturalHistory

•  Annuallossofvalvearea0.1-0.3cm2peryear•  Overall10-yearsurvivalofpatientswithMSis50-60%dependinguponsymptomsatpresentation.– Asymptomatic:80%–  Significant,limitingsymptoms:0-15%

•  Mortalityduetoprogressivesystemiccongestion,systemicembolization,infection

MitralStenosis-MedicalTherapy

•  Nomedicaltherapywillspecificallyrelieveobstructiontoinflowatthemitralvalve.

•  Avoidanceofunusualphysicalstressandtachycardia.Negativechronotropicdrugs(BBlockers,Ca-Channelblockers)maybebeneficialinpatientswithexertionalsymptoms.

•  Saltrestriction,diureticsinpatientswithcongestivesymptoms

•  Treatmentofatrialfibrillation(occursin30-40%ofsymptomaticMSpatients)

PercutaneousMitralBalloonValvotomy

•  Indicatedforsymptomaticpatients(NYHAfunctionalclassII,III,orIV),withmoderateorsevereMSandfavorablevalvemorphologyintheabsenceofleftatrialthrombusormoderatetosevereMR.

•  Results:•  85-95%successrate•  50-60%reductionin

transmitralgradient•  80-90%event-freesurvivalat

3-7yearsinpatientswithfavorableanatomy

•  Similarresultstosurgicalcommissurotomy

MitralRegurgitation

•  Morethan2millionpersonsintheU.S.havemoderateorsevereMR

•  Etiologies:degenerative(mitralvalveprolapse),rheumaticheartdisease,CAD,endocarditis,collagenvasculardisease,annulardilatation

DegenerativevsFunctionalMitralRegurgitation

NormalDegenerative:ProlapseDegenerative:FlailFunctional

PrevalenceofModerateorSevereValveDisease

MitralRegurgitation-Acute

•  Presentation–  RapidLA,LVvolumeoverloadresultinginpulmonarycongestionand

decreasedstrokevolume/forwardcardiacoutput–  Almostalwaysseverelysymptomatic–  Rales,S3,normalheartsize,early/holosystolicmurmur–  Confirmedbyechocardiography

•  Treatment–  Afterloadreduction(nitroprusside)toreduceafterloadandimproveforward

cardiacoutput–  Diureticstorelievecongestionanddecreasepreload–  Inotopes(dobutamine)–  IABP–  Surgicalintervention

MitralRegurgitation-Chronic

•  PatientswithmildtomoderateMRmayremainasymptomaticwithlittleornohemodynamiccompromiseformanyyears

•  NaturalhistoryofsevereMR–  6-7%mortality/year–  90%ofpatientsaredeadorhaveMVsurgeryby10years

•  Follow-upofAsymptomaticMR–  Mild:Annualfollow-up.Yearlyechonotindicatedunlesschangeinsymptoms–  Moderate:Annualclinicalfollow-upwithechocardiography–  Severe:Clinicalfollow-upwithechoevery6-12monthstoassessforsymptomsor

asymptomaticLVdysfunction

ChronicLA,LVVolumeOverload

LVDysfunction,ElevatedFilling

Pressures,Congestion,DiminishedOutput

LA,LVDilatationMaintainingForwardOutputatLowerFillingPressures

CompensatoryPhase Decompensation

ChronicMitralRegurgitation-MedicalTherapy

•  IntheasymptomaticpatientwithchronicMR,thereisnogenerallyacceptedmedicaltherapy

•  Nolarge,long-termstudiestoindicatethatACE/ARBarebeneficialinimprovingmortalityordelayingsurgicalintervention.

•  Intheabsenceofsystemichypertension,thereisnoknownindicationfortheuseofvasodilatingdrugsorACEinhibitorsinasymptomaticpatientswithMRandpreservedLVfunction.

•  ACE/ARB,B-BlockersshouldbeusedinsettingofLVdysfunctionorsymptomaticCHF

Repairvs.Replacement?

•  STSOperativeMortality:2%MVRepair;6%MVReplacement•  MVrepairresultsinimprovedmortalityandpreservationofLVfunctionvs.MV

replacement

JAmCollCardiol.2008;52(5):319-326.

PercutaneousMitralValveRepair:MitraClip

•  Byapproximatingtheanteriorandposteriormitralleafletsandformingadouble-orificevalve,theMitraClipdevicereducesMR

•  Currentlyapprovedforuseinpatientswithdegenerativemitralregurgitationwhoarehighriskforconventionalmitralvalvesurgery

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100

Perc

ent o

f Pat

ients

(%)

Baseline(N = 124)

01+2+3+4+

Discharge(N = 123)

1 Year(N = 84)

2 Years(N = 40)

MITRAL REGURGITATION GRADE

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Perc

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Baseline(N = 127)

30 Days(n = 113)

lllllllV

1 Year(n =84)

NYHA FUNCTIONAL CLASS

82%MR≤ 2+

9.7%MR ≤ 2+

83%MR≤ 2+

87%Class

l/ll

82%Class

l/ll

82.5%MR≤ 2+

13.4%Class I/II

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Perc

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Baseline(N = 124)

01+2+3+4+

Discharge(N = 123)

1 Year(N = 84)

2 Years(N = 40)

MITRAL REGURGITATION GRADE

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Baseline(N = 127)

30 Days(n = 113)

lllllllV

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NYHA FUNCTIONAL CLASS

82%MR≤ 2+

9.7%MR ≤ 2+

83%MR≤ 2+

87%Class

l/ll

82%Class

l/ll

82.5%MR≤ 2+

13.4%Class I/II

Reduction in MR Severity Improvement in Heart Failure Symptoms

30-day MR severity was used if discharge MR was unavailable.

1YearMitraClipOutcomes

*ProhibitiveSurgicalRiskDMRCohort(n=127):Apost-hocanalysisofdatacollectedfromtheEVERESTIIHRRandREALISMHRstudiesestablishedthesafety,effectiveness,andpositivebenefit-riskprofileofMitraCliptherapytoreduceMRinpatientswithdegenerativeMRwhoareatprohibitiveriskformitralvalvesurgery.Datafrom127patientswereanalyzedandsubsequentlyformedthebasisforU.S.FDAapprovalofMitraCliptherapy.†Insurvivingpatientswithpaireddata.

•  Fromdischargeto2-yearfollow-up,morethan80%ofsurvivingpatientsachievedandmaintainedreductioninMRseverityto≤2+1

•  TheproportionofpatientsinNYHAClassI/IIincreasedfrom13%atbaselineto87%ofsurvivingpatientsat1year1

•  88%ofsurvivingpatientsimprovedbyatleast1class,and36%improvedbyatleast2classes1

1YearMitraClipOutcomes

Significant reduction in left ventricular size1,* 73% reduction in heart failure-related symptoms and hospitalizations1: •  Between the 1-year

periods before and after the procedure1

*ProhibitiveSurgicalRiskDMRCohort(N=127):Apost-hocanalysisofdatacollectedfromtheEVERESTIIHRRandREALISMHRstudiesestablishedthesafety,effectiveness,andpositivebenefit-riskprofileofMitraCliptherapytoreduceMRinpatientswithdegenerativeMRwhoareatprohibitiveriskformitralvalvesurgery.Datafrom127patientswereanalyzedandsubsequentlyformedthebasisforU.S.FDAapprovalofMitraCliptherapy. †DataasofMarch2015.Proceduresuccesswasdefinedaspost-implantMRgrade≤2,withoutcardiovascularsurgeryandwithoutin-hospitalmortality.

ImpactofMRonSurvivalinPatientswithCHF

JAmCollCardiol.2008;52(5):319-326.

COAPT: All-cause Mortality A

ll-ca

use

Mor

talit

y (%

)

0%

20%

40%

60%

80%

100%

Time After Randomization (Months) 0 3 6 9 12 15 18 21 24

46.1%

29.1%

HR [95% CI] = 0.62 [0.46-0.82]

P<0.001

MitraClip + GDMT GDMT alone

302 286 269 253 236 191 178 161 124 312 294 271 245 219 176 145 121 88

No. at Risk:

MitraClip + GDMT GDMT alone

NNT (24 mo) = 5.9 [95% CI 3.9, 11.7]

DegreeofMR,functionalclass,QOL,needforVAD/transplantallbetterforMitraClipgroup

FutureDevelopments:TranscatheterMitralValveReplacement

Conclusions•  Valvularheartdiseaseisveryprevalentintheprimarycaresetting,particularlyintheagingpopulation(13.3%overage75)

•  Opensurgicalvalvularrepair/replacementhaspreviouslybeentheprimarytherapyforsymptomaticdisease.

•  Medicaltherapyisprimarilyusedforstabilizationforacutevalvedysfunction.

•  Newer,lessinvasivepercutaneoustechniquesmayallowtreatmentofpatientspreviouslydeemedaspoorsurgicalcandidateswithlessmorbidity