收缩性和舒张性心衰的治疗课件

Management of Systolic vs. Management of Systolic vs. Diastolic Heart FailureDiastolic Heart Failure Michael Michael WolkWolk, MD,FACC, MD,FACC WeillWeill-Cornell-Cornell Great Wall of China SymposiumGreat Wall of China Symposium October, 2004October, 2004 Basic conceptsBasic concepts The clinical syndrome of heart The clinical syndrome of heart failure can occur with failure can occur with eithereither normal or reduced LVEF normal or reduced LVEF Virtually all clinical trials of heart Virtually all clinical trials of heart failure therapies have enrolled failure therapies have enrolled onlyonly patients with reduced LVEF patients with reduced LVEF ThusThus Extrapolating recommended Extrapolating recommended therapy for HF with reduced therapy for HF with reduced EF to patients with HF and EF to patients with HF and normal EF is not “automatic”normal EF is not “automatic” Therapy for HF with Reduced EFTherapy for HF with Reduced EF Evidence base forEvidence base for ACEIACEI and and betabeta blockerblocker therapy among therapy among the largest and most the largest and most consistent in medicineconsistent in medicine diuretic digoxin diuretic digoxin ACEI diuretic digoxin ACEI diuretic digoxin ACEI Beta blocker diuretic digoxin ACEI Beta blocker diuretic digoxin ACEI Beta blocker ARB SOLVD-T (1991) RRR 21% CIBIS-2 (1999) RRR 33% CHARM-Added (2003) (Beta-blocker subgroup) RRR 30% Improving Survival in CHF One-year Mortality CV Death, MI, or HF by Treatment Pfeffer, McMurray, Velazquez, et al. N Engl J Med 2003;349 Captopril Months Valsartan vs. Captopril: HR = 0.96; P = 0.198 Valsartan + Captopril vs. Captopril: HR = 0.97; P = 0.369 0 0.1 0.2 0.3 0.4 061218243036 Probability of Event Valsartan Valsartan + Captopril ACE-I in HF - Who and How? HFSA Practice Guidelines 2004 All pts (symptomatic and asymptomatic) with LV systolic dysfunction (LVEF 2.0 mg/dl or serum potassium is 5.0 mmol/L. ACEI should be titrated as tolerated, in conjunction with BBs, to target doses used in clinical trials. Weight Of Evidence: -Blockade Over 18,000 patients evaluated in long-term placebo-controlled clinical trials Improvement in cardiac function and symptoms; (equivocal effects on exercise tolerance) Decrease in all-cause mortality by 30%-35% (P9 months NYHA Class I-IV Proposed CMS covered indication-9/04Proposed CMS covered indication-9/04 COMPANION Hypotheses Biventricular CRT alone decreases combined all-cause mortality and all- cause hospitalization. ICD prevents sudden death 1520 Patients Randomized Medical vs CRT vs CRT-ICD Endpoint: All-cause Mortality ICD Implants Mayo ICDs/ year CP985319-12 Year (1985-2003) “Even the wealthiest nations cannot afford to pay to use every medical advance in any patient who might benefit.” . Thomas Bigger, Lancet, 2001 Therapy for HF with Reduced EFTherapy for HF with Reduced EF Surgery for Surgery for somesome (few) patients: (few) patients: TransplantTransplant Surgical Ventricular Restoration (MVR)Surgical Ventricular Restoration (MVR) RESTORE EF 30 to 40%, JACC - RESTORE EF 30 to 40%, JACC - 9/049/04 “Destination” LVAD ?“Destination” LVAD ? HF with Normal EFHF with Normal EF 40 % of HF patients40 % of HF patients Most have no identifiable Most have no identifiable myocardial diseasemyocardial disease Elderly WomenElderly Women Hypertensive and diabeticHypertensive and diabetic HF with Normal EFHF with Normal EF MortalityMortality: : Nearly as profound as for reduced EFNearly as profound as for reduced EF 5-8% 5-8% vsvs 10-15% 10-15% ( (GaaschGaasch-NEJM, 2004)-NEJM, 2004) Morbidity:Morbidity: Includes frequent readmissionsIncludes frequent readmissions 22% within 12 weeks22% within 12 weeks HF with Normal EF - DiagnosisHF with Normal EF - Diagnosis Physiologic abnormalities may be Physiologic abnormalities may be seen on echo or invasivelyseen on echo or invasively IN IN PRACTICEPRACTICE DIAGNOSIS DIAGNOSIS PRIMARILY CLINICALPRIMARILY CLINICAL Therapy of HF with Normal EFTherapy of HF with Normal EF In the absence of controlled In the absence of controlled clinical trialsclinical trials MANAGEMENT BASED ON MANAGEMENT BASED ON CONTROL OF CONTROL OF PHYSIOLOGIC FACTORS KNOWNPHYSIOLOGIC FACTORS KNOWN TO AFFECT VENTRICULARTO AFFECT VENTRICULAR RELAXATIONRELAXATION PHYSIOLOGIC FACTORS AFFECTING VENTRICULAR RELAXATION Blood volume, e.g. DiureticsBlood volume, e.g. Diuretics Ischemia Ischemia Blood pressure-goal lower BP than Blood pressure-goal lower BP than published guidelines, e.g.-ACE, B published guidelines, e.g.-ACE, B Blockers Blockers Therapy of HF with Normal EFTherapy of HF with Normal EF FACTORS AFFECTING VENTRICULAR FACTORS AFFECTING VENTRICULAR RELAXATIONRELAXATION TACHYCARDIATACHYCARDIA PrinciplePrinciple: Tachycardia can shorten time available : Tachycardia can shorten time available for for ventricularventricular filling and coronary perfusion filling and coronary perfusion ThereforeTherefore: Drugs that slow HR or ventricular : Drugs that slow HR or ventricular response to atrial arrhythmias can relieve response to atrial arrhythmias can relieve symptomssymptoms BETA BLOCKERSBETA BLOCKERS Therapy of HF with Normal EFTherapy of HF with Normal EF FACTORS AFFECTING VENTRICULAR FACTORS AFFECTING VENTRICULAR RELAXATIONRELAXATION MYOCARDIAL ISCHEMIAMYOCARDIAL ISCHEMIA Consider coronary revascularization Consider coronary revascularization in patients with symptomatic or in patients with symptomatic or demonstrable myocardial ischemia demonstrable myocardial ischemia CHARM Program n=3025 LVEF 40% ACEI treated/not treated CHARM- “Added” CHARM- “Preserved” 3 component trials comparing candesartan to placebo CHARM- “Alternative” n=2028 LVEF 40% ACEI intolerant n=2548 LVEF 40% ACEI treated Primary outcome: CV death or CHF hosp CHARM-Preserved Investigator-reported CHF Hospitalizations P=0.014 P=0.017 Patients hospitalizedHospitalizations Placebo Candesartan Proportion of patients (%) Number of episodes HR = 0.85 RRR = 29% New Approaches to the Patient with Heart Failure Assessment of LV function Low LVEF Ejection fraction 40% Signs/symptoms of fluid retention No signs/symptoms of fluid retention Diuretic ACEI/or ARB Beta blocker Preserved LVEF Ejection fraction 40% ARB ARB No signs/symptoms of fluid retention Digoxin Spironolactone NYHA Class II/III NYHA Class III/IV Therapy of HF with Normal EFTherapy of HF with Normal EF Thus, according to this principle, the Thus, according to this principle, the condition should be treated with:condition should be treated with: DiureticsDiuretics Beta blockers-39%S-dys Beta blockers-39%S-dys vsvs 46%Di-dys* 46%Di-dys* ACEI/ARB-62%S-dys ACEI/ARB-62%S-dys vsvs 82%Di-Dys* 82%Di-Dys* Appropriate coronary revascularizationAppropriate coronary revascularization *ESC survey-2004*ESC survey-2004 DOES THIS SOUND FAMILIAR?DOES THIS SOUND FAMILIAR? Therapy of HF with Normal EFTherapy of HF with Normal EF FACTORS AFFECTING VENTRICULAR FACTORS AFFECTING VENTRICULAR RELAXATIONRELAXATION BLOOD VOLUMEBLOOD VOLUME Diuretics relieve Diuretics relieve SxSx in patients in patients with HF and normal EF with HF and normal EF They also help control BPThey also help control BP COPERNICUS: OUTCOMES CHARM “Added” CHARM “Preserved” CHARM Program 3 component trials comparing candesartan to placebo in patients with symptomatic heart failure CHARM “Alternative” n=2028 LVEF 40% ACEI intolerant n=2548 LVEF 40% ACEI treated n=3025 LVEF 40% ACEI treated/not treated Primary outcome for Overall Program: All-cause death Primary outcome for each trial: CV death or CHF hospitalization Mortality Benefit of Beta Blockers and ACEIs in CHF trials 11.915.67.812.4 0 2 4 6 8 10 12 14 16 % death at 1 year SOLVD (1991) diuretic digoxin diuretic digoxin ACEI diuretic digoxin ACEI diuretic digoxin ACEI Beta blocker CIBIS II MERIT-HF (1999) McMurray 2001 CHARM-Overall: Permanent Study Drug Discontinuations Placebo Candesartan 0 5 10 15 20 25 Percent of patients P9 months NYHA Class I-IV Proposed CMS covered indicationProposed CMS covered indication Use of the ICD in Patients with Non-Ischemic Dilated Cardiomyopathy Primary Prevention Trial-DEFINITE Mean QRS 116 ms No ICD ICD Total deaths 33 22 2 yr mortality 14% 8% p=.06 Mortality risk reduction - 34% Arrhythmic death risk reduction - 74% Kadish et al, AHA abstract, Nov, 2003 Endpoint: All-cause Mortality Mortality Reduction with ICD Treatment CP1108035-1 % Overall death Arrhythmic death AVIDCASHCIDSMADITMUSTT MADIT-II 0 20 40 60 80 100 SecondarySecondary PreventionPrevention PrimaryPrimary PreventionPrevention Therapy of HF with Normal EFTherapy of HF with Normal EF FACTORS AFFECTING VENTRICULAR FACTORS AFFECTING VENTRICULAR RELAXATIONRELAXATION TACHYCARDIATACHYCARDIA Benefits of restoring sinus rhythm Benefits of restoring sinus rhythm not clear in atrial arrhythmias not clear in atrial arrhythmias Presence of systolic or diastolic Presence of systolic or diastolic dysfunction may diminish dysfunction may diminish efficacy/enhance toxicity of drugs used efficacy/enhance toxicity of drugs used to maintain NSR to maintain NSR Conclusions is safe and well tolerated improves quality of life, functional class, and exercise capacity improves heart failure composite response may have a favorable effect on combined measures of morbidity and mortality In NYHA Class III and IV systolic heart failure patients with intraventricular conduction delays, cardiac resynchronization therapy: NEJM 2002;346:1845-53 MIRACLE Worldwide ICD Implantation Rate per Year CP1108035-3 Year 1980 First Human implant 1985 FDA approval of ICDs 1993 Smaller devices 1996 Steroid leads MADIT 2000 Cardiac resynchro- nization ICD implants (000s) 1989 Transvenous leads Biphasic waveform 1999 MUSTT 1988 Tiered therapy 1997/98 DC ICDs AT therapies AVID CASH CIDS Therapy of HF with Normal EFTherapy of HF with Normal EF FACTORS AFFECTING VENTRICULAR FACTORS AFFECTING VENTRICULAR RELAXATIONRELAXATION TACHYCARDIATACHYCARDIA Thus:Thus: Slowing HR is most importantSlowing HR is most important Beta blockers offer this effect Beta blockers offer this effect plusplus blood pressure control blood pressure control Therapy of HF with Normal EFTherapy of HF with Normal EF Need to treat Need to treat comorbidcomorbid conditions: conditions: DiabetesDiabetes Avoid “Avoid “glitazonesglitazones?”?” Use ACEI/ARB for renal protectionUse ACEI/ARB for renal protection DyslipidemiaDyslipidemia StatinsStatins CHARM-Preserved: Primary outcome CV death or CHF hospitalisation 0123years3.5 0 10 20 30 Placebo Candesartan 5 15 25 HR 0.89 (95% CI 0.77-1.03), p=0.118 Adjusted HR 0.86, p=0.051 % 366 (24.3%) 333 (22.0%) Therapy for HF with Reduced EFTherapy for HF with Reduced EF Clearly, easily, Clearly, easily, incontrovertiblyincontrovertibly EVIDENCE-BASEDEVIDENCE-BASED HF with Normal EFHF with Normal E