收縮性和舒張性心衰的治療課件

1、Management of Systolic vs. Diastolic Heart FailureMichael Wolk, MD,FACCWeill-CornellGreat Wall of China SymposiumOctober, 2004Management of Systolic vs. DiaBasic conceptsThe clinical syndrome of heart failure can occur with either normal or reduced LVEFVirtually all clinical trials of heart failure

2、therapies have enrolled only patients with reduced LVEFBasic conceptsThe clinical syThusExtrapolating recommended therapy for HF with reduced EF to patients with HF and normal EF is not “automatic”ThusExtrapolating recommendedTherapy for HF with Reduced EFEvidence base for ACEI and beta blocker ther

3、apy among the largest and most consistent in medicineTherapy for HF with Reduced EFdiureticdigoxindiureticdigoxinACEIdiureticdigoxinACEIdiureticdigoxinACEIBeta blockerdiureticdigoxinACEIBeta blockerdiureticdigoxinACEIBeta blockerARBSOLVD-T (1991)RRR 21% CIBIS-2 (1999)RRR 33%CHARM-Added (2003) (Beta-

4、blocker subgroup) RRR 30%Improving Survival in CHF One-year MortalitydiureticdiureticdiureticdiuretCV Death, MI, or HFby TreatmentPfeffer, McMurray, Velazquez, et al. N Engl J Med 2003;349CaptoprilMonthsValsartan vs. Captopril: HR = 0.96; P = 0.198Valsartan + Captopril vs. Captopril: HR = 0.97; P =

5、0.36900.10.20.30.4061218243036Probability of EventValsartanValsartan + CaptoprilCV Death, MI, or HFby Treatme收縮性和舒張性心衰的治療課件ACE-I in HF - Who and How?HFSA Practice Guidelines 2004All pts (symptomatic and asymptomatic) with LV systolic dysfunction (LVEF 2.0 mg/dl or serum potassium is 5.0 mmol/L.ACEI

6、should be titrated as tolerated, in conjunction with BBs, to target doses used in clinical trials.ACE-I in HF - Who and How?HFSWeight Of Evidence: -BlockadeOver 18,000 patients evaluated in long-term placebo-controlled clinical trialsImprovement in cardiac function and symptoms; (equivocal effects o

7、n exercise tolerance)Decrease in all-cause mortality by 30%-35% (P.0001); effect shown in 5 individual trialsDecrease in combined risk of death and hospitalization by 35%-40% (P.001); effect shown in 7 individual trialsEffect shown in patients already receiving ACE inhibitorsWeight Of Evidence: -Blo

8、ckadTherapy for HF with Reduced EFLifestyle changes:Salt restrictionAchieve ideal weightPursue regular exercise Avoid smoking, toxinsTherapy for HF with Reduced EFTherapy for HF with Reduced EFGeneral considerations for all patientsTreat reversible ischemiaManage contributing arrhythmiaTherapy for H

9、F with Reduced EFWHAT HAVE WE LEARNED ABOUT NESIRITIDE IN CHF?A simple regimen / predictable effect.Improves hemodynamics.Improves symptoms.Diuretic and natriuretic effect.Favorable neurohormonal effect Safer then drugs with inotropic effect (dobutamine, milrinone).WHAT HAVE WE LEARNED ABOUT NESRALE

10、S: All-Cause MortalityMonths Survival0.450.500.550.600.650.700.750.800.850.900.951.000369121518212427303336Risk reduction 29%95% CI (18%39%)P 9 monthsNYHA Class I-IVProposed CMS covered indication-9/04 ICD Indications for Primary COMPANIONHypothesesBiventricular CRT alone decreases combined all-caus

11、e mortality and all-cause hospitalization. ICD prevents sudden death1520 Patients Randomized Medical vs CRT vs CRT-ICD COMPANIONHypothesesBiventricuEndpoint: All-cause MortalityEndpoint: All-cause MortalityICD ImplantsMayo ICDs/ yearCP985319-12Year (1985-2003)ICD ImplantsMayo ICDs/ ye“Even the wealt

12、hiest nationscannot afford to pay to use every medical advance in any patient who might benefit.”.Thomas Bigger, Lancet, 2001“Even the wealthiest nationscTherapy for HF with Reduced EFSurgery for some (few) patients:TransplantSurgical Ventricular Restoration (MVR) RESTORE EF 30 to 40%, JACC - 9/04“D

13、estination” LVAD ?Therapy for HF with Reduced EF HF with Normal EF40 % of HF patientsMost have no identifiable myocardial diseaseElderly WomenHypertensive and diabetic HF with Normal EF40 % of HF p HF with Normal EFMortality:Nearly as profound as for reduced EF5-8% vs 10-15% (Gaasch-NEJM, 2004)Morbi

14、dity:Includes frequent readmissions22% within 12 weeks HF with Normal EFMortality: HF with Normal EF - DiagnosisPhysiologic abnormalities may be seen on echo or invasivelyIN PRACTICE DIAGNOSIS PRIMARILY CLINICAL HF with Normal EF - Diagnosis Therapy of HF with Normal EFIn the absence of controlled c

15、linical trialsMANAGEMENT BASED ON CONTROL OF PHYSIOLOGIC FACTORS KNOWNTO AFFECT VENTRICULARRELAXATION Therapy of HF with Normal EFIPHYSIOLOGIC FACTORS AFFECTING VENTRICULAR RELAXATIONBlood volume, e.g. DiureticsIschemia Blood pressure-goal lower BP than published guidelines, e.g.-ACE, B Blockers PHY

16、SIOLOGIC FACTORS AFFECTING Therapy of HF with Normal EFFACTORS AFFECTING VENTRICULAR RELAXATIONTACHYCARDIAPrinciple: Tachycardia can shorten time available for ventricular filling and coronary perfusionTherefore: Drugs that slow HR or ventricular response to atrial arrhythmias can relieve symptomsBE

17、TA BLOCKERS Therapy of HF with Normal EF Therapy of HF with Normal EFFACTORS AFFECTING VENTRICULAR RELAXATIONMYOCARDIAL ISCHEMIAConsider coronary revascularization in patients with symptomatic or demonstrable myocardial ischemia Therapy of HF with Normal EFCHARM Programn=3025LVEF 40%ACEI treated/not

18、 treatedCHARM- “Added”CHARM-“Preserved”3 component trials comparingcandesartan to placeboCHARM-“Alternative”n=2028 LVEF 40% ACEI intolerantn=2548LVEF 40%ACEI treatedPrimary outcome:CV death or CHF hospCHARM Programn=3025CHARM- “AdCHARM-Preserved Investigator-reported CHF HospitalizationsP=0.014P=0.0

19、17Patients hospitalizedHospitalizationsPlaceboCandesartanProportion of patients (%)Number of episodesHR = 0.85RRR = 29%CHARM-Preserved Investigator-New Approaches to the Patient with Heart FailureAssessment of LV functionLow LVEFEjection fraction 40%Signs/symptoms offluid retentionNo signs/symptoms

20、offluid retentionDiureticACEI/or ARBBeta blockerPreserved LVEFEjection fraction 40%ARBARBNo signs/symptoms offluid retentionDigoxinSpironolactoneNYHA Class II/IIINYHA Class III/IVNew Approaches to the Patient 收縮性和舒張性心衰的治療課件 Therapy of HF with Normal EFThus, according to this principle, the condition

21、 should be treated with:DiureticsBeta blockers-39%S-dys vs 46%Di-dys*ACEI/ARB-62%S-dys vs 82%Di-Dys* Appropriate coronary revascularization*ESC survey-2004DOES THIS SOUND FAMILIAR? Therapy of HF with Normal EF Therapy of HF with Normal EFFACTORS AFFECTING VENTRICULAR RELAXATIONBLOOD VOLUMEDiuretics

22、relieve Sx in patients with HF and normal EFThey also help control BP Therapy of HF with Normal EFCOPERNICUS: OUTCOMESCOPERNICUS: OUTCOMESCHARM “Added”CHARM“Preserved”CHARM Program3 component trials comparing candesartan to placebo in patients with symptomatic heart failureCHARM“Alternative”n=2028 L

23、VEF 40%ACEI intolerantn=2548LVEF 40%ACEI treatedn=3025LVEF 40%ACEI treated/not treatedPrimary outcome for Overall Program: All-cause deathPrimary outcome for each trial: CV death or CHF hospitalizationCHARM “Added”CHARM“PreservedMortality Benefit of Beta Blockers and ACEIs in CHF trials11.915.67.812

24、.40246810121416% death at 1 yearSOLVD (1991)diureticdigoxin diuretic digoxin ACEIdiuretic digoxin ACEIdiuretic digoxin ACEI Beta blockerCIBIS IIMERIT-HF(1999)McMurray 2001Mortality Benefit of Beta BlocCHARM-Overall:Permanent Study Drug DiscontinuationsPlaceboCandesartan0510152025Percent of patientsP

25、0.0001P0.0001P0.0001P0.0001Hypo-tensionIncreased creatinineIncreasedpotassiumAE/ lab. abnorm.16.71.73.00.621.03.56.22.2CHARM-Overall:Permanent StudyCardiovascularMortality and MorbidityCV Death, MI, or HF(3096 events)0.000001NoninferiorityVal Superior to CapCap Superior to ValNoninferiority not Demo

26、nstrated0.811.2Hazard Ratio(97.5% CI)1.13P-value(noninferiority)noninferiority marginCV Death(1657 events)0.001CV Death or HF(2661 events)0.0001CV Death or MI(2234 events)0.00001Favors ValsartanFavors CaptoprilCardiovascularMortality and MCHARM-Preserved Development of new diabetes 47770.600.005 (0.

27、41-0.86)Number of casesHRp-valueCandesartanPlacebo(CI) CHARM-Preserved Development oThusWhile the basic clinical picture of the two is the sameTheir basic pathophysiology may be differentat least we cannot just assume that it is the sameThusWhile the basic clinical Therapy for HF with Reduced EFDrug

28、s for all patients:Diuretics for fluid retentionACE Inhibitors/ARBsBeta blockersTherapy for HF with Reduced EFPossible Future Therapy for HF with Reduced EFDrugs Vasopressin receptor antagonists? Others?Devices External counterpulsation? Implantable hemodynamic monitors?Possible Future Therapy for H

29、FCHARM-Preserved Development of new diabetes 47770.600.005 (0.41-0.86)Number of casesHRp-valueCandesartanPlacebo(CI) CHARM-Preserved Development oTherapy for HF with Reduced EFDrugs for some patients:DigitalisAldosterone blockadeHydralazine/nitratesCombination diuretic RxTherapy for HF with Reduced

30、EFTherapy for HF with Reduced EFDevices for some patients: Biventricular pacing-Relative risk reduction 25% Implantable defibrillatorMechanical filtrationTherapy for HF with Reduced EFMADIT II Patient Eligibility Prior myocardial infarction, and EF 30 %Exclusion Criteria:NYHA Class IV at enrollmentM

31、I 1 monthCABG 3 monthsAdvanced organ system diseaseUnder age 21MADIT II Patient Eligibility MADIT II Patient Eligibility Prior myocardial infarction, and EF 30 %Exclusion Criteria:NYHA Class IV at enrollmentMI 1 monthCABG 9 months NYHA Class I-IVProposed CMS covered indication ICD Indications for Pr

32、imary Use of the ICD in Patients with Non-Ischemic Dilated CardiomyopathyPrimary Prevention Trial-DEFINITEMean QRS 116 ms No ICD ICDTotal deaths 33 222 yr mortality 14% 8% p=.06Mortality risk reduction - 34%Arrhythmic death risk reduction - 74%Kadish et al, AHA abstract, Nov, 2003Use of the ICD in P

33、atients witEndpoint: All-cause MortalityEndpoint: All-cause MortalityMortality Reduction with ICD TreatmentCP1108035-1%Overall deathArrhythmic deathAVIDCASHCIDSMADITMUSTTMADIT-II020406080100SecondaryPreventionPrimaryPreventionMortality Reduction with ICD T Therapy of HF with Normal EFFACTORS AFFECTI

34、NG VENTRICULAR RELAXATIONTACHYCARDIABenefits of restoring sinus rhythm not clear in atrial arrhythmiasPresence of systolic or diastolic dysfunction may diminish efficacy/enhance toxicity of drugs used to maintain NSR Therapy of HF with Normal EFConclusionsis safe and well toleratedimproves quality o

35、f life, functional class, and exercise capacityimproves heart failure composite responsemay have a favorable effect on combined measures of morbidity and mortalityIn NYHA Class III and IV systolic heart failure patients with intraventricular conduction delays, cardiac resynchronization therapy: NEJM

36、 2002;346:1845-53MIRACLEConclusionsis safe and well toWorldwide ICD Implantation Rate per YearCP1108035-3Year1980First Human implant1985FDA approval of ICDs1993Smaller devices1996Steroid leadsMADIT2000Cardiac resynchro-nizationICD implants (000s)1989Transvenous leadsBiphasic waveform1999MUSTT1988Tie

37、red therapy1997/98DC ICDsAT therapiesAVIDCASHCIDSWorldwide ICD Implantation Rat Therapy of HF with Normal EFFACTORS AFFECTING VENTRICULAR RELAXATIONTACHYCARDIAThus: Slowing HR is most importantBeta blockers offer this effect plus blood pressure control Therapy of HF with Normal EF Therapy of HF with Normal EFNeed to treat comorbid conditions:DiabetesAvoid “glitazones?”Use ACEI