1、N-proBNP在心衰诊断、预后、治疗的管理,广东省人民医院心内科广东省心血管病研究所陈鲁原,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 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,在初级保健中被误诊为
2、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 patientsin the emergency department 急诊室呼吸
3、困难患者急性心力衰竭的独立预测因素,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,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,Januzzi, et al, Eur Heart J 200
4、5 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 1620倍），检测相对较容易，是
5、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 dy
6、spnea 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 he
7、art 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 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 def
8、inite 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,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1
9、000 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 p
10、oints: 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,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
11、 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 4000 pg/ml after acute treatment is desirable. 尽管缺少关于检测NT-pro
12、BNP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是理想水平,Algorithm for use of NT-proBNP during hospitalization for acute HF 急性心力衰竭住院期间的NT-proBNP应用流程,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 dete
13、rminations of NT-proBNP levels appear to convey additional prognostic value for relevant adverse outcomes, 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
14、。）,NT-proBNP与慢性性心衰的预后,Target values for outpatient prognostication remain relatively undefined. However, 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
15、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,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 a
16、ddition 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 Trial of Intensified vs Standard Medical Therapy in
17、 Elderly Patients With Congestive Heart Failure (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/
18、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 trea
19、tment 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 guide
20、d management of 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 29t
21、h 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 Treatme
22、nt Follow-up at 2 weeks, 1,3,6,9,12,15,21,24 months ; Follow-up up minimal 1 year,PRIMA-study Main outcomeACC 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%,57/17
23、1 33.3%,Secondary analysis,PRIMA-study,Cardiovascular mortality 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: Pri
24、mary 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-stud
25、y,On NT-proBNP Target,Clinical Guided group,p0.001,11/101 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 d
26、oes not appear favorable in the overall populationHowever, 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 t
27、heir 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 groupsby N-terminal BNP level (P=.30).,TIME-CHF: N-terminal BNP level,JAMA. 2009;301(4):383-392,
