Pulmonary embolism biomarkers
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Editor(s)-In-Chief: The APEX Trial Investigators, C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]
Overview
The use of brain natriuretic peptide levels to diagnose PE is limited due to the reduced sensitivity of the test.[1] However, elevated BNP and pro-BNP levels accurately predict right ventricular dysfunction and associated mortality, hence may used as a prognostic marker. [2] The evaluation of troponin levels also serves as an good prognostic marker to identify right ventricular dysfunction minor myocardial injury.[3][4] Testing for BNP and troponin levels may not be used to predict all-cause mortality in stable patients presenting to the emergency dept with acute pulmonary embolism.[5]
Brain natriuretic peptide (BNP)
Patients with pulmonary embolism and ventilation-perfusion mismatch have been shown to have elevated BNP levels,[6] however the associated usefulness of routinely assessing BNP levels to diagnose PE is not indicated as it is non-specific and has reduced sensitivity secondary to the presence of other etiologies which falsely elevate BNP levels in acute case scenarios.[1]
In 2006 Sohne et al, demonstrated that the presence of elevated BNP levels at admission were associated with early fatal venous thromboembolism in hemodynamically stable patients with acute PE. This relationship appeared to be clinically insignificant when used as a guide to initiate early thrombolysis in this population. The sensitivity and specificity of assessing BNP levels as a diagnostic test was found to be 60% and 62%, respectively.[1]
The benefit of using elevated BNP and pro-BNP levels as a prognostic marker[2] may be derived from the results of three meta-analysis[7][8][9] which demonstrate that elevated BNP levels accurately predict right ventricular dysfunction and associated mortality in the setting of a PE.[8]
Troponin
Measurement of troponin subtype levels, particularly troponin I and troponin T, may be of value in patients presenting with undifferentiated chest pain and/or dyspnea.[10]
Serum troponin levels are often elevated in patients with an acute PE, however its use in diagnosing a PE is very limited. It remains a strong prognostic marker in identifying RV dysfunction in patients with a confirmed PE, and a useful tool to risk stratify patients and to optimize management strategies.[11][12][13] Troponin I specifically may be assessed to identify patients with RV dysfunction who have a significant amount of segmental defects on V/Q scan [3][4] or to detect minor myocardial injury in patients presenting with acute PE.[3]
Margit Müller-Bardorff et al describes the contrasting features of troponin elevation in patients with angiographically confirmed PE and no underlying coronary artery disease, compared with the elevated troponin levels in patients who have an acute myocardial infarction.[14] Based on this study, the troponin levels in patients with acute PE were found to have lower peak levels, and remained detectable for a shorter period when compared to its levels in acute myocardial infarction. The findings are summarized below.
- Peaked after a median of 10 h
- Persisted at >0.1 μg/L (0.03 μg/L) for a median of 30 h
- Remained detectable (>0.01 μg/L) for a median of 40 h after admission.
References
- ↑ 1.0 1.1 1.2 Söhne M, Ten Wolde M, Boomsma F, Reitsma JB, Douketis JD, Büller HR (2006). "Brain natriuretic peptide in hemodynamically stable acute pulmonary embolism". Journal of Thrombosis and Haemostasis : JTH. 4 (3): 552–6. doi:10.1111/j.1538-7836.2005.01752.x. PMID 16405522. Retrieved 2012-05-01. Unknown parameter
|month=ignored (help) - ↑ 2.0 2.1 Agnelli G, Becattini C (2010). "Acute pulmonary embolism". The New England Journal of Medicine. 363 (3): 266–74. doi:10.1056/NEJMra0907731. PMID 20592294. Retrieved 2012-05-01. Unknown parameter
|month=ignored (help) - ↑ 3.0 3.1 3.2 Meyer T, Binder L, Hruska N, Luthe H, Buchwald AB (2000). "Cardiac troponin I elevation in acute pulmonary embolism is associated with right ventricular dysfunction". Journal of the American College of Cardiology. 36 (5): 1632–6. PMID 11079669. Retrieved 2012-05-02. Unknown parameter
|month=ignored (help) - ↑ 4.0 4.1 Horlander KT, Leeper KV (2003). "Troponin levels as a guide to treatment of pulmonary embolism". Current Opinion in Pulmonary Medicine. 9 (5): 374–7. PMID 12904706. Retrieved 2012-05-02. Unknown parameter
|month=ignored (help) - ↑ Jiménez D, Díaz G, Molina J, Martí D, Del Rey J, García-Rull S; et al. (2008). "Troponin I and risk stratification of patients with acute nonmassive pulmonary embolism". Eur Respir J. 31 (4): 847–53. doi:10.1183/09031936.00113307. PMID 18094010.
- ↑ Kiely DG, Kennedy NS, Pirzada O, Batchelor SA, Struthers AD, Lipworth BJ (2005). "Elevated levels of natriuretic peptides in patients with pulmonary thromboembolism". Respiratory Medicine. 99 (10): 1286–91. doi:10.1016/j.rmed.2005.02.029. PMID 16099151. Retrieved 2012-05-01. Unknown parameter
|month=ignored (help) - ↑ Cavallazzi R, Nair A, Vasu T, Marik PE (2008). "Natriuretic peptides in acute pulmonary embolism: a systematic review". Intensive Care Medicine. 34 (12): 2147–56. doi:10.1007/s00134-008-1214-5. PMID 18626627. Retrieved 2012-05-01. Unknown parameter
|month=ignored (help) - ↑ 8.0 8.1 Klok FA, Mos IC, Huisman MV (2008). "Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism: a systematic review and meta-analysis". American Journal of Respiratory and Critical Care Medicine. 178 (4): 425–30. doi:10.1164/rccm.200803-459OC. PMID 18556626. Retrieved 2012-05-01. Unknown parameter
|month=ignored (help) - ↑ Lega JC, Lacasse Y, Lakhal L, Provencher S (2009). "Natriuretic peptides and troponins in pulmonary embolism: a meta-analysis". Thorax. 64 (10): 869–75. doi:10.1136/thx.2008.110965. PMID 19525265. Retrieved 2012-05-01. Unknown parameter
|month=ignored (help) - ↑ Douketis JD, Crowther MA, Stanton EB, Ginsberg JS (2002). "Elevated cardiac troponin levels in patients with submassive pulmonary embolism". Archives of Internal Medicine. 162 (1): 79–81. PMID 11784223. Retrieved 2012-05-02. Unknown parameter
|month=ignored (help) - ↑ Giannitsis E, Müller-Bardorff M, Kurowski V, Weidtmann B, Wiegand U, Kampmann M, Katus HA (2000). "Independent prognostic value of cardiac troponin T in patients with confirmed pulmonary embolism". Circulation. 102 (2): 211–7. PMID 10889133. Retrieved 2012-05-02. Unknown parameter
|month=ignored (help) - ↑ Pruszczyk P, Bochowicz A, Torbicki A, Szulc M, Kurzyna M, Fijałkowska A, Kuch-Wocial A (2003). "Cardiac troponin T monitoring identifies high-risk group of normotensive patients with acute pulmonary embolism". Chest. 123 (6): 1947–52. PMID 12796172. Retrieved 2012-05-02. Unknown parameter
|month=ignored (help) - ↑ Konstantinides S, Geibel A, Olschewski M, Kasper W, Hruska N, Jäckle S, Binder L (2002). "Importance of cardiac troponins I and T in risk stratification of patients with acute pulmonary embolism". Circulation. 106 (10): 1263–8. PMID 12208803. Retrieved 2012-05-02. Unknown parameter
|month=ignored (help) - ↑ Müller-Bardorff M, Weidtmann B, Giannitsis E, Kurowski V, Katus HA (2002). "Release kinetics of cardiac troponin T in survivors of confirmed severe pulmonary embolism". Clinical Chemistry. 48 (4): 673–5. PMID 11901075. Retrieved 2012-05-02.