Efficacy and Safety of Outpatient Treatment Based on the Hestia Clinical Decision Rule with or without N-Terminal Pro-Brain Natriuretic Peptide Testing in Patients with Acute Pulmonary Embolism. A Randomized Clinical Trial.

RATIONALE: Outpatient treatment of pulmonary embolism (PE) may lead to improved patient satisfaction and reduced healthcare costs. However, trials to assess its safety and the optimal method for patient selection are scarce. OBJECTIVES: To validate the utility and safety of selecting patients with PE for outpatient treatment by the Hestia criteria and to compare the safety of the Hestia criteria alone with the Hestia criteria combined with N-terminal pro-brain natriuretic peptide (NT-proBNP) testing. METHODS: We performed a randomized noninferiority trial in 17 Dutch hospitals. We randomized patients with PE without any of the Hestia criteria to direct discharge or additional NT-proBNP testing. We discharged the latter patients as well if NT-proBNP did not exceed 500 ng/L or admitted them if NT-proBNP was greater than 500 ng/L. The primary endpoint was 30-day adverse outcome defined as PE- or bleeding-related mortality, cardiopulmonary resuscitation, or intensive care unit admission. The noninferiority margin for the primary endpoint was 3.4%. MEASUREMENTS AND MAIN RESULTS: We randomized 550 patients. In the NT-proBNP group, 34 of 275 (12%) had elevated NT-proBNP values and were managed as inpatients. No patient (0 of 34) with an elevated NT-proBNP level treated in hospital (0%; 95% confidence interval [CI], 0-10.2%), versus no patient (0 of 23) with a post hoc-determined elevated NT-proBNP level from the direct discharge group (0%; 95% CI, 0-14.8%), experienced the primary endpoint. In both trial cohorts, the primary endpoint occurred in none of the 275 patients (0%; 95% CI, 0-1.3%) subjected to NT-proBNP testing, versus in 3 of 275 patients (1.1%; 95% CI, 0.2-3.2%) in the direct discharge group (P = 0.25). During the 3-month follow-up, recurrent venous thromboembolism occurred in two patients (0.73%; 95% CI, 0.1-2.6%) in the NT-proBNP group versus three patients (1.1%; 95% CI, 0.2-3.2%) in the direct discharge group (P = 0.65). CONCLUSIONS: Outpatient treatment of patients with PE selected on the basis of the Hestia criteria alone was associated with a low risk of adverse events. Given the low number of patients with elevated NT-proBNP levels, this trial was unable to draw definite conclusions regarding the incremental value of NT-proBNP testing in patients who fulfill the Hestia criteria. Clinical trial registered with www.trialregister.nl/trialreg/admin/rctview.asp?TC=2603 (NTR2603).

Outpatient versus inpatient treatment in patients with pulmonary embolism: a meta-analysis.

Our aim was to study the safety of outpatient treatment in low risk patients with acute pulmonary embolism compared with inpatient treatment, the current clinical standard. We searched Medline, Web of Science, Cochrane and EMBASE databases and included studies on outpatient treatment of pulmonary embolism. The outcomes were 3-month recurrent venous thromboembolism, major bleeding and all-cause mortality. We identified 13 studies (1657 patients) with outpatients (discharge <24 h), three studies (256 patients) with early discharge patients (discharged within 72 h) and five studies (383 patients) with inpatients. The pooled incidence of recurrent venous thromboembolism was 1.7% (95% CI 0.92-3.1%) in outpatients, 1.1% (0.22-5.4%) in patients discharged early and 1.2% (0.16-8.1%) in inpatients. The pooled incidence of major bleeding was 0.97% (0.58-1.6%) in outpatients, 0.78% (0.16-3.7%) in early discharge patients and 1.0% (0.39-2.8%) in inpatients. The pooled incidence of mortality was 1.9% (0.79-4.6%) in outpatients, 2.3% (1.1-5.1%) in early discharge patients and 0.74% (0.04-11%) in inpatients. Incidences of recurrent venous thromboembolism, major bleeding and, after correction for malignancies, mortality were comparable between outpatients, patients discharged early and inpatients. We conclude that home treatment or early discharge of selected low-risk patients with pulmonary embolism is as safe as inpatient treatment.

Hestia criteria can discriminate high- from low-risk patients with pulmonary embolism.

We investigated whether the clinical criteria used in the Hestia study for selection of pulmonary embolism (PE) patients for outpatient treatment could discriminate PE patients with high and low risk for adverse clinical outcome. We performed a cohort study with PE patients who were triaged with 11 criteria for outpatient treatment. Patients not eligible for outpatient treatment were treated in hospital. Study outcomes were recurrent venous thromboembolism, major bleeding and all-cause mortality during 3 months. In total, 530 patients were included, of which 297 were treated at home. In the outpatient group, six patients (2.0%, 95% CI 0.7-4.3%) had recurrent venous thromboembolism versus nine in-patients (3.9%, 95% CI 1.9-7.0%). Three patients (1.0%, 95% CI 0.2-2.9) died during the 3-months follow-up in the outpatient group versus 22 patients (9.6%, 95% CI 6.3-14) in the in-patient group (p<0.05). None of the outpatients died as a result of fatal PE versus five (2.2%) in-patients (p<0.05). In the outpatient group, 0.7% (95% CI 0.08-2.4) had major bleeding events versus 4.8% (95% CI 2.4-8.4) of in-patients (p<0.05). This study showed that the Hestia criteria can discriminate PE patients with low risk from patients with high risk for adverse clinical outcome. The low-risk patients can safely be treated at home.

Patient outcomes after acute pulmonary embolism. A pooled survival analysis of different adverse events.

RATIONALE: There is a lack of information on the long-term prognosis of patients with acute pulmonary embolism (PE). OBJECTIVES: To assess the long-term risk for adverse events after PE. METHODS: Consecutive patients diagnosed with PE between January 2001 and July 2007, and patients in whom PE was ruled out from a previous study were followed until July 2008 for the occurrence of adverse clinical events: mortality, symptomatic recurrent venous thromboembolism, cancer, arterial cardiovascular events and chronic thromboembolic pulmonary hypertension. Hazard ratios (HR) for all endpoints and a combined endpoint were calculated and adjusted for potential confounders. MEASUREMENTS AND MAIN RESULTS: Three hundred eight patients with unprovoked, 558 with provoked, and 334 without PE were studied with a median follow-up period of 3.3 years. Patients with unprovoked PE had a lower overall risk for mortality than patients with provoked PE (HR, 0.59; 95% confidence interval [CI], 0.43-0.82), but a higher risk for nonmalignancy-related mortality (HR, 1.8; 95% CI, 1.3-2.5), recurrent venous thromboembolism (HR, 2.1; 95% CI, 1.3-3.1), cancer (HR, 4.4; 95% CI, 2.0-10), cardiovascular events (HR, 2.6; 95% CI, 1.5-3.8) and chronic thromboembolic pulmonary hypertension (1.5 vs. 0%). The risk for the combined endpoint did not differ between both groups (HR, 0.98; 95% CI, 0.82-1.1). Patients without PE had similar risks for malignancy and cardiovascular events than patients with provoked PE, but lower risks for the remaining outcomes. The fraction of both patients with provoked and unprovoked PE without events after 1 year was only 70% and decreased to fewer than 60% after 2 years and fewer than 50% after 4 years, whereas this latter was 84% for the control patients. CONCLUSIONS: The clinical course of acute PE is complicated by high rates of serious adverse events, which occur in half of the patients within 4 years.

Reasons for Hospitalization of Patients with Acute Pulmonary Embolism Based on the Hestia Decision Rule.

BACKGROUND: The Hestia criteria can be used to select pulmonary embolism (PE) patients for outpatient treatment. The subjective Hestia criterion "medical/social reason for admission" allows the treating physician to consider any patient-specific circumstances in the final management decision. It is unknown how often and why this criterion is scored. METHODS: This is a patient-level post hoc analysis of the combined Hestia and Vesta studies. The main outcomes were the frequency of all scored Hestia items in hospitalized patients and the explicit reason for scoring the subjective criterion. Hemodynamic parameters and computed tomography-assessed right ventricular (RV)/left ventricular (LV) ratio of those only awarded with the subjective criterion were compared with patients treated at home. RESULTS: From the 1,166 patients screened, data were available for all 600 who were hospitalized. Most were hospitalized to receive oxygen therapy (45%); 227 (38%) were only awarded with the subjective criterion, of whom 51 because of "intermediate to intermediate-high risk PE." Compared with patients with intermediate risk PE (RV/LV ratio > 1.0) treated at home (179/566, 32%), hospitalized patients with only the subjective criterion had a higher mean RV/LV ratio (mean difference +0.30, 95% confidence interval [CI] 0.19-0.41) and a higher heart rate (+18/min, 95% CI 10-25). No relevant differences were observed for other hemodynamic parameters. CONCLUSION: The most frequent reason for hospital admission was oxygen therapy. In the decision to award the subjective criterion as sole argument for admission, the severity of the RV overload and resulting hemodynamic response of the patient was taken into account rather than just abnormal RV/LV ratio.

Comparison of two methods for selection of out of hospital treatment in patients with acute pulmonary embolism.

The aim of this study is to compare the performance of two clinical decision rules to select patients with acute pulmonary embolism (PE) for outpatient treatment: the Hestia criteria and the simplified Pulmonary Embolism Severity Index (sPESI). From 2008 to 2010, 468 patients with PE were triaged with the Hestia criteria for outpatient treatment: 247 PE patients were treated at home and 221 were treated as inpatients. The outcome of interest was all-cause 30-day mortality. In a post-hoc fashion, the sPESI items were scored and patients were classified according to the sPESI in low and high risk groups. Of the 247 patients treated at home, 189 (77%) patients were classified as low risk according to the sPESI and 58 patients (23%) as high risk. In total, 11 patients died during the first month; two patients treated at home and nine patients treated in-hospital. None of the patients treated at home died of fatal PE. Both the Hestia criteria and sPESI selected >50% of patients as low risk, with good sensitivity and negative predictive values for 30-day mortality: 82% and 99% for the Hestia criteria and 91% and 100% for the sPESI, respectively. The Hestia criteria and the sPESI classified different patients eligible for outpatient treatment, with similar low risks for 30-day mortality. This study suggests that the Hestia criteria may identify a proportion of high risk sPESI patiennts who can be safely treated at home, this however requires further validation.

Meta-analysis: serum creatinine changes following contrast enhanced CT imaging.

PURPOSE: Contrast induced nephropathy (CIN) is defined as a decrease in renal function following administration of contrast media. The aim of this meta-analysis was to asses the overall risk of CIN, chronic loss of kidney function and the need for renal replacement therapy (RRT) after intravenous contrast enhanced CT-scan. Secondly, we aimed to identify subgroups at increased risk for CIN. MATERIALS AND METHODS: A literature search in Pubmed, Medline, Embase and Cochrane databases was performed. Data extraction was carried out independently by two reviewers. Meta-analysis and meta-regression were performed using an exact likelihood approach. RESULTS: Forty studies evaluating the incidence of CIN after CT were included. The pooled incidence of CIN was 6.4% (95% CI 5.0-8.1). The risk of RRT after CIN was low, 0.06% (95% CI 0.01-0.4). The decline in renal function persisted in 1.1% of patients (95% CI 0.6-2.1%). Patients with chronic kidney disease (odds ratio 2.26, p<0.001) or diabetes mellitus (odds ratio 3.10, p<0.001) were at increased risk for the development of CIN. CONCLUSION: CIN occurred in 6% of patients after contrast enhanced CT. In 1% of all patients undergoing contrast enhanced CT the decline in renal function persisted.

Short-term hyperglycemic dysregulation in patients with type 1 diabetes does not change myocardial triglyceride content or myocardial function.

OBJECTIVE: To evaluate the effects of hyperglycemia due to partial insulin deprivation on myocardial triglyceride (TG) content and myocardial function in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Myocardial and hepatic TG content and left ventricular (LV) function were measured by magnetic resonance (MR) spectroscopy and MR imaging during optimal glucoregulation and after 24 h of partial insulin deprivation (n = 10). RESULTS: Mean insulin infusion rate was 45 +/- 5 units at baseline, whereas it was 27 +/- 5 units during hyperglycemia (per 24 h, P < 0.001). Plasma glucose levels increased from 8.4 +/- 0.6 to 15.9 +/- 0.8 mmol/l (P < 0.001), and plasma levels of nonesterified fatty acids from 0.31 +/- 0.05 to 0.46 +/- 0.07 mmol/l (P = 0.015). Hyperglycemia had no effects on myocardial or hepatic TG content and LV function. CONCLUSIONS: Short-term hyperglycemic dysregulation does not modulate myocardial or hepatic TG content or myocardial function, despite considerable metabolic adaptations.