Comparison of 3 Symptom Classification Methods to Standardize the History Component of the HEART Score.

OBJECTIVES: The History, Electrocardiography, Age, Risk factors, Troponin (HEART) score enables rapid risk stratification of emergency department patients presenting with chest pain. However, the subjectivity in scoring introduced by the history component has been criticized by some clinicians. We examined the association of 3 objective scoring models with the results of noninvasive cardiac testing. METHODS: Medical records for all patients evaluated in the chest pain center of an academic medical center during a 1-year period were reviewed retrospectively. Each patient's history component score was calculated using 3 models developed by the authors. Differences in the distribution of HEART scores for each model, as well as their degree of agreement with one another, as well as the results of cardiac testing were analyzed. RESULTS: Seven hundred forty nine patients were studied, 58 of which had an abnormal stress test or computed tomography coronary angiography. The mean HEART scores for models 1, 2, and 3 were 2.97 (SD 1.17), 2.57 (SD 1.25), and 3.30 (SD 1.35), respectively, and were significantly different (P < 0.001). However, for each model, the likelihood of an abnormal cardiovascular test did not correlate with higher scores on the symptom component of the HEART score (P = 0.09, 0.41, and 0.86, respectively). CONCLUSIONS: While the objective scoring models produced different distributions of HEART scores, no model performed well with regards to identifying patients with abnormal advanced cardiac studies in this relatively low-risk cohort. Further studies in a broader cohort of patients, as well as comparison with the performance of subjective history scoring, is warranted before adoption of any of these objective models.

Prospective study of the frequency and outcomes of patients with suspected pulmonary embolism administered heparin prior to confirmatory imaging.

OBJECTIVES: The administration of empiric systemic anticoagulation (ESA) before confirmatory radiographic testing in patients with suspected pulmonary embolism (PE) may improve outcomes, but no data have been published regarding current practice. We describe the use of ESA in a large prospective cohort of emergency department (ED) patients and report the outcomes of those treated with ESA compared with patients not receiving ESA. METHODS: 12-center, noninterventional study of ED patients who presented with symptoms concerning for PE. Clinical data including pretest probability and decision to start ESA were recorded at point of care by attending physicians. Patients were followed for adverse in-hospital outcomes and recurrence of venous thromboembolism. RESULTS: ESA was initiated 342/7932 (4.3%) of enrolled patients, including 142/618 (23%) patients with high pretest probability. Patients receiving ESA had more abnormal vital signs and were more likely to have a history of venous thromboembolism than those who did not receive ESA. Overall, 481/7,932 (6.1%) had PE diagnosed, 72/481 (15.0%) with PE had ESA, and 72/342 (21%) of ESA patients had PE. Three patients (0.9%, 95%CI: 0.2-2.5%) who received ESA suffered hemorrhagic complications compared with 38 patients (0.5%, 95%CI: 0.4-0.7%) who did not receive ESA. CONCLUSIONS: In this multicenter sample, ED physicians administered ESA to a small, generally more acutely ill subset of patients with high pretest probability of PE, and very few had hemorrhagic complications. ESA was not associated with any clear difference in outcomes. More study is needed to clarify the risk versus benefit of ESA.

Up-regulation of arginase II contributes to pulmonary vascular endothelial cell dysfunction during experimental pulmonary embolism.

Pulmonary embolism (PE) causes pulmonary hypertension by mechanical obstruction and constriction of non-obstructed vasculature. We tested if experimental PE impairs pulmonary vascular endothelium-dependent dilation via activation of arginase II. Experimental PE was induced in male Sprague-Dawley rats by infusing 25 µm microspheres in the right jugular vein, producing moderate pulmonary hypertension. Shams received vehicle injection. Pulmonary arterial rings were isolated after 18 h and isometric tensions were determined. Dilations were induced with acetylcholine, calcium ionophore A23187 or nitroglycerin (NTG) in pre-contracted rings (phenylephrine). Protein expression was assessed by Western blot and immunohistochemistry. Arginase activity was inhibited by intravenous infusion of N(w)-hydroxy-nor-l-arginine (nor-NOHA). l-Arginine supplementation was also given. Endothelium-dependent dilation responses were significantly reduced in PE vs. vehicle-treated animals (ACh: 50 ± 9% vs. 93 ± 3%; A23187: 19 ± 7% vs. 85 ± 7%, p < 0.05), while endothelium-independent dilations (NTG) were unchanged. Endothelial nitric oxide synthase (eNOS) protein content was unchanged by PE. Expression of arginase II increased 4.5-fold and immunohistochemistry revealed increased arginase II staining. Nor-NOHA treatment and l-arginine supplementation significantly improved pulmonary artery ring endothelium-dependent dilation in PE (ACh: 58 ± 6% PE, 88 ± 6% PE + nor-NOHA, 84 ± 4% PE + l-arginine). Experimental PE impairs endothelium-dependent pulmonary artery dilation, while endothelium-independent dilation remains unchanged. The data support the conclusion that up-regulation of arginase II protein expression contributes to pulmonary artery endothelial dysfunction in this model of experimental PE.

Right ventricular heart failure from pulmonary embolism: key distinctions from chronic pulmonary hypertension.

BACKGROUND: The right ventricle normally operates as a low pressure, high-flow pump connected to a high-capacitance pulmonary vascular circuit. Morbidity and mortality in humans with pulmonary hypertension (PH) from any cause is increased in the presence of right ventricular (RV) dysfunction, but the differences in pathology of RV dysfunction in chronic versus acute occlusive PH are not widely recognized. METHODS AND RESULTS: Chronic PH that develops over weeks to months leads to RV concentric hypertrophy without inflammation that may progress slowly to RV failure. In contrast, pulmonary embolism (PE) results in an abrupt vascular occlusion leading to increased pulmonary artery pressure within minutes to hours that causes immediate deformation of the RV. RV injury is secondary to mechanical stretch, shear force, and ischemia that together provoke a cytokine and chemokine-mediated inflammatory phenotype that amplifies injury. CONCLUSIONS: This review will briefly describe causes of pulmonary embolism and chronic PH, models of experimental study, and pulmonary vascular changes, and will focus on mechanisms of right ventricular dysfunction, contrasting mechanisms of RV adaptation and injury in these 2 settings.

Etiology of illness in patients with severe sepsis admitted to the hospital from the emergency department.

BACKGROUND: Patients identified with sepsis in the emergency department often are treated on the basis of the presumption of infection; however, various noninfectious conditions that require specific treatments have clinical presentations very similar to that of sepsis. Our aim was to describe the etiology of illness in patients identified and treated for severe sepsis in the emergency department. METHODS: We conducted a prospective observational study of patients treated with goal-directed resuscitation for severe sepsis in the emergency department. Inclusion criteria were suspected infection, 2 or more criteria for systemic inflammation, and evidence of hypoperfusion. Exclusion criteria were age of <18 years and the need for immediate surgery. Clinical data on eligible patients were prospectively collected for 2 years. Blinded observers used a priori definitions to determine the final cause of hospitalization. RESULTS: In total, 211 patients were enrolled; 95 (45%) had positive culture results, and 116 (55%) had negative culture results. The overall mortality rate was 19%. Patients with positive culture results were more likely to have indwelling vascular lines (P = .03), be residents of nursing homes (P = .04), and have a shorter time to administration of antibiotics in the emergency department (83 vs 97 min; P = .03). Of patients with negative culture results, 44% had clinical infections, 8% had atypical infections, 32% had noninfectious mimics, and 16% had an illness of indeterminate etiology. CONCLUSION: In this study, we found that >50% of patients identified and treated for severe sepsis in the emergency department had negative culture results. Of patients identified with a sepsis syndrome at presentation, 18% had a noninfectious diagnosis that mimicked sepsis, and the clinical characteristics of these patients were similar to those of patients with culture-positive sepsis.

12-lead ECG findings of pulmonary hypertension occur more frequently in emergency department patients with pulmonary embolism than in patients without pulmonary embolism.

STUDY OBJECTIVE: Acute pulmonary embolism can produce abnormalities on ECG that reflect severity of pulmonary hypertension. Early recognition of these findings may alter the estimated pretest probability of pulmonary embolism and prompt more aggressive treatment before hemodynamic instability ensues, but it is first important to test whether these findings are specific to patients with pulmonary embolism. We hypothesize that ECG findings consistent with pulmonary hypertension would be observed more frequently in patients with pulmonary embolism. METHODS: Secondary analysis of a prospective, observational cohort of emergency department patients who were tested for pulmonary embolism. ECGs were ordered at clinician's discretion and interpreted at presentation. RESULTS: Six thousand forty-nine patients had an ECG, 354 (5.9%) of whom were diagnosed with pulmonary embolism. The frequency, positive likelihood ratio (LR+) and 95% confidence interval (CI) of each predictor were as follows: S1Q3T3 8.5% with pulmonary embolism versus 3.3% without pulmonary embolism (LR+ 3.7; 95% CI 2.5 to 5.4); nonsinus rhythm, 23.5% versus 16.6% (LR+ 1.4; 95% CI 1.2 to 1.7); inverted T waves in V1 to V2, 14.4% versus 8.1% (LR+ 1.8; 95% CI 1.3 to 2.3); inversion in V1 to V3, 10.5% versus 4.0% (LR+ 2.6; 95% CI 1.9 to 3.6); inversion in V1 to V4, 7.3% versus 2.0% (LR+ 3.7; 95% CI 2.4 to 5.5); incomplete right bundle branch block, 4.8% versus 2.8% (LR+ 1.7; 95% CI 1.0 to 2.7); tachycardia (pulse rate >100 beats/min), 28.8% versus 15.7% (LR+ 1.8; 95% CI 1.5 to 2.2). Likelihood ratios and specificities were similar when patients with previous cardiopulmonary disease were excluded from analysis. CONCLUSION: Findings of acute pulmonary hypertension were infrequent overall but were observed more frequently in patients with the final diagnosis of pulmonary embolism compared with patients who do not have pulmonary embolism.

One year mortality of patients treated with an emergency department based early goal directed therapy protocol for severe sepsis and septic shock: a before and after study.

INTRODUCTION: Early structured resuscitation of severe sepsis has been suggested to improve short term mortality; however, no previous study has examined the long-term effect of this therapy. We sought to determine one year outcomes associated with implementation of early goal directed therapy (EGDT) in the emergency department (ED) care of sepsis. METHODS: We performed a longitudinal analysis of a prospective before and after study conducted at a large urban ED. Adult patients were enrolled if they had suspected infection, 2 or more systemic inflammatory response criteria, and either systolic blood pressure (SBP) <90 mmHg after a fluid bolus or lactate >4 mM. Exclusion criteria were: age <18 years, no aggressive care desired, or need for immediate surgery. Clinical and outcomes data were prospectively collected on consecutive eligible patients for 1 year before and 2 years after implementing EGDT. Patients in the pre-implementation phase received non-protocolized care at attending physician discretion. The primary outcome was mortality at one year. RESULTS: 285 subjects, 79 in the pre- and 206 in the post-implementation phases, were enrolled. Compared to pre-implementation, post-implementation subjects had a significantly lower ED SBP (72 vs. 85 mm Hg, P < 0.001) and higher sequential organ failure assessment score (7 vs. 5, P = 0.0004). The primary outcome of 1 year mortality was observed in 39/79 (49%) pre-implementation subjects and 77/206 (37%) post-implementation subjects (difference 12%; P = 0.04). CONCLUSIONS: Implementation of EGDT for the treatment of ED patients with severe sepsis and septic shock was associated with significantly lower mortality at one year.

Prospective evaluation of right ventricular function and functional status 6 months after acute submassive pulmonary embolism: frequency of persistent or subsequent elevation in estimated pulmonary artery pressure.

BACKGROUND: No published data have systematically documented pulmonary artery pressure over an intermediate time period after submassive pulmonary embolism (PE). The aim of this work was to document the rate of pulmonary hypertension, as assessed noninvasively by estimated right ventricular systolic pressure (RVSP) of >or= 40 mm Hg 6 months after the diagnosis of submassive PE. METHODS: We enrolled 200 normotensive patients with CT angiography-proven PE and a baseline echocardiogram to estimate RVSP. All patients received therapy with unfractionated heparin initially, but 21 patients later received alteplase in response to circulatory shock or respiratory failure. Patients returned at 6 months for repeat RVSP measurement, and assessments of the New York Heart Association (NYHA) score and 6-min walk distance (6MWD). RESULTS: Six months after receiving a diagnosis, 162 of 180 survivors (90%) returned for follow-up, including 144 patients who had been treated with heparin (heparin-only group) and 18 patients who had been treated with heparin plus alteplase (heparin-plus-alteplase group). Among the heparin-only patients, the RVSP at diagnosis was >or= 40 mm Hg in 50 of 144 patients (35%; 95% CI, 27% to 43%), compared with 10 of 144 patients at follow-up (7%; 95% CI, 3% to 12%). However, the RVSP at follow-up was higher than the baseline RVSP in 39 of 144 patients (27%; 95% CI, 9% to 35%), and 18 of these 39 patients had a NYHA score of >or= 3 or exercise intolerance (6MWD, < 330 m). Among heparin-plus-alteplase patients, the RVSP was >or= 40 mm Hg in 11 of 18 patients at diagnosis (61%; 95% CI, 36% to 83%), compared with 2 of 18 patients at follow-up (11%; 95% CI, 1% to 35%). The RVSP at follow-up was not higher than at the time of diagnosis in any of the heparin-plus-alteplase patients (95% CI, 0% to 18%). CONCLUSIONS: Six months after experiencing submassive PE, a significant proportion of patients had echocardiographic and functional evidence of pulmonary hypertension.

The significance of non-sustained hypotension in emergency department patients with sepsis.

OBJECTIVE: Few studies have documented the incidence and significance of non-sustained hypotension in emergency department (ED) patients with sepsis. We hypothesized that ED non-sustained hypotension increases risk of in-hospital mortality in patients with sepsis. METHODS: Secondary analysis of a prospective cohort study. ED patients aged > 17 years admitted to the hospital with explicitly defined sepsis were prospectively identified. INCLUSION CRITERIA: Evidence of systemic inflammation (> 1 criteria) and suspicion for infection. Patients with overt shock were excluded. The primary outcome was in-hospital mortality. RESULTS: Seven hundred patients with sepsis were enrolled, including 150 (21%) with non-sustained hypotension. The primary outcome of in-hospital mortality was present in 10% (15/150) of patients with non-sustained hypotension compared with 3.6% (20/550) of patients with no hypotension. The presence of non-sustained hypotension resulted in three times the risk of mortality than no hypotension (risk ratio = 2.8, 95% CI 1.5-5.2). Patients with a lowest systolic blood pressure < 80 mmHg had a threefold increase in mortality rate compared with patients with a lowest systolic blood pressure > or = 80 mmHg (5 vs. 16%). In logistic regression analysis, non-sustained hypotension was an independent predictor of in-hospital mortality. CONCLUSION: Non-sustained hypotension in the ED confers a significantly increased risk of death during hospitalization in patients admitted with sepsis. These data should impart reluctance to dismiss non-sustained hypotension, including a single measurement, as not clinically significant or meaningful.

Comparison of 8 biomarkers for prediction of right ventricular hypokinesis 6 months after submassive pulmonary embolism.

BACKGROUND: Elevated blood concentrations of troponin proteins or brain natriuretic peptide (BNP) worsen the prognosis of patients with pulmonary embolism (PE). Novel biomarkers that reflect mechanisms of right ventricle (RV) damage from PE may provide additional prognostic value. We compare the prognostic use of BNP, troponin I, D-dimer, monocyte chemoattractant protein-1, matrix metalloproteinase, myeloperoxidase, C-reactive protein, and caspase 3 as biomarkers of RV damage and adverse outcomes in submassive PE. METHODS: This article used a prospective cohort study of normotensive (systolic blood pressure always >100 mm Hg) patients with computed tomographic angiography-diagnosed PE. All patients underwent echocardiography and phlebotomy at diagnosis, and survivors had another echocardiography 6 months later. We tested each biomarker for prognostic significance, requiring a lower limit 95% CI >0.50 for the area under the receiver operating characteristic curve (AUROC) with a reference standard positive of RV hypokinesis on either echocardiogram. Biomarkers with prognostic significance were dichotomized at the concentration that yielded highest likelihood ratio positive and mortality rates compared (Fisher exact test). RESULTS: We enrolled 152 patients with complete data. Thirty-seven (24%, 95% CI 18%-32%) had RV hypokinesis. Only BNP and troponin had significant AUROC values as follows: 0.71 (95% CI 0.60-0.81) and 0.71 (95% CI 0.62-0.82), respectively. Overall mortality was 13/153 (8.5%); mortality rate for BNP >100 versus < or =100 pg/mL was 23% versus 3% (P = .003), respectively. Mortality rate for troponin I >0.1 versus < or =0.1 ng/mL was 13% versus 6% (P = .205), respectively. CONCLUSIONS: Of 8 mechanistically plausible biomarkers, only BNP and troponin I had significant prognostic use with BNP having an advantage for predicting mortality.