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Bethesda, MD
Dr. Moores is Associate Professor of Medicine and Assistant Dean of Clinical Sciences, The Uniformed Services University of the Health Sciences.
Correspondence to Lisa K. Moores, MD, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814; e-mail: lmoores{at}usuhs.mil
Venous thromboembolism (VTE) is a common and potentially life-threatening disorder, with > 600,000 incident cases occurring annually in the United States.1 Rapid treatment with unfractionated heparin (UFH) clearly reduces the rate of recurrent and potentially fatal events. Over the past decade, treatment with low-molecular-weight heparin (LMWH) has been shown to be as safe and effective as UFH in the initial treatment period.2 As laboratory monitoring is not necessary, this allows for potential outpatient therapy. Indeed, multiple randomized trials have confirmed the safety of this approach in patients presenting with deep vein thrombosis (DVT).2
There are only two trials34 in the literature addressing outpatient therapy for patients with acute pulmonary embolism (PE): one a prospective cohort and the other randomized. Both involve a small number of patients, and neither had a control arm of patients receiving traditional inpatient therapy. Nonetheless, both studies suggest that outpatient therapy with LMWH is safe and effective in select patients with acute PE. But who are these select patients? They must be chosen carefully, as patients presenting with acute PE have worse short-term outcomes and a higher risk of recurrent and fatal VTE than those who present with acute DVT.1 For this reason, physicians are reluctant to treat such patients outside of a monitored setting. Patient-related factors that have been identified are associated with a worse prognosis. These include age, active malignancy, congestive heart failure, COPD, renal failure, presentation with a PE rather than a DVT, and hypoxemia or hemodynamic instability on hospital admission. In addition, size of the perfusion defect, initial cardiac serum biomarkers, and evidence of right ventricular dysfunction on echocardiography have also been identified as markers of a worse outcome even when patients are normotensive.5 Until recently, however, these factors have not been studied systematically to identify risk groups that might guide treatment settings and appropriate escalations in care.
Wicki and colleagues6 were the first to develop and internally validate a risk score in patients with acute PE. By analyzing data from 296 consecutive patients with acute PE, they were able to identify cancer, heart failure, previous DVT, systolic BP < 100 mm Hg, arterial PaO2 <8 kPa (< 60 mm Hg), and the presence of DVT on ultrasound as significant predictors of an adverse short-term outcome. The Geneva risk score was derived from these variables by assigning 2 points for cancer and hypotension and 1 point each for the other predictors. A cutoff of 2 was able to discriminate low-risk from high-risk patients. In 2005 Aujesky and colleagues7 reported on the development and validation of a similar risk score derived from > 15,000 patients with acute PE. The Pulmonary Embolism Severity Index (PESI) score was based on 11 simple patient characteristics (age, male gender, cancer, heart failure, chronic lung disease, heart rate 
100 beats/min, systolic BP < 100 mm Hg, respiratory rate 30 breaths/min, temperature < 36°C, altered mental status, arterial oxygen saturation < 90%) independently associated with mortality that could be used to stratify patients into five severity classes. Patients in categories I and II had very low 30-day mortality rates of 0 to 1.6% and 1.7 to 3.5%, respectively. Both risk scores have since been validated by the authors in independent populations.89
In this issue of CHEST (see page 24), Jimenez and colleagues10 report on the first completely external validation study that directly compares the two risk scores in almost 600 consecutive ambulatory patients presenting with acute PE. Using either prediction score, mortality was < 6% in the low-risk group and at least 10% in the high-risk group. Compared to the Geneva score low-risk patients, however, the PESI low-risk patients had a significantly lower mortality (5.6% vs 0.9%; p < 0.0001). Overall, the PESI was able to identify 25% of the cohort who were at extremely low risk for mortality or other adverse outcomes and did not have other reasons for hospitalization, and thus could have been treated as outpatients. The potential impact of this work on the care of patients with acute PE, if confirmed in a prospective management trial, cannot be understated. Even if only one fourth of patients can be classified as extremely low risk, treating them entirely as outpatients would lead to substantial cost savings and increased patient satisfaction.
Importantly, the PESI consists of objective, easily identifiable factors that can be ascertained within minutes of the patient’s presentation without sophisticated diagnostic testing. Given the growing body of literature on the association of serum troponin and brain natriuretic peptide (BNP) levels11 and right-heart dysfunction on either echocardiography12 or CT angiography13 (CTPA) and adverse outcomes, some might ask why these have not been incorporated into the PESI risk score. The real value of the PESI, however, is to identify a subset of ambulatory patients who might not require admission to the hospital. As many patients who present to the emergency department with dyspnea will have a troponin or BNP level drawn in their evaluation anyway, further studies should concentrate on the utility of adding these serum levels to the PESI in identifying a larger proportion of patients who will have a favorable outcome. As CTPA is the most frequently performed imaging study for the diagnosis of acute PE, it holds further promise in predicting short-term outcomes. However, data thus far suggest that CT (or echocardiographic) findings of right-heart strain are more likely to identify higher-risk rather than lower-risk patients.13 Their role will thus be identifying a group of normotensive hospitalized patients who might benefit from a higher level of care or more aggressive therapy. For now, Jimenez and colleagues should be congratulated for taking this important next step in improving the care of patients with acute PE.
Footnotes
The author has no personal or financial conflicts associated with this article.
The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.
References
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