1、N-proBNP在心衰诊断、预后、治疗的管理,蚌埠市第三人民医院孙向东,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 judgemen 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,规范与指南,NT-proBNP 临床应用中
2、国专家共识Expert consensus of clinical application of NTproBNPNT-proBNP 临床应用中国专家共识小组【关键词】 脑钠肽； 末端 型利钠肽原；心力衰竭；心血管疾病【ey words】 ； ； ； doi：10.3969/jissn16725301201106001中图分类号 541；516 文献标识码 文章编号 1672-5301(2011)06-0401-08,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: 5
3、0% (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。,急诊室呼吸困难患者急性心力衰竭的独立预测因素Independent predictors of acute heart failure in dyspneic patients in the emergency department,Januzzi JL, Jr., Am J Cardiol 2005,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
4、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,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 1620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
5、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
6、 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,van Kimmenade
7、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,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 judgemen of prognosis of heart failure 应用
8、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,急性不稳定性心力衰竭的NT-proBNP监测 NT-proBNP and Therapy Monitoring for Acutely Destabilized HF,Since
9、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
10、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,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 du
11、ring hospitalization for acute destabilized HF is a reasonable goal. If a baseline measure of NT-proBNP is not available, a NT-proBNP level 4000 pg/ml after acute treatment is desirable. 尽管缺少关于检测NT-proBNP指导缺血性心脏病治疗的前瞻性研究,观察性研究表明 急性心衰病人经治疗后 NT-proBNP 水平降低30% 是合理的，如果不能提供基线NT-proBNP 水平，治疗后小于4000 pg/ml是
12、理想水平,急性心力衰竭住院期间的NT-proBNP应用流程 Algorithm for use of NT-proBNP during hospitalization for acute HF,NT-proBNP与慢性性心衰的预后,在慢性心衰患者中，NT-proBNp 是与临床终点相关的最强的独立预测因子之一 Among patients with chronic HF, repeated determinations of NT-proBNP levels appear to convey additional prognostic value for relevant adverse ou
13、tcomes, including death or destabilization of HF requiring hospitalization, and are thus recommended at each patient evaluation. （在慢性心衰患者中反复检测 NT-proBNP，能够提供独特的临床不良事件的预测，例如死亡、因为心衰恶化再入院等，故推荐在评价每个心衰患者时使用。）,NT-proBNP与慢性性心衰的预后,Target values for outpatient prognostication remain relatively undefined. How
14、ever, the risk for morbidity and mortality in HF appears to increase markedlywith an NT-proBNP concentration 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 jud
15、gemen 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 blo
16、ckers, 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 Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF),design: Patients with chronic systolic H
17、F 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-
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 During the 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 Second
19、ary 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,TIME-CHF: Primary and Secondary Outcomes,NT-proBNP guided management of chronic heart failure based on an individ
20、ual 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 29th 2009,PRIMA-study,Prospective, randomized, single-blinde
21、d 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 ; Fol
22、low-up up minimal 1 year,PRIMA-study Main outcome ACC Orlando March 2009,PRIMA-study,PRIMA-study Main outcomeACC Orlando March 2009,Total Mortality,PRIMA-study,Survival (%),Time (days),P=0.208,NT-proBNP guided,Clinical guided,46/174 26.5%,57/171 33.3%,Secondary analysis,PRIMA-study,Cardiovascular mo
23、rtality nsCombined endpoint CV mortality / readmissions nsHF related readmissions nsCreatinine above / below the median (123 mcm/L) nsAge above / below 73 years nsDischarge NT-proBNP above / below 2950 pg/ml ns,On NT-proBNP target analysis: Primary endpoint,PRIMA-study,On NT-proBNP Target,Clinical G
24、uided 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,p0.001,11/10
25、1 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 populationHoweve
26、r, 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
27、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？,There were no significant differences between the 2 treatment groupsby N-terminal BNP level (P=.30).,TIME-CHF: N-terminal BNP level,JAMA. 2009;301(4):383-392,Thank you,
