Rule-out of non-ST-segment elevation acute coronary syndrome by a single, pre-hospital troponin measurement: a randomized trial.

AIMS: Patients with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS) are routinely transferred to the emergency department (ED). A clinical risk score with point-of-care (POC) troponin measurement might enable ambulance paramedics to identify low-risk patients in whom ED evaluation is unnecessary. The aim was to assess safety and healthcare costs of a pre-hospital rule-out strategy using a POC troponin measurement in low-risk suspected NSTE-ACS patients. METHODS AND RESULTS: This investigator-initiated, randomized clinical trial was conducted in five ambulance regions in the Netherlands. Suspected NSTE-ACS patients with HEAR (History, ECG, Age, Risk factors) score ≤3 were randomized to pre-hospital rule-out with POC troponin measurement or direct transfer to the ED. The sample size calculation was based on the primary outcome of 30-day healthcare costs. Secondary outcome was safety, defined as 30-day major adverse cardiac events (MACE), consisting of ACS, unplanned revascularization or all-cause death. : A total of 863 participants were randomized. Healthcare costs were significantly lower in the pre-hospital strategy (€1349 ± €2051 vs. €1960 ± €1808) with a mean difference of €611 [95% confidence interval (CI): 353-869; P < 0.001]. In the total population, MACE were comparable between groups [3.9% (17/434) in pre-hospital strategy vs. 3.7% (16/429) in ED strategy; P = 0.89]. In the ruled-out ACS population, MACE were very low [0.5% (2/419) vs. 1.0% (4/417)], with a risk difference of -0.5% (95% CI -1.6%-0.7%; P = 0.41) in favour of the pre-hospital strategy. CONCLUSION: Pre-hospital rule-out of ACS with a POC troponin measurement in low-risk patients significantly reduces healthcare costs while incidence of MACE was low in both strategies. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT05466591 and International Clinical Trials Registry Platform id NTR 7346.

Rationale and design of the PRAETORIAN-COVID trial: A double-blind, placebo-controlled randomized clinical trial with valsartan for PRevention of Acute rEspiraTORy dIstress syndrome in hospitAlized patieNts with SARS-COV-2 Infection Disease.

There is much debate on the use of angiotensin receptor blockers (ARBs) in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-infected patients. Although it has been suggested that ARBs might lead to a higher susceptibility and severity of SARS-CoV-2 infection, experimental data suggest that ARBs may reduce acute lung injury via blocking angiotensin-II-mediated pulmonary permeability, inflammation, and fibrosis. However, despite these hypotheses, specific studies on ARBs in SARS-CoV-2 patients are lacking. METHODS: The PRAETORIAN-COVID trial is a multicenter, double-blind, placebo-controlled 1:1 randomized clinical trial in adult hospitalized SARS-CoV-2-infected patients (n = 651). The primary aim is to investigate the effect of the ARB valsartan compared to placebo on the composite end point of admission to an intensive care unit, mechanical ventilation, or death within 14 days of randomization. The active-treatment arm will receive valsartan in a dosage titrated to blood pressure up to a maximum of 160 mg bid, and the placebo arm will receive matching placebo. Treatment duration will be 14 days, or until the occurrence of the primary end point or until hospital discharge, if either of these occurs within 14 days. The trial is registered at clinicaltrials.gov (NCT04335786, 2020). SUMMARY: The PRAETORIAN-COVID trial is a double-blind, placebo-controlled 1:1 randomized trial to assess the effect of valsartan compared to placebo on the occurrence of ICU admission, mechanical ventilation, and death in hospitalized SARS-CoV-2-infected patients. The results of this study might impact the treatment of SARS-CoV-2 patients globally.

Pre-hospital rule-out of non-ST-segment elevation acute coronary syndrome by a single troponin: final one-year outcomes of the ARTICA randomised trial.

BACKGROUND AND AIMS: The healthcare burden of acute chest pain is enormous. In the randomized ARTICA trial, we showed that pre-hospital identification of low-risk patients and rule-out of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) with point-of-care (POC) troponin measurement reduces 30-day healthcare costs with low major adverse cardiac events (MACE) incidence. Here we present the final 1-year results of the ARTICA trial. METHODS: Low-risk patients with suspected NSTE-ACS were randomized to pre-hospital rule-out with POC troponin measurement or emergency department (ED) transfer. Primary 1-year outcome was healthcare costs. Secondary outcomes were safety, quality of life (QoL), and cost-effectiveness. Safety was defined as a 1-year MACE consisting of ACS, unplanned revascularization, or all-cause death. QoL was measured with EuroQol-5D-5L questionnaires. Cost-effectiveness was defined as 1-year healthcare costs difference per QoL difference. RESULTS: Follow-up was completed for all 863 patients. Healthcare costs were significantly lower in the pre-hospital strategy (€1932 ± €2784 vs. €2649 ± €2750), mean difference €717 [95% confidence interval (CI) €347 to €1087; P < 0.001]. In the total population, the 1-year MACE rate was comparable between groups [5.1% (22/434) in the pre-hospital strategy vs. 4.2% (18/429) in the ED strategy; P = 0.54]. In the ruled-out ACS population, 1-year MACE remained low [1.7% (7/419) vs. 1.4% (6/417)], risk difference 0.2% (95% CI -1.4% to 1.9%; P = 0.79). QoL showed no significant difference between strategies. CONCLUSIONS: Pre-hospital rule-out of NSTE-ACS with POC troponin testing in low-risk patients is cost-effective, as expressed by a sustainable healthcare cost reduction and no significant effect on QoL. One-year MACE remained low for both strategies.

Differences in risk and costs between prehospital identified low-risk men and women with chest pain.

OBJECTIVE: Prehospital rule-out of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) in low-risk patient with a point-of-care troponin measurement reduces healthcare costs with similar safety to standard transfer to the hospital. Risk stratification is performed identical for men and women, despite important differences in clinical presentation, risk factors and age between men and women with NSTE-ACS. Our aim was to compare safety and healthcare costs between men and women in prehospital identified low-risk patients with suspected NSTE-ACS. METHODS: In the Acute Rule-out of non-ST-segment elevation acute coronary syndrome in the (pre)hospital setting by HEART (History, ECG, Age, Risk factors and Troponin) score assessment and a single poInt of CAre troponin randomised trial, the HEAR (History, ECG, Age and Risk factors) score was assessed by ambulance paramedics in suspected NSTE-ACS patients. Low-risk patients (HEAR score ≤3) were included. In this substudy, men and women were compared. Primary endpoint was 30-day major adverse cardiac events (MACE), secondary endpoints were 30-day healthcare costs and the scores for the HEAR score components. RESULTS: A total of 863 patients were included, of which 495 (57.4%) were women. Follow-up was completed in all patients. In the total population, MACE occurred in 6.8% of the men and 1.6% of the women (risk ratio (RR) 4.2 (95% CI 1.9 to 9.2, p<0.001)). In patients with ruled-out ACS (97% of the total population), MACE occurred in 1.4% of the men and in 0.2% of the women (RR 7.0 (95% CI 2.0 to 14.2, p<0.001). Mean healthcare costs were €504.55 (95% CI €242.22 to €766.87, p<0.001) higher in men, mainly related to MACE. CONCLUSIONS: In a prehospital population of low-risk suspected NSTE-ACS patients, 30-day incidence of MACE and MACE-related healthcare costs were significantly higher in men than in women. TRIAL REGISTRATION NUMBER: NCT05466591.

Implementation of the ESC 0 h/1h algorithm and the HEART score in the emergency department: A prospective cohort study.

Background: The European Society of Cardiology (ESC) 0 h/1h algorithm is the preferred diagnostic strategy for chest pain patients in the emergency department (ED). It is suggested that adding clinical information to the algorithm improves its diagnostic performance. This study evaluates implementation of the ESC 0 h/1h algorithm in the ED and investigates the potential advantages of combining it with a clinical decision rule, which might be especially relevant in the heterogenous observation category. Methods: In this prospective cohort study, chest pain patients in whom the ESC 0 h/1h algorithm was applied were enrolled. HEART score components were collected. Diagnostic characteristics were determined for the algorithm with and without addition of the HEART score. Primary endpoint was a composite endpoint at 30-day follow-up, consisting of myocardial infarction and death. Results: A total of 668 patients were enrolled. The rule-in and rule-out categories consisted of 8.2% and 54.9% of the patients, respectively. Positive predictive value and specificity of the rule-in category were 67.3% and 97.1%, respectively. Negative predictive value (NPV) and sensitivity of the rule-out category were both 100%. In the observation category, a HEART score ≤ 3 yielded a NPV and sensitivity of 97.1% and 93.8%, respectively. Conclusion: The ESC 0 h/1h algorithm yielded a NPV and sensitivity of 100% for myocardial infarction and death at 30-day follow-up. Addition of the HEART score did not provide clinically relevant advantages. Although the HEART score can be used to guide diagnostic testing in the observation category, a low HEART score did not yield an NPV of > 99%.

Acute rule-out of non-ST-segment elevation acute coronary syndrome in the (pre)hospital setting by HEART score assessment and a single point-of-care troponin: rationale and design of the ARTICA randomised trial.

INTRODUCTION: Because of the lack of prehospital protocols to rule out a non-ST-segment elevation acute coronary syndrome (NSTE-ACS), patients with chest pain are often transferred to the emergency department (ED) for thorough evaluation. However, in low-risk patients, an ACS is rarely found, resulting in unnecessary healthcare consumption. Using the HEART (History, ECG, Age, Risk factors and Troponin) score, low-risk patients are easily identified. When a point-of-care (POC) troponin measurement is included in the HEART score, an ACS can adequately be ruled out in low-risk patients in the prehospital setting. However, it remains unclear whether a prehospital rule-out strategy using the HEART score and a POC troponin measurement in patients with suspected NSTE-ACS is cost-effective. METHODS AND ANALYSIS: The ARTICA trial is a randomised trial in which the primary objective is to investigate the cost-effectiveness after 30 days of an early rule-out strategy for low-risk patients suspected of a NSTE-ACS, using a modified HEART score including a POC troponin T measurement. Patients are included by ambulance paramedics and 1:1 randomised for (1) presentation at the ED (control group) or (2) POC troponin T measurement (intervention group) and transfer of the care to the general practitioner in case of a low troponin T value. In total, 866 patients will be included. Follow-up will be performed after 30 days, 6 months and 12 months. ETHICS AND DISSEMINATION: This trial has been accepted by the Medical Research Ethics Committee region Arnhem-Nijmegen. The results of this trial will be disseminated in one main paper and in additional papers with subgroup analyses. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NL7148).

Effect of Face-to-Face vs Virtual Reality Training on Cardiopulmonary Resuscitation Quality: A Randomized Clinical Trial.

Importance: Bystander cardiopulmonary resuscitation (CPR) is crucial for survival after cardiac arrest but not performed in most cases. New, low-cost, and easily accessible training methods, such as virtual reality (VR), may reach broader target populations, but data on achieved CPR skills are lacking. Objective: To compare CPR quality between VR and face-to-face CPR training. Design, Setting, and Participants: Randomized noninferiority trial with a prospective randomized open blinded end point design. Participants were adult attendees from the science section of the Lowlands Music Festival (August 16 to 18, 2019) in the Netherlands. Analysis began September 2019. Interventions: Two standardized 20-minute protocols on CPR and automated external defibrillator use: instructor-led face-to-face training or VR training using a smartphone app endorsed by the Resuscitation Council (United Kingdom). Main Outcomes and Measures: During a standardized CPR scenario following the training, we assessed the primary outcome CPR quality, measured as chest compression depth and rate using CPR manikins. Overall CPR performance was assessed by examiners, blinded for study groups, using a European Resuscitation Council-endorsed checklist (maximum score, 13). Additional secondary outcomes were chest compression fraction, proportions of participants with mean depth (50 mm-60 mm) or rate (100 min-1-120 min-1) within guideline ranges, and proportions compressions with full release. Results: A total of 381 participants were randomized: 216 women (57%); median (interquartile range [IQR]) age, 26 (22-31) years. The VR app (n = 190 [49.9%]) was inferior to face-to-face training (n = 191 [50.1%]) for chest compression depth (mean [SD], VR: 49 [10] mm vs face to face: 57 [5] mm; mean [95% CI] difference, -8 [-9 to -6] mm), and noninferior for chest compression rate (mean [SD]: VR: 114 [12] min-1 vs face to face: 109 [12] min-1; mean [95% CI] difference, 6 [3 to 8] min-1). The VR group had lower overall CPR performance scores (median [IQR], 10 [8-12] vs 12 [12-13]; P < .001). Chest compression fraction (median [IQR], 61% [52%-66%] vs 67% [62%-71%]; P < .001) and proportions of participants fulfilling depth (51% [n = 89] vs 75% [n = 133], P < .001) and rate (50% [n = 87] vs 63% [n = 111], P = .01) requirements were also lower in the VR group. The proportion of compressions with full release was higher in the VR group (median [IQR], 98% [59%-100%] vs 88% [55%-99%]; P = .002). Conclusions and Relevance: In this randomized noninferiority trial, VR training resulted in comparable chest compression rate but inferior compression depth compared with face-to-face training. Given the potential of VR training to reach a larger target population, further development is needed to achieve the compression depth and overall CPR skills acquired by face-to-face training. Trial Registration: ClinicalTrials.gov identifier: NCT04013633.