Care of Patients With Pulmonary DisordersPrognostic value of troponins in acute nonmassive pulmonary embolism: A meta-analysis
Introduction
Acute pulmonary embolism (PE) is the third leading cause of cardiovascular death.1 Acute PE has a wide spectrum of clinical manifestations and prognosis. The clinical presentation of acute PE varies from sudden death to cardiogenic shock to asymptomatic. Mortality attributable to PE ranges from 9% in patients who are hemodynamically unstable at the time of presentation to about 3% in patients who are stable in current era.2 So far, guidelines exist for treating hemodynamically unstable patients with thrombolytics because of high risk for short term mortality; however, we are still lacking in a prognostic strategy which can identify a subgroup of patients who are hemodynamically stable but at risk for poor outcomes.3 Risk stratification at the time of admission is important for the appropriate management of patients with acute PE. On one side of the spectrum are the patients who are normotensive at the time of admission and very low risk for death, who could be managed as an outpatient with newer anticoagulants. On the other side of the spectrum are the patients who are at risk for poor outcomes and need close monitoring and may benefit from more aggressive treatment like thrombolytics. Optimal management of these patients can lead to decrease health care cost and increased patient satisfaction.4 Patients who are hemodynamically stable at the time of admission, but manifest right ventricular dysfunction (RVD) have a poor prognosis when compared to patients without RVD.5, 6 Various clinical, imaging and serum biomarkers have been evaluated to identify a subgroup of patients who have RVD and are at high risk for poor outcomes. Echocardiogram is a useful tool in risk stratification in acute PE by diagnosing RVD; however, it is not available round the clock in all institutions. Also, the prognostic value of echocardiogram for RVD in predicting short term mortality is too low to be useful in clinical practice.7 Several serum biomarkers such as troponin, Brain Natriuretic peptide (BNP) or N terminal pro-BNP (NT-pro BNP), Heart-type fatty acid binding protein (H-FABP) has also been evaluated to identify patients with poor outcomes but the best prognostic tool is still unknown to date.8, 9, 10, 11 Previous meta-analysis on the use of troponin in patients with acute PE included few studies with small patient population size and the results were unsatisfactory for clinical usefulness in risk stratification.8 We aimed to update the meta-analysis by adding seventeen more studies with larger patient population to further clarify whether elevated cardiac troponin levels are useful in clinical decision making.
Section snippets
Study objectives
The primary objective of this meta-analysis was to update the evidence whether elevated troponin levels (T or I) are useful in predicting short term (in-hospital or 30 day) all cause mortality in normotensive patients with acute PE. The secondary objectives were to assess whether elevated troponin levels are useful in predicting short term mortality (in-hospital or 30 day) resulting from PE and serious adverse events.
Data source and searches
A systematic search of Medline, EMBASE and Cochrane Database were performed.
Results
Overall, 2560 articles were found until December 2014. Out of 2560 articles screened, only 26 studies fulfilled the eligibility criteria and included in our analysis.12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37 21 studies included patients with hypotension or hemodynamic instability at the time of admission and excluded from our analysis. Review articles, editorials, duplicates and abstracts were excluded. There were 6 studies which
All cause mortality
Twenty three studies reported all cause mortality data (Fig. 2). The overall mortality rate in acute PE was 5.7%. 274 of 2596 patients with elevated troponin levels and 143 out of 4707 with normal troponin levels died (10.5% versus 3.1%). Elevated troponin (T or I) levels were significantly associated with higher risk of death as compared to normal troponin levels (OR, 4.80; 95% CI, 3.25–7.08, I2 = 54%). Excluding three retrospective studies revealed the same results (OR, 4.69; 95% CI,
Discussion
Our meta-analysis shows that elevated troponin levels are associated with a fivefold increased risk for all cause short term mortality and about fourfold increased risk for serious adverse events. Our results are in agreement with the previous review of Jimenez et al. Our meta-analysis included total of 26 studies (with 23 studies reported primary end point) as compared to 9 studies in the previous review. All the studies included in our review resulted in similar findings. Even though elevated
Strengths
Studies were extensively searched independently by two authors and clarified by a third author for methods and outcomes. Authors were contacted to get the missing data to complete the analysis. Studies were extensively screened and duplicated and partially duplicated cohorts were removed after contacting the authors. Random-effect models were used for wider confidence interval and between study and within study variation. The likelihood ratios, which best describes the discriminatory power of
Limitations
The major limitation of our study is that our pooled analyses were not adjusted for confounding variables such as age, gender etc. The second limitation is that the threshold for abnormal values of troponin and assay differed across studies. Third, there was some heterogeneity in the OR of primary end point results which could have weakened the conclusion of our analysis somewhat.
Conclusion
Elevated levels of troponin identify subgroups of patients with increased risk for short term mortality and serious adverse events; however, the results are not satisfactory enough to make any change in current clinical practice. hs-cTnT may be a useful biomarker in conjunction with clinical tools in helping clinicians decide to recommend outpatient management and that will substantially reduce health care cost. More data is needed to define the role of hs-cTnT in acute PE.
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Cited by (0)
Name of Institute where Study was performed: The Wright Center for Graduate Medical Education, 501 Madison Avenue, Scranton, PA 18505, USA.
Financial support: There was no financial support provided by any institution for this study.
Conflict of interest: No conflict of interest.