Early and comprehensive care bundle in the elderly for acute heart failure in the emergency department: study protocol of the ELISABETH stepped-wedge cluster randomized trial

International audienceBackground: Acute heart failure (AHF) is one of the most common diagnoses for elderly patients in the emergency department (ED), with an admission rate above 80% and 1-month mortality around 10%. The European guidelines for the management of AHF are based on moderate levels of evidence, due to the lack of randomized controlled trials and the scarce evidence of any clinical added value of a specific treatment to improve outcomes. Recent reports suggest that the very early administration of full recommended therapy may decrease mortality. However, several studies have highlighted that elderly patients often received suboptimal treatment. Our hypothesis is that an early care bundle that comprises early and comprehensive management of symptoms, along with prompt detection and treatment of precipitating factors should improve AHF outcome in elderly patients.Methods/design: ELISABETH is a stepped-wedge, cluster randomized controlled, clinical trial in 15 emergency departments in France recruiting all patients aged 75 years and older with a diagnosis of AHF. The tested intervention is a care bundle with a checklist that mandates detection and early treatment of AHF precipitating factors, early and intensive treatment of congestion with intravenously administered nitrate boluses, and application of other recommended treatment (low-dose diuretics, non-invasive ventilation when indicated, and preventive low-molecular-weight heparin). Each center is randomized to the order in which they will switch from a "control period" to an "intervention period." All centers begin the trials with the control period for 2 weeks, then after each 2-week step a new center will enter the intervention period. At the end of the trial, all clusters will receive the intervention regimen. The primary outcome is the number of days alive and out of the hospital at 30 days.Discussion: If our hypothesis is confirmed, this trial will strengthen the level of evidence of AHF guidelines and stress the importance of the associated early and comprehensive treatment of precipitating factors. This trial could be the first to report a reduction in short-term morbidity and mortality in elderly AHF patients.Trial registration: ClinicalTrials.gov, ID: NCT03683212. Prospectively registered on 25 September 2018

Evaluation of the “hemoptysis” item in clinical decision rules for the diagnosis of pulmonary embolism in the emergency department

International audienceBackground: Hemoptysis is not common in pulmonary embolism (PE) and lacks specificity for its diagnosis. However, this item is present in different validated scores that estimate the clinical probability of PE. The relevance of this item in clinical decision rules (CDRs) is not clearly established.Objective: The aim of this study was to evaluate the impact of removing the "hemoptysis" item from the PERC, YEARS, and PEGeD CDR in patients with low clinical probability of PE.Design: This was a post hoc analysis of two European prospective cohorts, which included 2968 patients presenting to the ED with a low clinical probability of PE (PROPER and PERCEPIC) and a 3-month follow-up. The primary endpoint was the false-negative rate of a CDR score without the hemoptysis item. Secondary endpoints included the potential reduction of chest imaging if the item hemoptysis was to be removed and risk stratification of the Geneva and Wells scores without the hemoptysis item.Results: Of 2968 patients included (mean ± SD age 46 ± 18 years, 53% female), 87 patients (3%) had a PE diagnosed at 3 months. A total of 2908 were followed-up at 3 months and analyzed. Using the PERC rule with and without the hemoptysis item, there were 13 and 14 missed cases of PE, respectively (failure rate 0.45% [95% CI 0.25%-0.78%] and 0.48% [95% CI 0.27%-0.82%]). Using the YEARS strategy, there were 11 missed PE cases with or without the hemoptysis item (false-negative rate 0.57% [95% CI 0.30%-1.05%]). With the PERC and YEARS rule, removing the hemoptysis item would have led to a 1% reduction in chest imaging. The PEGeD strategy was not modified by the removal of the hemoptysis item.Conclusions: The hemoptysis item could be safely removed from the PERC, YEARS, and PEGeD CDRs. However, there was no subsequent clinically relevant reduction of chest imaging

Early and comprehensive care bundle in the elderly for acute heart failure in the emergency department: study protocol of the ELISABETH stepped-wedge cluster randomized trial

Background Acute heart failure (AHF) is one of the most common diagnoses for elderly patients in the emergency department (ED), with an admission rate above 80% and 1-month mortality around 10%. The European guidelines for the management of AHF are based on moderate levels of evidence, due to the lack of randomized controlled trials and the scarce evidence of any clinical added value of a specific treatment to improve outcomes. Recent reports suggest that the very early administration of full recommended therapy may decrease mortality. However, several studies have highlighted that elderly patients often received suboptimal treatment. Our hypothesis is that an early care bundle that comprises early and comprehensive management of symptoms, along with prompt detection and treatment of precipitating factors should improve AHF outcome in elderly patients. Methods/design ELISABETH is a stepped-wedge, cluster randomized controlled, clinical trial in 15 emergency departments in France recruiting all patients aged 75 years and older with a diagnosis of AHF. The tested intervention is a care bundle with a checklist that mandates detection and early treatment of AHF precipitating factors, early and intensive treatment of congestion with intravenously administered nitrate boluses, and application of other recommended treatment (low-dose diuretics, non-invasive ventilation when indicated, and preventive low-molecular-weight heparin). Each center is randomized to the order in which they will switch from a “control period” to an “intervention period.” All centers begin the trials with the control period for 2 weeks, then after each 2-week step a new center will enter the intervention period. At the end of the trial, all clusters will receive the intervention regimen. The primary outcome is the number of days alive and out of the hospital at 30 days. Discussion If our hypothesis is confirmed, this trial will strengthen the level of evidence of AHF guidelines and stress the importance of the associated early and comprehensive treatment of precipitating factors. This trial could be the first to report a reduction in short-term morbidity and mortality in elderly AHF patients. Trial registration ClinicalTrials.gov, ID: NCT03683212. Prospectively registered on 25 September 2018

Early and comprehensive care bundle in the elderly for acute heart failure in the emergency department: study protocol of the ELISABETH stepped-wedge cluster randomized trial

International audienceBackground: Acute heart failure (AHF) is one of the most common diagnoses for elderly patients in the emergency department (ED), with an admission rate above 80% and 1-month mortality around 10%. The European guidelines for the management of AHF are based on moderate levels of evidence, due to the lack of randomized controlled trials and the scarce evidence of any clinical added value of a specific treatment to improve outcomes. Recent reports suggest that the very early administration of full recommended therapy may decrease mortality. However, several studies have highlighted that elderly patients often received suboptimal treatment. Our hypothesis is that an early care bundle that comprises early and comprehensive management of symptoms, along with prompt detection and treatment of precipitating factors should improve AHF outcome in elderly patients.Methods/design: ELISABETH is a stepped-wedge, cluster randomized controlled, clinical trial in 15 emergency departments in France recruiting all patients aged 75 years and older with a diagnosis of AHF. The tested intervention is a care bundle with a checklist that mandates detection and early treatment of AHF precipitating factors, early and intensive treatment of congestion with intravenously administered nitrate boluses, and application of other recommended treatment (low-dose diuretics, non-invasive ventilation when indicated, and preventive low-molecular-weight heparin). Each center is randomized to the order in which they will switch from a "control period" to an "intervention period." All centers begin the trials with the control period for 2 weeks, then after each 2-week step a new center will enter the intervention period. At the end of the trial, all clusters will receive the intervention regimen. The primary outcome is the number of days alive and out of the hospital at 30 days.Discussion: If our hypothesis is confirmed, this trial will strengthen the level of evidence of AHF guidelines and stress the importance of the associated early and comprehensive treatment of precipitating factors. This trial could be the first to report a reduction in short-term morbidity and mortality in elderly AHF patients.Trial registration: ClinicalTrials.gov, ID: NCT03683212. Prospectively registered on 25 September 2018

Evaluation of the “hemoptysis” item in clinical decision rules for the diagnosis of pulmonary embolism in the emergency department

International audienceBackground: Hemoptysis is not common in pulmonary embolism (PE) and lacks specificity for its diagnosis. However, this item is present in different validated scores that estimate the clinical probability of PE. The relevance of this item in clinical decision rules (CDRs) is not clearly established.Objective: The aim of this study was to evaluate the impact of removing the "hemoptysis" item from the PERC, YEARS, and PEGeD CDR in patients with low clinical probability of PE.Design: This was a post hoc analysis of two European prospective cohorts, which included 2968 patients presenting to the ED with a low clinical probability of PE (PROPER and PERCEPIC) and a 3-month follow-up. The primary endpoint was the false-negative rate of a CDR score without the hemoptysis item. Secondary endpoints included the potential reduction of chest imaging if the item hemoptysis was to be removed and risk stratification of the Geneva and Wells scores without the hemoptysis item.Results: Of 2968 patients included (mean ± SD age 46 ± 18 years, 53% female), 87 patients (3%) had a PE diagnosed at 3 months. A total of 2908 were followed-up at 3 months and analyzed. Using the PERC rule with and without the hemoptysis item, there were 13 and 14 missed cases of PE, respectively (failure rate 0.45% [95% CI 0.25%-0.78%] and 0.48% [95% CI 0.27%-0.82%]). Using the YEARS strategy, there were 11 missed PE cases with or without the hemoptysis item (false-negative rate 0.57% [95% CI 0.30%-1.05%]). With the PERC and YEARS rule, removing the hemoptysis item would have led to a 1% reduction in chest imaging. The PEGeD strategy was not modified by the removal of the hemoptysis item.Conclusions: The hemoptysis item could be safely removed from the PERC, YEARS, and PEGeD CDRs. However, there was no subsequent clinically relevant reduction of chest imaging

Low compliance to guidelines in the management of acute heart failure in emergency elderly patients

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Early-onset pneumonia following bag-mask ventilation versus endotracheal intubation during cardiopulmonary resuscitation: A substudy of the CAAM trial

International audienceAim: Early-onset pneumonia (EOP) is a common in-hospital complication in survivors of out-of-hospital cardiac arrest. In this substudy of the CAAM trial, we aimed to compare whether bag mask ventilation (BMV) compared to endotracheal intubation (ETI) performed during cardiopulmonary resuscitation increases the risk of developing EOP.Methods: Adult patients from the CAAM trial that survived beyond 12 h of hospitalization were included. Information about in-hospital management and outcome of study subjects was systematically collected. Our primary aim was to compare the incidence of EOP in the BMV and ETI group using a series of bivariate analysis adjusting for one variable at a time and a logistic regression controlled for survival beyond 96 h, age, gender, catecholamine administration, no flow time, and initial shockable rhythm.Results: Of 627 patients from the CAAM trial that survived to hospital admission, 409 patients were hospitalized beyond 12 h and thus included (202 randomized to BMV and 20 7 randomized to ETI). Patients in the BMV group had a significantly longer period of unsecured airway during prehospital cardiopulmonary resuscitation (BMV (median): 33 min; ETI (median): 17 min, p < 0.0001). No significant difference in the development of EOP according to airway management was identified on univariate analysis (BMV: 53%, ETI: 53%, Odds Ratio 1.0 [0.7-1.5], p = 1.0). We found no difference in the development of EOP according to airway management in the series of bivariate analyses or in the multivariable regression analysis either.Conclusion: In this substudy of the CAAM trial, development of early-onset pneumonia in out-of-hospital cardiac arrest survivors did not depend on airway management technique during CPR

Patient care pathways in acute heart failure and their impact on in-hospital mortality, a French national prospective survey

International audienceBackground: Our purpose was to describe the care pathway of patients hospitalized for acute heart failure (AHF) and investigate whether a management involving a cardiology department had an impact on in-hospital mortality.Methods: Between June 2014 and October 2018, we included patients hospitalized for AHF in 24 French hospitals. Characteristics of the episode, patient's care pathway and outcomes were recorded on a specific assessment tool. The primary outcome was the association between patient care pathway and in-hospital mortality. The independent association between admission to a cardiology ward and in-hospital mortality was assessed through a multivariate regression model and propensity score matching.Results: A total of 3677 patients, mean age of 78, were included. The in-hospital mortality rate was 8% (n = 287) and was associated on multivariate regression with advanced age, presence of sepsis, of cardiogenic shock, high New York Heart Association (NYHA) score and increased plasma creatinine level on admission. High blood pressure and admission to a cardiology department appeared as protective factors. After propensity score matching, hospitalization in a cardiology department remained a protective factor of in-hospital mortality (OR = 0.61 [0.44-0.84], p = 0.002).Conclusion: A hospital course of care involving a cardiology department was associated with an increase in hospital survival in AHF patients. These finding may highlight the importance of collaboration between cardiologists and other in-hospitals specialties, such as emergency physicians, in order to find the best in-hospital pathway for patients with AHF.Clinical Trial NCT03903198

Effect of an Emergency Department Care Bundle on 30-Day Hospital Discharge and Survival Among Elderly Patients With Acute Heart Failure: The ELISABETH Randomized Clinical Trial

International audienceKey PointsQuestionDoes an intervention aimed at improving guideline adherence for the management of acute heart failure, including intensive intravenous nitrate therapy and management of precipitating factors, improve hospital discharge and survival at 30 days?FindingsIn this stepped-wedge cluster randomized trial that included 503 patients 75 years and older who presented to the emergency department with acute heart failure, implementation of an early and comprehensive care bundle compared with usual care improved guideline adherence, but had no significant effect on number of days alive and out of hospital at 30 days (median of 19 d in both groups).MeaningsThis emergency department care bundle did not improve 30-day outcomes among older patients with acute heart failure. AbstractImportanceClinical guidelines for the early management of acute heart failure in the emergency department (ED) setting are based on only moderate levels of evidence, with subsequent low adherence to these guidelines.ObjectiveTo test the effect of an early guideline-recommended care bundle on short-term prognosis in older patients with acute heart failure in the ED.Design, Setting, and ParticipantsStepped-wedge cluster randomized trial in 15 EDs in France of 503 patients 75 years and older with a diagnosis of acute heart failure in the ED from December 2018 to September 2019 and followed up for 30 days until October 2019.InterventionsA care bundle that included early intravenous nitrate boluses; management of precipitating factors, such as acute coronary syndrome, infection, or atrial fibrillation; and moderate dose of intravenous diuretics (n = 200). In the control group, patient care was left to the discretion of the treating emergency physician (n = 303). Each center was randomized to the order in which they switched to the “intervention period.” After the initial 4-week control period for all centers, 1 center entered in the intervention period every 2 weeks.Main Outcomes and MeasuresThe primary end point was the number of days alive and out of hospital at 30 days. Secondary outcomes included 30-day all-cause mortality, 30-day cardiovascular mortality, unscheduled readmission, length of hospital stay, and kidney impairment.ResultsAmong 503 patients who were randomized (median age, 87 years; 298 [59%] women), 502 were analyzed. In the intervention group, patients received a median (interquartile range) of 27.0 (9-54) mg of intravenous nitrates in the first 4 hours vs 4.0 (2.0-6.0) mg in the control group (adjusted difference, 23.8 [95% CI, 13.5-34.1]). There was a significantly higher percentage of patients in the intervention group treated for their precipitating factors than in the control group (58.8% vs 31.9%; adjusted difference, 31.1% [95% CI, 14.3%-47.9%]). There was no statistically significant difference in the primary end point of the number of days alive and out of hospital at 30 days (median [interquartile range], 19 [0- 24] d in both groups; adjusted difference, −1.9 [95% CI, −6.6 to 2.8]; adjusted ratio, 0.88 [95% CI, 0.64-1.21]). At 30 days, there was no significant difference between the intervention and control groups in mortality (8.0% vs 9.7%; adjusted difference, 4.1% [95% CI, −17.2% to 25.3%]), cardiovascular mortality (5.0% vs 7.4%; adjusted difference, 2.1% [95% CI, −15.5% to 19.8%]), unscheduled readmission (14.3% vs 15.7%; adjusted difference, −1.3% [95% CI, −26.3% to 23.7%]), median length of hospital stay (8 d in both groups; adjusted difference, 2.5 [95% CI, −0.9 to 5.8]), and kidney impairment (1% in both groups).Conclusions and RelevanceAmong older patients with acute heart failure, use of a guideline-based comprehensive care bundle in the ED compared with usual care did not result in a statistically significant difference in the number of days alive and out of the hospital at 30 days. Further research is needed to identify effective treatments for acute heart failure in older patients.Trial Registration ClinicalTrials.gov Identifier: NCT0368321

Effect of a Diagnostic Strategy Using an Elevated and Age-Adjusted D-Dimer Threshold on Thromboembolic Events in Emergency Department Patients With Suspected Pulmonary Embolism

International audienceImportance: Uncontrolled studies suggest that pulmonary embolism (PE) can be safely ruled out using the YEARS rule, a diagnostic strategy that uses varying D-dimer thresholds.Objective: To prospectively validate the safety of a strategy that combines the YEARS rule with the pulmonary embolism rule-out criteria (PERC) rule and an age-adjusted D-dimer threshold.Design, settings, and participants: A cluster-randomized, crossover, noninferiority trial in 18 emergency departments (EDs) in France and Spain. Patients (N = 1414) who had a low clinical risk of PE not excluded by the PERC rule or a subjective clinical intermediate risk of PE were included from October 2019 to June 2020, and followed up until October 2020.Interventions: Each center was randomized for the sequence of intervention periods. In the intervention period (726 patients), PE was excluded without chest imaging in patients with no YEARS criteria and a D-dimer level less than 1000 ng/mL and in patients with 1 or more YEARS criteria and a D-dimer level less than the age-adjusted threshold (500 ng/mL if age <50 years or age in years × 10 in patients ≥50 years). In the control period (688 patients), PE was excluded without chest imaging if the D-dimer level was less than the age-adjusted threshold.Main outcomes and measures: The primary end point was venous thromboembolism (VTE) at 3 months. The noninferiority margin was set at 1.35%. There were 8 secondary end points, including chest imaging, ED length of stay, hospital admission, nonindicated anticoagulation treatment, all-cause death, and all-cause readmission at 3 months.Results: Of the 1414 included patients (mean age, 55 years; 58% female), 1217 (86%) were analyzed in the per-protocol analysis. PE was diagnosed in the ED in 100 patients (7.1%). At 3 months, VTE was diagnosed in 1 patient in the intervention group (0.15% [95% CI, 0.0% to 0.86%]) vs 5 patients in the control group (0.80% [95% CI, 0.26% to 1.86%]) (adjusted difference, -0.64% [1-sided 97.5% CI, -∞ to 0.21%], within the noninferiority margin). Of the 6 analyzed secondary end points, only 2 showed a statistically significant difference in the intervention group compared with the control group: chest imaging (30.4% vs 40.0%; adjusted difference, -8.7% [95% CI, -13.8% to -3.5%]) and ED median length of stay (6 hours [IQR, 4 to 8 hours] vs 6 hours [IQR, 5 to 9 hours]; adjusted difference, -1.6 hours [95% CI, -2.3 to -0.9]).Conclusions and relevance: Among ED patients with suspected PE, the use of the YEARS rule combined with the age-adjusted D-dimer threshold in PERC-positive patients, compared with a conventional diagnostic strategy, did not result in an inferior rate of thromboembolic events.Trial registration: ClinicalTrials.gov Identifier: NCT04032769