Pulmonary embolism biomarkers

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Editor(s)-In-Chief: The APEX Trial Investigators, C. Michael Gibson, M.S., M.D. [1]

## Overview

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Although the usefulness of brain natriuretic peptide (BNP) concentrations to diagnose pulmonary embolism (PE) is limited,[1] elevated BNP and pro-BNP levels are associated with right ventricular dysfunction and increased mortality, and are therefore useful prognostic markers.[2] The evaluation of troponin concentration also serves as a useful prognostic marker to identify myocardial necrosis[3][4] and mortality associated with acute PE.[5]

## Biomarkers

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### Brain Natriuretic Peptide (BNP)

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* BNP levels can be elevated among patients with PE.[6] However, the routine assessment of 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.[1]

* BNP and pro-BNP levels are beneficial as a prognostic marker;[2] in fact, elevated BNP levels is associated with right ventricular dysfunction and associated mortality in the setting of a PE.[7][8][9] The presence of right ventricular dysfunction is one of the criteria used to classify a PE as submassive or intermediate risk.[10][11]

* The following values are considered a marker of right ventricular dysfunction:[10][11]
* BNP > 90 pg/mL
* N-terminal pro-BNP >500 pg/mL

### Troponin

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* 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.[12]

* Serum troponin concentrations can be elevated in patients with an acute PE, however its use in diagnosing a PE is very limited. The role of troponin in PE is to risk stratify patients and to optimize management strategies. In fact, elevated troponins are a marker of myocardial necrosis, one of the criteria used to classify PE into submassive or intermediate risk. Myocardial necrosis in PE is defined as the presence of:[10][11]
* Elevation of troponin I (>0.4 ng/mL), OR
* Elevation of troponin T (>0.1 ng/mL)

* Troponins are also a prognostic marker of right ventricular dysfunction in patients with a confirmed PE.[13][14][15] Troponin I specifically may be assessed to identify patients with right ventricular dysfunction who have a significant amount of segmental defects on V/Q scan.[3][4][3]

* When compared to patients with myocardial infarction (MI), the variation in troponin concentration among patients with acute PE follow a different pattern.[16] A study on 9 patients with elevated troponins revealed that elevation in troponins has a lower peak levels and remains detectable for a shorter period of time compared to that in acute MI.[16]

## References

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1. ↑ 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)CS1 maint: Multiple names: authors list (link)
2. ↑ 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. ↑ 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)CS1 maint: Multiple names: authors list (link)
4. ↑ 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)
5. ↑ 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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
6. ↑ 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)CS1 maint: Multiple names: authors list (link)
7. ↑ 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)CS1 maint: Multiple names: authors list (link)
8. ↑ 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)CS1 maint: Multiple names: authors list (link)
9. ↑ 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)CS1 maint: Multiple names: authors list (link)
10. ↑ 10.0 10.1 10.2 Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ; et al. (2011). "Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association". Circulation. 123 (16): 1788–830. doi:10.1161/CIR.0b013e318214914f. PMID 21422387.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
11. ↑ 11.0 11.1 11.2 Cannon CP, Goldhaber SZ (1996). "Cardiovascular risk stratification of pulmonary embolism". Am. J. Cardiol. 78 (10): 1149–51. PMID 8914880. Retrieved 2011-12-21. Unknown parameter `|month=` ignored (help)
12. ↑ 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)CS1 maint: Multiple names: authors list (link)
13. ↑ 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)CS1 maint: Multiple names: authors list (link)
14. ↑ 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)CS1 maint: Multiple names: authors list (link)
15. ↑ 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)CS1 maint: Multiple names: authors list (link)
16. ↑ 16.0 16.1 Müller-Bardorff M, Weidtmann B, Giannitsis E, Kurowski V, Katus HA (2002). "Release kinetics of cardiac troponin T in surught ventricularivors of confirmed severe pulmonary embolism". Clinical Chemistry. 48 (4): 673–5. PMID 11901075. Retrieved 2012-05-02.CS1 maint: Multiple names: authors list (link)

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