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Original Research: Pulmonary Vascular Disease |

The Prognostic Value of Undetectable Highly Sensitive Cardiac Troponin I in Patients With Acute Pulmonary EmbolismCardiac Troponin in Acute Pulmonary Embolism FREE TO VIEW

Emad U. Hakemi, MD; Tareq Alyousef, MD; Geetanjali Dang, MD; Jalal Hakmei, MD; Rami Doukky, MD
Author and Funding Information

From the Division of Adult Cardiology (Drs Hakemi and Doukky) and Department of Internal Medicine (Drs Dang and Hakmei), John H. Stroger, Jr Hospital of Cook County, Chicago, IL; Division of Cardiology (Dr Alyousef), University of Nebraska Medical Center, Omaha, NE; and Division of Cardiology (Dr Doukky), Rush University Medical Center, Chicago, IL.

CORRESPONDENCE TO: Rami Doukky, MD, John H. Stroger, Jr Hospital of Cook County, 1901 W Harrison St, Chicago, IL 60612; e-mail: Rami_Doukky@rush.edu


FOR EDITORIAL COMMENT SEE PAGE 589

Part of this article has been presented in abstract form at the American College of Cardiology 63rd Annual Scientific Session & Expo, March 29-31, 2014, Washington, DC.

FUNDING/SUPPORT: The study was internally funded.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(3):685-694. doi:10.1378/chest.14-0700
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BACKGROUND:  Elevated cardiac troponin levels have been shown to be associated with adverse outcomes in patients with acute pulmonary embolism (PE). However, few data address the management implications of undetectable cardiac troponin I (cTnI) using a highly sensitive assay. We hypothesized that undetectable cTnI predicts very low in-hospital adverse event rates.

METHODS:  In a retrospective cohort study, we classified patients with confirmed acute PE according to cTnI detectability into cTnI+ (≥ 0.012 ng/mL) and cTnI− (< 0.012 ng/mL) groups. The Pulmonary Embolism Severity Index (PESI) was used for clinical risk determination. The primary outcome was a composite of hard events defined as in-hospital death, CPR, or thrombolytic therapy. The secondary outcome was a composite of soft events defined as ICU admission or inferior vena cava filter placement.

RESULTS:  Among 298 consecutive patients with confirmed acute PE, 161 (55%) were cTnI+ and 137 (45%) cTnI−. No deaths occurred in the cTnI− group vs nine (6%) in the cTnI+ group (P = .004). No hard events were observed in the cTnI− group vs 15 (9%) in the cTnI+ group (P < .001). Soft events were observed at a lower rate in the cTnI– group (21[15%] vs 69 [43%], P < .001). Patients in the cTnI− group had a higher survival rate free of hard (P = .001) or soft (P < .001) events, irrespective of clinical risk. Furthermore, cTnI provided incremental prognostic value beyond clinical, ECG, and imaging data (P < .001).

CONCLUSIONS:  Highly sensitive cTnI assay provides an excellent prognostic negative predictive value; thus, it plays a role in identifying candidates for out-of-hospital treatment of acute PE.

Figures in this Article

An estimated 300,000 to 600,000 cases of VTE are diagnosed annually in the United States, with 10% to 30% mortality at 30-days occurring mostly among patients with acute pulmonary embolism (PE).1 However, a great disparity exists in mortality rate, ranging from < 1% in low-risk PE to as high as 50% to 65% for massive PE.24 Therefore, the initial patient triage and management should be tailored to patient risk.5 A variety of clinical, ECG, echocardiographic, and CT angiographic parameters and biomarkers have been found to be useful in helping clinicians to risk stratify patients with acute PE.3,4,615 This is important because outpatient management of low-risk acute PE has been under investigation in recent years.16 The role of cardiac troponin (cTn) in identifying patients with low-risk acute PE as candidates for outpatient management is not well defined.16

It is well established that elevated cTn levels are associated with adverse outcomes, signifying acute right ventricular strain and ischemic injury caused by a high-burden PE.15,17 Nonetheless, the prognostic negative predictive value of cTn using older assays has not been shown to be clinically useful because “negative” troponin was still associated with mortality events, albeit at a low rate.15 Therefore, older troponin assays with higher detection thresholds are not sensitive enough to identify very-low-risk patients who may be suitable for early discharge and outpatient management.15 In recent years, highly sensitive cTn assays have become widely available, enabling the detection of lower levels with higher accuracy.18 Being highly sensitive, these assays may serve as a screening tool for right ventricular injury caused by high-burden acute PE. We hypothesized that undetectable cardiac troponin I (cTnI) levels measured by a highly sensitive assay predict very low in-hospital adverse events and, thus, can identify patients with acute PE who may be candidates for out-of-hospital management.

Patients

A retrospective cohort study design was implemented. We queried the electronic health records of John H. Stroger, Jr. Hospital of Cook County (Chicago, Illinois) for consecutive admissions with a discharge diagnosis of acute PE from January 1, 2008, to December 31, 2012. Diagnosis of acute PE was confirmed by pulmonary CT angiography (CTA), high-probability ventilation/perfusion scan, or invasive pulmonary angiography.5 According to the initial cTnI level obtained within 24 h from diagnosis, patients were classified into two study groups: cTnI+ (≥ 0.012 ng/mL) and cTnI− (< 0.012 ng/mL).

The VITROS Troponin I ES Assay (Ortho-Clinical Diagnostics, Inc) was used in the study.19 The lower detection limit of the assay is 0.012 ng/mL.20 According to the assay manufacturer, the coefficient of variation at the 99th percentile upper reference limit (0.034 ng/mL) is 10%,18,20 meeting the recommendations for acceptable imprecision in a high-sensitivity cTn assay.21

Clinical Data

Based on detailed chart review, we determined patient baseline demographics, vital signs, and oxygen saturation at presentation. Comorbidities, including congestive heart failure, sepsis, malignancy, and renal insufficiency, were tabulated. Patients’ clinical risk was determined using the validated Pulmonary Embolism Severity Index (PESI) as illustrated in Table 1. The patients were classified into two subgroups: low clinical risk (very low or low PESI class) and high clinical risk (intermediate, high, or very high PESI class).6,22

Table Graphic Jump Location
TABLE 1 ]  Pulmonary Embolism Severity Index

Adapted with permission of the American Thoracic Society. Aujesky D et al. Am J Respir Crit Care Med. 2005;172(8):1041-1046.6

ECG and Imaging Data

An investigator blinded to clinical and outcome data analyzed all ECG tracings for rate, rhythm, and signs of right ventricular strain defined as right bundle branch block or T-wave inversion in leads V1 to V3.8,23 Echocardiography reports, as interpreted by an expert board-certified echocardiologist, were reviewed for pulmonary artery systolic pressure measurements and right ventricular dysfunction.24 Whenever possible, the pulmonary arterial peak systolic pressure was calculated using the simplified Bernoulli equation.25 Pulmonary CTA reports were reviewed to determine PE burden (saddle, main, lobar, segmental, and subsegmental) and to ascertain right ventricular dilatation, which was defined as a right ventricular-to-left ventricular diameter ratio of > 0.9 in the four-chamber view.26,27 We established evidence of lower-extremity DVT from compression and duplex venous ultrasonography reports.

Outcome Assessment

We conducted a detailed chart review to determine the occurrence, date, and time (hour and minutes) of the following adverse events: death, CPR, IV thrombolytic therapy, ICU admission, and inferior vena cava (IVC) filter placement. The primary outcome was a composite of hard events defined as death, CPR, or the use of IV thrombolytic therapy. The secondary outcome was a composite of soft events defined as ICU admission or IVC filter placement. We considered IVC filter placement a soft event because it represents an escalation of care that necessitates inpatient management and a surrogate of perceived clinical deterioration. We further classified ICU admissions into hard and soft admissions. A hard ICU admission included the use of a nonrebreather oxygen face mask, noninvasive ventilatory support to maintain oxygen saturation > 92%, or vasopressors to maintain systolic BP ≥ 90 mm Hg after failure of IV fluid resuscitation. A soft ICU admission was for patient monitoring, systolic BP < 90 mm Hg not requiring the use of vasopressors, or an indication other than acute PE (sepsis, myocardial infarction, congestive heart failure, arrhythmias, or GI bleeding).

Statistical Analysis

The χ2 test was used to compare dichotomous variables, which were expressed as number (percentage). Fisher exact test was used to compare dichotomous variables when the absolute number of events was fewer than five. The two-tailed independent-sample Student t test was used to compare normally distributed continuous variables, which were expressed as mean ± SD. The Mann-Whitney U test was used to compare skewed continuous variables, which were expressed as median (interquartile range).

Kaplan-Meyer curves and the log-rank test were used to compare time-to-event survival. Time zero in the survival curves represents the time of diagnosis of an acute PE, whereas censoring was at the time of hospital discharge.

Stepwise multivariate logistic regression analysis models were used to determine the incremental prognostic value of the PESI score, ECG, right ventricular imaging, and cTnI level. The absolute increment in global χ2 value of the model and the corresponding P value (Wald test) were used to determine the significance of the predictive value gained by each added variable. A two-tailed P < .05 was considered statistically significant. SPSS version 18 software (IBM) was used for all statistical analyses. The study was approved by the Institutional Review Board of John H. Stroger, Jr Hospital of Cook County (approval number: 13-065).

We identified 350 patients with a discharge diagnosis of acute PE confirmed by pulmonary CTA in 327 (93%) or ventilation/perfusion scan in 23 (7%). Fifty-two patients (15%) did not have a cTnI assay during their hospitalization, whereas 298 (85%) did; 161 patients (54%) were considered cTnI+ (≥ 0.012 ng/mL) and 137 (46%) cTnI− (< 0.012 ng/mL). The baseline characteristics of the study groups are summarized in Table 2. Notably, the cTnI+ group was older, had a higher mean heart rate and lower oxygen saturation at presentation, and were at greater overall clinical risk as determined by PESI.

Table Graphic Jump Location
TABLE 2 ]  Baseline Characteristics

Data are presented as mean ± SD or No. (%). CTA = CT angiography; cTnI = cardiac troponin I; DBP = diastolic BP; O2 = oxygen; PESI = Pulmonary Embolism Severity Index; SBP = systolic BP; V. /Q.  = ventilation/perfusion.

ECG analysis demonstrated that the cTnI+ group had a higher prevalence of sinus tachycardia, T-wave inversion in leads V1 to V3, or right bundle branch block (Table 3). They also were more likely to have right ventricular dysfunction and elevated pulmonary artery systolic pressures (Table 3). Pulmonary CTA demonstrated that patients in the cTn+ group had higher rates of right ventricular strain and saddle or main pulmonary artery embolism (Table 3).

Table Graphic Jump Location
TABLE 3 ]  ECG and Imaging Findings

Data are presented as No. (%) or mean ± SD. PA = pulmonary artery; PASP = pulmonary artery systolic pressure; RV = right ventricular. See Table 2 legend for expansion of other abbreviations.

Outcomes

After confirmatory acute PE diagnosis, the patients were followed for in-hospital events for a median of 5 days (interquartile range, 3-8 days). During follow-up, we observed nine deaths (3%), nine CPR events (3%), five IV thrombolytic therapy administrations (2%), 74 ICU admissions (25%), and 36 IVC filter placements (12%). All hard events (primary outcome), defined as a composite of death, CPR, or IV thrombolytic therapy, occurred in the cTnI+ group, and none were observed in the cTnI− group (15 [9%] vs 0 [0%], respectively, P < .001). The soft events (secondary outcome) defined as a composite of ICU admission or IVC filter placement, occurred more frequently in the cTnI+ group (69 [43%] vs 21 [15%], P < .001) (Table 4). ICU admissions occurred more frequently among patients in the cTnI+ group (38%) than those in the cTnI− group (9%, P < .001). Hard ICU admissions were observed in 26 (16%) in the cTnI+ group vs only three (2%) in the cTnI− group (P < .001). Nonetheless, we determined that three of 137 patients (2%) considered cTnI– had hard ICU admissions. Among these patients, one had a high-risk PESI class. Similarly, soft ICU admissions occurred more frequently in the cTnI+ group than in the cTnI– group (35 [22%] vs 10 [7%], respectively, P < .001). The rate of IVC filter placement was not significantly different between the study groups (Table 4). Length of stay after the diagnosis of acute PE was greater in the cTnI+ group (P = .001).

Table Graphic Jump Location
TABLE 4 ]  Outcomes

Data are presented as No. (%) or median (interquartile range). Hard ICU admission includes admission for hypoxemia requiring nonrebreather face mask or noninvasive ventilatory support to maintain oxygen saturation > 92% and need for vasopressors to maintain SBP > 90 mm Hg. Soft ICU admission includes admission for monitoring, SBP < 90 mm Hg that responded to fluid resuscitation, or an indication other than acute pulmonary embolism (sepsis, myocardial infarction, arrhythmia, congestive heart failure, GI bleeding). IVC = inferior vena cava. See Table 2 legend for expansion of other abbreviations.

Kaplan-Meier analyses demonstrated that the cTnI− group had greater survival free of hard (P = .001) or soft (P < .001) adverse events, irrespective of clinical risk (Figs 1, 2). As illustrated in Figure 3, stepwise multivariate logistic regression analysis indicated that cTnI provided incremental predictive values for in-hospital hard and soft adverse events beyond PESI score, ECG, and right ventricular imaging (CTA or echocardiography) (P < .001).

Figure Jump LinkFigure 1 –  A-C, Kaplan-Meier survival curves: death, CPR, or thrombolytic therapy (hard events). A, Entire cohort. B, High clinical risk. C, Low clinical risk. High clinical risk was defined as intermediate-, high-, or very-high-risk class according to the Pulmonary Embolism Severity Index, whereas low clinical risk was defined as very-low-risk or low-risk class. cTnI– = undetectable highly sensitive cardiac troponin I; cTnI+ = detectable highly sensitive cardiac troponin I.Grahic Jump Location
Figure Jump LinkFigure 2 –  A-C, Kaplan-Meier survival curves: ICU admission or inferior vena cava filter placement (soft events). A, Entire cohort. B, High clinical risk. C, Low clinical risk. High clinical risk was defined as intermediate-, high-, or very-high-risk class according to the Pulmonary Embolism Severity Index, whereas low clinical risk was defined as very-low-risk or low-risk class. See Figure 1 legend for expansion of abbreviations.Grahic Jump Location
Figure Jump LinkFigure 3 –  Incremental prognostic value. Hard events (primary outcome) were defined as death, CPR, or thrombolytic therapy. Soft events (secondary outcome) were defined as ICU admission or inferior vena cava filter placement. Outcome predictors in acute pulmonary embolism, including the PESI score, ECG (right bundle branch block or T-wave inversion in leads V1-V3), RV dilatation (by echocardiography or pulmonary CT angiography), and detectable cTnI level, were introduced in a stepwise fashion into two multivariable logistic regression models in which hard and soft events were the respective outcome variables. The gain in the global χ2 value was used to determine the significance of the incremental predictive value provided by each predictor. cTnI = cardiac troponin I; PESI = Pulmonary Embolism Severity Index; RV = right ventricular.Grahic Jump Location
Missing Troponin Values

The baseline characteristics of the 52 patients who did not undergo cTnI assay were similar to those who did, except that patients without measured cTnI were more likely to have a known history of cancer (Table 5). Notably, the mean PESI scores of patients with and without measured cTnI were similar, as were the observed rates of hard or soft events (Table 5).

Table Graphic Jump Location
TABLE 5 ]  Patients Without Troponin Assay

Data are presented as mean ± SD or No. (%). See Table 2 and 4 legends for expansion of abbreviations.

To demonstrate whether the missing cTnI values could have changed the overall results of the study, we performed sensitivity analyses examining two scenarios: one assuming that all patients with missing values were cTnI+ and the other assuming that all were cTnI–. In both scenarios, the cTnI+ status was predictive of hard and soft in-hospital events (all P < .001).

To our knowledge, this study is the first to investigate the prognostic negative predictive value of a highly sensitive cTnI assay for in-hospital adverse events in patients with confirmed acute PE. We demonstrated that patients with acute PE with undetectable cTnI had exceedingly low rates of in-hospital hard events of death, CPR, and use of thrombolytic therapy, irrespective of clinical risk. Furthermore, undetectable cTnI was predictive of significantly lower rates of the soft events of ICU admissions or IVC filter placement, irrespective of clinical risk. Additionally, cTnI level provided incremental prognostic value beyond established clinical, ECG, and imaging risk predictors. These findings complement similar data regarding cardiac troponin T and lay the foundation to investigate outpatient treatment of suitable patients with acute PE who are at low clinical risk and have undetectable cTnI.2830

It is well established that cTns play an important role in the risk stratification of acute PE15 because they have been shown to independently predict in-hospital hemodynamic instability and death in normotensive patients with acute PE.31,32 Nonetheless, older data indicated that patients with cTn levels below the normal reference value continue to experience adverse outcomes, albeit at lower rates than those with elevated levels.3337 These studies predominantly investigated low-sensitivity troponin assays or used higher diagnostic thresholds.15,3338 In concept, highly sensitive cTn assays allow for high-fidelity detection of right ventricular injury and, thus, better prediction of adverse outcome.15,38 Lankeit et al28,29 demonstrated that cardiac troponin T assay, combined with the PESI, improves risk stratification of acute PE and identifies possible candidates for out-of-hospital treatment. The present study demonstrates similar findings using highly sensitive cTnI assay. Moreover, we demonstrated that even among patients at high risk clinically, undetectable cTnI identified patients with subsequent low event rates, indicating that cTnI measurement can improve risk stratification across all risk strata. Additionally, we demonstrated that the prognostic value of cTnI was incremental to other risk predictors, namely ECG and right ventricular imaging. The analyses suggest that ECG and right ventricular imaging had substantial incremental value in predicting soft events (ie, ICU admission, IVC filter placement) (Fig 3). We suspect that decisions leading to ICU admission or IVC filter placement were clinically biased by the ECG findings, right ventricular imaging, or cTnI assay.

Combining PESI and cTnI seems to improve risk prediction.29 We illustrated this point statistically by demonstrating an incremental predictive value of cTnI– when used in combination with PESI (Fig 3). Thus, cTnI would function best as an adjunct to a comprehensive clinical evaluation by leveraging Bayes theorem to identify very-low-risk patients who may be considered for outpatient management.

In the present study, it seems that patients with a history of cancer were less likely to undergo cTnI assay (Table 5). Upon further examination, it appears that in some of these patients, the diagnosis of PE was established incidentally by chest CT scans performed during cancer staging. Because the diagnosis was evident in these cases, cTnI assay often was not performed. We also determined that cTnI was not assessed in some patients with metastatic cancer and grim prognosis.

The definition of high-sensitivity cTn assay has been evolving as a new generation of assays have become available, allowing for the detection of lower troponin levels with greater precision.3941 The latest generation of assays may allow for even greater prognostic negative predictive value than the one investigated in this study.

The current American College of Chest Physicians clinical practice guidelines on the management of venous thromboembolic disease state that early discharge after a few days of admission is feasible for patients with low-risk acute PE and good home circumstances.42 In a recent systematic review of 11 studies,16 including three randomized controlled trials and eight prospective cohort studies comparing early discharge to conventional hospital management in patients with low-risk symptomatic acute PE, a variety of risk assessment methods were used to identify low-risk acute PE, such as clinical gestalt, clinical scoring systems, and N-terminal pro-B-type natriuretic peptide level.4352 Only one study took cTn level into consideration.53 This meta-analysis showed that early discharge was associated with 3-month rates of recurrent VTE, fatal acute PE, and mortality of 1.47%, 0.47%, and 1.58%, respectively.16 Unlike complex clinical scoring systems, cTn assay allows for dichotomous decision-making, which simplifies and improves the triage process by identifying patients at very low risk of adverse events who may be candidates for early discharge after the initiation of antithrombin and oral anticoagulation therapies.42,54 Moreover, cTnI assay use is likely to be clinically effective because 45% of patients in the present study had undetectable cTnI; thus, these patients are candidates for early discharge with ensuing cost savings.1 The present data strongly argue for the routine implementation of cTn measurement in the risk assessment and triage of patients with acute PE. In this regard, we emphasize that the decision for early outpatient management in acute PE is complex and entails an assessment of clinical status, chemical biomarkers, imaging studies, comorbidities, bleeding risk, psychosocial status, and follow-up plans.

This study has some limitations. The most obvious is the single-center, retrospective design. Additionally, 15% of all patients with acute PE did not have cTnI levels measured and, thus, were excluded from the analysis. However, we demonstrated that patients without measured cTnI levels had similar clinical characteristics, PESI scores, and event rates as those with measured cTnI levels. Therefore, it is likely that patient selection for cTnI measurement was nondifferential, except for patients with a history of cancer. Furthermore, sensitivity analyses demonstrated that having included the patients with missing troponin values could not have changed the overall results of the study. It is unknown, however, whether the risk of hard events would remain at zero having had cTn levels from all patients.

Highly sensitive cTnI assay provides an excellent prognostic negative predictive value and thus, plays a role in identifying patients at low risk for adverse events who may be considered for out-of-hospital management of acute PE. The prognostic value of cTnI is incremental to clinical, ECG, and radiographic data. These findings support the implementation of cTnI as a pivotal risk stratification tool in acute PE.

Author contributions: E. U. H. and R. D. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. E. U. H. contributed to the study design, data acquisition and analysis, drafting of the manuscript, critical revisions, and approval of the final manuscript; T. A. contributed to the study concept and design, data interpretation, critical revisions, and approval of the final manuscript; G. D. and J. H. contributed to the data acquisition, critical revisions, and approval of the final manuscript; and R. D. contributed to the study concept and design, data analysis and interpretation, drafting of the manuscript, critical revisions, and approval of the final manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Doukky has received research grants from and served on the advisory board of Astellas Pharma, US, Inc. Dr Doukky also received internal university research grants. None of these research grants was used to conduct the present investigation. Drs Hakemi, Alyousef, Dang, and Hakmei have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.

Other contributions: The authors thank Kapil Yadav, MD, for contributing to the data collection.

CTA

CT angiography

cTn

cardiac troponin

cTnI

cardiac troponin I

IVC

inferior vena cava

PE

pulmonary embolism

PESI

Pulmonary Embolism Severity Index

Beckman MG, Hooper WC, Critchley SE, Ortel TL. Venous thromboembolism: a public health concern. Am J Prev Med. 2010;38(4 suppl):S495-S501. [CrossRef] [PubMed]
 
Jaff MR, McMurtry MS, Archer SL, et al; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; American Heart Association Council on Peripheral Vascular Disease; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011;123(16):1788-1830. [CrossRef] [PubMed]
 
Kucher N, Rossi E, De Rosa M, Goldhaber SZ. Massive pulmonary embolism. Circulation. 2006;113(4):577-582. [CrossRef] [PubMed]
 
Kasper W, Konstantinides S, Geibel A, et al. Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. J Am Coll Cardiol. 1997;30(5):1165-1171. [CrossRef] [PubMed]
 
Torbicki A, Perrier A, Konstantinides S, et al; ESC Committee for Practice Guidelines (CPG). Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008;29(18):2276-2315. [CrossRef] [PubMed]
 
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(8):1041-1046. [CrossRef] [PubMed]
 
Rehman A, Yousaf S, Chugh A. Thrombolysis in submassive pulmonary embolism, prudent or puerile? BMJ Case Rep. 2013. http://casereports.bmj.com/content/2013/bcr-2012-007549.long. Accessed March 23, 2014.
 
Rodger M, Makropoulos D, Turek M, et al. Diagnostic value of the electrocardiogram in suspected pulmonary embolism. Am J Cardiol. 2000;86(7):807-809. [CrossRef] [PubMed]
 
Elias A, Cazanave A, Elias M, et al. Diagnostic management of pulmonary embolism using clinical assessment, plasma D-dimer assay, complete lower limb venous ultrasound and helical computed tomography of pulmonary arteries. A multicentre clinical outcome study. Thromb Haemost. 2005;93(5):982-988. [PubMed]
 
ten Wolde M, Söhne M, Quak E, Mac Gillavry MR, Büller HR. Prognostic value of echocardiographically assessed right ventricular dysfunction in patients with pulmonary embolism. Arch Intern Med. 2004;164(15):1685-1689. [CrossRef] [PubMed]
 
Pruszczyk P, Kostrubiec M, Bochowicz A, et al. N-terminal pro-brain natriuretic peptide in patients with acute pulmonary embolism. Eur Respir J. 2003;22(4):649-653. [CrossRef] [PubMed]
 
Kruger S, Merx MW, Graf J. Utility of brain natriuretic peptide to predict right ventricular dysfunction and clinical outcome in patients with acute pulmonary embolism. Circulation. 2003;108(13):e94. [CrossRef] [PubMed]
 
Tulevski II, Hirsch A, Sanson BJ, et al. Increased brain natriuretic peptide as a marker for right ventricular dysfunction in acute pulmonary embolism. Thromb Haemost. 2001;86(5):1193-1196. [PubMed]
 
Pieralli F, Olivotto I, Vanni S, et al. Usefulness of bedside testing for brain natriuretic peptide to identify right ventricular dysfunction and outcome in normotensive patients with acute pulmonary embolism. Am J Cardiol. 2006;97(9):1386-1390. [CrossRef] [PubMed]
 
Becattini C, Vedovati MC, Agnelli G. Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. Circulation. 2007;116(4):427-433. [CrossRef] [PubMed]
 
Piran S, Le Gal G, Wells PS, et al. Outpatient treatment of symptomatic pulmonary embolism: a systematic review and meta-analysis. Thromb Res. 2013;132(5):515-519. [CrossRef] [PubMed]
 
Meyer T, Binder L, Hruska N, Luthe H, Buchwald AB. Cardiac troponin I elevation in acute pulmonary embolism is associated with right ventricular dysfunction. J Am Coll Cardiol. 2000;36(5):1632-1636. [CrossRef] [PubMed]
 
Apple FS, Jesse RL, Newby LK, et al; IFCC Committee on Standardization of Markers of Cardiac Damage; National Academy of Clinical Biochemistry. National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: analytical issues for biochemical markers of acute coronary syndromes. Clin Chem. 2007;53(4):547-551. [CrossRef] [PubMed]
 
Thygesen K, Mair J, Giannitsis E, et al; Study Group on Biomarkers in Cardiology of ESC Working Group on Acute Cardiac Care. How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J. 2012;33(18):2252-2257. [CrossRef] [PubMed]
 
Ortho-Clinical Diagnostics, Inc. Instructions for Use: VITROS Immunodiagnostic Products Troponin I ES Reagent Pack. Buckinghamshire, England: Ortho-Clinical Diagnostics, Inc; 2009:10.
 
Thygesen K, Alpert JS, Jaffe AS, et al; Joint ESC/ACCF/AHA/WHF Task Force for Universal Definition of Myocardial Infarction. Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012;60(16):1581-1598. [CrossRef] [PubMed]
 
Zhou XY, Ben SQ, Chen HL, Ni SS. The prognostic value of pulmonary embolism severity index in acute pulmonary embolism: a meta-analysis. Respir Res. 2012;13:111. [CrossRef] [PubMed]
 
Ferrari E, Imbert A, Chevalier T, Mihoubi A, Morand P, Baudouy M. The ECG in pulmonary embolism. Predictive value of negative T waves in precordial leads—80 case reports. Chest. 1997;111(3):537-543. [CrossRef] [PubMed]
 
Rudski LG, Lai WW, Afilalo J, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23(7):685-713. [CrossRef] [PubMed]
 
Oh JK, Hagler DJ, Cabalka A, Reeder GS, Cetta F Jr, Seward JB. Transesophageal and intracardiac echocardiography.. In:Oh JK, Seward JB, Tajik AJ., eds. The Echo Manual.3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:29-58.
 
Schoepf UJ, Kucher N, Kipfmueller F, Quiroz R, Costello P, Goldhaber SZ. Right ventricular enlargement on chest computed tomography: a predictor of early death in acute pulmonary embolism. Circulation. 2004;110(20):3276-3280. [CrossRef] [PubMed]
 
Quiroz R, Kucher N, Schoepf UJ, et al. Right ventricular enlargement on chest computed tomography: prognostic role in acute pulmonary embolism. Circulation. 2004;109(20):2401-2404. [CrossRef] [PubMed]
 
Lankeit M, Friesen D, Aschoff J, et al. Highly sensitive troponin T assay in normotensive patients with acute pulmonary embolism. Eur Heart J. 2010;31(15):1836-1844. [CrossRef] [PubMed]
 
Lankeit M, Jiménez D, Kostrubiec M, et al. Predictive value of the high-sensitivity troponin T assay and the simplified Pulmonary Embolism Severity Index in hemodynamically stable patients with acute pulmonary embolism: a prospective validation study. Circulation. 2011;124(24):2716-2724. [CrossRef] [PubMed]
 
Lankeit M, Konstantinides S. Is it time for home treatment of pulmonary embolism? Eur Respir J. 2012;40(3):742-749. [CrossRef] [PubMed]
 
Gallotta G, Palmieri V, Piedimonte V, et al. Increased troponin I predicts in-hospital occurrence of hemodynamic instability in patients with sub-massive or non-massive pulmonary embolism independent to clinical, echocardiographic and laboratory information. Int J Cardiol. 2008;124(3):351-357. [CrossRef] [PubMed]
 
Ozsu S, Karaman K, Mentese A, et al. Combined risk stratification with computerized tomography/echocardiography and biomarkers in patients with normotensive pulmonary embolism. Thromb Res. 2010;126(6):486-492. [CrossRef] [PubMed]
 
Douketis JD, Leeuwenkamp O, Grobara P, et al. The incidence and prognostic significance of elevated cardiac troponins in patients with submassive pulmonary embolism. J Thromb Haemost. 2005;3(3):508-513. [CrossRef] [PubMed]
 
Yalamanchili K, Sukhija R, Aronow WS, Sinha N, Fleisher AG, Lehrman SG. Prevalence of increased cardiac troponin I levels in patients with and without acute pulmonary embolism and relation of increased cardiac troponin I levels with in-hospital mortality in patients with acute pulmonary embolism. Am J Cardiol. 2004;93(2):263-264. [CrossRef] [PubMed]
 
Scridon T, Scridon C, Skali H, Alvarez A, Goldhaber SZ, Solomon SD. Prognostic significance of troponin elevation and right ventricular enlargement in acute pulmonary embolism. Am J Cardiol. 2005;96(2):303-305. [CrossRef] [PubMed]
 
Hsu JT, Chu CM, Chang ST, Cheng HW, Cheng NJ, Chung CM. Prognostic role of right ventricular dilatation and troponin I elevation in acute pulmonary embolism. Int Heart J. 2006;47(5):775-781. [CrossRef] [PubMed]
 
Giannitsis E, Müller-Bardorff M, Kurowski V, et al. Independent prognostic value of cardiac troponin T in patients with confirmed pulmonary embolism. Circulation. 2000;102(2):211-217. [CrossRef] [PubMed]
 
Jiménez D, Uresandi F, Otero R, et al. Troponin-based risk stratification of patients with acute nonmassive pulmonary embolism: systematic review and metaanalysis. Chest. 2009;136(4):974-982. [CrossRef] [PubMed]
 
Reichlin T, Hochholzer W, Bassetti S, et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med. 2009;361(9):858-867. [CrossRef] [PubMed]
 
Jaffe AS. The 10 commandments of troponin, with special reference to high sensitivity assays. Heart. 2011;97(11):940-946. [CrossRef] [PubMed]
 
Korley FK, Jaffe AS. Preparing the United States for high-sensitivity cardiac troponin assays. J Am Coll Cardiol. 2013;61(17):1753-1758. [CrossRef] [PubMed]
 
Kearon C, Akl EA, Comerota AJ, et al; American College of Chest Physicians. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2_suppl):e419S-494S. [CrossRef] [PubMed]
 
Zondag W, Mos IC, Creemers-Schild D, et al; Hestia Study Investigators. Outpatient treatment in patients with acute pulmonary embolism: the Hestia Study. J Thromb Haemost. 2011;9(8):1500-1507. [CrossRef] [PubMed]
 
Aujesky D, Roy PM, Verschuren F, et al. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial. Lancet. 2011;378(9785):41-48. [CrossRef] [PubMed]
 
Agterof MJ, Schutgens RE, Snijder RJ, et al. Out of hospital treatment of acute pulmonary embolism in patients with a low NT-proBNP level. J Thromb Haemost. 2010;8(6):1235-1241. [CrossRef] [PubMed]
 
Rodríguez-Cerrillo M, Alvarez-Arcaya A, Fernández-Díaz E, Fernández-Cruz A. A prospective study of the management of non-massive pulmonary embolism in the home. Eur J Intern Med. 2009;20(6):598-600. [CrossRef] [PubMed]
 
Davies CW, Wimperis J, Green ES, et al. Early discharge of patients with pulmonary embolism: a two-phase observational study. Eur Respir J. 2007;30(4):708-714. [CrossRef] [PubMed]
 
Olsson CG, Bitzén U, Olsson B, et al. Outpatient tinzaparin therapy in pulmonary embolism quantified with ventilation/perfusion scintigraphy. Med Sci Monit. 2006;12(2):PI9-PI13. [PubMed]
 
Wells PS, Anderson DR, Rodger MA, et al. A randomized trial comparing 2 low-molecular-weight heparins for the outpatient treatment of deep vein thrombosis and pulmonary embolism. Arch Intern Med. 2005;165(7):733-738. [CrossRef] [PubMed]
 
Siragusa S, Arcara C, Malato A, et al. Home therapy for deep vein thrombosis and pulmonary embolism in cancer patients. Ann Oncol. 2005;16(suppl 4):iv136-iv139. [PubMed]
 
Beer JH, Burger M, Gretener S, Bernard-Bagattini S, Bounameaux H. Outpatient treatment of pulmonary embolism is feasible and safe in a substantial proportion of patients. J Thromb Haemost. 2003;1(1):186-187. [CrossRef] [PubMed]
 
Kovacs MJ, Anderson D, Morrow B, Gray L, Touchie D, Wells PS. Outpatient treatment of pulmonary embolism with dalteparin. Thromb Haemost. 2000;83(2):209-211. [PubMed]
 
Otero R, Uresandi F, Jiménez D, et al. Home treatment in pulmonary embolism. Thromb Res. 2010;126(1):e1-e5. [CrossRef] [PubMed]
 
Büller HR, Prins MH, Lensin AW, et al; EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14):1287-1297. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 –  A-C, Kaplan-Meier survival curves: death, CPR, or thrombolytic therapy (hard events). A, Entire cohort. B, High clinical risk. C, Low clinical risk. High clinical risk was defined as intermediate-, high-, or very-high-risk class according to the Pulmonary Embolism Severity Index, whereas low clinical risk was defined as very-low-risk or low-risk class. cTnI– = undetectable highly sensitive cardiac troponin I; cTnI+ = detectable highly sensitive cardiac troponin I.Grahic Jump Location
Figure Jump LinkFigure 2 –  A-C, Kaplan-Meier survival curves: ICU admission or inferior vena cava filter placement (soft events). A, Entire cohort. B, High clinical risk. C, Low clinical risk. High clinical risk was defined as intermediate-, high-, or very-high-risk class according to the Pulmonary Embolism Severity Index, whereas low clinical risk was defined as very-low-risk or low-risk class. See Figure 1 legend for expansion of abbreviations.Grahic Jump Location
Figure Jump LinkFigure 3 –  Incremental prognostic value. Hard events (primary outcome) were defined as death, CPR, or thrombolytic therapy. Soft events (secondary outcome) were defined as ICU admission or inferior vena cava filter placement. Outcome predictors in acute pulmonary embolism, including the PESI score, ECG (right bundle branch block or T-wave inversion in leads V1-V3), RV dilatation (by echocardiography or pulmonary CT angiography), and detectable cTnI level, were introduced in a stepwise fashion into two multivariable logistic regression models in which hard and soft events were the respective outcome variables. The gain in the global χ2 value was used to determine the significance of the incremental predictive value provided by each predictor. cTnI = cardiac troponin I; PESI = Pulmonary Embolism Severity Index; RV = right ventricular.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1 ]  Pulmonary Embolism Severity Index

Adapted with permission of the American Thoracic Society. Aujesky D et al. Am J Respir Crit Care Med. 2005;172(8):1041-1046.6

Table Graphic Jump Location
TABLE 2 ]  Baseline Characteristics

Data are presented as mean ± SD or No. (%). CTA = CT angiography; cTnI = cardiac troponin I; DBP = diastolic BP; O2 = oxygen; PESI = Pulmonary Embolism Severity Index; SBP = systolic BP; V. /Q.  = ventilation/perfusion.

Table Graphic Jump Location
TABLE 3 ]  ECG and Imaging Findings

Data are presented as No. (%) or mean ± SD. PA = pulmonary artery; PASP = pulmonary artery systolic pressure; RV = right ventricular. See Table 2 legend for expansion of other abbreviations.

Table Graphic Jump Location
TABLE 4 ]  Outcomes

Data are presented as No. (%) or median (interquartile range). Hard ICU admission includes admission for hypoxemia requiring nonrebreather face mask or noninvasive ventilatory support to maintain oxygen saturation > 92% and need for vasopressors to maintain SBP > 90 mm Hg. Soft ICU admission includes admission for monitoring, SBP < 90 mm Hg that responded to fluid resuscitation, or an indication other than acute pulmonary embolism (sepsis, myocardial infarction, arrhythmia, congestive heart failure, GI bleeding). IVC = inferior vena cava. See Table 2 legend for expansion of other abbreviations.

Table Graphic Jump Location
TABLE 5 ]  Patients Without Troponin Assay

Data are presented as mean ± SD or No. (%). See Table 2 and 4 legends for expansion of abbreviations.

References

Beckman MG, Hooper WC, Critchley SE, Ortel TL. Venous thromboembolism: a public health concern. Am J Prev Med. 2010;38(4 suppl):S495-S501. [CrossRef] [PubMed]
 
Jaff MR, McMurtry MS, Archer SL, et al; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; American Heart Association Council on Peripheral Vascular Disease; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011;123(16):1788-1830. [CrossRef] [PubMed]
 
Kucher N, Rossi E, De Rosa M, Goldhaber SZ. Massive pulmonary embolism. Circulation. 2006;113(4):577-582. [CrossRef] [PubMed]
 
Kasper W, Konstantinides S, Geibel A, et al. Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. J Am Coll Cardiol. 1997;30(5):1165-1171. [CrossRef] [PubMed]
 
Torbicki A, Perrier A, Konstantinides S, et al; ESC Committee for Practice Guidelines (CPG). Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008;29(18):2276-2315. [CrossRef] [PubMed]
 
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(8):1041-1046. [CrossRef] [PubMed]
 
Rehman A, Yousaf S, Chugh A. Thrombolysis in submassive pulmonary embolism, prudent or puerile? BMJ Case Rep. 2013. http://casereports.bmj.com/content/2013/bcr-2012-007549.long. Accessed March 23, 2014.
 
Rodger M, Makropoulos D, Turek M, et al. Diagnostic value of the electrocardiogram in suspected pulmonary embolism. Am J Cardiol. 2000;86(7):807-809. [CrossRef] [PubMed]
 
Elias A, Cazanave A, Elias M, et al. Diagnostic management of pulmonary embolism using clinical assessment, plasma D-dimer assay, complete lower limb venous ultrasound and helical computed tomography of pulmonary arteries. A multicentre clinical outcome study. Thromb Haemost. 2005;93(5):982-988. [PubMed]
 
ten Wolde M, Söhne M, Quak E, Mac Gillavry MR, Büller HR. Prognostic value of echocardiographically assessed right ventricular dysfunction in patients with pulmonary embolism. Arch Intern Med. 2004;164(15):1685-1689. [CrossRef] [PubMed]
 
Pruszczyk P, Kostrubiec M, Bochowicz A, et al. N-terminal pro-brain natriuretic peptide in patients with acute pulmonary embolism. Eur Respir J. 2003;22(4):649-653. [CrossRef] [PubMed]
 
Kruger S, Merx MW, Graf J. Utility of brain natriuretic peptide to predict right ventricular dysfunction and clinical outcome in patients with acute pulmonary embolism. Circulation. 2003;108(13):e94. [CrossRef] [PubMed]
 
Tulevski II, Hirsch A, Sanson BJ, et al. Increased brain natriuretic peptide as a marker for right ventricular dysfunction in acute pulmonary embolism. Thromb Haemost. 2001;86(5):1193-1196. [PubMed]
 
Pieralli F, Olivotto I, Vanni S, et al. Usefulness of bedside testing for brain natriuretic peptide to identify right ventricular dysfunction and outcome in normotensive patients with acute pulmonary embolism. Am J Cardiol. 2006;97(9):1386-1390. [CrossRef] [PubMed]
 
Becattini C, Vedovati MC, Agnelli G. Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. Circulation. 2007;116(4):427-433. [CrossRef] [PubMed]
 
Piran S, Le Gal G, Wells PS, et al. Outpatient treatment of symptomatic pulmonary embolism: a systematic review and meta-analysis. Thromb Res. 2013;132(5):515-519. [CrossRef] [PubMed]
 
Meyer T, Binder L, Hruska N, Luthe H, Buchwald AB. Cardiac troponin I elevation in acute pulmonary embolism is associated with right ventricular dysfunction. J Am Coll Cardiol. 2000;36(5):1632-1636. [CrossRef] [PubMed]
 
Apple FS, Jesse RL, Newby LK, et al; IFCC Committee on Standardization of Markers of Cardiac Damage; National Academy of Clinical Biochemistry. National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: analytical issues for biochemical markers of acute coronary syndromes. Clin Chem. 2007;53(4):547-551. [CrossRef] [PubMed]
 
Thygesen K, Mair J, Giannitsis E, et al; Study Group on Biomarkers in Cardiology of ESC Working Group on Acute Cardiac Care. How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J. 2012;33(18):2252-2257. [CrossRef] [PubMed]
 
Ortho-Clinical Diagnostics, Inc. Instructions for Use: VITROS Immunodiagnostic Products Troponin I ES Reagent Pack. Buckinghamshire, England: Ortho-Clinical Diagnostics, Inc; 2009:10.
 
Thygesen K, Alpert JS, Jaffe AS, et al; Joint ESC/ACCF/AHA/WHF Task Force for Universal Definition of Myocardial Infarction. Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012;60(16):1581-1598. [CrossRef] [PubMed]
 
Zhou XY, Ben SQ, Chen HL, Ni SS. The prognostic value of pulmonary embolism severity index in acute pulmonary embolism: a meta-analysis. Respir Res. 2012;13:111. [CrossRef] [PubMed]
 
Ferrari E, Imbert A, Chevalier T, Mihoubi A, Morand P, Baudouy M. The ECG in pulmonary embolism. Predictive value of negative T waves in precordial leads—80 case reports. Chest. 1997;111(3):537-543. [CrossRef] [PubMed]
 
Rudski LG, Lai WW, Afilalo J, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23(7):685-713. [CrossRef] [PubMed]
 
Oh JK, Hagler DJ, Cabalka A, Reeder GS, Cetta F Jr, Seward JB. Transesophageal and intracardiac echocardiography.. In:Oh JK, Seward JB, Tajik AJ., eds. The Echo Manual.3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:29-58.
 
Schoepf UJ, Kucher N, Kipfmueller F, Quiroz R, Costello P, Goldhaber SZ. Right ventricular enlargement on chest computed tomography: a predictor of early death in acute pulmonary embolism. Circulation. 2004;110(20):3276-3280. [CrossRef] [PubMed]
 
Quiroz R, Kucher N, Schoepf UJ, et al. Right ventricular enlargement on chest computed tomography: prognostic role in acute pulmonary embolism. Circulation. 2004;109(20):2401-2404. [CrossRef] [PubMed]
 
Lankeit M, Friesen D, Aschoff J, et al. Highly sensitive troponin T assay in normotensive patients with acute pulmonary embolism. Eur Heart J. 2010;31(15):1836-1844. [CrossRef] [PubMed]
 
Lankeit M, Jiménez D, Kostrubiec M, et al. Predictive value of the high-sensitivity troponin T assay and the simplified Pulmonary Embolism Severity Index in hemodynamically stable patients with acute pulmonary embolism: a prospective validation study. Circulation. 2011;124(24):2716-2724. [CrossRef] [PubMed]
 
Lankeit M, Konstantinides S. Is it time for home treatment of pulmonary embolism? Eur Respir J. 2012;40(3):742-749. [CrossRef] [PubMed]
 
Gallotta G, Palmieri V, Piedimonte V, et al. Increased troponin I predicts in-hospital occurrence of hemodynamic instability in patients with sub-massive or non-massive pulmonary embolism independent to clinical, echocardiographic and laboratory information. Int J Cardiol. 2008;124(3):351-357. [CrossRef] [PubMed]
 
Ozsu S, Karaman K, Mentese A, et al. Combined risk stratification with computerized tomography/echocardiography and biomarkers in patients with normotensive pulmonary embolism. Thromb Res. 2010;126(6):486-492. [CrossRef] [PubMed]
 
Douketis JD, Leeuwenkamp O, Grobara P, et al. The incidence and prognostic significance of elevated cardiac troponins in patients with submassive pulmonary embolism. J Thromb Haemost. 2005;3(3):508-513. [CrossRef] [PubMed]
 
Yalamanchili K, Sukhija R, Aronow WS, Sinha N, Fleisher AG, Lehrman SG. Prevalence of increased cardiac troponin I levels in patients with and without acute pulmonary embolism and relation of increased cardiac troponin I levels with in-hospital mortality in patients with acute pulmonary embolism. Am J Cardiol. 2004;93(2):263-264. [CrossRef] [PubMed]
 
Scridon T, Scridon C, Skali H, Alvarez A, Goldhaber SZ, Solomon SD. Prognostic significance of troponin elevation and right ventricular enlargement in acute pulmonary embolism. Am J Cardiol. 2005;96(2):303-305. [CrossRef] [PubMed]
 
Hsu JT, Chu CM, Chang ST, Cheng HW, Cheng NJ, Chung CM. Prognostic role of right ventricular dilatation and troponin I elevation in acute pulmonary embolism. Int Heart J. 2006;47(5):775-781. [CrossRef] [PubMed]
 
Giannitsis E, Müller-Bardorff M, Kurowski V, et al. Independent prognostic value of cardiac troponin T in patients with confirmed pulmonary embolism. Circulation. 2000;102(2):211-217. [CrossRef] [PubMed]
 
Jiménez D, Uresandi F, Otero R, et al. Troponin-based risk stratification of patients with acute nonmassive pulmonary embolism: systematic review and metaanalysis. Chest. 2009;136(4):974-982. [CrossRef] [PubMed]
 
Reichlin T, Hochholzer W, Bassetti S, et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med. 2009;361(9):858-867. [CrossRef] [PubMed]
 
Jaffe AS. The 10 commandments of troponin, with special reference to high sensitivity assays. Heart. 2011;97(11):940-946. [CrossRef] [PubMed]
 
Korley FK, Jaffe AS. Preparing the United States for high-sensitivity cardiac troponin assays. J Am Coll Cardiol. 2013;61(17):1753-1758. [CrossRef] [PubMed]
 
Kearon C, Akl EA, Comerota AJ, et al; American College of Chest Physicians. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2_suppl):e419S-494S. [CrossRef] [PubMed]
 
Zondag W, Mos IC, Creemers-Schild D, et al; Hestia Study Investigators. Outpatient treatment in patients with acute pulmonary embolism: the Hestia Study. J Thromb Haemost. 2011;9(8):1500-1507. [CrossRef] [PubMed]
 
Aujesky D, Roy PM, Verschuren F, et al. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial. Lancet. 2011;378(9785):41-48. [CrossRef] [PubMed]
 
Agterof MJ, Schutgens RE, Snijder RJ, et al. Out of hospital treatment of acute pulmonary embolism in patients with a low NT-proBNP level. J Thromb Haemost. 2010;8(6):1235-1241. [CrossRef] [PubMed]
 
Rodríguez-Cerrillo M, Alvarez-Arcaya A, Fernández-Díaz E, Fernández-Cruz A. A prospective study of the management of non-massive pulmonary embolism in the home. Eur J Intern Med. 2009;20(6):598-600. [CrossRef] [PubMed]
 
Davies CW, Wimperis J, Green ES, et al. Early discharge of patients with pulmonary embolism: a two-phase observational study. Eur Respir J. 2007;30(4):708-714. [CrossRef] [PubMed]
 
Olsson CG, Bitzén U, Olsson B, et al. Outpatient tinzaparin therapy in pulmonary embolism quantified with ventilation/perfusion scintigraphy. Med Sci Monit. 2006;12(2):PI9-PI13. [PubMed]
 
Wells PS, Anderson DR, Rodger MA, et al. A randomized trial comparing 2 low-molecular-weight heparins for the outpatient treatment of deep vein thrombosis and pulmonary embolism. Arch Intern Med. 2005;165(7):733-738. [CrossRef] [PubMed]
 
Siragusa S, Arcara C, Malato A, et al. Home therapy for deep vein thrombosis and pulmonary embolism in cancer patients. Ann Oncol. 2005;16(suppl 4):iv136-iv139. [PubMed]
 
Beer JH, Burger M, Gretener S, Bernard-Bagattini S, Bounameaux H. Outpatient treatment of pulmonary embolism is feasible and safe in a substantial proportion of patients. J Thromb Haemost. 2003;1(1):186-187. [CrossRef] [PubMed]
 
Kovacs MJ, Anderson D, Morrow B, Gray L, Touchie D, Wells PS. Outpatient treatment of pulmonary embolism with dalteparin. Thromb Haemost. 2000;83(2):209-211. [PubMed]
 
Otero R, Uresandi F, Jiménez D, et al. Home treatment in pulmonary embolism. Thromb Res. 2010;126(1):e1-e5. [CrossRef] [PubMed]
 
Büller HR, Prins MH, Lensin AW, et al; EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14):1287-1297. [CrossRef] [PubMed]
 
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