Abstract: Treatment of patients with VTE, whether determining setting or intensity of care or duration of secondary prevention, is shifting from a disease-specific to an individualized approach. Current evidence-based treatment guidelines are fairly straightforward for some patients, such as those who present with isolated DVT or hemodynamic shock or sudden cardiac death.1Kearon C Akl EA Comerota AJ et al.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: e419S-494SAbstract Full Text Full Text PDF PubMed Scopus (3038) Google Scholar There is growing recognition, however, that patients with acute pulmonary embolism (PE) who are hemodynamically stable are not homogeneous. Some of these patients, particularly those with evidence of higher clot burden and right ventricular strain, might benefit from more aggressive care, to include ICU admission and the consideration of thrombolytic therapy. Other patients may suffer minimal physiologic consequences from the acute clot and could potentially be treated in the outpatient environment.2Aujesky 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: 41-48Abstract Full Text Full Text PDF PubMed Scopus (482) Google Scholar Contemporary risk stratification tools of normotensive patients with PE should accurately differentiate patients at high risk of early adverse outcomes who will benefit from aggressive therapy from those at extremely low risk of such events who might be candidates for early discharge or entirely outpatient therapy. Outpatient management of low-risk patients with PE may lead to cost savings, avoidance of hospital-acquired conditions, and increased patient satisfaction.3Jiménez D Aujesky D Yusen RD Risk stratification of normotensive patients with acute symptomatic pulmonary embolism.Br J Haematol. 2010; 151: 415-424Crossref PubMed Scopus (63) Google Scholar With the recent approval of the new oral anticoagulants that do not require bridging or monitoring, outpatient therapy is also now more feasible.4King CS Holley AB Moores LK Moving toward a more ideal anticoagulant: the oral direct thrombin and factor Xa inhibitors.Chest. 2013; 143: 1106-1116Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar Research over the last decade has provided us with several tools to risk stratify patients with acute PE. Clinical prediction scores, which account for hemodynamic status on presentation and existing comorbidities, have been derived and validated and are being used in ongoing management studies.3Jiménez D Aujesky D Yusen RD Risk stratification of normotensive patients with acute symptomatic pulmonary embolism.Br J Haematol. 2010; 151: 415-424Crossref PubMed Scopus (63) Google Scholar It is well established that patients with acute PE and evidence of right ventricular dysfunction have worse outcomes. Evidence of right ventricular strain on imaging studies such as echocardiography and CT angiography has been shown to correlate with an adverse outcome.3Jiménez D Aujesky D Yusen RD Risk stratification of normotensive patients with acute symptomatic pulmonary embolism.Br J Haematol. 2010; 151: 415-424Crossref PubMed Scopus (63) Google Scholar In addition, serum biomarker evidence of right ventricular ischemia and strain, such as elevated serum troponin and brain natriuretic peptide (BNP) levels, also portend a higher short-term risk.5Jiménez 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: 974-982Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar, 6Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism: a systematic review and meta-analysis.Am J Respir Crit Care Med. 2008; 178: 425-430Crossref PubMed Scopus (288) Google Scholar More recent studies also suggest that serum sodium levels (as a marker of neurohormonal activation)7Scherz N Labarère J Méan M Ibrahim SA Fine MJ Aujesky D Prognostic importance of hyponatremia in patients with acute pulmonary embolism.Am J Respir Crit Care Med. 2010; 182: 1178-1183Crossref PubMed Scopus (65) Google Scholar and heart-type fatty acid binding protein8Dellas C Puls M Lankeit M et al.Elevated heart-type fatty acid-binding protein levels on admission predict an adverse outcome in normotensive patients with acute pulmonary embolism.J Am Coll Cardiol. 2010; 55: 2150-2157Crossref PubMed Scopus (121) Google Scholar may add additional prognostic information. Finally, assessment of the overall clot burden, whether through imaging studies, the circulating D-dimer level,9Lobo JL Zorrilla V Aizpuru F et al.RIETE Investigators. D-dimer levels and 15-day outcome in acute pulmonary embolism. Findings from the RIETE Registry.J Thromb Haemost. 2009; 7: 1795-1801Crossref PubMed Scopus (54) Google Scholar or the presence of concomitant DVT also provides important information.10Jiménez D Aujesky D Díaz G et al.RIETE Investigators. Prognostic significance of deep vein thrombosis in patients presenting with acute symptomatic pulmonary embolism.Am J Respir Crit Care Med. 2010; 181: 983-991Crossref PubMed Scopus (137) Google Scholar Although the latter markers are commonly used to identify high-risk patients with PE, their absence can be useful in identifying low-risk patients, particularly in the setting of a low clinical predication score. Each of these components varies in their sensitivity and thus their negative predictive value and ability to safely exclude poor short-term outcome. Thus, a combination of these variables provides the most accurate and clinically useful information.3Jiménez D Aujesky D Yusen RD Risk stratification of normotensive patients with acute symptomatic pulmonary embolism.Br J Haematol. 2010; 151: 415-424Crossref PubMed Scopus (63) Google Scholar In this issue of CHEST (see page 685), Dr Hakemi and colleagues11Hakemi EU Alyousef T Dang G Hakmei J Doukky R The prognostic value of undetectable highly sensitive cardiac troponin I in patients with acute pulmonary embolism.Chest. 2015; 147: 685-694Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar take us another step closer in our attempts to optimize accurate identification of low-risk patients. The authors report that an undetectable level of highly sensitive cardiac troponin I (hs-cTnI) in patients with acute PE has a very high negative predictive value for adverse short-term outcome. In addition, the authors demonstrate an incremental added value of hs-cTnI levels to clinical prediction scores (in this case the Pulmonary Embolism Severity Index), ECGs, and imaging studies. This is very helpful, as many studies over the past few years have focused on the combination of tools for the identification of high-risk patients. In addition, older-generation studies that attempted to combine clinical prediction scores with cardiac biomarkers were not able to show any incremental value, likely secondary to the lower sensitivity of the assays available at that time. An important and encouraging finding of this study was that 45% of the cohort fell into the low-risk group, suggesting significant clinical usefulness of such an approach. A word of caution is due in the interpretation of this study. The absolute number of adverse outcomes was small, potentially limiting the precision and generalizability of the study. A number of patients did not have hs-cTnI levels measured. This was more common in patients with active malignancy, so caution should be taken in applying the results to this group of patients. Perhaps most importantly, 10 patients identified as low risk ultimately experienced an escalation in care. Although none of these patients underwent thrombolysis or CPR or died, three of them had legitimate reasons for ICU admission (hypoxemia requiring nonrebreather mask or noninvasive ventilation or hypotension requiring vasopressor support). Of these three, one of them was in the high-risk Pulmonary Embolism Severity Index group, and, thus, the combination of a clinical score and the hs-cTnI level may have prevented this miscategorization. Prior studies have confirmed the very high negative predictive value of N-terminal pro-BNP levels in patients with acute PE. Would the addition of this biomarker reduce the number of patients inaccurately classified as low risk?6Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism: a systematic review and meta-analysis.Am J Respir Crit Care Med. 2008; 178: 425-430Crossref PubMed Scopus (288) Google Scholar Further, would a panel of cardiac biomarkers (serum sodium, hs-cTnI or hs-cTnt, N-terminal pro-BNP, heart-type fatty acid binding protein, and D-dimer level) assist accurate discrimination? These are questions that deserve further investigation. Will the results of this study modify our clinical practice regarding risk stratification of patients with acute PE? I think the answer to this is yes, particularly if the findings are confirmed in management studies. We are getting closer to the point where we can confidently tell patients with acute PE to take their medicine and go home. Other contributions: The opinions expressed here are entirely those of the author and do not represent the official opinion of the United States Army, the Uniformed Services University of the Health Sciences, or the Department of Defense. /cms/asset/c24e129f-af06-4878-a5e3-c076eae889d8/mmc1.mp3Loading ... Download .mp3 (11.64 MB) Help with .mp3 files Supplementary audioCardiac Troponin I in Patients with Pulmonary EmbolismDuration: 25 minModerator: D. Kyle Hogarth, MD, FCCP, Podcast Editor, CHESTParticipants: Rami Doukky, MD; Lisa K. Moores, MD, FCCP