急性失代偿性心功能不全的治疗

1、急性失代偿性心功能不全的治疗 约70% 慢性心衰恶化 和左室收缩功能不全有关 (LVEF) 25% 无心衰 大面积心梗后; 左室顺应性降低同时伴有血压突然升高 5% 严重心衰 难治性心功能不全; 伴有严重的左室收缩功能不全, 恶化的严重的低心排Gheorghiade M. Circulation. 2005;112:3958-3968. 第1页/共93页人口统计学资料人口统计学资料:65,180例患者例患者起止时间起止时间: 10/01-7/03 年龄: 72.5 + 13.9岁 性别: 52%女性 冠心病: 58% 高血压病史: 72% 糖尿病: 44% 房颤: 30% 肾功能不全: 29%

2、Abraham et al. JACC 2005; 46:57第2页/共93页谁是谁是“真实世界真实世界”的心衰患者的心衰患者?Heart Failure Clinical TrialsVMAC(N=489)ADHERE(N=169,239)年龄年龄55-7062 (43% 65 yr.)75男性男性80%69%48%冠心病冠心病50%65%58%高血压高血压40%70%74%糖尿病糖尿病25%47%44%房颤房颤20%35%31%肾功能不全肾功能不全通常排除通常排除(Mean SCr. 1.1-1.3)21% (2.0 mg/dL)(Baseline SCr.0.4-11.1 mg/dL)3

3、7% (1.5 mg/dL)左室射血分数左室射血分数 40%通常排除通常排除15%43%References:Krum H, Gilbert RE. Demographics & Concomitant disorders in heart failure. Lancet 2003;362:147-58.Publication Committee for the VMAC Investigators (Vasodilation in the Management of Acute CHF). Intravenous nesiritide vs nitroglycerinfor the

4、treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA. 2002;287:1531-1540.Q1 2005 National Benchmark Report - Core Module. Adhere Registry, August 2005.第3页/共93页结果结果:65,180 patients起止时间起止时间: 10/01-7/03 ICU 住院时间: 3.9 - 6.9 天 总的住院时间: 7.1 10.9 天 院内死亡率: 4.7% - 13.9% 75%

5、 的患者只增加利尿剂的疗程!Abraham et al. JACC 2005; 46:57第4页/共93页正常正常收缩功能收缩功能不全不全舒张功能不全舒张功能不全Aurigemma, Zile, GaaschCirculation 2005第5页/共93页Cleland et al. European Heart J 2003;24:442Left Ventricular Ejection Fraction24个国家, 115家医院, 6周: 11,327 例怀疑或证实为心衰的患者2000-2001欧洲心衰调查第6页/共93页012345678910患病率 %心衰的患病率心衰的患病率年龄范围平

6、均年龄 66-103787575 50- 406055-956575-86-70-84767.55.1英国英国(Poole)6.44.5丹麦丹麦.(Copen.)4.92.9西班牙西班牙(Asturias)8.24.2芬兰芬兰(Helsinki)葡萄牙葡萄牙(EPICA)1.74.225682.1 1.5Nether.(Rotter.)6.7瑞典瑞典(Vasteras)3.1美国美国(CHS)8.84.8左室收缩功能下降的比例左室收缩功能下降的比例左室收缩功能正常的比例左室收缩功能正常的比例Slide courtesy of Barrie Massie, MD第7页/共93页OConnor e

7、t al. J Cardiac Failure 2005;11:200IMPACT-HF注册研究注册研究第8页/共93页肺动脉压力升高肺动脉压力升高 全身淤血全身淤血(JVD, edema) 右室右房右室右房症症状状有症状的只是心衰患者中的冰山一角有症状的只是心衰患者中的冰山一角左室功能异常左室功能异常 (收缩和收缩和/舒张舒张) 左房左室舒张压左房左室舒张压 左室舒张压左室舒张压 + 容量压力调控曲线失控容量压力调控曲线失控呼吸困难呼吸困难肺毛细血管嵌顿压升高肺毛细血管嵌顿压升高 (淤血淤血 )肺血管床血液再分布肺血管床血液再分布+ 肺间质水肿肺间质水肿肺泡性肺水肿肺泡性肺水肿 Hydros

8、tatic 压压 Oncotic 压压 渗透性渗透性 淋巴回流量淋巴回流量肺泡毛细血管肺泡毛细血管 膜完整性膜完整性二尖瓣反流二尖瓣反流肺功能异常肺功能异常呼吸肌失代偿呼吸肌失代偿其它因素其它因素第9页/共93页Adamson PB et al. J Am Coll Cardiol. 2003; 41: 565入院前已出现肺淤血入院前已出现肺淤血压力变化压力变化住院住院住院前的天数住院前的天数 Baseline -7 -6 -5 -4 -3 -2 -1 Recovery变化变化 (%)-10010203040右室收缩压右室收缩压 估测的肺动脉压估测的肺动脉压 舒张压舒张压心率心率第10页/共9

9、3页7%6%13%24%33%15%3%2%05101520253035Patients (%)(10)Change in Weight (lbs)超过超过 50%的患者住院期间的患者住院期间 体重没有或几乎没有减少体重没有或几乎没有减少Fonarow GC. Rev Cardiovasc Med. 2003; 4 (Suppl. 7): 21第11页/共93页下述几种急性心衰的潜在的诱发因素需被认为是心衰的并存病 ，认识到这一点在指导治疗中很关键: 急性冠脉综合症或冠脉缺血 严重的高血压 房性或室性心律失常 感染 肺栓塞 肾功能衰竭 医疗或饮食方面不配合住院患者住院患者 新新I I I II

10、aIIaIIa IIbIIbIIb III III IIII I I IIaIIaIIa IIbIIbIIb III III IIII I I IIaIIaIIa IIbIIbIIb III III IIIIIaIIaIIa IIbIIbIIb III III III急性心衰的诱发因素 第12页/共93页03691215SepsisAS/MS 3+Syst. BP 200 mmHgPatients (%)2并存疾病的恶化并存疾病的恶化 47% 的人群的人群 53% 没有认识到的共存因素或心血管疾病促发了心衰住院纽约舒张功能不全注册研究Klapholz et al. JACC 2004;43:1

11、432第13页/共93页住院患者住院患者紧急心导管检查并血运重建当患者出现急性心衰的表现，已知或怀疑因冠脉闭塞而导致的急性心肌缺血尤其提示有外周灌注不足的症状时，紧急行冠脉造影并血运重建可能提高患者的生存率I IIa IIb III新第14页/共93页ADHERE CART: 死亡的预测因素死亡的预测因素高于高于低于低于最高与最低相对危险比最高与最低相对危险比 12.9 (95% CI 10.4-15.9)Fonarow GC, et al. Risk stratification for in-hospital mortality in heart failure using classif

12、ication and regression tree (CART) methodology. JAMA. 2005;293:572-580.33,324例患者!第15页/共93页JACC 2008; 52:347-5648, 612 例患者第16页/共93页急性舒张性心衰的处理急性舒张性心衰的处理 血流动力学目标是缓解症状和血流动力学稳定 降低左右心室的充盈压 降低外周血管阻力 增加心排血量 治疗选择利尿剂利尿剂血管扩张剂血管扩张剂增强心肌收缩力增强心肌收缩力减少循环血量减少循环血量降低前后负荷降低前后负荷增加收缩力增加收缩力血管扩张血管扩张减少循环血量减少循环血量抑制抑制 RAAS/SNS

13、活性活性尿钠肽尿钠肽机械的方法去除循环容量机械的方法去除循环容量减少循环血量减少循环血量第17页/共93页deGoma, E. M. et al. J Am Coll Cardiol 2006;48:2397-2409治疗舒张性心衰新出现的药物治疗的概貌治疗舒张性心衰新出现的药物治疗的概貌第18页/共93页deGoma, E. M. et al. J Am Coll Cardiol 2006;48:2397-2409血管扩张剂、利尿剂及促进水钠排泄的药物血管扩张剂、利尿剂及促进水钠排泄的药物第19页/共93页住院期间急性心衰静脉用利尿剂的效住院期间急性心衰静脉用利尿剂的效果果Risk Adju

14、sted Data from ADHERE, Emerman C et al. HFSA 2004天DaysPercent4.45.22.23.02.02.3第20页/共93页尿钠肽的生理学作用尿钠肽的生理学作用Potter LR et al. Endocr Rev. 2006;27:47尿钠肽受体尿钠肽受体第21页/共93页VMAC: 呼吸困难缓解呼吸困难缓解*Added to standard carePublication Committee for the VMAC Investigators. JAMA. 2002;287:1531发作发作3小时呼吸困难小时呼吸困难受试者比例受试者比

15、例 (%)硝酸甘油硝酸甘油* (n = 143)奈西立肽* (n = 204)安慰剂安慰剂* (n = 142)403020100102030405060708090100P=0.191P=0.034显著缓解显著缓解中度缓解中度缓解轻度缓解轻度缓解无变化无变化轻度到显著恶化轻度到显著恶化# p0.05 Natrecor or nitroglycerin compared to placebo* p0.05 compared to nitroglycerin-70-60-50-40-30-20-100102030405060708090100No ChangeMinimally-Markedly

16、 WorseMinimally BetterModerately BetterMarkedly Better15 Mins1 Hour3 Hours#No ChangeMinimally-MarkedlyWorse# p0.05 Natrecor or nitroglycerin compared to placebo* p0.05 compared to nitroglycerin-70-60-50-40-30-20-100102030405060708090100No ChangeMinimally-Markedly WorseMinimally BetterModerately Bett

17、erMarkedly Better15 Mins1 Hour3 Hours#No ChangeMinimally-MarkedlyWorse# p0.05 Natrecor or nitroglycerin compared to placebo* p0.05 compared to nitroglycerin-70-60-50-40-30-20-100102030405060708090100No ChangeMinimally-Markedly WorseMinimally BetterModerately BetterMarkedly Better15 Mins1 Hour3 Hours

18、#No ChangeMinimally-MarkedlyWorse# p0.05 Natrecor or nitroglycerin compared to placebo* p0.05 compared to nitroglycerin-70-60-50-40-30-20-100102030405060708090100No ChangeMinimally-Markedly WorseMinimally BetterModerately BetterMarkedly Better15 Mins1 Hour3 Hours#No ChangeMinimally-MarkedlyWorse# p0

19、.05 Natrecor or nitroglycerin compared to placebo* pV1利希普坦V2 受体拮抗剂 V1第26页/共93页托伐普坦托伐普坦不降低心衰患者的住院率不降低心衰患者的住院率42% vs. 40%HR=1.04P=0.55Konstam MA, Gheorghiade M et al. JAMA 2007; 297: 1319-31.第27页/共93页deGoma, E. M. et al. J Am Coll Cardiol 2006;48:2397-2409新的治疗急性失代偿性心衰的药物概况新的治疗急性失代偿性心衰的药物概况第28页/共93页Got

20、tlieb SS et al. Circulation 2002; 105: 1348-53醛固酮拮抗剂醛固酮拮抗剂 BG9719 增加利尿作用同时肾小球滤过率正常增加利尿作用同时肾小球滤过率正常(63例因急性心功能不全住院的患者例因急性心功能不全住院的患者)第29页/共93页Rolofylline对急性心衰伴肾功能不全患者的作用对急性心衰伴肾功能不全患者的作用 : 选择选择性性 A1拮抗剂拮抗剂Rolofylline 对急性失代偿性心衰和容量超对急性失代偿性心衰和容量超负荷伴肾功能不全住院患者作用的随机安慰剂对照研究负荷伴肾功能不全住院患者作用的随机安慰剂对照研究 (PROTECT)M. M

21、etra1, for the PROTECT Study GroupExecutive Committee Co-Chairs: B. Massie2, C. OConnor3 1University of Brescia, Brescia, Italy; 2San Francisco VA Medical Center, San Francisco, USA; 3Duke University Medical Center, Durham, USA第30页/共93页一级终点一级终点患者百分比 事件概率 (95% CI) vs Pbo: 0.92 (0.78, 1.09) 36.044.219

22、.840.637.521.80102030405060708090100PlaceboRo 30 mg治疗成功无变化治疗失败 p=0.348 for comparison of distribution using the van Elteren extension of Wilcoxon test第31页/共93页deGoma, E. M. et al. J Am Coll Cardiol 2006;48:2397-2409增强心肌收缩力的治疗增强心肌收缩力的治疗第32页/共93页Abraham WT et al. J Am Coll Cardiol. 2005;46:57院内结果院内结果第

23、33页/共93页失代偿行心功能不全患者住院期间静脉用增强心肌收缩力药物失代偿行心功能不全患者住院期间静脉用增强心肌收缩力药物Cuffe MS et al. JAMA. 2002; 287: 15411547.OPTIME-CHF事件发生率事件发生率 (%)副反应事件副反应事件持续低血压持续低血压急性心梗急性心梗死亡率死亡率米力农组安慰剂安慰剂组组房颤房颤危险比危险比 6.0P 0.001危险比危险比 3.3P 65 yr.)75Male80%69%48%Coronary Artery Disease50%65%58%Hypertension40%70%74%Diabetes25%47%44%A

24、trial Fibrillation20%35%31%Renal InsufficiencyUsually excluded(Mean SCr. 1.1-1.3)21% (2.0 mg/dL)(Baseline SCr.0.4-11.1 mg/dL)37% (1.5 mg/dL)LVEF 40%Usually excluded15%43%References:Krum H, Gilbert RE. Demographics & Concomitant disorders in heart failure. Lancet 2003;362:147-58.Publication Commi

25、ttee for the VMAC Investigators (Vasodilation in the Management of Acute CHF). Intravenous nesiritide vs nitroglycerinfor the treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA. 2002;287:1531-1540.Q1 2005 National Benchmark Report - Core Module. Adhere Registry,

26、 August 2005.第46页/共93页Outcomes:65,180 patientsADHERE: 10/01-7/03 ICU length of stay: 3.9 - 6.9 days Total length of stay: 7.1 10.9 days In hospital mortality: 4.7% - 13.9% 75% of patients were treated with enhanced diuretic therapy alone!Abraham et al. JACC 2005; 46:57第47页/共93页NormalSystolicHeart Fa

27、ilureDiastolicHeart FailureAurigemma, Zile, GaaschCirculation 2005第48页/共93页Cleland et al. European Heart J 2003;24:442Left Ventricular Ejection Fraction24 countries, 115 hospitals, 6 weeks: 11,327 patients with suspected or confirmed HF2000-2001EuroHeart Failure survey第49页/共93页012345678910prevalence

28、 %Prevalence of Heart Failureage rangemean age 66-103787575 50- 406055-956575-86-70-84767.55.1England(Poole)6.44.5Den.(Copen.)4.92.9Spain(Asturias)8.24.2Finland(Helsinki)Portugal(EPICA)1.74.225682.1 1.5Nether.(Rotter.)6.7Sweden(Vasteras)3.1USA(CHS)8.84.8Proportion with decreasedLV systolic functionP

29、roportion with preservedLV systolic functionSlide courtesy of Barrie Massie, MD第50页/共93页OConnor et al. J Cardiac Failure 2005;11:200IMPACT-HF Registry第51页/共93页Increase PA pressure Systemic congestion(JVD, edema) RV + RA pressureSYMPTOMSSymptoms: The Tip of the Congestion Iceberg in Heart FailureAbno

30、rmal LV function (Sys and/or Dia) LA and LV diastolic pressure LVDP + Impaired volume regulationDyspneaIncreased PCWP (congestion )Redistribution in pulmonary vascular bed+ Interstitial edemaAlveolar edema Hydrostatic pressure Oncotic pressure Permeability Lymphatic drainage capacityAlveolar-capilla

31、ry membrane integrityMitralRegurgitationAbnormal lung functionRespiratory muscle dysfunctionOther factors第52页/共93页Adamson PB et al. J Am Coll Cardiol. 2003; 41: 565Congestion Precedes HospitalizationPressure ChangeHospitalizationDays Relative to the Event Baseline -7 -6 -5 -4 -3 -2 -1 Recovery Chang

32、e (%)-10010203040RV Systolic PressureEstimated PA Diastolic PressureHeart Rate第53页/共93页More than 50% of Patients Have Little or no Weight Loss During HospitalizationFonarow GC. Rev Cardiovasc Med. 2003; 4 (Suppl. 7): 21第54页/共93页It is recommended that the following common potential precipitating fact

33、ors for acute HF be identified as recognition of these comorbidities, is critical to guide therapy: acute coronary syndromes/coronary ischemia severe hypertension atrial and ventricular arrhythmias infections pulmonary emboli renal failure medical or dietary noncomplianceThe Hospitalized Patient New

34、I I I IIaIIaIIa IIbIIbIIb III III IIII I I IIaIIaIIa IIbIIbIIb III III IIII I I IIaIIaIIa IIbIIbIIb III III IIIIIaIIaIIa IIbIIbIIb III III IIIPrecipitating Factors for Acute HF 第55页/共93页2Exacerbation of Co-existing Conditions 47% of the population 53% without any identifiable co-existing medical or

35、cardiovascular condition precipitating hospitalization.NY Heart Failure Diastolic Dysfunction Registry GroupKlapholz et al. JACC 2004;43:1432第56页/共93页The Hospitalized PatientUrgent Cardiac Catheterization and RevascularizationWhen patients present with acute HF and known or suspected acute myocardia

36、l ischemia due to occlusive coronary disease, especially when there are signs and symptoms of inadequate systemic perfusion, urgent cardiac catheterization and revascularization is reasonable where it is likely to prolong meaningful survival. I IIa IIb IIINew第57页/共93页ADHERE CART: Predictors of Morta

37、lityGreater thanLess thanHighest to Lowest Risk CohortOR 12.9 (95% CI 10.4-15.9)Fonarow GC, et al. Risk stratification for in-hospital mortality in heart failure using classification and regression tree (CART) methodology. JAMA. 2005;293:572-580.33,324 patients!第58页/共93页JACC 2008; 52:347-5648, 612 p

38、atients第59页/共93页Management of ADHF Hemodynamic goals for achieving symptom relief and stabilization Reduce right and left heart filling pressures Reduce systemic vascular resistance Increase cardiac output Treatment optionsDiureticsVasodilatorsInotropesReducefluidvolumeDecreasepreloadandafterloadAug

39、mentcontractilityVasodilate; reduce fluid volume;counteract RAAS/SNSNatriuretic PeptidesMechanicalVolume RemovalReducefluidvolume第60页/共93页deGoma, E. M. et al. J Am Coll Cardiol 2006;48:2397-2409Overview of Emerging Pharmacotherapies for ADHF第61页/共93页deGoma, E. M. et al. J Am Coll Cardiol 2006;48:239

40、7-2409Vasodilators, Diuretics and Aquaretics第62页/共93页Effects of IV Diuretics During Hospitalization for Acute Heart FailureRisk Adjusted Data from ADHERE, Emerman C et al. HFSA 2004DaysDaysPercent4.45.22.23.02.02.3第63页/共93页Physiologic Effects of Natriuretic PeptidesPotter LR et al. Endocr Rev. 2006;

41、27:47Natriuretic Peptide Receptors第64页/共93页VMAC: Dyspnea Improvement*Added to standard carePublication Committee for the VMAC Investigators. JAMA. 2002;287:1531Dyspnea at 3 hrProportion of Subjects (%)Nitroglycerin* (n = 143)Nesiritide* (n = 204)Placebo* (n = 142)403020100102030405060708090100P=0.19

42、1P=0.034Markedly betterModerately betterMinimally betterNo changeMinimally markedly worse# p0.05 Natrecor or nitroglycerin compared to placebo* p0.05 compared to nitroglycerin-70-60-50-40-30-20-100102030405060708090100No ChangeMinimally-Markedly WorseMinimally BetterModerately BetterMarkedly Better1

43、5 Mins1 Hour3 Hours#No ChangeMinimally-MarkedlyWorse# p0.05 Natrecor or nitroglycerin compared to placebo* p0.05 compared to nitroglycerin-70-60-50-40-30-20-100102030405060708090100No ChangeMinimally-Markedly WorseMinimally BetterModerately BetterMarkedly Better15 Mins1 Hour3 Hours#No ChangeMinimall

44、y-MarkedlyWorse# p0.05 Natrecor or nitroglycerin compared to placebo* p0.05 compared to nitroglycerin-70-60-50-40-30-20-100102030405060708090100No ChangeMinimally-Markedly WorseMinimally BetterModerately BetterMarkedly Better15 Mins1 Hour3 Hours#No ChangeMinimally-MarkedlyWorse# p0.05 Natrecor or ni

45、troglycerin compared to placebo* p0.05 compared to nitroglycerin-70-60-50-40-30-20-100102030405060708090100No ChangeMinimally-Markedly WorseMinimally BetterModerately BetterMarkedly Better15 Mins1 Hour3 Hours#No ChangeMinimally-MarkedlyWorse# p0.05 Natrecor or nitroglycerin compared to placebo* pV1L

46、ixivaptanV2 receptor antagonist V1第69页/共93页42% vs. 40%HR=1.04P=0.55Konstam MA, Gheorghiade M et al. JAMA 2007; 297: 1319-31.第70页/共93页deGoma, E. M. et al. J Am Coll Cardiol 2006;48:2397-2409Overview of Emerging Pharmacotherapies for ADHF第71页/共93页Gottlieb SS et al. Circulation 2002; 105: 1348-53Adenos

47、ine Antagonist BG9719 Augments Diuresis and Preserves GFR(63 Patients Admitted with ADHF)第72页/共93页Effects of Rolofylline in Patients with Acute Heart Failure Syndrome and Renal Impairment: Findings from the Placebo-controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofyl

48、line for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal FuncTion (PROTECT) Study M. Metra1, for the PROTECT Study GroupExecutive Committee Co-Chairs: B. Massie2, C. OConnor3 1University of Brescia, Brescia, Italy; 2

49、San Francisco VA Medical Center, San Francisco, USA; 3Duke University Medical Center, Durham, USA第73页/共93页Primary EndpointPercent of Patients Odds ratio (95% CI) vs Pbo: 0.92 (0.78, 1.09) 36.044.219.840.637.521.80102030405060708090100PlaceboRo 30 mgTreatment SuccessPatient UnchangedTreatment Failure

50、 p=0.348 for comparison of distribution using the van Elteren extension of Wilcoxon test第74页/共93页deGoma, E. M. et al. J Am Coll Cardiol 2006;48:2397-2409Inotropic Therapies第75页/共93页Abraham WT et al. J Am Coll Cardiol. 2005;46:57In-Hospital Outcomes第76页/共93页Intravenous Inotropic Agents During Hospita

51、lization for Decompensated Heart FailureCuffe MS et al. JAMA. 2002; 287: 15411547.OPTIME-CHFEvent Rate (%)Adverse EventSustained HypotensionAcute MIMortalityMilrinonePlaceboAfibHR 6.0P 0.001HR 3.3P 50- 406055-956575-86-70-84767.55.1England(Poole)6.44.5Den.(Copen.)4.92.9Spain(Asturias)8.24.2Finland(Helsinki)Portugal(EPICA)1.74.225682.1 1.5Nether.(Rotter.)6.7Sweden(Vasteras)3.1USA(CHS)8.84.8Proportion with decreasedLV systolic functionProportion with preservedLV systoli