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

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

• References

• 1 Kahn SR, de Wit K. Pulmonary embolism. N Engl J Med 2022; 387 (01) 45-57
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 17 Saraf A, De Staercke C, Everitt I. et al. Biomarker profile in stable Fontan patients. Int J Cardiol 2020; 305: 56-62
• 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
• 19 Youden WJ. Index for rating diagnostic tests. Cancer 1950; 3 (01) 32-35
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 29 Becattini C, Vedovati MC, Agnelli G. Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. Circulation 2007; 116 (04) 427-433
• 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
• 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