心力衰竭的诊断与治疗面临的选择与挑战

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,*,Click to edit Master title style,单击此处编辑母版标题样式,*,*,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,心力衰竭的诊断与治疗面临的选择与挑战,心力衰竭的诊断与治疗面临的选择与挑战心力衰竭的诊断与治疗面临的选择与挑战,内 容,脑钠肽、N端脑钠肽,前体在心力衰竭,诊断和处理中的地位,他汀类药物治疗心力衰竭,力不从心？,在,初级保健,中被误诊为心力衰竭的比例：,-,Framingham: 40% (McKee 1971) - Boston:42% (Carlson 1985) - Kuopio: 50% (Remes 1991),急诊室,中,25-50%,的失代偿心力衰竭病人被误诊,充血性心力衰竭,:,在临床上是否易于诊断?,三大症状非特异性（气促、踝肿和疲劳）,特别,对于肥胖、老年和妇女。,心衰体征仅提示心衰存在,，但仍需有心功能评,价的客观证据。,BNP 100 but 500 HF likely,NT-proBNP年龄分层降低了假阳性和假阴性，提高了阳性预测值,ICON 的三重界值无需根据肾功能对NT-proBNP界值进一步调整,83%,55%,92%,73%,85%,1800 pg/ml,所有 75 岁 (n=519),86%,66%,88%,84%,90%,总计,85%,88%,82%,82%,90%,900 pg/ml,所有 50-75 岁 (n=554),95%,99%,76%,93%,97%,450 pg/ml,所有 50 岁 (n=183),精确度,阴性预测值,阳性预测值,特异性,敏感性,合适界值,年龄分层,Januzzi, et al, Eur Heart J 2005,Anwaruddin, et al, JACC, 2006,诊断急性心力衰竭,国际氨基末端脑钠肽原协助数据,根据年龄分层的,NT-proBNP,“诊断”界值,诊断心衰的三大常规,胸片是心衰初步诊断的重要部分,心脏超声是现在的“金标准”,（仍不能完全解决急性呼吸困难的鉴别问题）,到目前为止，由美国和欧洲心脏病协会推荐使用的BNP或NT-proBNP是唯一用于诊断心力衰竭的实验室检测指标,胸片、心脏超声和BNP/NT-proBNP检测是诊断心衰的三大常规,Richards et al.,J Am Coll Cardiol,2006;47:5260,BNP,和,NT-proBNP,的检测分析,NT-proBNP,半衰期相对较长，浓度相对较稳定，含量相对较高（比,BNP 约高 16,20倍），,检测相对较容易，是较理想的预测标志物,BNP,半衰期相对较短，（18分钟），检测血液时间要求高；在了解病人即刻情况时较有价值,BNP或NT-proBNP,的临床应用价值基本相同,每天或隔天检测BNP并无临床价值，治疗1W后BNP才出现明显变化,Am J Cardiol,2004;93:1562-1563,Am J Cardiol,2008;101:3A,病人因,急性呼吸困难,来急诊,病史采集, 体格检查,ECG,胸片 +,NTproBNP,充血性心力衰竭,高度不可能,充血性心力衰竭,高度可能,充血性心力衰竭不可能？,可能？其他检查,NTproBNP,450,p,g/mL -,病人 900pg/mL -,病人 50-75 岁,1800pg/mL ,病人 75岁,Bayes-Genis A. Rev Esp Cardiol 2005,体征,OR,95% CI,p-value,咳嗽,0.18,0.06-0.52,0.001,利用袢利尿剂,3.99,1.58-10.1,0.003,夜间阵发性呼吸困难,4.50,1.32-15.4,0.02,颈静脉怒张,3.05,1.06-8.79,0.04,心力衰竭前,2.63,1.02-6.80,0.05,下肢水肿,2.96,0.94-9.31,0.06,第三心音奔马律,10.4,0.82-130.7,0.07,COPD/哮喘前,0.48,0.20-1.19,0.,11,端坐呼吸,2.06,0.73-5.83,0.17,喘鸣,0.81,0.29-2.22,0.17,灰色区域中心力衰竭的独立预测因子,van Kimmenade, et al, AJC, 2006,Acute Heart Failure-BNP levels and risk stratification from the ED to discharge,UNDER 100 HEART FAILURE UNLIKELY CAUSE OF SOB,UNDER 250 PATIENT IS AT LOW RISK AND MAY BE DISCHARGED SAFELY,CONSIDER BNP IN THE CONTEXT OF CLINICAL SYMPTOMS,ABOVE 600 pg/ml PATIENT IS CONSIDERED STILL AT HIGH RISK,ED ADMISSIONINPATIENTDISCHARGE,ARRIVAL(Tiime),1,500,600,250,100,BNP,Values,(pg/ml),600 pg/ml,400/pg/ml,急性心力衰竭,5000 pg/ml,是短期预后的界值,判断急性心力衰竭短期（60天）预后,Januzzi et al. Arch Intern Med 2006,判断,急性心力衰竭,长期（,1,年）预后,对于1年危险度的分层，最佳界值是,1000 pg/ml,Van Kimmenade et al. JACC 2006,多种标志物检测:,+,GFR,联合传统标志物， NT-proBNP预后价值加强,BNP药理作用：治疗急性失代偿性心衰,扩血管（vasodilator）,利 钠 （natriuretic）,利 尿 （diuretic）,抗纤维化（antifibrotic）,Nesiritide（natrecor）,Fitzgerald, ACC 2004,BNP:,-,治疗过程中明显升高，不能反应体内分泌,BNP,浓度,-,治疗结束后,2,小时才低于基线,NT-proBNP -,治疗中,12,小时即可以明显低于基线水平，反映治疗效果,-,治疗结束,24,小时可以达到最大程度的降低,在接受奈西立肽治疗的心衰患者中 对,BNP,和,NT-proBNP,变化的监测,12 hrs,24 hrs Infusion,Jourdain P et al et al. JACC 2007;49:1733-9,BNP,的监测指导治疗,:STARS-BNP,多中心研究,BNP,/NT-proBNP,可以指导治疗吗,?,内 容,脑钠肽、N端脑钠肽,前体在心力衰竭,诊断和处理中的地位,他汀类药物治疗心力衰竭,力不从心？,Beneficial Effects of Statins,Anti-Inflammatory Effects,Antioxidant Effects,Endothelial Function,Effects on Angiogenesis,Cardiac Hypertrophy and LV Remodeling,Neurohormonal Activation,J Am Coll Cardiol. 2008;51(4),Statins and Risks for Death and Heart Failure,Hospitalisation in 25,000 heart failure patients,Go A et al.,JAMA,2006;296:21052111,0,5,10,15,20,25,30,35,Rate per 100 person-years,Baseline,CHD,No Baseline,CHD,Overall,Rate of Death,No.,24598,19705,4893,0,5,10,15,20,25,30,35,Baseline,CHD,No Baseline,CHD,Overall,Rate of Hospitalization,No.,24598,19705,4893,No Statin,Statin,Adjusted mortality among patients,with,ischemic etiology,(n = 62,273),Mortality among patients with heart failure,of,nonischemic etiology,(n = 31,551),A,B,既往的研究结果使人们对他汀治疗心衰充满希望,然而，这些试验只是产生假说的初步研究,他汀类能否进一步用于临床的心衰治疗,尚需要开展大规模的前瞻性研究,率先完成的是CORNOA试验,Patients (n=5011),Chronic ischaemic systolic heart failure receiving optimal HF treatment (diuretics, ACE inhibitors, ARBs, beta-blocker therapy),Ejection fraction0.40 (NYHA class III/IV)or 0.35 (NYHA class II),60 years,rosuvastatin 10 mg (n=2514),placebo (n=2497),End points:,Time to cardiovascular death, non-fatal MI, non-fatal stroke,Total mortality,Visit:,Week:,1,8 to 2,2,4 to 2,3,0,4,6,521,3 monthly,Final,3 y,A Randomized, Double-Blind, Placebo-Controlled Study with Rosuvastatin in Patients with Chronic Symptomatic Systolic Heart Failure,CORONA - Study Design,Eligibility,Optimal HF treatment instituted,Median follow-up 2.7 years,Placebo,run-in,Kjekshus J et al.,Eur J Heart Fail,2005;7:1059-1069,Mean age,(years),73 73,75 years,(%),4141,Female sex,(%),2424,NYHA class,(%),II3737,III6261,IV1.61.4,Ejection Fraction0.310.31,Myocardial infarction (%) 60 60,Angina pectoris (%) 7273,CABG or PCI (%) 2626,Hypertension (%) 6363,PlaceboRosuvastatinn=2497n=2514,CORONA - Baseline characteristics,Kjekshus J et al.,N Eng J Med,2007; 357 doi 10.1056/NEJMoa0706201,Total cholesterol (mmol/L) 5.35 5.36,LDL cholesterol (mmol/L) 3.563.54,hsCRP, median (mg/L) 3.53.5,Loop or thiazide diuretic (%) 8889,Aldosterone antagonist (%) 3939,ACE inhibitor (%) 8080,Beta-blocker (%) 7575,Antiplatelet or anticoagulant (%) 90 90,PlaceboRosuvastatin n=2497n=2514,CORONA - Medical History,Kjekshus J et al.,N Eng J Med,2007; 357 doi 10.1056/NEJMoa0706201,-50,-40,-30,-20,-10,0,10,LDL-C,HDL-C,TG,CRP,CORONA,Effects on LDL-C, HDL-C, TG and CRP at 3 months;,Absolute difference between rosuvastatin and placebo,Between group difference,from baseline (%),45%,5.0%,20.5%,37.1%,p0.001,p0.001,p0.001,p0.001,Kjekshus J et al.,N Eng J Med,2007; 357 doi 10.1056/NEJMoa0706201,CORONA - Primary Endpoint,The combined endpoint of cardiovascular,death,or non-fatal MI or non-fatal stroke (time to first event),Hazard ratio = 0.92,95% CI 0.83 to 1.02,p=0.12,Months of follow-up,0,36,30,24,18,12,6,0,10,20,30,Placebo,Rosuvastatin 10 mg,No. at risk,Placebo249723152156200318511431811,Rosuvastatin251423452207206819321484855,Percent of patients with,primary endpoint,Kjekshus J et al.,N Eng J Med,2007; 357 doi 10.1056/NEJMoa0706201,Months of follow-up,0,36,30,24,18,12,6,Placebo,Rosuvastatin 10 mg,0,3,6,12,9,15,Hazard ratio = 0.84,95% CI 0.70 to 1.00,p = 0.05,No. at risk,Placebo249723152156200318511431811,Rosuvastatin251423452207206819321484855,Data on File,CORONA,Post hoc analysis of the number fatal/non-fatal MI or stroke in the primary endpoint,Percent of patients with,event,p=0.01,p=0.007,p0.001,4,074,2,464,1,299,1,510,3,694,2,193,1,109,1,501,0,1,000,2,000,3,000,4,000,Heart failure,All cause,CV cause,Non-CV cause,Placebo (n=2,497),Rosuvastatin 10 mg (n=2,514),CORONA - Secondary Endpoints,Total number of hospitalizations,No. hospitalisations,Kjekshus J et al.,N Eng J Med,2007; 357 doi 10.1056/NEJMoa0706201,对CORONA试验的解释,入选患者平均年龄达73岁， 63%患者的NYHA心功能为 和级 。试图通过改变粥样硬化自然史，影响心血管罹患率和死亡率的作用可能有限,在CORONA试验的亚组分析中，发现对于那些心衰程度轻，一般状况良好的年轻患者，他汀更能凸显其优势。或他汀在年龄相对较年轻的轻度心衰患者中可能会得到不同的结果。,同一类药物不等于同一种药物。还不能确定CORONA研究的局限是瑞舒伐他汀本身的问题,还是他汀类治疗老年心衰患者无确切疗效。,对CORONA试验的思考,当我们仔细思考慢性心衰的病理生理基础时，就能容易理解CORONA的结果。,他汀类药物是“一类神奇的药物”，但并不能包治疗百病。,CORONA的主要研究者也承认： “心力衰竭患者对他汀类药物的反应与非心力衰竭患者明显不同。”,我们需要“还原他汀类药物降脂功效的本质”,GISSI-HF- Effects of n-3 PUFA and Rosuvastatin on Mortality-Morbidity of Patients With Symptomatic CHF,a prospective, multicenter, randomized, double blind, placebo controlled study,rosuvastatin (10 mg daily) or placebo,4624 heart failure patients have been included in the trial,Primary Objectives: All-cause mortality or hospitalizations for cardiovascular reason,Starting date: August 2002 ; Last updated: January 12, 2007,Eur J Heart Fail 2004;6:635-641.,Thank you,谢谢观赏！,2020/11/5,34,