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 Progressive Development The Progressive Development of Cardiovascular Diseaseof Cardiovascular DiseaseEndstage Heart DiseaseEndstage Heart DiseaseCongestive Heart FailureCongestive Heart FailureVentricular DilationVentricular DilationRemodelingRemodelingArrhythmia & Loss of MuscleArrhythmia & Loss of MuscleMyocardial 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 progressive 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 side 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 nimpairment 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 stenosis,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 pulmonary 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 myocardiumn 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 increased 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 _ZhangQingEffects 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 vasoconstrictionArterial 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 RemodelingLeft-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 _ZhangQingopendocument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 OUTPUTHEART 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 renalblood 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 Therapeutic 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 exertionDyspnea 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, anorexia, 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 refluxHepatojugular 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: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 anklesmeals,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 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 symptoms 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 Ordinary 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.Ordinary 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 comfortable 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,increased 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 nImbalance 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 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 radionuclideopendocument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 nocturnal 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 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:Differentiation 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 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 who 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 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 dyspneaopendocument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,dobutaminen 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 Progression 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)Heart 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.(Nitrates)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 therapyTransplantSymptomatic 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 of 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 _ZhangQingTHIAZIDESMECHANISM 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+Elimination 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 = 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 distensibilityNeurohormonal 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: 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 _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.oralDurationTherapeutic 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 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 Failure _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 significantly 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;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 responseCHF 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- 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 TOXICITYEXTRACARDIAC 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 agonistsPHOSPHODIESTERASE INHIBITORS Amrinone EnoximoneOthersMilrinonePiroximonePOSITIVE INOTROPESopendocument上海交通大学医学院(3)Heart Failure _ZhangQing -ADRENERGIC STIMULANTSCLASSIFICATIONB1 StimulantsIncrease contractilityDobutamineDoxaminolXamoterolButopaminePrenalterolTazololB2 StimulantsProduce arterialarterial vasodilatation and reduce SVRPirbuterolCarbuterolRimiterolFenoterolTretoquinolSalbutamolTerbutalineSalmefamolSoterenolQuinterenolMixedDopamineopendocument上海交通大学医学院(3)Heart Failure _ZhangQing DOPAMINE AND DOBUTAMINEEFFECTSReceptorsContractilityHeart RateArterial Press.Renal perfusionArrhythmiaDA (g / Kg / 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 antagonists 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 Myocardial 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)MONTHS0.70.50.30.40.20.1VHefT-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 NITRATESCONTRAINDICATIONSPrevious 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 congestionOrthopnea 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 IIInhibitorALDOSTERONESYMPATHETICVASOPRESSINPROSTAGLANDINStPAANGIOTENSIN 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, coronary 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)Heart 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 _ZhangQing 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 1992;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(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-3SAVESMILEAIRE 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)Heart 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- 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 ACTIONRENINAngiotensinogenAngiotensin 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 selective 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, kidney)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 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 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 groupMortality 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 _ZhangQing-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 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 recommendedVasoselective (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 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;malignant 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 all 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 _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 _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 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