nprobnp在心衰诊断预后治疗管理陈鲁原

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,37,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,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,*,*,nprobnp在心衰诊断预后治疗管理陈鲁原,内 容,NT-proBNP,在心力衰竭患者诊断中的应用,NT-proBNP in the diagnosis of definite heart failure,NT-proBNP,判断心衰预后及对治疗的反应,NT-proBNP in the j,udgemen of prognosis,of heart failure,应用,NT-proBNP,指导急性失代偿性心竭的治疗,NT-proBNP and Therapy Monitoring for Acutely Destabilized HF,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。,Independent predictors of acute heart failure in dyspneic patients,in the emergency department,急诊室呼吸困难患者急性心力衰竭的独立预测因素,Elevated NT-proBNP,NT-proBNP升高,44.0,21.0-91.0,.0001,Interstitial edema on chest X-ray,胸片间质水肿,11.0,4.5-26.0,.0001,Orthopnea,端坐呼吸,9.6,4.0-23.0,75 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,NT-proBNP 和 BNP,对有症状并疑诊为心衰患者的诊断路径,临床检查，心电图，胸部X线，超声心动图,利钠肽,慢性心衰 不可能,慢性心衰 可能,不确定,2008 ESC,心衰指南,Eur Heart J 2008; 29:2388- 2442,脑钠肽在心衰诊断中有着重要的地位,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/,NT-proBNP,并无临床价值，治疗1W后才出现明显变化,Am J Cardiol,2004;93:1562-1563,Am J Cardiol,2008;101:3A,NT-proBNP,用于急性呼吸困难患者诊断的灰色地带值,Although age stratification of NT-proBNP cut-points for the evaluation of patients with acute dyspnea reduces the likelihood of a grey zone value, this finding was still present in 17% of subjects in the ICON study,尽管临床工作中推荐采用,NT-proBNP切点标准的年龄分层方式可提高心衰的诊断水平，但仍然有17%患者的NT-proBNP仍处于灰色地带值,Am J Cardiol,2008;101:3A,Diagnoses associated with an intermediate NT-proBNP concentration but without acute heart failure as cause of their dyspnea in ICON.,ICON 研究中NT-proBNP中度升高但无急性心力衰竭患者的呼吸困难原因,Diagnosis,Patients (n =99),Chronic obstructive pulmonary disease/asthma,COPD/,哮喘,12 (12%),Pneumonia/bronchitis,肺炎,/,支气管炎,12 (12%),Acute cor,onary syndrome/chest pain,ACS/,胸痛,12 (12%),Arrhythmia/bradycardia,心律失常,/,心动过缓,8 (8%),Lung cancer (including metastases),肺癌（含转移性）,5 (5%),Anxiety disorder,焦虑状态,5 (5%),Pulmonary emboli,肺栓塞,3 (3%),Pulmonary hypertension,肺动脉高压,1 (1%),Pericarditis,心包炎,1 (1%),Other*,其他,21 (21%),Unknown,原因不明,19 (19%),van Kimmenade RRJ.,Am J Cardiol,2006,对,NT-proBNP灰度值并不代表良性预测,更不能认为其为阴性结果,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,当,NT-proBNP 4002000 pg/ml,时，主要根据临床判断,van Kimmenade, et al, AJC, 2006,内 容,NT-proBNP,在心力衰竭患者诊断中的应用,NT-proBNP in the diagnosis of definite heart failure,NT-proBNP,判断心衰预后及对治疗的反应,NT-proBNP in the j,udgemen of prognosis,of heart failure,应用,NT-proBNP,指导急性失代偿性心竭的治疗,NT-proBNP and Therapy Monitoring for Acutely Destabilized HF,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,NT-proBNP and Therapy Monitoring for Acutely Destabilized HF,急性不稳定性心力衰竭的NT-proBNP监测,Since criteria for determining restabilization from destabilized HF include clinical factors as well as biochemical measures, the frequency of NT-proBNP measurement should be optimally applied at two time points: baseline/presentation,由于决定不稳定性心力衰竭到病情稳定包括临床因素和生化指标，NT-proBNP的检测频率应该在两个时间点进行：基线/入院时（用于诊断、筛查及设定治疗的“起点”），和病情稳定时，以决定是否可出院或治疗程度,NT-proBNP in acute HF,Dias,200,100,0,Survival without readmissions,1,0,0,8,0,6,0,4,0,2,0,0,Decrease,30%,Within 30%,Increase,30%,p0.0001,Bettencourt P. Circulation 2004,对急性失代偿性心衰住院患者治疗反应的检测,Although prospective studies on the effect of NT-proBNP measurement in guiding therapy in acute destabilized HF are lacking, observational data suggest that a 30% decrease in NT-proBNP values during hospitalization for acute destabilized HF is a reasonable goal. If a baseline measure of NT-proBNP is not available, a NT-proBNP level 1000 pg/ml.,门诊病人的靶目标水平仍未确定，但,NT-proBNP 水平大于1000 pg/ml ，则心衰的发病和死亡率明显上升,内 容,NT-proBNP,在心力衰竭患者诊断中的应用,NT-proBNP in the diagnosis of definite heart failure,NT-proBNP,判断心衰预后及对治疗的反应,NT-proBNP in the j,udgemen of prognosis,of heart failure,应用,NT-proBNP,指导急性失代偿性心竭的治疗,NT-proBNP and Therapy Monitoring for Acutely Destabilized HF,检测NT-proBNP能指导急性失代偿性心衰住院患者的治疗吗？,NT-proBNP levels decrease in response to the addition of therapies with proven benefit for HF, including ACE-inhibitors, angiotensin receptor blockers, diuretics,spironolactone, exercise therapy and biventricular pacing.,已往已经证明有益的心衰冶疗（包括,ACEI,、血管紧张素受体阻滞剂、利尿剂、安体舒通、运动疗法和双心室腔起搏）均可降低,NT-proBNP,水平,The,T,rial of,I,ntensified vs Standard,M,edical Therapyin,E,lderly Patients With,C,ongestive,H,eart,F,ailure (TIME-CHF),design:,Patients with chronic systolic HF were randomized to,intensified BNP-guided therapy,or standard therapy,Patients:,499 patients,with systolic heart failure,EF 45%,NYHA,II IV, prior hospitalization for HF,1 year, and BNP level,400 pg/mL in,75yr and,800 pg/mL in,75yr,Clinical outcomes were compared at 18 months.,Primary outcomes,: 18-month survival free of all-cause Ho- spitalizations and quality of life,JAMA. 2009;301(4):383-392,ACEI or ARB and -Blocker Doses Duringthe Study,There were no significant differences between the 2 treatment groups by BNP level (P=.30).,JAMA. 2009;301(4):383-392,TIME-CHF,TIME-CHF:,Primary and Secondary Outcomes,JAMA. 2009;301(4):383-392,hospitalization-free survival (p = 0.46), but in CHF,Greater reductions in patients younger than 75 years,JAMA. 2009;301(4):383-392,Age75yr,Age75yr,NT-proBNP guided managementof chronic heart failure based on,an,individual,target value,PRIMA-study,Luc Eurlings, Study Coordinator,Maastricht University Medical Center,Maastricht, the Netherlands,Yigal Pinto, Principal Investigator,Academic Medical Center,Amsterdam, the Netherlands,ACC Congress Orlando March 29,th,2009,PRIMA-study,Prospective, randomized, single-blinded study,Admitted,with symptomatic heart failure,;,Elevated,NT-,proBNP,levels, 1,700,pg/ml,on hospital,admission,NT-proBNP guided Treatment,Individual NT-proBNP target level,(Lowest level at discharge or 2 weeks follow-up),Clinical guided Treatment,Follow-up at 2 weeks, 1,3,6,9,12,15,21,24 months,;,Follow-up up minimal 1 year,PRIMA-study,Main outcome,ACC Orlando March 2009,PRIMA-study,Number of increases HF medication,NT-proBNP,Clinical,P,n,174,171,Diuretics,168,120,0.018,Beta blockers,105,95,ns,ACE-inhibitors,77,55,0.099,AT-II antagonists,41,22,ns,Aldosteron antagonists,19,15,ns,Digoxin,14,19,ns,Total,424,326,0.006,PRIMA-study,Main outcome,ACC Orlando March 2009,Total Mortality,PRIMA-study,Survival (%),Time (days),NT-proBNP guided,Clinical guided,46/174,26.5%,57/171,33.3%,Secondary analysis,PRIMA-study,Cardiovascular mortalityns,Combined endpoint CV mortality / readmissionsns,HF related readmissionsns,Creatinine,above / below the median (123,mcm,/L)ns,Age above / below 73 yearsns,Discharge NT-,proBNP,above / below 2950 pg/mlns,On NT-proBNP target analysis: Primary endpoint,PRIMA-study,On NT-proBNP,Target,Clinical,Guided group,院外平均存活天数,(median + IQR),721,(578-730),p.001,664,(435-726),101 of 174 patients in NT-proBNP guided group (58%) maintained their target in more than 75% of visits,按出院后维持,NT-proBNP靶标作对照,p.001,On NT-proBNP target:,Mortality (%),PRIMA-study,On NT-proBNP,Target,Clinical,Guided group,11/101,10.9%,57/171,33.3%,101 of 174 patients in NT-proBNP guided group (58%) maintained their target in more than 75% of visits,按出院后维持,NT-proBNP靶标作对照,Conclusions,Management of heart failure guided by an individually defined optimal NT-proBNP level does not appear favorable in the overall population,However, maintaining this individual optimal NT-proBNP level portends significantly better outcome,The PRIMA-study allows to identify patients where it is feasible to maintain the optimal NT-proBNP level and who may benefit from treatment guided by their own optimal NT-proBNP,PRIMA-study,血浆中利钠肽:在HF诊断和慢性HF患者管理 （结束语）,在HF诊断和慢性HF患者管理中，血浆中利钠肽浓度是有用的生物标志物。利钠肽可作为HF诊断、分期、住院/出院的依据,利钠肽也可能有助于在出院之前评估预后，并且监测HF治疗的有效性,然而它们用在调整药物治疗的证据并不明确，需要扩大样本量研究哪些人群可以明显改善预后,或许,NT-proBNP,联合肾功能、贫血、心肌损伤或炎症指标的检测，对,改善预后更有帮助？,Thank you,There were no significant differences between the 2 treatment groups,by N-terminal BNP level (,P,=.30).,TIME-CHF: N-terminal BNP level,JAMA. 2009;301(4):383-392,谢谢！,