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Prognostic Value of Biomarkers in Acute Non-massive Pulmonary Embolism: A Systematic Review and Meta-analysis

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Abstract

Background

Various biomarkers have been evaluated to risk stratify patients with acute pulmonary embolism (PE). We aimed to summarize the available evidence to compare the prognostic value of three most widely studied biomarkers in normotensive patients with acute PE.

Method

A systematic literature review of database, including Pubmed, EMBASE and Cochrane, was done. Studies were included if those were done on patients with acute PE and serum troponin or brain natriuretic peptide and N-terminal proBNP (BNP/NT-proBNP) or Heart-type fatty acid-binding protein (H-FABP) assay was done. The primary end point was short-term all-cause mortality. The secondary end points were PE-related mortality and serious adverse events.

Results

All three biomarkers were significantly associated with increased risk for short-term all-cause mortality, PE-related mortality and serious adverse events. All-cause mortality: troponin [odds ratio (OR) 4.80; 95 % CI 3.25–7.08, I 2 = 54 %], BNP or NT-proBNP (OR 7.98; 95 % CI 4.34–14.67, I 2 = 0 %); PE-related mortality: troponin (OR 3.80; 95 % CI 2.74–5.27, I 2 = 0 %), BNP or NT-proBNP (OR 7.57; 95 % CI 2.89–19.81, I 2 = 0 %) and H-FABP (OR 25.97; 95 % CI 6.63–101.66, I 2 = 40 %). H-FABP has the lowest negative likelihood ratio (NLR) of 0.17 for mortality followed by high-sensitive cardiac troponin T (hs-cTnT) with NLR of 0.21.

Conclusion

None of the biomarker identifies a subgroup of patients who can be managed as an outpatient versus patients who may get benefit from thrombolytics with certainty; however, H-FABP and hs-cTnT showed some promising results and should be investigated further.

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Abbreviations

PE:

Pulmonary embolism

BNP/NT-proBNP:

Brain natriuretic peptide/N-terminal brain natriuretic peptide

H-FABP:

Heart-type fatty acid-binding protein

Hs-cTnT:

High-sensitive cardiac troponin T

PLR:

Positive likelihood ratio

NLR:

Negative likelihood ratio

OR:

Odds ratio

References

  1. Goldhaber SZ, Bounameaux H (2012) Pulmonary embolism and deep vein thrombosis. Lancet 379(9828):1835–1846

    Article  PubMed  Google Scholar 

  2. Goldhaber SZ, Visani L, De Rosa M (1999) Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 353:1386–1389

    Article  CAS  PubMed  Google Scholar 

  3. Jaff MR, McMurtry MS, Archer SL, On behalf of the American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation, Council on Peripheral Vascular Disease, and Council on Arteriosclerosis, Thrombosis and Vascular Biology. et al (2011) Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension. Circulation 123:1788–1830

    Article  PubMed  Google Scholar 

  4. Aujesky D, Smith KJ, Cornuz J, Roberts MS (2005) Cost-effectiveness of low-molecular-weight heparin for treatment of pulmonary embolism. Chest 128:1601–1610

    Article  CAS  PubMed  Google Scholar 

  5. Kucher N, Rossi E, De Rosa M, Goldhaber SZ (2005) Prognostic role of echocardiography among patients with acute pulmonary embolism and a systolic arterial pressure of 90 mm Hg or higher. Arch Intern Med 165:1777–1781

    Article  PubMed  Google Scholar 

  6. Grifoni S, Olivotto I, Cecchini P et al (2000) Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction. Circulation 101:2817–2822

    Article  CAS  PubMed  Google Scholar 

  7. Coutance G, Cauderlier E, Ehtisham J, Hamon M, Hamon M (2011) The prognostic value of markers of right ventricular dysfunction in pulmonary embolism: a meta-analysis. Crit Care 15:R103

    Article  PubMed Central  PubMed  Google Scholar 

  8. Bajaj A (2014) The prognostic value of plasma heart-type fatty acid-binding protein in acute pulmonary embolism. Chest 146:e236–e237

    Article  PubMed  Google Scholar 

  9. Vuilleumier N, Limacher A, Méan M et al (2015) Cardiac biomarkers and clinical scores for risk stratification in elderly patients with non-high-risk pulmonary embolism. J Intern Med 277(6):707–716

  10. Bulj N, Potočnjak I, Sharma M, Pintaric H, Degoricija V (2013) Timing of troponin T measurements in triage of pulmonary embolism patients. Croat Med J 54(6):561–568

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Becattinii C, Casazza F, Forgione C, Imperadore F, Bongarzoni A, Agnelli G et al (2013) Acute pulmonary embolism: external validation of an integrated risk stratification model. Chest 144(5):1539–1545

    Article  Google Scholar 

  12. Sanchez O, Trinquart L, Planquette B et al (2013) Echocardiography and pulmonary embolism severity index have independent prognostic roles in pulmonary embolism. Eur Respir J 42(3):681–688

    Article  PubMed  Google Scholar 

  13. Ozsu S, Abul Y, Orem A (2013) Predictive value of troponins and simplified pulmonary embolism severity index in patients with normotensive pulmonary embolism. Multidiscip Respir Med 8(1):34

    Article  PubMed Central  PubMed  Google Scholar 

  14. Lankeit M, Jiménez D, Kostrubiec M et al (2011) Predictive value of the high-sensitivity troponin T assay and the simplified Pulmonary Embolism Severity Index in hemodynamically stable patients with acute pulmonary embolism: a prospective validation study. Circulation 124(24):2716–2724

    Article  CAS  PubMed  Google Scholar 

  15. Kang DK, Sun JS, Park KJ, Lim HS (2011) Usefulness of combined assessment with computed tomographic signs of right ventricular dysfunction and cardiac troponin T for risk stratification of acute pulmonary embolism. Am J Cardiol 108(1):133–140

    Article  PubMed  Google Scholar 

  16. Jiménez D, Aujesky D, Moores L et al (2011) Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolism. Thorax 66(1):75–81

    Article  PubMed  Google Scholar 

  17. Vanni S, Nazerian P, Pepe G (2011) Comparison of two prognostic models for acute pulmonary embolism; clinical vs right ventricular dysfunction-guided approach. J Thromb Haemost 9:1916–1923

    Article  CAS  PubMed  Google Scholar 

  18. Lankeit M, Friesen D, Aschoff J et al (2010) Highly sensitive troponin T assay in normotensive patients with acute pulmonary embolism. Eur Heart J 31(15):1836–1844

    Article  CAS  PubMed  Google Scholar 

  19. Stein PD, Matta F, Janjua M, Yaekoub AY, Jaweesh F, Alrifai A (2010) Outcome in stable patients with acute pulmonary embolism who had right ventricular enlargement and/or elevated levels of troponin I. Am J Cardiol 106(4):558–563

    Article  CAS  PubMed  Google Scholar 

  20. Ozsu S, Karaman K, Mentese A et al (2010) Combined risk stratification with computerized tomography/echocardiography and biomarkers in patients with normotensive pulmonary embolism. Thromb Res 126(6):486–492

    Article  CAS  PubMed  Google Scholar 

  21. Singanayagam A, Scally C, Al-Khairalla MZ et al (2011) Are biomarkers additive to pulmonary embolism severity index for severity assessment in normotensive patients with acute pulmonary embolism? QJM 104(2):125–131

    Article  CAS  PubMed  Google Scholar 

  22. Kostrubiec M, Łabyk A, Pedowska-Włoszek J et al (2010) Assessment of renal dysfunction improves troponin-based short-term prognosis in patients with acute symptomatic pulmonary embolism. J Thromb Haemost 8(4):651–658

    Article  CAS  PubMed  Google Scholar 

  23. Vuilleumier N, Le Gal G, Verschuren F et al (2009) Cardiac biomarkers for risk stratification in non-massive pulmonary embolism: a multicenter prospective study. J Thromb Haemost 7(3):391–398

    Article  CAS  PubMed  Google Scholar 

  24. Post F, Mertens D, Sinning C, Peetz D, Münzel T (2009) Decision for aggressive therapy in acute pulmonary embolism: implication of elevated troponin T. Clin Res Cardiol 98(6):401–408

    Article  CAS  PubMed  Google Scholar 

  25. Bova C, Pesavento R, Marchiori A et al (2009) TELESIO Study Group. Risk stratification and outcomes in hemodynamically stable patients with acute pulmonary embolism: a prospective, multicentre, cohort study with three months of follow-up. J Thromb Haemost 7(6):938–944

    Article  CAS  PubMed  Google Scholar 

  26. Moores L, Aujesky D, Jiménez D et al (2010) Pulmonary Embolism Severity Index and troponin testing for the selection of low-risk patients with acute symptomatic pulmonary embolism. J Thromb Haemost 8(3):517–522

    Article  CAS  PubMed  Google Scholar 

  27. Jiménez D, Díaz G, Molina J et al (2008) Troponin I and risk stratification of patients with acute nonmassive pulmonary embolism. Eur Respir J 31(4):847–853

    Article  PubMed  Google Scholar 

  28. Palmieri V, Gallotta G, Rendina D et al (2008) Troponin I and right ventricular dysfunction for risk assessment in patients with nonmassive pulmonary embolismin the Emergency Department in combination with clinically based risk score. Intern Emerg Med 3(2):131–138

    Article  PubMed  Google Scholar 

  29. Tulevski II, ten Wolde M, van Veldhuisen DJ et al (2007) Combined utility of brain natriuretic peptide and cardiac troponin T may improve rapid triage and risk stratification in normotensive patients with pulmonary embolism. Int J Cardiol 116:161–166

    Article  PubMed  Google Scholar 

  30. Kline JA, Hernandez-Nino J, Rose GA, Norton HJ, Camargo CA Jr (2006) Surrogate markers for adverse outcomes in normotensive patients with pulmonary embolism. Crit Care Med 34:2773–2780

    Article  PubMed  Google Scholar 

  31. Douketis JD, Leeuwenkamp O, Grobara P et al (2005) The incidence and prognostic significance of elevated cardiac troponins in patients with submassive pulmonary embolism. J Thromb Haemost 3:508–513

    Article  CAS  PubMed  Google Scholar 

  32. Kostrubiec M, Pruszczyk P, Bochowicz A et al (2005) Biomarker-based risk assessment model in acute pulmonary embolism. Eur Heart J 26:2166–2172

    Article  CAS  PubMed  Google Scholar 

  33. Bova C, Crocco F, Ricchio R, Serafini O, Greco F, Noto A (2005) Importance of troponin T for the risk stratification of normotensive patients with pulmonary embolism: a prospective, cohort study with a three-month follow-up. Haematologica 90:423–424

    PubMed  Google Scholar 

  34. Pruszczyk P, Bochowicz A, Torbicki A et al (2003) Cardiac troponin T monitoring identifies high-risk group of normotensive patients with acute pulmonary embolism. Chest 123:1947–1952

    Article  CAS  PubMed  Google Scholar 

  35. Ten Wolde M, Tulevski II, Mulder JW et al (2003) Brain natriuretic peptide as a predictor of adverse outcome in patients with pulmonary embolism. Circulation 107:2082–2084

    Article  PubMed  Google Scholar 

  36. Pieralli F, Olivotto I, Vanni S et al (2006) Usefulness of bedside testing for brain natriuretic peptide to identify right ventricular dysfunction and outcome in normotensive patients with acute pulmonary embolism. Am J Cardiol 97:1386–1390

    Article  CAS  PubMed  Google Scholar 

  37. Logeart D, Lecuyer L, Thabut G et al (2007) Biomarker-based strategy for screening right ventricular dysfunction in patients with non-massive pulmonary embolism. Intensive Care Med 33:286–292

    Article  CAS  PubMed  Google Scholar 

  38. Maziere F, Birolleau S, Medimagh S et al (2007) Comparison of troponin I and N-terminal-pro Btype natriuretic peptide for risk stratification in patients with pulmonary embolism. Eur J Emerg Med 14:207–211

    Article  PubMed  Google Scholar 

  39. Klok FA, Van Der Bijl N, Eikenboom HC et al (2010) Comparison of CT assessed right ventricular size and cardiac biomarkers for predicting short-term clinical outcome in normotensive patients suspected of having acute pulmonary embolism. J Thromb Haemost 8(4):853–856

    Article  CAS  PubMed  Google Scholar 

  40. Zondag W, Agterof MJ, Schutgens RE et al (2011) Repeated NT-proBNP testing and risk for adverse outcome after acute pulmonary embolism. Thromb Haemost 106(6):1226–1227

    Article  CAS  PubMed  Google Scholar 

  41. Lankeit M, Jimenez D, Kostrubiec M et al (2014) Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism. Eur Respir J 43(6):1669–1677

    Article  CAS  PubMed  Google Scholar 

  42. Jimenes D, Lobo JL, Monreal M et al (2014) PROTECT investigators. Prognostic significance of multidetector CT in normotensive paients with pulmonary embolism: results of the protect study. Thorax 69(2):109–115

    Article  Google Scholar 

  43. Gül E, Can I, Güler I et al (2012) Association of pulmonary artery obstruction index with elevated heart-type fatty acid binding protein and short-term mortality in patients with pulmonary embolism at intermediate risk. Diagn Interv Radiol 18:531–536

    PubMed  Google Scholar 

  44. Boscheri A, Wunderlich C, Langer M et al (2010) Correlation of heart-type fatty acid-binding protein with mortality and echocardiographic data in patients with pulmonary embolism at intermediate risk. Am Heart J 160:294–300

    Article  CAS  PubMed  Google Scholar 

  45. Chen Y, Liu S, Guo W, Wang ZZ (2013) Heart-type fatty acid binding protein for the assessment of the short-term prognosis in acute pulmonary embolism patients with hemodynamic stability on admission. Zhonghua Jie He He Hu Xi Za Zhi. 36:516–521

    PubMed  Google Scholar 

  46. Dellas C, Tschepe M, Seeber V (2014) A novel H-FABP assay and a fast prognostic score for risk assessment of normotensive pulmonary embolism. Thromb Haemost 111:996–1003

    Article  CAS  PubMed  Google Scholar 

  47. Gul EE, Can I, Kayrak M, Abdulhalikov T, Erdogan HI, Altunbas G, Ozdemir K, Gok H (2014) Thrombolysis in patients with pulmonary embolism and elevated heart-type fatty acid-binding protein levels. J Thromb Thrombolysis 37:483–489

    Article  CAS  PubMed  Google Scholar 

  48. Grimes DA, Schulz KF (2005) Refining clinical diagnosis with likelihood ratios. Lancet 365:1500–1505

    Article  PubMed  Google Scholar 

  49. Moses LE, Shapiro D, Littenberg B (1993) Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. Stat Med 12:1293–1316

    Article  CAS  PubMed  Google Scholar 

  50. Stroup DF, Berlin JA, Morton SC et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting: meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA 283:2008–2012

    Article  CAS  PubMed  Google Scholar 

  51. Herbison P, Hay-Smith J, Gillespie WJ (2006) Adjustment of meta-analyses on the basis of quality scores should be abandoned. J Clin Epidemiol 59(12):1249–1256

    Article  PubMed  Google Scholar 

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Conflict of interest

Anurag Bajaj, Parul Rathor, Vishal Sehgal, Besher Kabak, Ajay Shetty, Ossama Al Masalmeh and Srikant Hosur state that there is no conflict of interest involved in this study.

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Authors and Affiliations

  1. The Wright Center for Graduate Medical Education, 501 Madison Avenue, Scranton, PA, 18510, USA

    Anurag Bajaj & Ossama Al Masalmeh

  2. Zhengzhou University, 100 Ke Xue Da Dao, Zhongyuan, Zhengzhou, Henan, China

    Parul Rathor

  3. The Common Wealth Medical College, 525 Pine Street, Scranton, PA, USA

    Vishal Sehgal, Besher Kabak & Ajay Shetty

  4. Critical Care Division, Geisinger Community Medical Center, 1800 Mulberry Street, Scranton, USA

    Srikanth Hosur

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  1. Anurag Bajaj
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  2. Parul Rathor
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Correspondence to Anurag Bajaj.

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Bajaj, A., Rathor, P., Sehgal, V. et al. Prognostic Value of Biomarkers in Acute Non-massive Pulmonary Embolism: A Systematic Review and Meta-analysis. Lung 193, 639–651 (2015). https://doi.org/10.1007/s00408-015-9752-4

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