Troponin-Based Risk Stratification of Patients With Acute Nonmassive Pulmonary Embolism: Systematic Review and Metaanalysis

doi:10.1378/chest.09-0608

Chest

Volume 136, Issue 4, October 2009, Pages 974-982

https://doi.org/10.1378/chest.09-0608 Get rights and content

Background

Controversy exists regarding the usefulness of troponin testing for the risk stratification of patients with acute pulmonary embolism (PE). We conducted an updated systematic review and a metaanalysis of troponin-based risk stratification of normotensive patients with acute symptomatic PE. The sources of our data were publications listed in Medline and Embase from 1980 through April 2008 and a review of cited references in those publications.

Methods

We included all studies that estimated the relation between troponin levels and the incidence of all-cause mortality in normotensive patients with acute symptomatic PE. Two reviewers independently abstracted data and assessed study quality. From the literature search, 596 publications were screened. Nine studies that consisted of 1,366 normotensive patients with acute symptomatic PE were deemed eligible. Pooled results showed that elevated troponin levels were associated with a 4.26-fold increased odds of overall mortality (95% CI, 2.13 to 8.50; heterogeneity χ² = 12.64; degrees of freedom = 8; p = 0.125). Summary receiver operating characteristic curve analysis showed a relationship between the sensitivity and specificity of troponin levels to predict overall mortality (Spearman rank correlation coefficient = 0.68; p = 0.046). Pooled likelihood ratios (LRs) were not extreme (negative LR, 0.59 [95% CI, 0.39 to 0.88]; positive LR, 2.26 [95% CI, 1.66 to 3.07]). The Begg rank correlation method did not detect evidence of publication bias.

Conclusions

The results of this metaanalysis indicate that elevated troponin levels do not adequately discern normotensive patients with acute symptomatic PE who are at high risk for death from those who are at low risk for death.

Section snippets

Study Eligibility

All studies of patients with PE were considered eligible for the metaanalysis if they fulfilled the following criteria: original publication; inclusion of normotensive patients with an objectively confirmed diagnosis of acute symptomatic PE; measurement of cardiac-specific troponin levels (cardiac troponin T [cTnT] or cardiac troponin I [cTnI]) in nanograms per milliliter, or the reporting of proportions of patients in different categories surrounding a predefined cut point for elevation

Description of Studies

Of the 596 articles screened, 28 appeared potentially eligible and were reviewed in depth.4, 5, 6, 7, 10, 11, 12, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 Nineteen studies were deemed ineligible4, 5, 6, 7, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 (Fig 1), and 9 studies met the eligibility criteria.10, 11, 12, 36, 37, 38, 39, 40, 41 Agreement between the two reviewers for study eligibility was very high (κ = 0.9).

The year of publication

Acknowledgments

Author contributions: Drs. Jiménez, Uresandi, Otero, Lobo, Monreal, Martí, and Yusen contributed to the study concept and design. Drs. Jiménez, Zamora, Muriel, Monreal, Aujesky, and Yusen contributed to the acquisition of data, analysis and interpretation of data, and statistical analysis. Drs. Jiménez, Martí, Monreal, and Yusen contributed to the drafting of the manuscript. Drs. Jiménez, Uresandi, Monreal, Aujesky, and Yusen contributed to the critical revision of the manuscript for important

References (0)

Cited by (177)

Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report
2021, Chest
This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously.
We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology.
The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update.
New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations.
Mechanical Thrombectomy in Pulmonary Embolism: Ready for Prime Time?
2021, JACC: Cardiovascular Interventions
The PERT Concept: A Step-by-Step Approach to Managing Pulmonary Embolism
2021, Chest
Pulmonary embolism (PE) is a major source of morbidity and mortality. The presentation of acute PE varies, ranging from few or no symptoms to sudden death. Patient outcome depends on how well the right ventricle can sustain the increased afterload caused by the embolic burden. Careful risk stratification is critical, and the PE response team (PERT) concept offers a rapid and multidisciplinary approach. Anticoagulation is essential unless contraindicated; thrombolysis, surgical embolectomy, and catheter-directed approaches are also available. Clinical consensus statements have been published that offer a guide to PE management, but areas remain for which the evidence is inadequate. Although the management of low-risk and high-risk patients is more straightforward, optimal management of intermediate-risk patients remains controversial. In this document, we offer a case-based approach to PE management, beginning with diagnosis and risk stratification, followed by therapeutic alternatives, and finishing with follow-up care.
An emergency medicine approach to troponin elevation due to causes other than occlusion myocardial infarction
2020, American Journal of Emergency Medicine
Troponin is an integral component of the evaluation for acute coronary syndrome (ACS) and occlusion myocardial infarction (OMI). However, troponin may be elevated in conditions other than OMI.
This narrative review provides emergency clinicians with a focused evaluation of troponin elevation in patients with myocardial injury due to conditions other than OMI.
ACS includes the diagnosis of myocardial infarction (MI), which incorporates assessment for elevated troponin. Troponin I and T are the most common biomarkers used in assessment of myocardial injury and may be released with myocyte injury and necrosis, myocyte apoptosis and cell turnover, and oxygen supply demand mismatch. Troponin elevation is a reflection of myocardial injury, and many conditions associated with critical illness may result in troponin elevation. These include cardiac and non-cardiac conditions. Cardiac conditions include heart failure, dysrhythmia, and dissection, while non-cardiac causes include pulmonary embolism, sepsis, stroke, and many others. Clinicians should consider the clinical context, patient symptoms, electrocardiogram, and ultrasound in their assessment of the patient with troponin elevation. In most cases, elevated troponin is a marker for poor outcomes including increased rates of mortality.
Troponin can be elevated in many critical settings. The causes of troponin elevation include cardiac and non-cardiac conditions. Clinicians must consider the clinical context and other factors, as an inappropriate diagnosis of OMI may result in patient harm and misdiagnosis of another condition.
Percutaneous Interventions for Acute Pulmonary Embolism
2020, Image-Guided Interventions: Expert Radiology Series, Third Edition
Elevated serum cardiac troponin and mortality in acute pulmonary embolism: Systematic review and meta-analysis
2019, Respiratory Medicine
To evaluate whether elevated levels of cardiac troponin increases the risk of mortality in patients with acute PE.
We conducted a systematic review and meta-analysis with rigorous statistical evaluation using publications (2000–2018) from Cochrane Library, MEDLINE, PubMed, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform, and Google Scholar databases. We searched for retrospective, prospective, and randomized controlled trials (RCT) or quasi-RCT studies that assessed the effect of elevated troponin versus normal levels on the outcomes of PE. The main outcome of interest was all-cause mortality. Extracted data included authors, the origin of studies, source population, study settings and duration, inclusion/exclusion criteria, data sources and measurement, sample size, and mortality. Data heterogeneity was assessed using the Cochrane Q homogeneity test with a significance set at p < 0.10. If the studies were statistically homogeneous, a fixed effect model was selected.
Out of 1825 references, 46 analytical studies were included with a total of 10842 patients with PE. The effect of elevated troponin on mortality had a pooled odd ratio (OR) of 4.33 for all studies, 3.7for HsTnT, 14.81 for HsTnI, 7.85 for cTnT, 2.81 for cTnI, 9.02 for low-risk PE and 4.80 for 90-day mortality. The pooled negative likelihood ratios for all-cause mortality using HsTnI, cTnI and cTnT assay were 0.21, 0.33 and 0.65, respectively.
Regardless of the troponin assay, pooled analysis indicates that elevated troponin is significantly associated with higher mortality in patients with PE.

View all citing articles on Scopus

: Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).

View full text