Cardiac Troponins in Low-Risk Pulmonary Embolism Patients: A Systematic Review and Meta-Analysis
BACKGROUND: Patients with low-risk pulmonary embolism (PE) should be considered as per current scoring systems for ambulatory treatment. However, there is uncertainty whether patients with low scores and positive troponins should require hospitalization.
METHODS: We searched MEDLINE, SCOPUS, and Cochrane Library databases from inception to December 2016 and collected longitudinal studies that evaluated the prognostic value of troponins in patients with low-risk PE. The primary outcome measure was 30-day all-cause mortality. We calculated odds ratio (OR), likelihood ratios (LRs), and 95% confidence intervals (CI) by using random-effects models.
RESULTS: The literature search identified 117 candidate articles, of which 16 met the criteria for review. Based on pulmonary embolism severity index (PESI) or simplified PESI score, 1.2% was the all-cause mortality rate across 2,662 participants identified as low-risk. A positive troponin status in patients with low-risk PE was associated with an increased risk of 30-day all-cause mortality (odds ratio [OR]: 4.79; 95% confidence interval [CI]: 1.11 to 20.68). The pooled likelihood ratios (LRs) for all-cause mortality were positive LR 2.04 (95% CI, 1.53 to 2.72) and negative LR 0.72 (95% CI, 0.37 to 1.40).
CONCLUSION: The use of positive troponin status as a predictor of increased mortality in low-risk PE patients exhibited relatively poor performance given the crossed negative LR CI (1.0) and modest positive LR. Larger prospective trials must be conducted to elucidate if patients with low-risk PE and positive troponin status can avoid hospitalization.
© 2018 Society of Hospital Medicine
Hospital stays for pulmonary embolism (PE) represent a significant cost burden to the United States healthcare system.1 The mean total hospitalization costs for treating a patient with PE ranges widely from $8,764 to $37,006, with an average reported length of stay between 4 and 5 days.2,3 This cost range is attributed to many factors, including type of PE, therapy-induced bleeding risk requiring close monitoring, comorbidities, and social determinants of health. Given that patients with low-risk PE represent the majority of the cases, changes in approaches to care for this population can significantly impact the overall healthcare costs for PE. The European Society of Cardiology (ESC) guidelines incorporate well-validated risk scores, known as the pulmonary embolism severity index (PESI) and the simplified PESI (sPESI) score, and diagnostic test recommendations, including troponin test, echocardiography, and computed tomography, to evaluate patients with PE at varying risk for mortality.4 In these guidelines, the risk stratification algorithm for patients with a low PESI score or a sPESI score of zero does not include checking for the presence of troponin. In reality, practicing hospitalists frequently find that patients receiving a workup in the emergency department for suspected PE undergo troponin test. The ESC guidelines categorize patients with a low-risk score on PESI/sPESI, who subsequently have a positive troponin status, as intermediate low-risk and suggest consideration of hospitalization. The guidelines recommend patients with positive cardiac biomarkers to undergo assessment of right ventricular function through echocardiogram or computed tomography analysis. Moreover, the guidelines support early discharge or ambulatory treatment for low-risk patients who have a negative troponin status.4
The American College of Chest Physicians (ACCP) guidelines on venous thromboembolism (VTE) recommend that cardiac biomarkers should not be measured routinely in all patients with PE and that positive troponin status should discourage physicians from pursuing ambulatory treatment.5 Therefore, ambiguity lies within both guidelines with regard to how hospitalists should interpret a positive troponin status in patients with low risk, which in turn may lead to unnecessary hospitalizations and further imaging. This systematic review and meta-analysis aims to provide clarity, both about gaps in literature and about how practicing hospitalists should interpret troponins in patients with low-risk PE.
METHODS
Data Sources and Searches
This systematic review and meta-analysis was performed in accordance with the established methods and Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. We searched MEDLINE, SCOPUS, and Cochrane Controlled Trial Registry databases for studies published from inception to December 2016 by using the following key words: pulmonary embolism AND PESI OR “pulmonary embolism severity index.” Only articles written in English language were included. The full articles of potentially eligible studies were reviewed, and articles published only in abstract form were excluded.
Study Selection
Two investigators independently assessed the abstract of each article, and the full article was assessed if it fulfilled the following criteria: (1) the publication must be original; (2) inclusion of objectively diagnosed, hemodynamically stable patients (normotensive patients) with acute PE in the inpatient or outpatient setting; (3) inclusion of patients>19 years old; (4) use of the PESI or sPESI model to stratify patients into a low-risk group irrespective of any evidence of right ventricular dysfunction; and (5) testing of cardiac troponin levels (TnI-troponin I, TnT-troponin T, or hs-TnI/TnT-high sensitivity troponin I/T) in patients. Study design, sample size, duration of follow-up, type of troponin used, definition of hemodynamic stability, and specific type of outcome measured (endpoint) did not affect the study eligibility.
Data Extraction and Risk of Bias Assessment
