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Thromb Haemost
DOI: 10.1055/s-0044-1786820
Stroke, Systemic or Venous Thromboembolism

Optimizing Use of High-Sensitivity Troponin for Risk-Stratification of Acute Pulmonary Embolism

Sayhaan R. Goraya 
1   University of Michigan Medical School, Ann Arbor, Michigan, United States
,
Connor O'Hare
2   Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, United States
,
Kelsey A. Grace   *
2   Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, United States
,
William J. Schaeffer   **
2   Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, United States
,
S. Nabeel Hyder
3   Division of Cardiovascular Medicine, Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, United States
,
Geoffrey D. Barnes 
1   University of Michigan Medical School, Ann Arbor, Michigan, United States
3   Division of Cardiovascular Medicine, Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, United States
,
Colin F. Greineder
1   University of Michigan Medical School, Ann Arbor, Michigan, United States
2   Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, United States
4   Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, United States
5   BioInterfaces Institute, University of Michigan, Ann Arbor, Michigan, United States
› Author Affiliations Funding Principal Investigator: Colin F. Greineder. National Heart, Lung, and Blood Institute: R01-HL163438, K08-HL130430.
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Abstract

Background High-sensitivity troponin T (HS-TnT) may improve risk-stratification in hemodynamically stable acute pulmonary embolism (PE), but an optimal strategy for combining this biomarker with clinical risk-stratification tools has not been determined.

Study Hypothesis We hypothesized that different HS-TnT cutoff values may be optimal for identifying (1) low-risk patients who may be eligible for outpatient management and (2) patients at increased risk of clinical deterioration who might benefit from advanced PE therapies.

Methods Retrospective analysis of hemodynamically stable patients in the University of Michigan acute ED-PE registry with available HS-TnT values. Primary and secondary outcomes were 30-day mortality and need for intensive care unit-level care. Receiver operating characteristic curves were used to determine optimal HS-TnT cutoffs in the entire cohort, and for those at higher risk based on the simplified Pulmonary Embolism Severity Index (PESI) or imaging findings.

Results The optimal HS-TnT cutoff in the full cohort, 12 pg/mL, was significantly associated with 30-day mortality (odds ratio [OR]: 3.94, 95% confidence interval [CI]: 1.48–10.50) and remained a significant predictor after adjusting for the simplified PESI (sPESI) score and serum creatinine (adjusted OR: 3.05, 95% CI: 1.11–8.38). A HS-TnT cutoff of 87 pg/mL was associated with 30-day mortality (OR: 5.01, 95% CI: 2.08–12.06) in patients with sPESI ≥1 or right ventricular dysfunction.

Conclusion In this retrospective, single-center study of acute PE patients, we identified distinct optimal HS-TnT values for different clinical uses—a lower cutoff, which identified low-risk patients even in the absence of other risk-stratification methods, and a higher cutoff, which was strongly associated with adverse outcomes in patients at increased risk.

Keywords

risk stratification - sPESI - intensive care unit - 30-day mortality - thrombolysis

Authors' Contribution

C.F.G. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis, including and especially any adverse effects. S.N.H., S.G., C.O., K.A.G., W.J.S., S.N.H., G.D.B., and C.F.G. contributed substantially to the study design, data analysis and interpretation, and/or the writing of the manuscript.


* Current affiliation: Department of Emergency Medicine, Trinity Health Ann Arbor Hospital, Ypsilanti, Michigan, United States.


** Current affiliation: Department of Emergency Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.


Supplementary Material



Publication History

Received: 30 January 2024

Accepted: 11 April 2024

Article published online:
24 May 2024

© 2024. Thieme. All rights reserved.

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  • References

  • 1 Kahn SR, de Wit K. Pulmonary embolism. N Engl J Med 2022; 387 (01) 45-57
    CrossrefPubMedGoogle Scholar
  • 2 Maughan BC, Frueh L, McDonagh MS, Casciere B, Kline JA. Outpatient treatment of low-risk pulmonary embolism in the era of direct oral anticoagulants: a systematic review. Acad Emerg Med 2021; 28 (02) 226-239
    CrossrefPubMedGoogle Scholar
  • 3 Aujesky D, Obrosky DS, Stone RA. et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med 2005; 172 (08) 1041-1046
    CrossrefPubMedGoogle Scholar
  • 4 Jiménez D, Aujesky D, Moores L. et al; RIETE Investigators. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med 2010; 170 (15) 1383-1389
    CrossrefPubMedGoogle Scholar
  • 5 Barnes GD, Muzikansky A, Cameron S. et al. Comparison of 4 acute pulmonary embolism mortality risk scores in patients evaluated by pulmonary embolism response teams. JAMA Netw Open 2020; 3 (08) e2010779
    CrossrefPubMedGoogle Scholar
  • 6 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
    CrossrefPubMedGoogle Scholar
  • 7 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
    CrossrefPubMedGoogle Scholar
  • 8 Konstantinides SV, Meyer G, Becattini C. et al; The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). Eur Respir J 2019; 54 (03) 1901647
    CrossrefPubMedGoogle Scholar
  • 9 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
    CrossrefPubMedGoogle Scholar
  • 10 El-Menyar A, Asim M, Nabir S, Ahmed MN, Al-Thani H. Implications of elevated cardiac troponin in patients presenting with acute pulmonary embolism: an observational study. J Thorac Dis 2019; 11 (08) 3302-3314
    CrossrefPubMedGoogle Scholar
  • 11 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
    CrossrefPubMedGoogle Scholar
  • 12 Ebner M, Guddat N, Keller K. et al. High-sensitivity troponin I for risk stratification in normotensive pulmonary embolism. ERJ Open Res 2020; 6 (04) 00625-02020
    CrossrefPubMedGoogle Scholar
  • 13 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Nithianandan H, Reilly A, Tritschler T, Wells P. Applying rigorous eligibility criteria to studies evaluating prognostic utility of serum biomarkers in pulmonary embolism: a systematic review and meta-analysis. Thromb Res 2020; 195: 195-208
    CrossrefPubMedGoogle Scholar
  • 15 Ardeshna NS, Song M, Hyder SN. et al. Effect of pulmonary embolism response team on advanced therapies administered: The University of Michigan experience. Thromb Res 2023; 221: 73-78
    CrossrefPubMedGoogle Scholar
  • 16 O'Hare C, Grace KA, Schaeffer WJ. et al. Adverse clinical outcomes among patients with acute low-risk pulmonary embolism and concerning computed tomography imaging findings. JAMA Netw Open 2023; 6 (05) e2311455
    CrossrefPubMedGoogle Scholar
  • 17 Saraf A, De Staercke C, Everitt I. et al. Biomarker profile in stable Fontan patients. Int J Cardiol 2020; 305: 56-62
    CrossrefPubMedGoogle Scholar
  • 18 Gunnerson KJ, Bassin BS, Havey RA. et al. Association of an emergency department-based intensive care unit with survival and inpatient intensive care unit admissions. JAMA Netw Open 2019; 2 (07) e197584-e197584
    CrossrefPubMedGoogle Scholar
  • 19 Youden WJ. Index for rating diagnostic tests. Cancer 1950; 3 (01) 32-35
    CrossrefPubMedGoogle Scholar
  • 20 Thygesen K, Alpert JS, Jaffe AS. et al; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth universal definition of myocardial infarction (2018). Circulation 2018; 138 (20) e618-e651
    CrossrefPubMedGoogle Scholar
  • 21 Sandoval Y, Smith SW, Schulz K, Sexter A, Apple FS. Rapid identification of patients at high risk for acute myocardial infarction using a single high-sensitivity cardiac troponin I measurement. Clin Chem 2020; 66 (04) 620-622
    CrossrefPubMedGoogle Scholar
  • 22 Boeddinghaus J, Reichlin T, Cullen L. et al. Two-hour algorithm for triage toward rule-out and rule-in of acute myocardial infarction by use of high-sensitivity cardiac troponin I. Clin Chem 2016; 62 (03) 494-504
    CrossrefPubMedGoogle Scholar
  • 23 Twerenbold R, Neumann JT, Sörensen NA. et al. Prospective validation of the 0/1-h algorithm for early diagnosis of myocardial infarction. J Am Coll Cardiol 2018; 72 (06) 620-632
    CrossrefPubMedGoogle Scholar
  • 24 Collet JP, Thiele H, Barbato E. et al; ESC Scientific Document Group. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2021; 42 (14) 1289-1367
    CrossrefPubMedGoogle Scholar
  • 25 Wereski R, Kimenai DM, Taggart C. et al. Cardiac troponin thresholds and kinetics to differentiate myocardial injury and myocardial infarction. Circulation 2021; 144 (07) 528-538
    CrossrefPubMedGoogle Scholar
  • 26 Sandoval Y, Apple FS, Mahler SA, Body R, Collinson PO, Jaffe AS. International Federation of Clinical Chemistry and Laboratory Medicine Committee on the Clinical Application of Cardiac Biomarkers. High-sensitivity cardiac troponin and the 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR guidelines for the evaluation and diagnosis of acute chest pain. Circulation 2022; 146 (07) 569-581
    CrossrefPubMedGoogle Scholar
  • 27 Musey Jr PI, Bellolio F, Upadhye S. et al. Guidelines for reasonable and appropriate care in the emergency department (GRACE): recurrent, low-risk chest pain in the emergency department. Acad Emerg Med 2021; 28 (07) 718-744
    CrossrefPubMedGoogle Scholar
  • 28 Tomaszewski CA, Nestler D, Shah KH, Sudhir A, Brown MD. American College of Emergency Physicians Clinical Policies Subcommittee (Writing Committee) on Suspected Non–ST-Elevation Acute Coronary Syndromes. Clinical policy: critical issues in the evaluation and management of emergency department patients with suspected non-ST-elevation acute coronary syndromes. Ann Emerg Med 2018; 72 (05) e65-e106
    CrossrefPubMedGoogle Scholar
  • 29 Becattini C, Vedovati MC, Agnelli G. Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. Circulation 2007; 116 (04) 427-433
    CrossrefPubMedGoogle Scholar
  • 30 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
    CrossrefPubMedGoogle Scholar
  • 31 Bajaj A, Saleeb M, Rathor P, Sehgal V, Kabak B, Hosur S. Prognostic value of troponins in acute nonmassive pulmonary embolism: a meta-analysis. Heart Lung 2015; 44 (04) 327-334
    CrossrefPubMedGoogle Scholar