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"Isheartfailureonediseaseortwo,isitallonebigcontinuum?ThisHFpEFandHFrEF,aretheytwo differentdiseaseprocesses?"Theydefinitelyproducethesameclinicalexpression. Breathlessness,fatigue,theymayhavepulmonaryedema,peripheraledema,butaretheydifferent diseaseprocesses?AndIwouldsaythetotalityevidencesupportsthattheyaretwodifferentdiseases andthisisoneofthepiecesofevidencethatsupportsthat.Thisisthedistributionofejectionfractions inabout5,000patientsinOlmstedCounty,andyoucanseeit'sclearlybimodal.Youcanseethatinthe lowEFarea,HFrEF,mentendtooutnumberwomen. That'sonlylargelyduetotheirgreaterburdenofcoronarydisease.Butthenthere'sthissecondhump herearound60-65%wherewomenclearlyoutnumbermen.Thisisadifferentdisease.Thisisheart failurewithpreservedejectionfraction.HFpEFisontheincrease,sothisisdatainOlmstedcounty againshowingaverystablehospitalizationsforsystolicfailure,HFrEF,overthistimespansincethe '80sthere'sbeenbasicallyadoublinginHFpEF.HFpEFisgrowingrelativetoHFrEFby10%perdecade, soit'sgoingtobethemostcommonformofheartfailurebyabout2020,soit'svery,verycommon. ParticularlyaswegetolderintheUnitedStates,it'sadiseaseofaging.NowdespitethefactthattheEF isfine,thesepatientshaveverypooroutcomes,andyoucanseeheresurvivalatfiveyearsisabysmal inpeoplewithheartfailurewhetherit'sHFpEForHFrEF.Andthere'sastatisticallysignificant differenceherebutit'snotaclinicallysignificantdifference.Soit'sabigproblem. It'slargelyadiseaseoftheelderly.Thisistheagedistributionfromoneofourstudies,youcanseethe medianis76years.Mostofthepeople,we'refindingthemupintheir80s,sowereallywanttothink aboutthisinolderfolks.Nowaswe'reseeingmoreandmoremorbidlyobesepeople,andobesityisa bigriskfactorforHFpEF,that'sgettingpusheddownnow.Nowwe'reseeingitclearlyinthe50sand 40s,andevensomeinthe30s.Butusuallythat'speoplewithalotofobesityandotherriskfactorslike diabetes. UnlikeHFrEF,whichismostlymale,2:1male.HFpEFis2:1femaleforreasonsthatarenottotallyclear. Mighthavetodowiththewaytheventriclesremodel,withthingslikeaorticstenosiswhichputsabig pressureloadontheventricle.There'smoreremodeling,concentricremodeling,moreleftventricular hypertrophyinwomenthaninmen.There'sdifferentclustersofriskfactors,sohypertensionand valvulardiseaseinfemalesexaremuchmorestrongriskfactorsforHFpEFthenforHFrEF.Having coronarydiseaseandpriorMIismoresomethingthatyouthinkaboutforHFrEF. Theventricleslookdifferent.Thisisautopsyspecimensbutthesamethingwouldapplyonan echocardiogram.InHFrEF,theleftventricleisdilated,inHFpEF,theleftventriclechambersizeis actuallynormal.There'softenconcentrichypertrophy,butyoudon'tneedtohaveconcentric hypertrophy.Thatusedtobethethinking,isthatyouhadtohaveconcentricleftventricular hypertrophy,that'snotthecase.ButthisismoretypicalofHFpEFthanHFrEF,theclinicalpresentation looksthesame.Exertionalbreathlessness,PND,orthopnea.Physicalfindings,itdoesn'tmatter.Those thingslookthesame,exercisecapacityisthesame.It'sjustasbadinpatientswithHFpEFasHFrEF.So againeventhoughtheEFisnormal,they'rejustasdisabled,theyhavesimilarlypooroutcomesandit's ahugepublichealthprobleminHFpEF. Sohowdowemakethediagnosis?Westartwiththepremise,andyouallknowthisfromyour practices,exertionaldyspneaandfatigueareverycommoncomplaintsthatweallsee. Nowifyou'vegotHFrEFyou'vegotabigdilatedLV,andyou'vegotalowEF.That'seasytomakethat diagnosis.TheymayhavehighLVfillingpressuresifthey'recongestedatthattime,youcanstillhave theclinicaldisorderofheartfailureandnothavehighfillingpressures.InHFpEFyou'vegotanormal sizedventricle.BydefinitionyouhaveanormalEF.Youmayhavehighfillingpressuresifyouhappento becongestedatthetimeyou'reseeingthemintheclinic.That'snotsoeasy.It'snotveryeasytoassess fillingpressuresfromphysicalexaminations,evenamongstthemostseasonedcardiologists. Sothisissortofthelaundrylistthatwelookattotryandmakethediagnosis.Sohistoryphysicalchest X-ray.SothoseFraminghamCriteria,thosearenotgoinganywhere.Somebodyhasjugulardistention andrales,orathirdheartsound,thatisstrongconcreteevidenceofheartfailure.Soifthey'vegotthat stuffinanormalEF,that'sHFpEF.Welookforotherthingsontheechobecauseofthelimitationsof physicalexamtoassesintercardiacpressures.Iftheyhaveahighpulmonaryarterysystolicpressureor RVsystolicpressureasestimatedbytheecho,ifyouseethatinanolderpatientthat'saverystrong indicatorthattheyhaveheartfailurewithpreservedejectionfraction.Probablynotso-calledprimary pulmonaryhypertension.ThereareotherechodopplerindicatorsliketheE-Eprimeratio,youknow they'llsaythere'sdiastolicdysfunctionbutifyoulookatthisnumberandit'sveryhighthat'sanother goodindicator. Whenthere'schronicincreaseindiastolicpressureintheleftventricle,theleftatriumdilatesandgets biggerbecausetheatriumhastosqueezebloodintothat...that'sitsafterloadisitshighLVpressure.So theLAvolumeisareallygoodindicatortolookat,it'sbeenconsideredthehemoglobinA1cofdiastolic dysfunction.Soifyourleftatriumisbigonyourechothat'sanotherverystrongindicator.Iftheecho orECGshowsleftventricularhypertrophythat'sveryconsistent. Iftheechojustshowsconcentricremodelingwhichisanincreaseinthewallthicknessrelativetothe heartsize,that'sanindicator.BNP,ifBNPishigh,that'sveryverysupportive.ButifBNPisnormal,that doesnotexcludeHFpEF.ComparedtoHFrEF,BNPlevelsaremuchlowerinpatientswithHFpEFand they'reoftennormal.Alotoftimeswedocardiopulmonaryexercisetestinginthesepatientsandlike systolicheartfailuretheyhavelowexercisecapacity,theirpeakoxygenconsumptionduringamaximal effortexercisetestisreduced.Andthenwelooktoseeiftheyhavetypicaldemographics.Yourclassic HFpEFpatientishypertensive.Maybewithdiabetesormetabolicsyndrome,probablyobeseanda womanabovetheageof65.Iftheyhaveallofthosethingsthatincreasesthepost-testprobabilityvery much.Ifit'sjusta32-year-oldman,withnoneofthosecomorbitities,that'sprobablynot.Soifthey havethe...ifthatpatienthastheclinicalsyndromeofheartfailure,weprobablywanttolookforother things,likevalvulardiseaseorpericardialdisease.Maybetheyhavesomethingverystrange,likea storagediseaseintheirmyocardialcells,andwemighthavetodoabiopsy.Sotheseareallofthe thingsthatwetypicallylookat.Themoreboxesthatyouhavechecked,theincreasetheprobability. There'snotuniversalagreementonhowtomakethisdiagnosisamongsttheguidelinesrightnow. Hopefullytherewillbesoon. Solet'slookatacase,a70-year-oldladywithexertionalbreathlessness,normalEF,ClassIIsymptoms ofexertionalbreathlessness,butshe'sneverbeenadmittedwithvolumeoverload.She'sneverhad pulmonaryedema.Intheclinic,shelookseuvolemic,andherBNPisnormal.Yougetanecho,asyou should,anditshowssomeabnormalities,alittlebitofleftatrialenlargement,alittlebitofdiastolic dysfunction.Thisisn'tquitehighenoughthatweconsiderclearlyabnormalbutit'ssortofahint.But weknowthatmany70-year-oldwomenwithhypertensionandriskfactorshavediastolicdysfunction. Diastolicdysfunctiondoesnotequaldiastolicheartfailure,okay?It'spartofnormalaging.Sowhatdo youdowithsomebodylikethis?Notatallclear. Soapatientlikethisinourpracticewouldoftengetadmittedorgetreferredforinvasive hemodynamicevaluation.YoucanseehereLVpressureinpink.Andthisisthepulmonarycapillary wedgepressurewhichisasurrogateofleftatrialpressureinyellow.Andthey're12,whicharenormal. Solooksgreat,right?Wellshe'snotsymptomaticatrest,she'ssymptomaticwhenshedoesstuff.Soin ordertomakethatdiagnosis,weneedtomeasureherhemodynamicsduringthestresswhenshe's symptomatic. Sothisiswhathappenswhenshedoesjustlow-levelexerciseonthecathlabtable.40watts,verylow level,youcanseethatthatwedgepressureinyellowandtheLVend-diastolicpressureinpinkare throughtheroof.Andthesearechangingthestarlingforcesinthelungsandmakingherveryvery, shortofbreath.They'rebothnorthof40millimetersofmercury.SothisisHFpEF.Andwhenit'sclear cut,whentheyhaveclearcutclinicalcriteriait'sgreat.Alotoftimestheydon't,andinthese circumstancesweneedtoreferthemformoreadvancedtesting.Likeinvasiveexercisetesting,it's extremelyaccurateandconsideredbasicallythegoldstandardtomakethediagnosis. Sooneoftheobjectiveswastotalkaboutwhathappenswithexercisenormallyandwhatgoeswrong withHFpEF.Sothisaplot,thisisLVvolume,thiswouldbeend-diastolicvolumewhichisthepreload, andthendownhereisend-systolicvolume,thattheventriclesqueezesdownto.Andthewidthhere, thedifferencebetweenthetwo,isthestrokevolume.Withexerciseinanormalperson,youhave what'scalledpreloadreserves,soeventhoughyourheartrategoesupandthetimeavailableforfilling theventriclegoesdown,anormal,healthyheartcanfilltoalargerend-diastolicvolumedueto diastolicreserve.Itcanalsoincreasestrokevolumebycontractingdowntoasmallervolume,sotheEF goesup,theend-systolicvolumegoesdownandthat'srelatedtocontractilereserveandalsoafterload reduction,sothereductioninvascularresistancethatyouseewithexercise. WhathappensinHFpEF?Inpinkhere,theylookthesameatrest.Withexercise,theydon'thaveas goodofpreloadreserveandtheyalsodon'thaveasgoodsystolicreserve.SopatientswithHFpEFdo nothavethisabilitytoenhancetheirstrokevolumeasmuchduringexercise,andthisgreatlyinhibits theircardiacoutput.Remember,cardiacoutputisequaltostrokevolumetimesheartrate.Stroke volumecan'tgoupasmuch.ThisisLVpressureandwedgepressureinpatientswithHFpEF.Asarule, thesepressuresgoupduringexercise,andthatcanpromotesymptomsofbreathlessness,cancause secondaryelevationinpulmonaryarterypressures.Anotherthingthatweveryconsistentlyseeisan abnormalincreaseinheartrateonexerciseinpatientswithHFpEF.Sotheyalreadydon'thavethat strokevolumereserve,theyalsohavechronotropicincompetence.Sothetwoofthosethingsreally zapstheirabilitytoenhancecardiacoutputwithactivityandthatmakesthemshortofbreath.And again,allofthesethingsgreatlylimittheabilitytoincreasecardiacoutputduringexerciseinpatients withHFpEF.Sonormalexercisephysiology,increaseinchambervolume,improvementincontractility anddiastolicfunction,increaseinheartrate,allofthosethingsarezappedtovaryingextentsin patientswithHFpEF. SowepublishedthispaperacoupleofyearsagowherepatientslikethecaseIshowedyou,normal exam,badsymptoms,butnoclearcutclinicalevidenceofheartfailure.Whenyoutakethemtothe cathlab,tothetableoftruth,eveniftheirBNPisnormal,theywillshowhemodynamicderangements thatarediagnosticofheartfailureabouthalfofthetime.Soveryveryeffectivetest. Thisiswhywedoit.Sothisisthefillingpressure,thisisthatcriticaldeterminant.ThisistheLVand diastolicpressure,thewedgepressure,thatweuseasourmainwaytodiagnosethis.Whenyoulook atHFpEFpatientsinthisearlystageatrest,theylooknodifferentthannormalpeople.Whenyouget theirfeetupintothepedals,inthecathlab,westarttoseesomeseparationbetweenthetwogroups. Soyougotalotofbloodthatsitsintheveinsofyourlegs.Translocatethatbackintothecentral circulationifthere'salotofdiastolicdysfunctionoftheheartstiff,itcan'taccommodatethatincrease inbloodreturnwithoutincreaseinpressure.Andreallyjustwithverylowlevelexercisethisiswhere weseethegroupscompletelyseparate.ThepatientswithHFpEFdevelopmarkedincreasein pressures,comesrightbackdownassoonastheystopexercising.Soit'sveryephemeral,verydifficult tomakethisdiagnosiswithoutacatheter,withoutacatheterization. SoagainthisistheapproachIshowedyouearlier,we'renotgoingtogothroughthisallagain,ifyou gotseveraloftheseboxeschecked,theyclearlymeettheseclinicalcriteria,you'redone.Iftheyjust haveoneortwo,that'sthekindofpatientwherewewouldprobablyreferthemtoacardiologistto thengototheCathlabandgetarestandexerciseinvasivehemodynamicassessment.Andthat'sreally ourgoldstandardtesttoidentifypatientswithHFpEF.Andwedotheseallthetime,so...asdomany othercentersnow. Nowareallyimportantpoint.Onceyou'vemadethisdiagnosis,andtheyhaveheartfailure,andthey haveanormalEF,youwanttoruleoutothernon-HFpEFcauses.WhatImeanbythat?I'mtalking aboutdiseasesthatcausetheclinicalsyndromeofheartfailure,rememberthatsymptomsof breathlessnessplusanormalEF,butiftheyhaveadifferentnaturalhistoryoradifferenttreatmentwe wanttoidentifythat.Andthisisoneofthemthatwedefinitelywanttoidentify.SothisisLVpressure inyellowandRVpressureinpink,andnormallywhenthepatienttakesabreathin,thepressuregoes down,becausethethoracicpressuregoesdown.Theyshouldbothgodown.Whatyouseehereis downhere,uphere.That'safindingthatweseewhenthere'spurecardialconstriction.Sothisis somebodywithconstrictivepericarditis,thisistheirangiogramandthisblackstuffaroundtheheartis acalcifiedpericardiumsoifyouseethisonaplainfilmchestX-rayandtheyhavesymptoms,that's definitelyconstriction.Echo,verystrongtestforthis.Classicallyit'ssomeonewithnormalejection fraction,theyusuallyhavemoresystemicvenuscongestionratherthanorthopneaandPND,sothey havemorejugulardistention,hepatomegalyascites,peripheraledemas.Butiftheyhavethatnormally, youreallyreallywanttothinkcarefullyaboutconstrictivepericarditis.Constrictivepericarditisdoes notcausechestpain,acutepericarditisisthetypicalpleuriticchestpainthat'sworstwhentheylie down,betterwhentheysitforward.Differentdisease.Constrictivepericarditisistheonethatcauses theclinicalsyndromeofheartfailure.Ifyoustripoffthatpericardiumsurgicallywithpericardiectomy, youcancurethemofheartfailure.Soveryveryimportanttomakethisdiagnosis.Seealotofpatients thatgo...theliverguyspickthisupalotbecausetheyhavethischronicsevereasitesthatrefractory andtheyusuallyseethatit'sconstriction. Again,notallHFpEFisHFpEF.Here'sanotherdiseasethatcausesanormalEFandclinicalheartfailure, butit'snotthesamethingasthatHFpEFintheolderwoman.Whatisthis?Gotyourmacroglossia, you'vegotyourapplegreenbirefringence,thisisamyloid.Andthisismuchmorecommon,Ithink, thanwehadpreviouslyappreciated,especiallysenileamyloid.Clearlyifit'sALtypeamyloid,wehave goodtreatmentsforthatnow,andnowatleastinclinicaltrialswehavenewtreatmentsforsenile transthyretinamyloid.Sothere'sreasontofindbothofthese,andwecanmakethisdiagnosisinthe cathlabwithabiopsy. Soinsummary,HFpEFisverycommon,rightnowit'shalfofallheartfailure,it'sincreasing.Signs, symptoms,outcomes.Really,notsignificantlydifferentthanpatientswithheartfailureandreduced EF.Diagnosisisoftenchallenging,itreliesonobjectiveevidenceofcongestionandhighfilling pressures.Itcanbewithphysicalexam,echo,BNPchestfilm.Butifyoucan'tmakeitorthat's equivocalthenyouneedtogotothecathlabforadditionaltesting,potentiallywithexercise.Once you'vemadethediagnosis,youwanttoruleoutothercausesthatwetreatdifferently,likecoronary disease,constrictivepericarditis,amyloid,orotherthingslikevalvularheartdisease.