Semin Thromb Hemost 2019; 45(08): 784-792
DOI: 10.1055/s-0039-1698762
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Measurement of High-Sensitivity Cardiac Troponin in Pulmonary Embolism: Useful Test or a Clinical Distraction

Giuseppe Lippi
1   Section of Clinical Biochemistry, University of Verona, Verona, Italy
,
Emmanuel J. Favaloro
2   Department of Haematology, Sydney Centres for Thrombosis and Haemostasis, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, Australia
,
Peter Kavsak
3   Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
› Author Affiliations
Further Information

Publication History

Publication Date:
17 October 2019 (online)

Abstract

The ability to predict death or other unfavorable outcomes after an acute pulmonary embolism (PE) is challenging, with current available risk score models having relatively unsatisfactory prognostic performance in this area. For example, the simplified pulmonary embolism severity index (sPESI), the most frequently used stratification tool, misclassifies a significant percentage of low- and high-risk patients. This gap in care, along with the increasing clinical availability of high-sensitivity cardiac troponin (hs-cTn) laboratory tests and the recent emphasis on detecting myocardial injury, may foster further evaluation of hs-cTn testing in patients with acute PE. Our analysis of the current scientific literature on hs-cTn in patients with acute PE identified that hs-cTn testing may provide valuable information for predicting future adverse outcomes and mortality, independently from baseline clinical risk assessment. Although the risk of an adverse event is indeed higher in patients with higher sPESI scores, cTns retain their prognostic value also in those at low risk, suggesting that a combination of hs-cTn with sPESI may provide an incremental value over assessment of either variable alone. Accordingly, the future development of updated risk stratification models, with the inclusion of laboratory tests such as hs-cTn, may represent an enhanced approach for risk stratification in patients with acute PE. Additional research, however, is needed to verify whether the combination of cTns, specifically as measured with hs-cTn assays, with other biomarkers may further improve the current capacity to efficiently manage patients with acute PE.

 
  • References

  • 1 Reichlin T, Hochholzer W, Bassetti S. , et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med 2009; 361 (09) 858-867
  • 2 Kavsak PA, MacRae AR, Yerna MJ, Jaffe AS. Analytic and clinical utility of a next-generation, highly sensitive cardiac troponin I assay for early detection of myocardial injury. Clin Chem 2009; 55 (03) 573-577
  • 3 Kavsak PA. Editorial commentary: high-sensitivity cardiac troponin: like every new tool there is a learning curve. Trends Cardiovasc Med 2017; 27 (01) 48-50
  • 4 Kavsak PA, Worster A, Hill SA, MacRae AR, Jaffe AS. Analytical comparison of three different versions of a high-sensitivity cardiac troponin I assay over 10years. Clin Chim Acta 2017; 475: 51-55
  • 5 Thygesen K, Alpert JS, Jaffe AS. , et al; ESC Scientific Document Group. Fourth universal definition of myocardial infarction (2018). Eur Heart J 2019; 40 (03) 237-269
  • 6 Wu AHB, Christenson RH, Greene DN. , et al. Clinical laboratory practice recommendations for the use of cardiac troponin in acute coronary syndrome: expert opinion from the Academy of the American Association for Clinical Chemistry and the Task Force on Clinical Applications of Cardiac Bio-Markers of the International Federation of Clinical Chemistry and Laboratory Medicine. Clin Chem 2018; 64 (04) 645-655
  • 7 Lippi G, Cervellin G. Clinical interpretation of high-sensitivity troponin testing. JAMA Intern Med 2019; 179 (05) 725-726
  • 8 van der Linden N, Klinkenberg LJ, Bekers O. , et al. Prognostic value of basal high-sensitive cardiac troponin levels on mortality in the general population: a meta-analysis. Medicine (Baltimore) 2016; 95 (52) e5703
  • 9 Fan Y, Jiang M, Gong D, Man C, Chen Y. Cardiac troponin for predicting all-cause mortality in patients with acute ischemic stroke: a meta-analysis. Biosci Rep 2018; 38 (02) DOI: 10.1042/BSR20171178.
  • 10 Fan Y, Zhao X, Li X, Li N, Hu X. Cardiac troponin and adverse outcomes in atrial fibrillation: a meta-analysis. Clin Chim Acta 2018; 477: 48-52
  • 11 Pavasini R, d'Ascenzo F, Campo G. , et al. Cardiac troponin elevation predicts all-cause mortality in patients with acute exacerbation of chronic obstructive pulmonary disease: systematic review and meta-analysis. Int J Cardiol 2015; 191: 187-193
  • 12 Benjamin EJ, Muntner P, Alonso A. , et al; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation 2019; 139 (10) e56-e528
  • 13 Morillo R, Moores L, Jiménez D. Prognostic scores for acute pulmonary embolism. Semin Thromb Hemost 2017; 43 (05) 486-492
  • 14 Gadre A, Deshwal H, Mahar J. , et al. Predictive scoring for severity of acute pulmonary embolism: does timing matter?. Semin Thromb Hemost 2018; 44 (04) 397-399
  • 15 Konstantinides SV, Torbicki A, Agnelli G. , et al; Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2014; 35 (43) 3033-3069 , 3069a–3069k
  • 16 Becattini C, Vedovati MC, Agnelli G. Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. Circulation 2007; 116 (04) 427-433
  • 17 Meyer G, Vicaut E, Danays T. , et al; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med 2014; 370 (15) 1402-1411
  • 18 Latini R, Masson S, Anand IS. , et al; Val-HeFT Investigators. Prognostic value of very low plasma concentrations of troponin T in patients with stable chronic heart failure. Circulation 2007; 116 (11) 1242-1249
  • 19 Kavsak PA, Beattie J, Pickersgill R, Ford L, Caruso N, Clark L. A practical approach for the validation and clinical implementation of a high-sensitivity cardiac troponin I assay across a North American city. Pract Lab Med 2015; 1: 28-34
  • 20 Kavsak PA, Andruchow JE, McRae AD, Worster A. Profile of Roche's Elecsys Troponin T Gen 5 STAT blood test (a high-sensitivity cardiac troponin assay) for diagnosing myocardial infarction in the emergency department. Expert Rev Mol Diagn 2018; 18 (06) 481-489
  • 21 Kavsak PA, Malinowski P, Roy C, Clark L, Lamers S. Assessing matrix, interferences and comparability between the Abbott Diagnostics and the Beckman Coulter high-sensitivity cardiac troponin I assays. Clin Chem Lab Med 2018; 56 (07) 1176-1181
  • 22 Becattini C, Agnelli G, Lankeit M. , et al. Acute pulmonary embolism: mortality prediction by the 2014 European Society of Cardiology risk stratification model. Eur Respir J 2016; 48 (03) 780-786
  • 23 Becattini C, Vedovati MC, Pruszczyk P. , et al. Oxygen saturation or respiratory rate to improve risk stratification in hemodynamically stable patients with acute pulmonary embolism. J Thromb Haemost 2018; 16 (12) 2397-2402
  • 24 Jen WY, Jeon YS, Kojodjojo P. , et al. A new model for risk stratification of patients with acute pulmonary embolism. Clin Appl Thromb Hemost 2018; DOI: 10.1177/1076029618808922. [Epub ahead of print]
  • 25 Vinson DR, Ballard DW, Mark DG. , et al; MAPLE investigators of the KP CREST Network. Risk stratifying emergency department patients with acute pulmonary embolism: Does the simplified Pulmonary Embolism Severity Index perform as well as the original?. Thromb Res 2016; 148: 1-8
  • 26 Zhang S, Zhai Z, Yang Y. , et al. Pulmonary embolism risk stratification by European Society of Cardiology is associated with recurrent venous thromboembolism: findings from a long-term follow-up study. Int J Cardiol 2016; 202: 275-281
  • 27 Roy PM, Corsi DJ, Carrier M. , et al. Net clinical benefit of hospitalization versus outpatient management of patients with acute pulmonary embolism. J Thromb Haemost 2017; 15 (04) 685-694
  • 28 Elias A, Mallett S, Daoud-Elias M, Poggi JN, Clarke M. Prognostic models in acute pulmonary embolism: a systematic review and meta-analysis. BMJ Open 2016; 6 (04) e010324
  • 29 Lankeit M, Friesen D, Aschoff J. , et al. Highly sensitive troponin T assay in normotensive patients with acute pulmonary embolism. Eur Heart J 2010; 31 (15) 1836-1844
  • 30 Lankeit M, Jiménez D, Kostrubiec M. , et al. 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 2011; 124 (24) 2716-2724
  • 31 Spirk D, Aujesky D, Husmann M. , et al. Cardiac troponin testing and the simplified Pulmonary Embolism Severity Index. The SWIss Venous ThromboEmbolism Registry (SWIVTER). Thromb Haemost 2011; 106 (05) 978-984
  • 32 Hogg K, Haslam S, Hinchliffe E, Sellar L, Lecky F, Cruickshank K. Does high-sensitivity troponin measurement aid in the diagnosis of pulmonary embolism?. J Thromb Haemost 2011; 9 (02) 410-412
  • 33 Ozsu S, Abul Y, Orem A. , et al. Predictive value of troponins and simplified pulmonary embolism severity index in patients with normotensive pulmonary embolism. Multidiscip Respir Med 2013; 8 (01) 34
  • 34 Apfaltrer P, Walter T, Gruettner J. , et al. Prediction of adverse clinical outcome in patients with acute pulmonary embolism: evaluation of high-sensitivity troponin I and quantitative CT parameters. Eur J Radiol 2013; 82 (03) 563-567
  • 35 Walter T, Apfaltrer P, Weilbacher F. , et al. Predictive value of high-sensitivity troponin I and D-dimer assays for adverse outcome in patients with acute pulmonary embolism. Exp Ther Med 2013; 5 (02) 586-590
  • 36 Kaeberich A, Seeber V, Jiménez D. , et al. Age-adjusted high-sensitivity troponin T cut-off value for risk stratification of pulmonary embolism. Eur Respir J 2015; 45 (05) 1323-1331
  • 37 Vuilleumier N, Limacher A, Méan M. , et al. Cardiac biomarkers and clinical scores for risk stratification in elderly patients with non-high-risk pulmonary embolism. J Intern Med 2015; 277 (06) 707-716
  • 38 Hobohm L, Hellenkamp K, Hasenfuß G, Münzel T, Konstantinides S, Lankeit M. Comparison of risk assessment strategies for not-high-risk pulmonary embolism. Eur Respir J 2016; 47 (04) 1170-1178
  • 39 Faller N, Limacher A, Méan M. , et al. Predictors and causes of long-term mortality in elderly patients with acute venous thromboembolism: a prospective cohort study. Am J Med 2017; 130 (02) 198-206
  • 40 Kartal M, Unal A, Goksu E, Yilmaz D, Gungor F. Outpatient treatment of pulmonary embolism: sPESI score and highly sensitive troponin may prove helpful. Hong Kong J Emerg Med 2017; 24: 132-137
  • 41 Kozlowska M, Plywaczewska M, Koc M. , et al. D-Dimer assessment improves the Simplified Pulmonary Embolism Severity Index for in-hospital risk stratification in acute pulmonary embolism. Clin Appl Thromb Hemost 2018; 24 (08) 1340-1346
  • 42 Xi X. Predictive value of the high-sensitivity troponin I assay in patients with acute pulmonary embolism. Chest 2016; 149 (4, Suppl): A525
  • 43 Kriechbaum SD, Wiedenroth CB, Keller T. , et al. Dynamics of high-sensitivity cardiac troponin T during therapy with balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension. PLoS One 2018; 13 (09) e0204683
  • 44 Filusch A, Giannitsis E, Katus HA, Meyer FJ. High-sensitive troponin T: a novel biomarker for prognosis and disease severity in patients with pulmonary arterial hypertension. Clin Sci (Lond) 2010; 119 (05) 207-213
  • 45 Daquarti G, March Vecchio N, Mitrione CS. , et al. High-sensitivity troponin and right ventricular function in acute pulmonary embolism. Am J Emerg Med 2016; 34 (08) 1579-1582
  • 46 Granér M, Harjola VP, Selander T. , et al. N-terminal pro-brain natriuretic peptide, high-sensitivity troponin and pulmonary artery clot score as predictors of right ventricular dysfunction in echocardiography. Heart Lung Circ 2016; 25 (06) 592-599
  • 47 Folsom AR, Lutsey PL, Nambi V. , et al. Troponin T, NT-proBNP, and venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE). Vasc Med 2014; 19 (01) 33-41
  • 48 Konstam MA, Kiernan MS, Bernstein D. , et al; American Heart Association Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; and Council on Cardiovascular Surgery and Anesthesia. Evaluation and management of right-sided heart failure: a scientific statement from the American Heart Association. Circulation 2018; 137 (20) e578-e622
  • 49 Kostrubiec M, Jankowski K, Pedowska-Włoszek J. , et al. Signs of myocardial ischemia on electrocardiogram correlate with elevated plasma cardiac troponin and right ventricular systolic dysfunction in acute pulmonary embolism. Cardiol J 2010; 17 (02) 157-162
  • 50 Müller-Bardorff M, Weidtmann B, Giannitsis E, Kurowski V, Katus HA. Release kinetics of cardiac troponin T in survivors of confirmed severe pulmonary embolism. Clin Chem 2002; 48 (04) 673-675
  • 51 Liedl G, Nazerian P, Pepe G, Caviglioli C, Grifoni S, Vanni S. Different time course of plasma lactate, troponin I and Nt-proBNP concentrations in patients with acute pulmonary embolism. Thromb Res 2017; 156: 26-28
  • 52 Daubert MA, Jeremias A. The utility of troponin measurement to detect myocardial infarction: review of the current findings. Vasc Health Risk Manag 2010; 6: 691-699
  • 53 Morrone D, Morrone V. Acute pulmonary embolism: focus on the clinical picture. Korean Circ J 2018; 48 (05) 365-381
  • 54 Harjola VP, Mebazaa A, Čelutkienė J. , et al. Contemporary management of acute right ventricular failure: a statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology. Eur J Heart Fail 2016; 18 (03) 226-241
  • 55 Barco S, Mahmoudpour SH, Planquette B, Sanchez O, Konstantinides SV, Meyer G. Prognostic value of right ventricular dysfunction or elevated cardiac biomarkers in patients with low-risk pulmonary embolism: a systematic review and meta-analysis. Eur Heart J 2019; 40 (11) 902-910
  • 56 Windecker S, Stortecky S, Meier B. Paradoxical embolism. J Am Coll Cardiol 2014; 64 (04) 403-415
  • 57 Costabel JP, Urdapilleta M, Lambardi F. , et al. High-sensitivity cardiac troponin levels in supraventricular tachyarrhythmias. Pacing Clin Electrophysiol 2016; 39 (06) 588-591
  • 58 Burchfield JS, Xie M, Hill JA. Pathological ventricular remodeling: mechanisms: part 1 of 2. Circulation 2013; 128 (04) 388-400
  • 59 Giannitsis E, Katus HA. Biomarkers for clinical decision-making in the management of pulmonary embolism. Clin Chem 2017; 63 (01) 91-100
  • 60 Kavsak PA, Neumann JT, Cullen L. , et al. Clinical chemistry score versus high-sensitivity cardiac troponin I and T tests alone to identify patients at low or high risk for myocardial infarction or death at presentation to the emergency department. CMAJ 2018; 190 (33) E974-E984
  • 61 Koerbin G, Abhayaratna WP, Potter JM. , et al. Effect of population selection on 99th percentile values for a high sensitivity cardiac troponin I and T assays. Clin Biochem 2013; 46 (16–17): 1636-1643
  • 62 Gunsolus IL, Jaffe AS, Sexter A. , et al. Sex-specific 99th percentiles derived from the AACC Universal Sample Bank for the Roche Gen 5 cTnT assay: comorbidities and statistical methods influence derivation of reference limits. Clin Biochem 2017; 50 (18) 1073-1077
  • 63 Kavsak PA, Allen LC, Apple FS. , et al. Cardiac troponin testing in the acute care setting: ordering, reporting, and high sensitivity assays--an update from the Canadian Society of Clinical Chemists (CSCC). Clin Biochem 2011; 44 (16) 1273-1277
  • 64 Gore MO, Seliger SL, Defilippi CR. , et al. Age- and sex-dependent upper reference limits for the high-sensitivity cardiac troponin T assay. J Am Coll Cardiol 2014; 63 (14) 1441-1448
  • 65 Welsh P, Preiss D, Shah ASV. , et al. Comparison between high-sensitivity cardiac troponin T and cardiac troponin I in a large general population cohort. Clin Chem 2018; 64 (11) 1607-1616
  • 66 Hickman PE, Abhayaratna WP, Potter JM, Koerbin G. Age-related differences in hs-cTnI concentration in healthy adults. Clin Biochem 2019; 69: 26-29
  • 67 Aggarwal V, Nicolais CD, Lee A. , et al. Acute management of pulmonary embolism. Available at: https://www.acc.org/latest-in-cardiology/articles/2017/10/23/12/12/acute-management-of-pulmonary-embolism . Accessed June 21, 2019
  • 68 Lippi G, Plebani M. Understanding cardiac troponin biology: all other cardiac biomarkers shall rest in peace?. J Lab Precis Med 2019; 4: 9
  • 69 Kavsak PA, Ainsworth C, Arnold DM. , et al. The potential role of a turbidimetric heart-type fatty acid-binding protein assay to aid in the interpretation of persistently elevated, non-changing, cardiac troponin I concentrations. Clin Biochem 2018; 58: 53-59
  • 70 Dellas C, Tschepe M, Seeber V. , et al. A novel H-FABP assay and a fast prognostic score for risk assessment of normotensive pulmonary embolism. Thromb Haemost 2014; 111 (05) 996-1003
  • 71 Qian HY, Huang J, Yang YJ, Yang YM, Li ZZ, Zhang JM. Heart-type fatty acid binding protein in the assessment of acute pulmonary embolism. Am J Med Sci 2016; 352 (06) 557-562
  • 72 Dellas C, Lobo JL, Rivas A. , et al. Risk stratification of acute pulmonary embolism based on clinical parameters, H-FABP and multidetector CT. Int J Cardiol 2018; 265: 223-228