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1、Heart Failure张张 清清 副教授副教授opendocument上海交通大学医学院(3)Heart Failure _ZhangQingnHeart failure is the pathophysiological state in which the heart is unable to pump sufficient blood to satisfy the metabolic demands of the body with enough preload.opendocument上海交通大学医学院(3)Heart Failure _ZhangQingThe Progressi
2、ve Development The Progressive Development of Cardiovascular Diseaseof Cardiovascular DiseaseEndstage Heart DiseaseEndstage Heart DiseaseCongestive Heart FailureCongestive Heart FailureVentricular DilationVentricular DilationRemodelingRemodelingArrhythmia & Loss of MuscleArrhythmia & Loss of MuscleM
3、yocardial InfarctionMyocardial InfarctionMyocardial IschemiaMyocardial IschemiaCADCADAtherosclerosisAtherosclerosisEndothelial DysfunctionEndothelial DysfunctionRisk FactorsRisk FactorsCoronary ThrombosisCoronary Thrombosisopendocument上海交通大学医学院(3)Heart Failure _ZhangQingFor progressive durationFor p
4、rogressive durationn nCongestive heart failure Congestive heart failure is classified into acute is classified into acute and chronic heart failureand chronic heart failuren nCongestive heart Congestive heart failure is classified failure is classified into left side, right into left side, right sid
5、e and biventricular side and biventricular heart failureheart failureFor anatomical typeFor anatomical typeopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Chronic heart failureopendocument上海交通大学医学院(3)Heart Failure _ZhangQingCauses Fundamental causes:Fundamental causes:n nimpa
6、irment of myocardium, impairment of myocardium, such as such as AMI,cardiomyopathy,myocarAMI,cardiomyopathy,myocarditisditisn noverloading of the heart, overloading of the heart, such as hypertension, aortic such as hypertension, aortic stenosis, mitral stenosis, mitral stenosis,emphysema,aortic ste
7、nosis,emphysema,aortic insufficiency,mitral insufficiency,mitral insufficiency,VSD,PDA,ASD.insufficiency,VSD,PDA,ASD.n ndiminished LV compliance, diminished LV compliance, such as ventricular such as ventricular hypertrophyhypertrophy Precipitating factorsPrecipitating factors infection,especially p
8、ulmonary infection, fever physical,environmental,or emotional stress increased sodium load arrhythmia, pulmonary emboli pregnancy and delivery anemia,bleeding,excessive transfusionopendocument上海交通大学医学院(3)Heart Failure _ZhangQingPathophysiology of heart failuren n Impaired myocardiumImpaired myocardi
9、umn n n nCardiac output , heart failureCardiac output , heart failuren n n nNeurohumoral stimulationNeurohumoral stimulationn nRAS and sympathetic-adrenergicRAS and sympathetic-adrenergicn n n nVasoconstriction increased heart rateVasoconstriction increased heart raten nSalt and water retention incr
10、eased energySalt and water retention increased energyn n(augments preload) expenditure (augments preload) expenditure n nHypertrophy Hypertrophy n n n nLeads to deterioration and death of cardiac cellLeads to deterioration and death of cardiac cellopendocument上海交通大学医学院(3)Heart Failure _ZhangQingEffe
11、cts of Neurohormonal Stimulation in Heart FailureHeart Heart rateHeart rate ContractilityContractility Stroke volumeStroke volume Cardiac outputCardiac output Conduction velocityConduction velocity Myocardial oxygen Myocardial oxygen consumption consumption Peripheral Circulation Arterial vasoconstr
12、ictionArterial vasoconstriction VenoconstrictionVenoconstriction Systemic vascular Systemic vascular resistanceresistance Redistribution of blood Redistribution of blood flowflow Renal vasoconstrictionRenal vasoconstrictionopendocument上海交通大学医学院(3)Pathophysiology of Heart Failure: Left Ventricular Re
13、modelingLeft-ventricular (LV) remodeling is defined as a Left-ventricular (LV) remodeling is defined as a change in LV geometry, mass and volume that change in LV geometry, mass and volume that occurs over a period of timeoccurs over a period of timeopendocument上海交通大学医学院(3)Heart Failure _ZhangQingop
14、endocument上海交通大学医学院(3)Heart Failure _ZhangQingVentricular Remodeling: Compensatory MechanismDilationHypertrophy Globular shapeShort term:CompensatoryLong term:Harmfulopendocument上海交通大学医学院(3)Heart Failure _ZhangQing DETERMINANTS OF VENTRICULAR FUNCTION STROKE VOLUMEPRELOADCONTRACTILITYCARDIAC OUTPUTH
15、EART RATE - Synergistic LV contractionSynergistic LV contraction - LV wall integrity - LV wall integrity - Valvular competence - Valvular competenceAFTERLOADopendocument上海交通大学医学院(3)Heart Failure _ZhangQingVicious Cycle of Heart FailureMyocardial dysfunctionDiminished Cardiac outputDiminished renalbl
16、ood flowRenin releaseAngiotensin IIAldosteroneIncreased SympatheticActivityVasoconstrictionIncreased forceand rate ofmyocardial contractionIncreasedcardiacworkloadRenalretention ofsodium and waterIncreasedvenousreturnEdemaopendocument上海交通大学医学院(3)Heart Failure _ZhangQingPathophysiology and Therapeuti
17、c Approaches to Heart FailureLV FunctionCardiac OutputNeurohormonalActivationSalt and Water RetentionPeripheral vasoconstrictionBlood flowVasodialtorsACE InhibitorsDiureticsACE Inhibitors BlockersDigoxinopendocument上海交通大学医学院(3)Heart Failure _ZhangQingCommon Symptoms of Heart Failuren nDyspnea on exe
18、rtionDyspnea on exertionn nParoxysmal nocturnal dyspneaParoxysmal nocturnal dyspnean nOrthopneaOrthopnean nFatigueFatiguen nLower extremity edemaLower extremity edeman nCough, usually worse at nightCough, usually worse at nightn nNausea, vomiting, anorexia, RUQ pain, ascitesNausea, vomiting, anorexi
19、a, RUQ pain, ascitesn nNocturiaNocturian nSleep disordersSleep disordersn nIncreased abdominal girthIncreased abdominal girthopendocument上海交通大学医学院(3)Heart Failure _ZhangQingCommon Physical Findings of Heart Failuren nElevated jugular venous pressureElevated jugular venous pressuren nHepatojugular re
20、fluxHepatojugular refluxn nDisplaced apical impulseDisplaced apical impulsen nS3 gallopS3 gallopn nPulmonary ralesPulmonary ralesn nHepatomegalyHepatomegalyn nPeripheral edemaPeripheral edeman nAscitesAscitesopendocument上海交通大学医学院(3)Heart Failure _ZhangQingClinical manifestationn nLeft heart failure:
21、SOB,cough,rales,gallopLeft heart failure:SOB,cough,rales,gallopn nRight heart failure:gastrointestinal Right heart failure:gastrointestinal congestion,anorexia,nausea,a sense of fullness after congestion,anorexia,nausea,a sense of fullness after meals,hepato-jugular reflux,swelling of feet or ankles
22、meals,hepato-jugular reflux,swelling of feet or anklesn nLow cardiac output:fatigue and weakness,oliguriaLow cardiac output:fatigue and weakness,oligurian nBiventricular heart failure:both clinical manifestation of left Biventricular heart failure:both clinical manifestation of left and right heart
23、failure,one of which maybe predominant.and right heart failure,one of which maybe predominant.opendocument上海交通大学医学院(3)Heart Failure _ZhangQingFunctional Classificationn nA classification of patients with heart disease based on the relation between with heart disease based on the relation between sym
24、ptoms and the amount of effort required to provoke symptoms and the amount of effort required to provoke them has been developed by the New York Heart them has been developed by the New York Heart Association.Association.opendocument上海交通大学医学院(3)Heart Failure _ZhangQingn nClass 1-No limitation Ordina
25、ry physical activity does not cause undue Ordinary physical activity does not cause undue fatigue,dyspnea,or palpitationfatigue,dyspnea,or palpitationn nClass 2-Slight limitation of physical activity Such patients are comfortable at rest.Ordinary physical Such patients are comfortable at rest.Ordina
26、ry physical activity results in fatigue,palpitation,dyspnea,or anginaactivity results in fatigue,palpitation,dyspnea,or anginaopendocument上海交通大学医学院(3)Heart Failure _ZhangQingn nClass 3-Marked limitation of physical activity Although patients are comfortable at rest,less than Although patients are co
27、mfortable at rest,less than ordinary activity will lead to symptoms.ordinary activity will lead to symptoms.n nClass 4-Inability to carry on any physical activity Symptoms of congestive failure are present even at Symptoms of congestive failure are present even at rest.With any physical activity,inc
28、reased discomfort is rest.With any physical activity,increased discomfort is experienced.experienced.opendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingComplicationn nPulmonary embolism,n nCongestive hepatomegaly,n nAscites,n nHepatic sclerosis,n nImbalan
29、ce of electrolytesopendocument上海交通大学医学院(3)Heart Failure _ZhangQingLaboratory Findingn nVenous pressure:elevatedVenous pressure:elevatedn nChest roentgenogram:cardiothoracic ratio,pulmonary Chest roentgenogram:cardiothoracic ratio,pulmonary edemaKerleys lines,perivascular and subpleural edemaKerleys
30、lines,perivascular and subpleural edema (butterfly and pleural effusion)edema (butterfly and pleural effusion)n nInvasive assessment of cardiac function: ventricular Invasive assessment of cardiac function: ventricular pressure,PCWP,pressure,PCWP,n nEcho and radionuclideEcho and radionuclideopendocu
31、ment上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingDiagnosis and differential diagnosisn nLeft heart failure:Left heart failure: Symptoms: orthopnea and paroxysmal nocturnal Symptoms: orthopnea and paroxysmal noctur
32、nal dyspneadyspnea Signs: moist and fine crepitant rales, PCWP25mmHg Signs: moist and fine crepitant rales, PCWP25mmHgn nRight heart failure:Right heart failure: Symptoms: anorexia ,nausea,a sense of fullness after Symptoms: anorexia ,nausea,a sense of fullness after meals and constipationmeals and
33、constipation Signs: peripheral edema,congestive Signs: peripheral edema,congestive heptomegaly,hepatojugular reflux,ascitesheptomegaly,hepatojugular reflux,ascitesopendocument上海交通大学医学院(3)Heart Failure _ZhangQingDifferential diagnosis Differentiation between cardiac and pulmonary dyspnea:Differentiat
34、ion between cardiac and pulmonary dyspnea:n nChronic obstructive lung disease is usually associated with sputum Chronic obstructive lung disease is usually associated with sputum production,the dyspnea is relieved after patients rid themselves of production,the dyspnea is relieved after patients rid
35、 themselves of secretions by coughing rather than specifically by sitting upsecretions by coughing rather than specifically by sitting upn nAcute cardiac asthma (paroxysmal nocturnal dyspnea with Acute cardiac asthma (paroxysmal nocturnal dyspnea with prominent wheezing) usually occurs in patients w
36、ho have obvious prominent wheezing) usually occurs in patients who have obvious clinical evidence of heart diseaseclinical evidence of heart diseasen nAirway obstruction and dyspnea that respond to bronchodilators or Airway obstruction and dyspnea that respond to bronchodilators or smoking cessation
37、 favor a pulmonary origin of the dyspnea, while smoking cessation favor a pulmonary origin of the dyspnea, while the response of these manifestations to diuretics supports heart the response of these manifestations to diuretics supports heart failure as the cause of dyspneafailure as the cause of dy
38、spneaopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingTherapyn nTo get rid of induction factors and complicationTo get rid of induction factors and complicationn nUses of inotropic agents:digitalis,dobutamineUses of inotropic agents:digitalis,dobutamine
39、n nUses of diureticsUses of diureticsn nUses of vasodilatorsUses of vasodilatorsn nOther treatment: sedative drug and oxygen Other treatment: sedative drug and oxygen supplysupplyopendocument上海交通大学医学院(3)Heart Failure _ZhangQing SurvivalMorbidityExercise capacityQuality of lifeNeurohormonal changes P
40、rogression of CHFSymptomsTREATMENT OBJECTIVESopendocument上海交通大学医学院(3)Heart Failure _ZhangQing TREATMENTCorrection of aggravating factorsMEDICATIONSEndocarditisObesityHypertensionPhysical activityDietary excessPregnancyArrhythmias (AF)InfectionsHyperthyroidismThromboembolismopendocument上海交通大学医学院(3)He
41、art Failure _ZhangQing TREATMENTPHARMACOLOGIC THERAPYDIURETICSINOTROPESVASODILATORSNEUROHORMONAL ANTAGONISTSOTHERS (Anticoagulants, antiarrhythmics, etc)opendocument上海交通大学医学院(3)Heart Failure _ZhangQing PHARMACOLOGIC THERAPYDIURETICS Improved symptomsDecreasedmortalityPreventionof CHFyes?Vasodil.(Nit
42、rates)yesyes?DIGOXINyes=minimalINOTROPESyes mort.?Other neurohormonal control drugsyes+ / -?ACEIyesYESyesNeurohumoralControlNOyesnonoYESYESopendocument上海交通大学医学院(3)Heart Failure _ZhangQing TREATMENTNormalAsymptomaticLV dysfunctionEF 40%Symptomatic CHFNYHA IIInotropesSpecialized therapyTransplantSympt
43、omatic CHFNYHA - IVSymptomatic CHFNYHA - IIISecondary preventionModification of physical activityACEI Diuretics mildNeurohormonal inhibitors Digoxin?Loop Diureticsopendocument上海交通大学医学院(3)Heart Failure _ZhangQingCortexMedullaThiazidesInhibit active exchange of Cl-Na in the cortical diluting segment o
44、f the ascending loop of HenleK-sparingInhibit reabsorption of Na in thedistal convoluted and collecting tubuleLoop diuretics Inhibit exchange of Cl-Na-K in the thick segment of the ascending loop of HenleLoop of HenleCollecting tubuleDIURETICSopendocument上海交通大学医学院(3)Heart Failure _ZhangQingTHIAZIDES
45、MECHANISM OF ACTIONExcrete 5 - 10% of filtered Na+Elimination of KInhibit carbonic anhydrase: increase elimination of HCO3Excretion of uric acid, Ca and MgNo dose - effect relationshipopendocument上海交通大学医学院(3)Heart Failure _ZhangQingLOOP DIURETICSMECHANISM OF ACTIONExcrete 15 - 20% of filtered Na+Eli
46、mination of K+, Ca+ and Mg+Resistance of afferent arterioles- Cortical flow and GFR- Release renal PGs- NSAIDs may antagonize diuresisopendocument上海交通大学医学院(3)Heart Failure _ZhangQingK-SPARING DIURETICS MECHANISM OF ACTIONEliminate 5% of filtered Na+ Inhibit exchange of Na+ for K+ or H+Spironolactone
47、 = competitive antagonist for the aldosterone receptorAmiloride and triamterene block Na+ channels controlled by aldosteroneopendocument上海交通大学医学院(3)Heart Failure _ZhangQingVolume and preloadImprove symptoms of congestionNo direct effect on CO, but excessive preload reduction may Improves arterial di
48、stensibilityNeurohormonal activatioLevels of NA, Ang II and ARPException: with spironolactoneDIURETIC EFFECTSopendocument上海交通大学医学院(3)Heart Failure _ZhangQingDIURETICS ADVERSE REACTIONS Thiazide and Loop Diuretics Changes in electrolytes: Volume Na+, K+, Ca+, Mg+ metabolic alkalosis Metabolic changes
49、: glycemia, uremia, gout LDL-C and TGCutaneous allergic reactionsopendocument上海交通大学医学院(3)Heart Failure _ZhangQingDIURETICSADVERSE REACTIONSK-SPARING DIURETICSChanges in electrolytes Na+, K+, acidosisMusculoskeletal:Cramps, weaknessCutaneous allergic reactions :opendocument上海交通大学医学院(3)Heart Failure _
50、ZhangQingNa+K+K+Na+Na+Ca+Ca+Na-K ATPaseNa-Ca ExchangeMyofilamentsDIGOXINCONTRACTILITYopendocument上海交通大学医学院(3)Heart Failure _ZhangQingDIGOXIN PHARMACOKINETIC PROPERTIESOral absorption (%)Protein binding (%)Volume of distribution (l/Kg)Half lifeEliminationOnset (min)i.v.oralMaximal effect (h)i.v.oralD
51、urationTherapeutic level (ng/ml)60 - 75256 (3-9)36 (26-46) hRenal5 - 3030 - 902 - 43 - 62 - 6 days0.5 - 2opendocument上海交通大学医学院(3)Heart Failure _ZhangQing DIGOXINDIGITALIZATION STRATEGIES(mg)0.125-0.5 / d0.25 / di.v0.5 + 0.25 / 4 hILD: 0.75-1oral 12-24 h0.75 + 0.25 / 6 h1.25-1.5oral 2-5 d0.25 / 6-12
52、h1.5-1.75Loading dose (mg)Maintenance Dose ILD = average INITIAL dose required for digoxin loadingopendocument上海交通大学医学院(3)Heart Failure _ZhangQing DIGOXINHEMODYNAMIC EFFECTSCardiac outputLV ejection fractionLVEDPExercise toleranceNatriuresisNeurohormonal activationopendocument上海交通大学医学院(3)Heart Failu
53、re _ZhangQing DIGOXIN NEUROHORMONAL EFFECTS Plasma Noradrenaline Peripheral nervous system activity RAAS activity Vagal toneopendocument上海交通大学医学院(3)Heart Failure _ZhangQing WORSENING OF CHF %p = 0.001DIGOXIN: 0.125 - 0.5 mg /d (0.7 - 2.0 ng/ml)EF 35%Class I-III (digoxin+diuretic+ACEI)Also significan
54、tly decreased exercisetime and LVEF.DIGOXIN EFFECT ON CHF PROGRESSIONRADIANCEN Engl J Med 1993;329:1Placebo n=93DIGOXIN WithdrawalDIGOXIN n=853010020100802004060Daysopendocument上海交通大学医学院(3)Heart Failure _ZhangQing 50403020100Placebon=3403DIGOXINn=3397480122436OVERALL MORTALITY %DIGN Engl J Med 1997;
55、336:525Monthsp = 0.8opendocument上海交通大学医学院(3)Heart Failure _ZhangQing DIGOXIN LONG TERM EFFECTSSurvival similar to placeboFewer hospital admissionsMore serious arrhythmiasMore myocardial infarctionsopendocument上海交通大学医学院(3)Heart Failure _ZhangQing DIGOXIN CLINICAL USESAF with rapid ventricular respons
56、eCHF refractory to other drugs Other indications?Can be combined with other drugsopendocument上海交通大学医学院(3)Heart Failure _ZhangQing DIGOXINCONTRAINDICATIONSABSOLUTE:- Digoxin toxicityRELATIVE- Advanced A-V block without pacemaker- Bradycardia or sick sinus without PM- PVCs and TV- Marked hypokalemia-
57、W-P-W with atrial fibrillationopendocument上海交通大学医学院(3)Heart Failure _ZhangQing DIGOXIN TOXICITYCARDIAC MANIFESTATIONSARRHYTHMIAS :- Ventricular (PVCs, TV, VF)- Supraventricular (PACs, SVT)BLOCKS:- S-A and A-V blocksCHF EXACERBATIONopendocument上海交通大学医学院(3)Heart Failure _ZhangQing DIGOXIN TOXICITYEXTR
58、ACARDIAC MANIFESTATIONSGASTROINTESTINAL:- Nausea, vomiting, diarrhea NERVOUS:- Depression, disorientation, paresthesias VISUAL:- Blurred vision, scotomas and yellow-green vision opendocument上海交通大学医学院(3)Heart Failure _ZhangQingCARDIAC GLYCOSIDESSYMPATHOMIMETICSCatecholamines-adrenergic agonistsPHOSPH
59、ODIESTERASE INHIBITORS Amrinone EnoximoneOthersMilrinonePiroximonePOSITIVE INOTROPESopendocument上海交通大学医学院(3)Heart Failure _ZhangQing -ADRENERGIC STIMULANTSCLASSIFICATIONB1 StimulantsIncrease contractilityDobutamineDoxaminolXamoterolButopaminePrenalterolTazololB2 StimulantsProduce arterialarterial va
60、sodilatation and reduce SVRPirbuterolCarbuterolRimiterolFenoterolTretoquinolSalbutamolTerbutalineSalmefamolSoterenolQuinterenolMixedDopamineopendocument上海交通大学医学院(3)Heart Failure _ZhangQing DOPAMINE AND DOBUTAMINEEFFECTSReceptorsContractilityHeart RateArterial Press.Renal perfusionArrhythmiaDA (g / K
61、g / min)Dobutamine 51 + a a+1+opendocument上海交通大学医学院(3)Heart Failure _ZhangQing POSITIVE INOTROPES CONCLUSIONSMay increase mortalitySafer in lower dosesUse only in refractory CHF NOT for use as chronic therapyopendocument上海交通大学医学院(3)Heart Failure _ZhangQing Venous VasodilatationMIXEDCalcium antagonis
62、ts a-adrenergic BlockersACEIAngiotensin II inhibitors K+ channel activatorsNitroprussideVENOUSNitratesMolsidomineARTERIALMinoxidilHydralazineVASODILATORSCLASSIFICATIONArterial Vasodilatationopendocument上海交通大学医学院(3)Heart Failure _ZhangQing 1- VENOUS VASODILATATION Preload2- Coronary vasodilatation My
63、ocardial perfusion3- Arterial vasodilatation Afterload4- OthersPulmonary congestionVentricular sizeVent. Wall stressMVO2NITRATESHEMODYNAMIC EFFECTS Cardiac output Blood pressureopendocument上海交通大学医学院(3)Heart Failure _ZhangQing 0.6PROBABILITYOF DEATH0Placebo (273)Prazosin (183)Hz + ISDN (186)MONTHS0.7
64、0.50.30.40.20.1VHefT-1N Engl J Med 1986;314:1547NITRATESSURVIVAL06121824303642opendocument上海交通大学医学院(3)Heart Failure _ZhangQing NITRATESTOLERANCECan be avoided or minimized- Intermittent administration- Use the lowest possible dose opendocument上海交通大学医学院(3)Heart Failure _ZhangQing NITRATESCONTRAINDICA
65、TIONSPrevious hypersensitivityHypotension ( 80 mmHg)AMI with low ventricular filling pressure 1st trimester of pregnancyWITH CAUTION:Constrictive pericarditisIntracranial hypertensionHypertrophic cardiomyopathyopendocument上海交通大学医学院(3)Heart Failure _ZhangQing NITRATES CLINICAL USESPulmonary congestio
66、nOrthopnea and paroxysmal nocturnal dyspneaCHF with myocardial ischemiaIn acute CHF and pulmonary edema: NTG s.l. or i.v.opendocument上海交通大学医学院(3)Heart Failure _ZhangQing VASOCONSTRICTIONVASODILATATION KininogenKallikreinInactive FragmentsAngiotensinogenAngiotensin IRENINKininase IIInhibitorALDOSTERO
67、NESYMPATHETICVASOPRESSINPROSTAGLANDINStPAANGIOTENSIN IIBRADYKININACE-i. Mechanism of ActionA.C.E.opendocument上海交通大学医学院(3)Heart Failure _ZhangQing ACEIHEMODYNAMIC EFFECTSArteriovenous Vasodilatation- PAD, PCWP and LVEDP-SVR and BP-CO and exercise toleranceNo change in HR / contractilityRenal, coronar
68、y and cerebral flowopendocument上海交通大学医学院(3)Heart Failure _ZhangQing 7595No Additional TreatmentNecessary(%)Quinapril Heart Failure TrialJACC 1993;22:1557ACEIFUNCTIONAL CAPACITYQuinaprilcontinuedn=114QuinaprilstoppedPlacebon=110p0.001100908580WeeksClass II-III1612621048182014opendocument上海交通大学医学院(3)H
69、eart Failure _ZhangQing ACEIADVANTAGESInhibit LV remodeling post-MIModify the progression of chronic CHF- Survival- Hospitalizations- Improve the quality of lifeIn contrast to others vasodilators, do not produce neurohormonal activationor reflex tachycardiaopendocument上海交通大学医学院(3)Heart Failure _Zhan
70、gQing PlaceboEnalapril12111098765PROBABILITYOF DEATHMONTHS0.10.800.20.30.70.40.50.6p 0.001p 0.002CONSENSUSN Engl J Med 1987;316:1429ACEI SURVIVAL43210opendocument上海交通大学医学院(3)Heart Failure _ZhangQing 50403020100Months0612p = 0.30241830364248Enalapriln=2111Placebon=2117SOLVD (Prevention)N Engl J Med 1
71、992;327:685MORTALITY %ACEI SURVIVALn = 4228No CHF symptomsEF 35opendocument上海交通大学医学院(3)Heart Failure _ZhangQing 50403020100Months0612p = 0.0036MORTALITY %241830364248Enalapriln=1285Placebon=1284SOLVD (Treatment)N Engl J M 1991;325:293ACEI SURVIVALn = 2589CHF - NYHA II-III- EF 35opendocument上海交通大学医学院
72、(3)Heart Failure _ZhangQing Mortality %4SAVEN Engl J Med 1992;327:669Years3020100123PlaceboCaptopril0n=1115n=1116p=0.019 -19%ACEI SURVIVALn = 22313 - 16 days post AMIEF 4012.5 - 150 mg / dayAsymptomatic ventriculardysfunction post MIopendocument上海交通大学医学院(3)Heart Failure _ZhangQing ISIS-4GISSI-3SAVES
73、MILEAIRE ACEIBenefitPt SelectionCaptoprilLisinoprilCaptoprilZofenoprilRamipril0.5 / 5 wk0.8 / 6 wk4.2 / 3.5 yr4.1 / 1 yr6 / 1 yrAll with AMIAll with AMIEF 40asymptomaticAnt. AMI, No TRLClinical CHFTRACETrandolapril7.6 / 3 yrVent Dysfx / Clinical CHFEF 35ACEISURVIVAL POST MIopendocument上海交通大学医学院(3)He
74、art Failure _ZhangQingACEIINDICATIONSClinical cardiac insufficiency- All patients Asymptomatic ventricular dysfunction- LVEF 35 % opendocument上海交通大学医学院(3)Heart Failure _ZhangQing ACEIUNDESIRABLE EFFECTSInherent in their mechanism of action- Hypotension- Hyperkalemia- Angioneurotic edema- Dry cough-
75、Renal Insuff.opendocument上海交通大学医学院(3)Heart Failure _ZhangQing ACEICONTRAINDICATIONS Renal artery stenosisRenal insufficiencyHyperkalemiaArterial hypotensionIntolerance (due to side effects)opendocument上海交通大学医学院(3)Heart Failure _ZhangQing ANGIOTENSIN II INHIBITORS （ARB)MECHANISM OF ACTIONRENINAngiote
76、nsinogenAngiotensin IANGIOTENSIN II ACEOther pathsVasoconstrictionProliferative ActionVasodilatation Antiproliferative ActionAT1 AT2AT1 RECEPTOR BLOCKERSRECEPTORSopendocument上海交通大学医学院(3)Heart Failure _ZhangQingAT1 RECEPTOR BLOCKERSDRUGSLosartanValsartanIrbersartanCandersartanCompetitive and selectiv
77、e blocking of AT1 receptorsopendocument上海交通大学医学院(3)Heart Failure _ZhangQing ALDOSTERONERetention Na+Retention H2OExcretion K+Excretion Mg2+Collagen depositionFibrosis - myocardium - vesselsSpironolactone Edema ArrhythmiasCompetitive antagonist of thealdosterone receptor(myocardium, arterial walls, k
78、idney)ALDOSTERONE INHIBITORSopendocument上海交通大学医学院(3)Heart Failure _ZhangQing ALDOSTERONE INHIBITORSINDICATIONSFOR DIURETIC EFFECT Pulmonary congestion (dyspnea) Systemic congestion (edema)FOR ELECTROLYTE EFFECTS Hypo K+, Hypo Mg+ Arrhythmias Better than K+ supplementsFOR NEUROHORMONAL EFFECTS Please
79、 see RALES results, N Engl J Med 1999:341:709-717opendocument上海交通大学医学院(3)Heart Failure _ZhangQing Hyperkalemia Severe renal insufficiency Metabolic acidosisALDOSTERONE INHIBITORSCONTRAINDICATIONSopendocument上海交通大学医学院(3)Heart Failure _ZhangQing-ADRENERGIC BLOCKERS POSSIBLE BENEFICIAL EFFECTS Density
80、of 1 receptors Inhibit cardiotoxicity of catecholamines Neurohormonal activation HRAntihypertensive and antianginalAntiarrhythmicAntioxidantAntiproliferativeopendocument上海交通大学医学院(3)Heart Failure _ZhangQing BLOCKERSCARVEDILOL4 studies in U.S.; 1 in Australia/New ZealandU.S. studies with control group
81、Mortality with Placebo8.2%Mortality with Carvedilol2.9%Initial low doses, progressivep 0.0001opendocument上海交通大学医学院(3)Heart Failure _ZhangQing-ADRENERGIC BLOCKERS INDICATIONS and UTILIZATIONBegin with very low doses Slow augmentation of doseSlow withdrawal ?opendocument上海交通大学医学院(3)Heart Failure _Zhan
82、gQing-ADRENERGIC BLOCKERSIDEAL CANDIDATE?Suspected adrenergic activationArrhythmiasHypertensionAnginaopendocument上海交通大学医学院(3)Heart Failure _ZhangQing -ADRENERGIC BLOCKERSCONTRAINDICATIONSHypotension: BP 100 mmHgBradycardia: HR 50 bpmClinical instabilityChronic bronchitis, ASTHMASevere chronic renal
83、insufficiencyopendocument上海交通大学医学院(3)Heart Failure _ZhangQing CALCIUM ANTAGONISTSPOTENTIAL EFFECTSAntiischemicPeripheral Vasodilatation Inotropyopendocument上海交通大学医学院(3)Heart Failure _ZhangQing CALCIUM ANTAGONISTSPOSSIBLE UTILITYDiltiazem contraindicatedVerapamil and Nifedipine not recommendedVasosel
84、ective (amlodipine, nisoldipine),may be useful in ischemia + CHFopendocument上海交通大学医学院(3)Heart Failure _ZhangQing ANTICOAGULANTSPREVIOUS EMBOLIC EPISODEATRIAL FIBRILLATIONIdentified thrombusLV Aneurysm (3-6 mo post MI)Class III-IV in the presence of:- EF 30- Aneurysm or very dilated LVopendocument上海交
85、通大学医学院(3)Heart Failure _ZhangQing ANTIARRHYTHMICSSustained VT, with/without symptoms- Blockers- AmiodaroneSudden death from VF- Consider implantable defibrillatoropendocument上海交通大学医学院(3)Heart Failure _ZhangQingIntractable heart failuren n1.To find induction factorsn n2.To use better doses of drug n
86、n3.IABP in severe coronary heart diseasen n4.interventional treatment for coronary heart diseasen n5.CABG for severe heart diseasen n6.heart transplantationopendocument上海交通大学医学院(3)Heart Failure _ZhangQingAcute Left Heart Failuren nCauses: extensive acute myocardial infarction;acute myocarditis;malig
87、nant or accelerated hypertension;mitral stenosis;severe cardiac arrhythmias;rapid and excessive volume injectionopendocument上海交通大学医学院(3)Heart Failure _ZhangQingDiagnosisn nAccording to clinical manifestation:sudden onset orthopnea,coughs,cyanosis ,moist ralse is prominent and wheezing may be heard a
88、ll over the chest, rapid pulse and weakness. Shock may be presentopendocument上海交通大学医学院(3)Heart Failure _ZhangQingTherapyn n1.sedative drugn n2.oxygenn n3.diureticsn n4.vasodilatorsn n5.inotropic agentsn n6.reduce venous returnn n7.IABPopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大
89、学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Resynchronization Therapy For Heart Failureopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocume
90、nt上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(
91、3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Fail
92、ure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQingopendocument上海交通大学医学院(3)Heart Failure _ZhangQi
93、ngThe Endopendocument上海交通大学医学院(3)2E6H9KcOfRiUmXp#s&v)z0C3F7IaLdPgSkVnYq$t*w-A1D5G8JbNeQhTlWo#r%u(y+B2E6H9LcOfRjUmXp!s&w)z0C4F7IaMdPhSkVnZq$t*x-A2D5G8KbNeQiTlWo#r%v(y+B3E6H9LcOgRjUmYp!s&w)z1C4F7JaMdPhSkWnZq$u*x-A2D5H8KbNfQiTlXo#s%v(y0B3E6I9LdOgRjVmYp!t&w)z1C4G7JaMePhSkWnZr$u*x+A2D5H8KcNfQiUlXo#s%v)y0
94、B3F6I9LdSkWnZq$u*x-A2D5H8KbNfQiTlXo#s%v(y0B3E6I9LcOgRjVmYp!t&w)z1C4G7JaMePhSkWnZr$u*x+A2D5H8KcNfQiUlXo#s%v)y0B3F6I9LdOgSjVmYq!t&w-z1D4G7JbMePhTkWnZr$u(x+A2E5H8KcNfRiUlXp#s%v)y0C3F6IaLdOgSjVnYq!t*w-z1D4G8JbMeQhTkWoZr%u(x+B2E5H9KcOfRiUmXp#s&v)y0C3F7IaLdPgSjVnYq$t*w-A1D4G8JbNeQhTlWoZr%u(y+B2E6H9KcOfRjU
95、mXp!s&v)z0C4F7IaMdPgSkVnZq$t*x-A1D5G8KbNeQiTlWo#r%u(y+B3E6H9LcOfRjUmYp!s&w)z0C4F7JaMdPhSkVnZq$u*x-A2D5G8KbNfQiTlXo#r%v(y0B3E6I9LcOgRjVmYp!t&w)z1C4F7JaMePhSkWnZq$u*x+A2D5H8KbNfQiUlXo#s%v(y0B3F6I9LdOgRjVmYq!t&w-z1C4G7JbMePhTkWnZr$u(x+A2E5H8KcNfRiUlXp#s%v)y0B3F6IaLdOgSjVmYq!t*w-z1D4G7JbMeQhTkWoZr$u(x+B
96、2E5H9KcNfRiUmXp#s&v)y0C3F7IaLdPgSjVnYq$t*w-A1D4G8JbMeQhTlWoZr%u(x+B2E6H9KcOfRiUmXp!s&v)z0C3F7IaMdPgSkVnYq$t*x-A1D5G8JbNeQiTlWo#r%u(y+B3E6H9LcOfRjUmXp!s&w)z0C4F7IaMdPhSkVnZq$t*x-A2D5G8KbNeQiTlXo#r%v(y+B3E6I9LcOgRjUmYp!t&w)z1C4F7JaMePhSkWnZq$u*x+A2D5H8KbNfQiTlXo#s%v(y0B3E6I9LdOgRjVmYp!t&w-z1C4G7JaMePh
97、TkWnZr$u*x+A2E5H8KcNfQiUlXp#s%v)y0B3F6IaLdOgSjVmYq!t&w-z1D4G7JbMePhTkWoZr$u(x+A2E5H9KcNfRiUlXp#s&v)y0C3F6IaLdPgSjVnYq!t*w-A1D4G8JbMeQhTlWoZr%u(x+B2E5H9KcOfRiUmXp#s&v)z0C3F7IaLdPgSkVnYq$t*w-A5H9KcNfRiUlXp#s&v)y0C3F6IaLdPgSjVnYq!t*w-A1D4G8JbMeQhTkWoZr%u(x+B2E5H9KcOfRiUmXp#s&v)z0C3F7IaLdPgSkVnYq$t*w-A1
98、D5G8JbNeQhTlWo#r%u(y+B2E6H9LcOfRjUmXp!s&v)z0C4F7IaMdPgSkVnZq$t*x-A1D5G8KbNeQiTlWo#r%v(y+B3E6H9LcOgRjUmYp!s&w)z1C4F7JaMdPhSkWnZq$u*x-A2D5H8KbNfQiTlXo#r%v(y0B3E6I9LcOgRjVmYp!t&w)z1C4G7JaMePhSkWnZr$u*x+A2D5H8KcNfQiUlXo#s%v)y0B3F6I9LdOgSjVmYq!t&w-z1C4G7JbMePhTkWnZr$u(x+A2E5H8KcNfRiUlXp#s%v)y0C3F6IaLdOgS
99、jVnYq!t*w-z1D4G8JbMeQhTkWoZr%u(x+B2E5H9KcNfRiUmXp#s&v)y0C3F7IaLdPgSjVnYq$t*w-A1D4G8JbNeQhTlWoZr%u(y+B2E6H9KcOfRjUmXp!s&v)z0C4F7IaMdPgSkVnZq$t*x-A1D5G8JbNeQiTlWo#r%u(y+B3ELdPgSjVnYq$t*w-A1D4G8JbNeQhTlWoZr%u(y+B2E6H9KcOfRjUmXp!s&v)z0C3F7IaMdPgSkVnYq$t*x-A1D5G8JbNeQiTlWo#r%u(y+B3E6H9LcOfRjUmYp!s&w)z0C4
100、F7JaMdPhSkVnZq$u*x-A2D5G8KbNfQiTlXo#r%v(y+B3E6I9LcOgRjUmYp!t&w)z1C4F7JaMePhSkWnZq$u*x+A2D5H8KbNfQiUlXo#s%v(y0B3F6I9LdOgRjVmYq!t&w-z1C4G7JaMePhTkWnZr$u*x+A2E5H8KcNfQiUlXp#s%v)y0B3F6IaLdOgSjVmYq!t*w-z1D4G7JbMeQhTkWoZr$u(x+B2E5H9KcNfRiUmXp#s&v)y0C3F6IaLdPgSjVnYq!t*w-A1D4G8JbMeQhTlWoZr%u(x+B2E6H9KcOfRiU
101、mXp!s&v)z0C3F7IaMdPgSkVnYq$t*x-A1D5G8JbNeQhTlWo#r%u(y+B2E6H9LcOfRjUmXp!s&w)z0C4F7IaMdPhSkVnZq$t*x-A6H9KcOfRiUmXp!s&v)z0C3F7IaLdPgSkVnYq$t*w-A1D5G8JbNeQhTlWo#r%u(y+B2E6H9LcOfRjUmXp!s&w)z0C4F7IaMdPhSkVnZq$t*x-A2D5G8KbNeQiTlXo#r%v(y+B3E6H9LcOgRjUmYp!s&w)z1C4F7JaMdPhSkWnZq$u*x-A2D5H8KbNfQiTlXo#s%v(y0B3E
102、6I9LdOgRjVmYp!t&w-z1C4G7JaMePhSkWnZr$u*x+A2D5H8KcNfQiUlXo#s%v)y0B3F6I9LdOgSjVmYq!t&w-z1D4G7JbMePhTkWoZr$u(x+A2E5H9KcNfRiUlXp#s&v)y0C3F6IaLdOgSjVnYq!t*w-z1D4G8JbMeQhTkWoZr%u(x+B2E5H9KcOfRiUmXp#s&v)z0C3F7IaLdPgSkVnYq$t*w-A1D5G8JbNeQhTlWoZr%u(y+B2E6H9KcOfRjUmXp!s&v)z0C4F7IaMdPgSkVnZq$t*x-A1D5G8KbNeQiTl
103、Wo#r%v(y+B3E6H9LcOgRjUmYp!s&w)z0C4F7JaMdPhSkVnZq$u*x-A2D5G8KbNfQiTlXo#r%v(y0B3E6I9LcOgRjVmYp!t&w)z1C4G7JaMePhSkWnZr$u*x+A2D5H8KcNfQiUlXow)z0C4F7JaMdPhSkVnZq$u*x-A2D5G8KbNfQiTlXo#r%v(y0B3E6I9LcOgRjVmYp!t&w)z1C4G7JaMePhSkWnZq$u*x+A2D5H8KbNfQiUlXo#s%v(y0B3F6I9LdOgRjVmYq!t&w-z1C4G7JbMePhTkWnZr$u(x+A2E5H
104、8KcNfRiUlXp#s%v)y0C3F6IaLdOgSjVmYq!t*w-z1D4G7JbMeQhTkWoZr$u(x+B2E5H9KcNfRiUmXp#s&v)y0C3F7IaLdPgSjVnYq$t*w-A1D4G8JbNeQhTlWoZr%u(x+B2E6H9KcOfVmYq!t*w-z1D4G7JbMeQhTkWoZr$u(x+B2E5H9KcNfRiUmXp#s&v)y0C3F7IaLdPgSjVnYq$t*w-A1D4G8JbMeQhTlWoZr%u(x+B2E6H9KcOfRiUmXp!s&v)z0C3F7IaMdPgSkVnYq$t*x-A1D5G8JbNeQiTlWo#r
105、%u(y+B3E6H9LcOfRjUmXp!s&w)z0C4F7IaMdPhSkVnZq$t*x-A2D5G8KbNeQiTlXo#r%v(y+B3E6I9LcOgRjUmYp!t&w)z1C4F7JaMePhSkWnZq$u*x-A2D5H8KbNfQiTlXo#s%v(y0B3E6I9LdOgRjVmYp!t&w-z1C4G7JaMePhTkWnZr$u*x+A2E5H8KcNfQiUlXp#s%v)y0B3F6IaLdOgSjVmYq!t&w-z1D4G7JbMePhTkWoZr$u(x+A2E5H9KcNfRiUlXp#s&v)y0C3FMePhTkWnZr$u*x+A2E5H8KcN
106、fQiUlXo#s%v)y0B3F6I9LdOgSjVmYq!t&w-z1D4G7JbMePhTkWoZr$u(x+A2E5H9KcNfRiUlXp#s&v)y0C3F6IaLdPgSjVnYq!t*w-A1D4G8JbMeQhTkWoZr%u(x+B2E5H9KcOfRiUmXp#s&v)z0C3F7IaLdPgSkVnYq$t*w-A1D5G8JbNeQhTlWo#r%u(y+B2E6H9LcOfRjUmXp!s&v)z0C4F7IaMdPgSkVnZq$t*x-A1D5G8KbNeQiTlWo#r%v(y+B3E6H9LcOgRjUmYp!s&w)z1C4F7JaMdPhSkWnZq$u
107、*x-A2D5G8KbNfQiTlXo#v)z0C4F7IaMdPgSkVnZq$t*x-A1D5G8KbNeQiTlWo#r%v(y+B3E6H9LcOgRjUmYp!s&w)z1C4F7JaMdPhSkVnZq$u*x-A2D5G8KbNfQiTlXo#r%v(y0B3E6I9LcOgRjVmYp!t&w)z1C4G7JaMePhSkWnZr$u*x+A2D5H8KcNfQiUlXo#s%v(y0B3F6I9LdOgRjVmYq!t&w-z1C4G7JbMePhTkWnZr$u(x+A2E5H8KcNfRiUlXp#s%v)y0C3F6IaLdOgSjVnYq!t*w-z1D4G8JbMe
108、QhTkWoZr$u(x+B2E5H9KcNfRiUmXp#s&v)y0C3F7IaLdPgSjVnYq(x+A2E5H8KcNfRiUlXp#s%v)y0C3F6IaLdOgSjVmYq!t*w-z1D4G7JbMeQhTkWoZr$u(x+B2E5H9KcNfRiUmXp#s&v)y0C3F7IaLdPgSjVnYq$t*w-A1D4G8JbNeQhTlWoZr%u(y+B2E6H9KcOfRiUmXp!s&v)z0C3F7IaMdPgSkVnYq$t*x-A1D5G8JbNeQiTlWo#r%u(y+B3E6H9LcOfRjUmYp!s&w)z0C4F7JaMdPhSkVnZq$t*x-A2D5G8KbNeQiTlXo#r%v(y+B3E6I9LcOgRjUmYp!t&w)z1C4F7JaMePhSkWnZq$u*3E6H9LcOfRjUmXp!s&w)z0C4F7IaMdPhSkVnZq$t*x-A2D5G8KbNeQiTlXo#r%v(y+B3E6I9LcOgRjUmYp!t&w)z1C4F7JaMePhSkWnZq$u*x+A2D5H8KbNfQiTlXo#s%v(y0B3E6I9LdOgRjVmYp!t&w-z1C4G7JaMePhTkopendocument上海交通大学医学院(3)
