內(nèi)科學(xué)英文課件：Heart-Failure

HeartFailureHeartFailureEpidemiologyHeartfailureiscommon,yetitisdifficulttotreat.HFremainsoneofthemostcommonreasonsforhospitaladmission,aswellasoneofthemostcostlycardiovasculardisorders.HFpatientshaveapoorprognosis,withanaverage1-yearmortalityrateof33%MortalityriskbetweenmenandwomenissimilarEpidemiologyHeartfailureiscEpidemiologyinChinaPrevalencerateofChineseadult35-74ys:0.9%;65-74ys:1.3%TotalinChina:5,850,000

Male0.7%;Female1.0%North1.4%;South0.5%City1.1%;:Countryside0.8%2003中國慢性心力衰竭患病情況流行病學(xué)調(diào)查EpidemiologyinChinaPrevalencEpidemiologyEpidemiology內(nèi)科學(xué)英文課件：Heart-FailureWhatisHeartFailure?

Limitationoflifeability…WhatisHeartFailure?DefinitionofheartfailureHeartfailureisapathophysiologicalstateinwhichanabnormalityofcardiacfunctionisresponsibleforthefailureofthehearttopumpbloodtocommensuratewiththerequirementsofthemetabolizingtissues.(HeartDisease,2ndEd)

Heartfailureisacomplexclinicalsyndromethatcanresultfromanystructureorfunctionaldisorderthatimpairtheabilityoftheventricletofillwithorejectblood.(ACC2005)HFisapathophysiologicalstateinwhichcardiacoutputisinsufficientforthebody'sneeds.DefinitionofheartfailureHeaClassificationofheartfailurethespeedofheartfunctiondeteriorate(chronicversusacute)thesideoftheheartinvolved,(leftheartfailureversusrightheartfailure)whethertheabnormalityisduetocontractionorrelaxationoftheheart(systolicdysfunctionvs.diastolicdysfunction)whethertheabnormalityisduetolowcardiacoutputwithhighsystemicvascularresistanceorhighcardiacoutputwithlowvascularresistance(low-outputheartfailurevs.high-outputheartfailure)ClassificationofheartfailuSystolicvsDiastolicDysfunctionSystolicvsDiastolicDysfunctLeftvsRightHeartFailureLeftHeartFailureInvolvestheleftventricle(lowerchamber)oftheheartSystolicfailureTheheartloosesit’sabilitytocontractorpumpbloodintothecirculationDiastolicfailureTheheartloosesit’sabilitytorelaxbecauseitbecomesstiffHeartcannotfillproperlybetweeneachbeatRightHeartFailureUsuallyoccursasaresultofleftheartfailureTherightventriclepumpsbloodtothelungsforoxygenOccasionallyisolatedrightheartfailurecanoccurduetolungdiseaseorbloodclotstothelung(pulmonaryembolism)LeftvsRightHeartFailureLefCommoncausesofHFIschaemicHeartDisease62%CigaretteSmoking16%Hypertension(highbloodpressure)10%Obesity8%Diabetes3%ValvularHeartDisease2%(muchhigherinolderpopulations)A19yearstudyof13000healthyadultsintheUnitedStates(theNationalHealthandNutritionExaminationSurvey(NHANESI)CommoncausesofHFIschaemicHCommoncausesofHFIschaemicHeartDisease

57.1%Hypertension

30.4%ValvularHeartDisease

29.6%我國基層醫(yī)院慢性心力衰竭主要原因的初步調(diào)查[J].中華內(nèi)科雜志2005,44(7):487-489CommoncausesofHFIschaemicHRarercausesofheartfailure

ViralMyocarditis(aninfectionoftheheartmuscle)Infiltrationsofthemusclesuchasamyloidosis

HIVcardiomyopathy(causedbyHumanImmunodeficiencyVirus)ConnectiveTissueDiseasessuchasSystemiclupuserythematosus

AbuseofdrugssuchasalcoholPharmaceuticaldrugssuchaschemotherapeuticagents.ArrhythmiasRarercausesofheartfailureCommoncausesofdeathPumpfailure

59%Arrhythmias

13%Suddendeath

13%

中華醫(yī)學(xué)會(huì)心血管病學(xué)分會(huì).中國部分地區(qū)1980、1990、2000年慢性心力衰竭住院病例回顧性調(diào)查[J].中華心血管病雜志,2002,30(8):450-454CommoncausesofdeathPumpfaiPrecipitatingFactorsInfection(pulmonary)ArrhythmiaExcessivesaltintakeinadequateexercise/emotionalcrisisinadequatetreatment:digitalis/inadequateusagediureticpulmonaryemboluspregnancyanddeliveryThyrotoxicosis/anemiaPrecipitatingFactorsInfectionPathophysiology(1)Hemodynamicdisorder:SVDeterminantsofpumpfunction1.preload2.afterload3.contractility4.HRCO=SV*HRSV=EDV-ESVEF=SV/EDVPathophysiology(1)HemodynamicPreload/afterload/contractilityPreload/afterload/contractilitPreloadonSV

Frank–StarlingLaw

PreloadonSV

Frank–StarlingSV&pre/afterloadSV&pre/afterloadRAS,renin-angiotensinsystem;SNS,sympatheticnervoussystem.Myocardialinjurytotheheart(CAD,HTN,CMP,Valvulardisease)MorbidityandmortalityArrhythmiasPumpfailurePeripheralvasoconstrictionHemodynamicalterationsHeartfailuresymptomsRemodelingandprogressiveworseningofLVfunctionInitialfallinLVperformance,wallstressActivationofRASandSNSFibrosis,apoptosis,

hypertrophy,cellular/

molecularalterations,

myotoxicityFatigue

Activityaltered

Chestcongestion

Edema

ShortnessofbreathNeurohormonalActivationin

HeartFailureRAS,renin-angiotensinsystem;PathophysiologyofHeartFailure:LeftVentricularRemodelingLeft-ventricular(LV)remodelingisdefinedasachangeinLVgeometry,massandvolumethatoccursoveraperiodoftimePathophysiologyofHeartFailuCommonSymptomsofHeartFailureDyspneaonexertionParoxysmalnocturnaldyspneaOrthopneaFatigueLowerextremityedemaCough,usuallyworseatnightNausea,vomiting,anorexia,ascitesSleepdisordersCommonSymptomsofHeartFailuCommonSymptomsofHeartFailureCommonSymptomsofHeartFailuNYHAFunctionalclassificationNoticeablelimitationsinabilitytoexerciseorparticipateinmildlystrenuousactivitiesComfortableonlyatrestNosymptomsCanperformordinaryactivitieswithoutanylimitationsMildsymptomsOccasionalswellingSomewhatlimitedinabilitytoexerciseordootherstrenuousactivitiesNosymptomsatrestUnabletodoanyphysicalactivitywithoutdiscomfortSymptomsatrestNYHAFunctionalclassificationCommonPhysicalFindings

ofHeartFailureElevatedjugularvenouspressureHepatojugularrefluxDisplacedapicalimpulseS3gallopPulmonaryralesHepatomegalyPeripheraledemaAscitesCommonPhysicalFindings

ofHAssessmentofjugularvenousdistentionAssessmentofjugularvenousClinicalmanifestationLeftheartfailure:SOB(shortnessofbreath),cough,rales,gallopRightheartfailure:gastrointestinalcongestion,nausea,asenseoffullnessaftermeals,hepato-jugularreflux,swellingoffeetoranklesLowcardiacoutput:fatigueandweakness,oliguriaBiventricularheartfailure:bothclinicalmanifestationofleftandrightheartfailure,oneofwhichmaybepredominant.ClinicalmanifestationLeftheaHowtomakeadiagnosisofHF?SearchfortheevidenceoflowerEF,but……HowtomakeadiagnosisofHF?FraminghamCriteriamain·Paroxysmalnocturnaldyspnea

·Neckveindistention

·Rales

·Radiographiccardiomegaly(increasingheartsizeonchestradiography)

·Acutepulmonaryedema

·S3gallop

·Increasedcentralvenouspressure(>16cmH2Oatrightatrium)

·Hepatojugularreflux

·Weightloss>4.5kgin5daysinresponsetotreatmentNEnglJMed.1971Dec23;285(26):1441-6.FraminghamCriteriamain·PaFraminghamCriteriaminor

Bilateralankleedema

·Nocturnalcough

·Dyspneaonordinaryexertion

·Hepatomegaly

·Pleuraleffusion

·Decreaseinvitalcapacitybyonethirdfrommaximumrecorded

·Tachycardia(heartrate>120beats/min.)If2mainor1main+1minor=HFSensitivity100%;Sepecifity78%NEnglJMed.1971Dec23;285(26):1441-6.FraminghamCriteriaminorBiEcho&X-rayEF=ejectfractionCTR=cardiacThoracicratioEcho&X-rayEF=ejectfractionCNuclearEFNuclearEFMRIMRILVAngiogramLVAngiogramDifferentialdiagnosis

Differentiationbetweencardiacandpulmonarydyspnea:Chronicobstructivelungdiseaseisusuallyassociatedwithsputumproduction,thedyspneaisrelievedafterpatientsridthemselvesofsecretionsbycoughingratherthanspecificallybysittingupAcutecardiacasthma(paroxysmalnocturnaldyspneawithprominentwheezing)usuallyoccursinpatientswhohaveobviousclinicalevidenceofheartdiseaseAirwayobstructionanddyspneathatrespondtobronchodilatorsorsmokingcessationfavorapulmonaryoriginofthedyspnea,whiletheresponseofthesemanifestationstodiureticssupportsheartfailureasthecauseofdyspneaDifferentialdiagnosisDiffBrainNatriureticPeptides(BNP)inHFBNP:

half-time18minNT-proBNP:half-time60-120minDiagnosticcut-off

NT-proBNP<400pg/ml，BNP<100pg/mlnoHFNT-proBNP>2000pg/ml，BNP>400pg/mlHFNT-proBNP=400-2000pg/ml，BNP=100-400pg/mlPulmonaryembolism，COPD，Decompensated

heartfailureBrainNatriureticPeptides(BNFourStageofHF(ACC/AHA2005)StageA:PatientsathighriskfordevelopingHFinthefuturebutnofunctionalorstructuralheartdisorder;StageB:astructuralheartdisorderbutnosymptomsatanystage;StageC:previousorcurrentsymptomsofheartfailureinthecontextofanunderlyingstructuralheartproblem,butmanagedwithmedicaltreatment;StageD:advanceddiseaserequiringhospital-basedsupport,ahearttransplantorpalliativecare.FourStageofHF(ACC/AHA2005)TreatmentofHeartFailureTreatmentofTreatriskfactorsPreventdiseaseprogressionImprovesymptomsImproveexercisetoleranceImprovequalityoflifeReducemorbidityReducemortalityGoalsofTherapyTreatriskfactorsGoalsofThe

TREATMENTCorrectionofaggravatingfactorsMEDICATIONSEndocarditisObesityHypertensionPhysicalactivityDietaryexcessPregnancyArrhythmias(AF)InfectionsHyperthyroidismThromboembolismTREATMENTMEDICATIONSEndocardiPathophysiologyandTherapeuticApproachestoHeartFailureDr.C.Pham2016PathophysiologyandTherapeuti內(nèi)科學(xué)英文課件：Heart-FailureDr.C.Pham2016ACE-InhibitorsDr.C.Pham2016ACE-InhibitoDr.C.Pham2016ViciousCycleDr.C.Pham2016ViciousCyclACE-InhibitorsACE-IMOAInhibitsACEIndicationsChronicHF,HTN,diabeticrenaldiseaseBenefitsMortality,ClassI-IVMorbidity(hospitalization)LandmarkTrialsCONSENSUSI&II,SAVE,SOLVD,TRACE,AIREDosingStrategyStartlow,titratetotargetdoseoverseveralweeksRisks/MonitoringHypotension,hyperkalemia,renaldysfunction,cough,angioedemaContraindicationsRenalinsufficiency,hyperkalemia,hypotension,hyponatremiaACE-InhibitorsACE-IMOAInhibitsPer3yearsofTreatmentRRRNNTx3yMortality~20%~18HFAdmission~25%~28Reinfarction(ifpriorMI)~20%~42ACE-InhibitorsFlatherMDetal.Lancet2000;255:1575Per3yearsofTreatmentRRRNNTACE-IStartingdoseTargetdoseCaptopril6.25mg–12.5mgtid25mg–50mgtidEnalapril1.25mg–2.5mgbid10mgbidRamipril1.25mg–2.5mgbid5mgbidLisinopril2.5mg–5mgod20mg–25mgodTrandaolapril1mgod4mgod6ACE-InhibitorsEBMnote:DosingmattersforMORBIDITY,buttheevidenceislessforMORTALITY.*CCS2006Guidelines.CanJCardiol2006;22*LonE.CurrControlTrialsCardiovascMed.2001;2:155ACE-IStartingdoseTargetdoseCACE-inhibitorUnloadinggoodsanddecreaseslopeACE-inhibitorUnloadinggoodsa內(nèi)科學(xué)英文課件：Heart-FailureDr.C.Pham2016ViciousCycleDr.C.Pham2016ViciousCyclNervousSystemCNSPNSSomaticNS(voluntary)PeripheralNS(involuntary)SympatheticNSParasympatheticNSAdreno-ReceptorsCholinergicReceptorsAcetylcholineAdrenaline/Noradrenaline-,-Muscurinic(vagus)PhysiologytoPharmacologyDr.C.Pham2016NervousSystemCNSPNSSomaticNSBeta-BlockersBeta-BlockersMOABlocksbeta-receptorsIndicationsChronicHF,HTN,angina,arrhythmias,migraine,hyperthyroidismBenefitsMortality,ClassI-IVMorbidity(hospitalization)LandmarkTrialsMERIT-HF(metoprololSR),CIBISII(bisoprolol),MOCHA(carvedilol),USCarvedilolStudy,COMET(metoprololvscarvedilol)DosingStrategyStartlow,goslowandworktowardtargetdoseoverseveralweeksRisks/MonitoringBradycardia,hypotension,heartblock>1,asthma,severeCOPD,severePVD,hypoglycemiariskContraindicationsBradycardia,worsenedasthma,fatigue,hypotensionBeta-BlockersBeta-BlockersBeta-BlockersMOABPer1yearofTreatmentRRRNNTx1yMortality~30%~26HFAdmission~30%~25Beta-BlockersPer1yearofTreatmentRRRNNTGoldstein.ArchIntMed.2002;162:641Beta-Blockers“Thebenefitsofβblockersinpatientswithheartfailurewithreducedejectionfractionseemtobemainlyduetoaclasseffect,asnostatisticalevidencefromcurrenttrialssupportsthesuperiorityofanysingleagentovertheothers.”ChatterjeeS,etal.BMJ.2013Jan16;346(jan161):f55–5.Goldstein.ArchIntMed.2002;Beta-blockerStartingdoseTargetdoseCarvedilol3.125mgbid25mgbidBisoprolol1.25mgod10mgbidMetoprololCR/XL12.5mg–25mgod200mgodBeta-BlockersBeta-blockerStartingdoseTargeLimitthevelocity,saveenergyconsumption限制速度最小Beta-BlockersLimitthevelocity,saveenergCanJCardiol2009;25(2):85Dr.C.Pham2016CanJCardiol2009;25(2):85Dr.DiureticsDiuretics內(nèi)科學(xué)英文課件：Heart-FailureDiuretics

Furosemide,HCTZ,MetolazoneDiureticsMOADiuresisIndicationsFurosemide:acute/chronicHF,severeHTN,edemaHCTZ:mildHF,HTNBenefitsMorbidity(iffluidoverloaded),ClassII-IVLandmarkTrialsNoneDosingStrategyFurosemide10-160mgdailyHCTZmaybeadded(synergy);AddMetolazoneifresistanttofurosemideRisks/MonitoringHypovolemia,hypokalemia,hypomagnesemia,hyperglycemia,hypericemia(HCTZ),hypocalcemia(furosemide),ototoxicity(furosemide)ContraindicationsAllergy(sulfonamide)Diuretics

Furosemide,HCTZ,MUnloadinggoodsinthewagonDiuretics

Furosemide,HCTZ,MetolazoneUnloadinggoodsinthewagonDi內(nèi)科學(xué)英文課件：Heart-FailureAldosteroneAntagonists

Spironolactone,EplerinoneAldosteroneAntagonists

SpironMOABlockAldosteronereceptorIndicationsChronicHF,hyperaldosteronism,HTNBenefitsMortality,ClassI-IVMorbidityLandmarkTrialsRALES(spironolactone)EPHESUS,EMPHASIS-HF(eplerinone)DosingStrategyAdd25mgdailytostableClassIII/IVpatientsalreadyonACE-IandB-blockerRisks/MonitoringHyperkalemia,breasttenderness/gynecomastia,hypotensionContraindicationsHyperkalemia,moderate-severerenalinsufficiencyAldosteroneAntagonists

Spironolactone,EplerinoneMOABlockAldosteronereceptorICanJCardiol2009;25(2):85Dr.C.Pham2016CanJCardiol2009;25(2):85Dr.ARBsARBsAngiotensinReceptorBlockerACE-IMOABlockAT-1receptorsIndicationsChronicHF,HTN,diabeticrenaldiseaseBenefitsMorbidity(vs.placebo,andwhenaddedtostandardtherapy),ClassI-IVMortality(candersartan)LandmarkTrialsValHEFT(valsartan),VALIANT(valsartan),CHARMtrials(candesartan),ELITEII(losartan)DosingStrategyStartlow,andgoslowwhenaddingtoACE-I.SwitchfromACE-ItoARBatcomparabledose.Risks/MonitoringRenaldysfunction,hypotension,hyperkalemiaNB.AE’soutweighbenefitsofACEI+ARBContraindicationsModerate-severerenalinsufficiency,hyperkalemia,hypotension,hypovolemiaAngiotensinReceptorBlockerACARBStartingdoseTargetdoseCandesartan4mgod32mgodValsartan40mgbid160mgbidAngiotensinReceptorBlockerARBStartingdoseTargetdoseCan內(nèi)科學(xué)英文課件：Heart-FailureDigoxinDigoxinDigoxinMOAInhibitsNa-K-ATPaseIndicationsChronicsymptomaticHF,arrhythmiasBenefitsMorbidity,ClassII-IIILandmarkTrialsDIGtrial,RADIANCE,PROMISEDosingStrategy0.0625-0.375mgdaily(dependantonrenalfunction,age,tolerability)Risks/MonitoringCNSADRs(confusion,hallucinations),diarrhea,Dig-Toxwithhypokalemia,renalfunctionContraindicationsHighdegreeofheartblock,hypokalemiaDigoxinDigoxinMOAInhibitsNa-K-ATPaseDigoxinRadishaheadof

illdonkeyDigoxinRadishaheadofilldoNewTherapiesIvabradineMOAInhibitsSAnoderesultinginareductioninHR.(Hyperpolarization-activatedcyclicnucleotide-gatedchannelblocker)IndicationsChronicHF.NOTAPPROVEDINCANADA.BenefitsReducedhospitalization,nomortalitydifferenceLandmarkTrialsSHIFT(2010)Sacubitril/ValsartanMOASacubitrilinhibitsneprilysinandangiotensinII(Angiotensinreceptor-neprilysininhibitor–ARNi)IndicationsChronicHF–NYHAClassII,IIIBenefitsReducedmortality,reducedhospitalizationLandmarkTrialsPARADIGM-HF(2014)NewTherapiesIvabradineMOAInhi

PHARMACOLOGICTHERAPYImprovedsymptomsDecreasedmortalityPreventionofCHFNeurohumoralControlDiureticsyes??noDigoxinyes=minimalyesInotropesyesmort?noVasodil(Nitrates)yesyes?noACEIyesyesyesyesβ-blockers+/-yesyesyesOtherneurohormaonalcontroldrugsyes+/-?yesPHARMACOLOGICTHERAPYImproved

TREATMENTNormalAsymptomatic

LVdysfunctionEF<40%SymptomaticCHFNYHAIIInotropesSpecializedtherapyTransplantSymptomaticCHFNYHA-IVSymptomaticCHFNYHA-IIISecondarypreventionModificationofphysicalactivityACEIBBDiureticsmildNeurohormonal

inhibitors

Digoxin?Loop

DiureticsTREATMENTNormalAsymptomatic

LNon-adherencetoHFmedicationsNSAIDsPageetal.ArchInternMed2000;160:777Heerdinketal.ArchInternMed1998;158:1108Mamdanietal.Lancet2004;363:1751GlitazonesSinghetal.JAMA2007;298:1189Lincoffetal.JAMA2007;298;1180EXAMINE&SAVORtrialsNon-dihydropyridineCCBsDiltiazem,VerapamilVWAnti-arrythmicClass-1agentsBeta-blockersDon’tforgetDrugsthatcanprecipitateHFNon-adherencetoHFmedicationImportantspecifictypeofHFImportantspecificIntractableheartfailure1.Tofindinductionfactors2.Tousebetterdosesofdrug3.IABPinseverecoronaryheartdisease4.interventionaltreatmentforcoronaryheartdisease5.CABGforsevereheartdisease6.hearttransplantationIntractableheartfailure1.ToAcuteLeftHeartFailureCauses:

extensiveacutemyocardialinfarction;acutemyocarditis;malignantoracceleratedhypertension;mitralstenosis;severecardiacarrhythmias;rapidandexcessivevolumeinjectionAcuteLeftHeartFailureCausesDiagnosisAccordingtoclinicalmanifestation:suddenonsetorthopnea,coughs,cyanosis,moistralseisprominentandwheezingmaybeheardalloverthechest,rapidpulseandweakness.ShockmaybepresentDiagnosisAccordingtoclinicalAcuteHFExacerbationsOptionsConsiderationFurosemide(+/-HCTZormetalozone)NEJM2011;364:797O2Hypoxemia?Morphine?WithholdBeta-Blocker?B-CONVINCED.EurHeartJ2009;30:2186AggressiveH2OandNadepletionJAMAInternalMedicine2013;1-7VasodilatorsAnyhemodynamicinstability?Beta-Agonists(dobutamine,dopamine,epinephrine)Anyhemodynamicinstability?AddACE-IAvoidinacuteHFInvestigateforcausesIschemia,Na+intake,Rxnon-adherenceBNP(Nesiritide)AcuteHFExacerbationsOptionsCBeta-AgonistsBeta-AgonistsMOADobutamine:B1agonistDopamine:DA,B1andalphaagonistEpinephrine:alpha&betaagonistIndicationsAcutedecompensatedHF,shockRisks/MonitoringArrhythmiasBeta-AgonistsMOADobutamine:B1agonistIndicMilrinoneMOAInhibitphosphodiesterase-3(decreasecAMPbreakdown)IndicationsAcutedecompensatedHFRisks/MonitoringArrhythmias,hypotensionBipyridinesMilrinoneMOAInhibitphosphodieBNPAgonistBNPAgonistNes