[雙語(yǔ)翻譯]醫(yī)學(xué)外文翻譯--bnp在急性肺動(dòng)脈栓塞預(yù)后中的意義（英文）

1、Invited critical reviewB-type natriuretic peptide in acute pulmonary embolismAnna Kaczyńska, Maciej Kostrubiec, Micha? Ciurzyński, Piotr Pruszczyk ?Department of Internal Medicine and Cardiology, Medical University of Wa

2、rsaw, Polanda b s t r a c t a r t i c l e i n f oArticle history:Received 14 May 2008Received in revised form 25 June 2008Accepted 19 July 2008Available online 24 July 2008Keywords:Acute pulmonary embolismBNPNT-proBNPRig

3、ht ventricle dysfunctionPrognosisMyocardial stretch leads to the natriuretic peptides release in acute or chronic left ventricular dysfunction.However, there is an accumulating evidence that B-type natriuretic peptide (B

4、NP) and its N-terminalfragment (NT-proBNP) may originate from right ventricle and their concentrations are elevated in patientswith acute pulmonary embolism (APE) especially when resulting in right ventricular dysfunctio

5、n (RVD).Recently it is underlined that severity assessment of APE as well as the risk stratification and therapyselection is based both on patients' hemodynamic status and markers of myocardial injury and RVD.BNP and

6、 NT-proBNP are helpful in identifying patients with RVD in APE, emerging as an adjunctive tool toechocardiography. Elevated BNP or NT-proBNP levels are also significant predictors of death and/orcomplicated clinical cour

7、se in APE.© 2008 Elsevier B.V. All rights reserved.Contents1. Studies selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12. BNP and N

8、T-proBNP assays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13. BNP and NT-proBNP in the detection of RVD. . . . . . . . . . . . . . . . . . . . . . . .

9、 . . . . . . . . . . . . . . . . . . . . . . . . 24. Prognostic value of BNP and NT-proBNP in APE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25. Conclusions . . . . . . .

10、. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

11、. . . . . . . . . . . . . . . . . . 4It is well known that myocardial stretch leads to the natriureticpeptides release in acute or chronic left ventricular dysfunction.However, there is an accumulating evidence that conc

12、entrations of B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP)are elevated in patients with acute pulmonary embolism (APE)especially when resulting in right ventricular dysfunction. Recently itis

13、underlined that severity assessment of acute pulmonary embolism(APE) as well as the risk stratification and therapy selection is based bothon patients' hemodynamic status and markers of myocardial injury andright ven

14、tricular dysfunction (RVD). Right ventricular function can bedirectly assessed at echocardiography and/or contrast enhanced spiralcomputed tomography. Since plasma concentration of brain natriureticpeptide reflects the s

15、everity of RVD its assessment was implored in APErisk stratification as well.We performed a systematic review aimed on B-type natriureticpeptides in APE especially for the RVD detection and clinical courseprediction.1. S

16、tudies selectionOverall 49 articles were found searching PubMed by terms‘pulmonary embolism’, ‘BNP’ and ‘NT-proBNP’ from 1997 to March2008. Thirty two papers were excluded from current review becausethey were case report

17、s, review papers, editorials or letters. They didnot report on end-points or did not provide values of biomarkersconcentration.Eventually, 17 studies concerning the influence of elevated BNPand NT-proBNP on short-term mo

18、rtality, adverse outcome events(death, cardiogenic shock, need for thrombolysis, catheter or surgicalembolectomy, use of vasopressors, need for endotracheal intubationand mechanical ventilation, cardiopulmonary resuscita

19、tion) and RVDwere selected (Table 1).2. BNP and NT-proBNP assaysPropeptide for B-type natriuretic peptide (proBNP) is cleaved toequimolar amounts of B-type natriuretic peptide (BNP) and N-terminal fragment (NT-proBNP). B

20、NP is physiologically active.BNP concentration is assessed using several radioimmunologicassays or immunofluorometric assays, while for NT-proBNP one test isClinica Chimica Acta 398 (2008) 1–4? Corresponding author. Depa

21、rtment of Internal Medicine and Cardiology, MedicalUniversity of Warsaw, ul. Lindleya 4 02-005 Warsaw, Poland. Tel.: +48 22 502 11 44; fax:+48 22 502 21 42.E-mail address: piotr.pruszczyk@amwaw.edu.pl (P. Pruszczyk).0009

22、-8981/$ – see front matter © 2008 Elsevier B.V. All rights reserved.doi:10.1016/j.cca.2008.07.020Contents lists available at ScienceDirectClinica Chimica Actajournal homepage: www.elsevier.com/locate/clinchimcomplic

23、ated clinical course with OR 8.0 (95% CI 1.3–50.1, p=0.026).Interestingly authors also attempted to identify the most sensitiveBNP cut-off level for identifying low-risk APE patients. It turned to beb50 pg/ml with its ne

24、gative predictive value of 97% [2].Elevated BNP was also found to be a predictor of all-cause as wellas APE-related mortality in group of 110 patients [12]. Three-monthmortality was 10%. Interestingly all deaths occurred

25、 in patients withBNP concentration in second and third tertile i. e. exceeding 2.5 pmol/land 21.7 pmol/l, respectively. In the study by Krüger et al. [3], however,BNP cut-off value of N90 pg/ml, as calculated from R

26、OC analysis, wasnot directly associated neither with in-hospital complicated coursenor with short-term mortality. However, as mentioned earlier it wasreported to be useful in RVD prediction. Importantly, as expected,high

27、er incidence of complications as well as trend toward highermortality was observed in patients with RVD.Conversely, a small study on unselected group of 17 patients withAPE, including patients both with and without RVD r

28、eportedsignificantly higher concentration of BNP in patients who died of PEthan in those who survived (91.6 (77.5–336.2) vs 14.4 (11.9–27.4)pmol/l, p=0.02) [13].The following study comprising 61 initially hemodynamically

29、stable patients reported higher BNP concentration on admission inpatients with subsequent complicated clinical course than withfavorable outcome (950±314 vs 296±353 pg/ml, pb0.0001) [14].Importantly all 4 in-ho

30、spital deaths and 11 complications observed inthis study occurred in patients with BNP in the highest tertile, namely527–1300 pg/ml. ROC analysis confirmed cut-off point of 487 pg/ml asindicating patients with higher ris

31、k of complications (AUC 0.98 95% CI0.96–0.99, sensitivity 86%, specificity 100%).In the analysis of clinical trial (MATISSE Study) assessing efficacyand safety of fondaparinux in APE, Söhne et al. performed ROCanaly

32、sis for BNP assessed on admission in predicting fatal outcomeand/or venous thromboembolism recurrence within following3 months [15]. The calculated cut-off point of 1.25 pmol/l showedsensitivity of 60% and specificity of

33、 60% with positive predictive valuefor combined end-point of 57% (AUC 0.63 95% CI 0.56–0.70).The following observation on elderly patients (N65 years) alsoreported significantly higher BNP concentration in patients withc

34、omplicated than with uncomplicated clinical course (274 (142–581)vs 78 (33–230) pg/ml, pb0.05) [16]. In this study, however, the bestthreshold in ROC analysis for serious adverse event prediction was200 pg/ml with negati

35、ve predictive value of 86% for unfavorableoutcome (AUC 0.72 95% CI 0.58–0.83).Similarly, in the study on 67 patients, all 9 patients withcomplicated clinical course had BNP N100 pg/ml (applied cut-offvalue used in predic

36、ting RVD) [4].In the study of Tulevski et al. half of patients had elevated BNPconcentration on admission (arbitrary chosen level N10 pmol/l). Tworeported deaths occurred in patients with BNP N10 pmol/l [17].In the first

37、 report on NT-proBNP in APE from Kucher et al. [6] ingroup of 73 patients, NT-proBNP was significantly higher in patientswith adverse outcome than in patients with favorable outcome (4250(80–49,607) vs 121 (16–34,802) pg

38、/ml, pb0.0001). Authors identifiedin ROC analysis cut-off point of 500 pg/ml. Negative predictive value ofNT-proBNP b500 pg/ml for adverse outcome was 97%. Also inmultivariable analysis NT-proBNP has proved to be predict

39、or forcomplicated clinical course (OR 14.6 95% CI 1.5–139.0), p=0.02).The following three single-center observations [7,8,18] confirmedthe role of NT-proBNP in APE risk stratification. NT-proBNP concen-tration was a sign

40、ificant predictor of both in-hospital mortality (OR2.15 95% CI 1.3–3.56) and complicated clinical course (OR 1.88 95% CI1.29–2.74) [7].In observation by German group on 124 patients with LV ejectionfraction ≥30% ROC anal

41、ysis identified a concentration of 1000 pg/ml asa cut-off level for predicting death or complicated clinical course [19].Among patients with NT-proBNP b1000 pg/ml no in-hospital deathoccurred. NT-proBNP b1000 pg/ml had n

42、egative predictive value of95% for complicated clinical course and 100% for mortality.The same value of 1000 pg/ml was positively verified in anotherstudy (AUC 0.809) [20]. NT-proBNPN1000 pg/ml allowed to predict anadver

43、se outcome (OR 11.79 95% CI 1.6–527, p=0.007). There was alsoan observed trend toward 4-fold higher mortality in patients with NT-proBNPN1000 pg/ml than with b1000 pg/ml (16.4% vs 4.1%, p=0.056).In patients with APE effe

44、ctive early treatment should significantlydecrease the load of pulmonary artery thromboemboli and result inprogressive improvement of right ventricular function. Therefore,serial measurement of NT-proBNP performed within

45、 the first 24 h oftreatment is of potential value in risk assessment. Indeed, NT-proBNPconcentrations assessed on admission and after 12 and 24 h in 113patients with APE decreased significantly in survivors. In non-survi

46、vors, median NT-proBNP concentrations at baseline (11,491(618–60,958) pg/ml) remained elevated after 24 h (8139 (35–70,018)pg/ml, p=NS). The 30-day mortality rate in the group of 18 patientswith NT-proBNPN7500 pg/ml on a

47、dmission and a less than 50%decrease of NT-proBNP within 24 h was associated with 30-daymortality of 61% (95% CI: 39%–84%) [18].As was mentioned before, unlikely in case of LV congestive heartfailure, there is no establi

48、shed single cut-off point for detecting RVD.For BNP concentration it ranges from 90 to 200 pg/ml as calculatedfrom ROC analysis [5,14,3,4]. For NT-proBNP one analysis reports cut-off value of 500 pg/ml [6] (Table 2). Low

49、er threshold values of 90–100 pg/ml have higher sensitivity with moderate specificity, whiletaking higher threshold values improves specificity in detecting RVD.Also there are several cut-off points counted for predictin

50、gunfavorable outcome in APE. As for BNP assessment with RIA method3 values were proposed: 1.25 pmol/l, 2.5 pmol/l and 10 pmol/l[15,17,12]. Two latter have similar sensitivity, but higher specificityfavors value of 10 pmo

51、l/l (Table 3).For BNP assessed with immunoassay threshold values between50 pg/ml and 487 pg/ml were evaluated [14,3,16,4,2]. Proposed cut-offTable 2BNP and NT-proBNP in predicting RVDAuthor Peptide Cut-off value Sensitiv

52、ity % Specificity %Krüger et al. [3] BNP 90 pg/ml 64 94Pierelli et al. [14] BNP 189 pg/ml 86 100Logeart et al. [4] BNP 200 pg/ml 83 87100 pg/ml 100 64Yardan et al. [5] BNP 90 pg/ml 93 91Kucher et al. [6] NT-proBNP 5

53、00 pg/ml 97 75Table 3BNP and NT-proBNP in predicting complicated clinical courseAuthor Peptide End-point Cut-offvalueSensitivity%Specificity%Söhne et al. [15] BNP CCC 1.25 pmol/l 60 62Tulevski et al. [17] BNP Death

54、10 pmol/l 100 54ten Wolde et al. [12] BNP Death 2.5 pmol/l 100 37Pierelli et al. [14] BNP CCC 487 pg/ml 100 83Krüger et al. [3] BNP Death 90 pg/ml 50 60CCC 26 39Ray et al. [16] BNP CCC 200 pg/ml 69 66Logeart et al.

55、[4] BNP CCC 100 pg/ml 100 34Kucher et al. [2] BNP CCC 50 pg/ml 95 60Binder et al. [19] NT-proBNP Death 1000 pg/ml 85 52CCC 100 49Kucher et al. [6] NT-proBNP CCC 500 pg/ml 95 57Kostrubiec et al. [8] NT-proBNP Death 7600 p