Effect of Cangrelor on Infarct Size in ST-Segment Elevation Myocardial Infarction Treated By Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

Background: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarct (MI) size in the pre-clinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction (MVO) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Methods: This was a Phase 2, multi-center, randomized, double-blind, placebo controlled clinical trial conducted between November 2017 to November 2021 in six cardiac centers in Singapore (NCT03102723). Patients were randomized to receive either cangrelor or placeboinitiated prior to the PPCI procedure on top of oral ticagrelor. The key exclusion criteria included: presenting <6 hours of symptom onset, prior MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance (CMR). The primary efficacy endpoint was acute MI size by CMR within the first week expressed as percentage of the left ventricle mass ( %LVmass). MVO was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety endpoint was Bleeding Academic Research Consortium (BARC)-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test [reported as median (1st quartile- 3rd quartile)] and categorical variables were compared by Fisher's exact test. A 2-sided P<0.05 was considered statistically significant. Results: Of 209 recruited patients, 164 patients (78% ) completed the acute CMR scan. There were no significant differences in acute MI size [placebo: 14.9 (7.3 - 22.6) %LVmass versus cangrelor: 16.3 (9.9 - 24.4)%LVmass, P=0.40] or the incidence [placebo: 48% versus cangrelor: 47%, P=0.99] and extent of MVO [placebo:1.63 (0.60 - 4.65)%LVmass versus cangrelor: 1.18 (0.53 - 3.37)%LVmass, P=0.46] between placebo and cangrelor despite a two-fold decrease in platelet reactivity with cangrelor. There were no BARC-defined major bleeding events in either group in the first 48 hours. Conclusions: Cangrelor administered at time of PPCI did not reduce acute MI size or prevent MVO in STEMI patients given oral ticagrelor despite a significant reduction of platelet reactivity during the PCI procedure.

Protocol for a multi-site randomized controlled trial of a stepped-care intervention for emergency department patients with panic-related anxiety.

BACKGROUND: Approximately 40% of Emergency Department (ED) patients with chest pain meet diagnostic criteria for panic-related anxiety, but only 1-2% are correctly diagnosed and appropriately managed in the ED. A stepped-care model, which focuses on providing evidence-based interventions in a resource-efficient manner, is the state-of-the art for treating panic disorder patients in medical settings such as primary care. Stepped-care has yet to be tested in the ED setting, which is the first point of contact with the healthcare system for most patients with panic symptoms. METHODS: This multi-site randomized controlled trial (RCT) aims to evaluate the clinical, patient-centred, and economic effectiveness of a stepped-care intervention in a sample of 212 patients with panic-related anxiety presenting to the ED of Singapore's largest public healthcare group. Participants will be randomly assigned to either: 1) an enhanced care arm consisting of a stepped-care intervention for panic-related anxiety; or 2) a control arm consisting of screening for panic attacks and panic disorder. Screening will be followed by baseline assessments and blocked randomization in a 1:1 ratio. Masked follow-up assessments will be conducted at 1, 3, 6, and 12 months. Clinical outcomes will be panic symptom severity and rates of panic disorder. Patient-centred outcomes will be health-related quality of life, daily functioning, psychiatric comorbidity, and health services utilization. Economic effectiveness outcomes will be the incremental cost-effectiveness ratio of the stepped-care intervention relative to screening alone. DISCUSSION: This trial will examine the impact of early intervention for patients with panic-related anxiety in the ED setting. The results will be used to propose a clinically-meaningful and cost-effective model of care for ED patients with panic-related anxiety. TRIAL REGISTRATION: ClinicalTrials.gov NCT03632356. Retrospectively registered 15 August 2018.

Improved neurologically intact survival with the use of an automated, load-distributing band chest compression device for cardiac arrest presenting to the emergency department.

INTRODUCTION: It has been unclear if mechanical cardiopulmonary resuscitation (CPR) is a viable alternative to manual CPR. We aimed to compare resuscitation outcomes before and after switching from manual CPR to load-distributing band (LDB) CPR in a multi-center emergency department (ED) trial. METHODS: We conducted a phased, prospective cohort evaluation with intention-to-treat analysis of adults with non-traumatic cardiac arrest. At these two urban EDs, systems were changed from manual CPR to LDB-CPR. Primary outcome was survival to hospital discharge, with secondary outcome measures of return of spontaneous circulation, survival to hospital admission and neurological outcome at discharge. RESULTS: A total of 1,011 patients were included in the study, with 459 in the manual CPR phase (January 01, 2004, to August 24, 2007) and 552 patients in the LDB-CPR phase (August 16, 2007, to December 31, 2009). In the LDB phase, the LDB device was applied in 454 patients (82.3%). Patients in the manual CPR and LDB-CPR phases were comparable for mean age, gender and ethnicity. The mean duration from collapse to arrival at ED (min) for manual CPR and LDB-CPR phases was 34:03 (SD16:59) and 33:18 (SD14:57) respectively. The rate of survival to hospital discharge tended to be higher in the LDB-CPR phase (LDB 3.3% vs Manual 1.3%; adjusted OR, 1.42; 95% CI, 0.47, 4.29). There were more survivors in LDB group with cerebral performance category 1 (good) (Manual 1 vs LDB 12, P = 0.01). Overall performance category 1 (good) was Manual 1 vs LDB 10, P = 0.06. CONCLUSIONS: A resuscitation strategy using LDB-CPR in an ED environment was associated with improved neurologically intact survival on discharge in adults with prolonged, non-traumatic cardiac arrest.

Cardiopulmonary resuscitation interruptions with use of a load-distributing band device during emergency department cardiac arrest.

STUDY OBJECTIVE: Our primary aim is to measure no-flow time and no-flow ratio before and after an emergency department (ED) switched from manual to a load-distributing band mechanical cardiopulmonary resuscitation (CPR) device. METHODS: This was a phased, before-after cohort evaluation at an urban tertiary hospital ED. We collected continuous video and chest compression data with the Physiocontrol CodeStat Suite 7.0 for resuscitations during the period just before and after adoption of load-distributing band CPR. All out-of-hospital, nontraumatic cardiac arrest, adult patients were eligible. From February 2007 to July 2008, there were 26 manual and 41 load-distributing band cases. RESULTS: Patients in both phases were comparable in terms of demographics, medical history, witnessed arrest, arrest location, bystander CPR rates, out-of-hospital defibrillation, initial rhythm, and ED defibrillation. The median no-flow time, defined as the sum of all pauses between compressions longer than 1.5 seconds, during the first 5 minutes of resuscitation, was manual CPR 85 seconds (interquartile range [IQR] 45 to 112 seconds) versus load-distributing band 104 seconds (IQR 69 to 151 seconds). The mean no-flow ratio, defined as no-flow time divided by segment length, was manual 0.28 versus load-distributing band 0.40 (difference=-0.12; 95% confidence interval -0.22 to -0.02). However, from 5 to 10 minutes into the resuscitation, median no-flow time was manual 85 seconds (IQR 59 to 151 seconds) versus load-distributing band 52 seconds (IQR 34 to 82 seconds) and mean no-flow ratio manual 0.34 versus load-distributing band 0.21 (difference=0.13; 95% confidence interval 0.02 to 0.24). The average time to apply load-distributing band CPR during this period was 152 seconds. CONCLUSION: Application of a load-distributing band in the ED is associated with a higher no-flow ratio than manual CPR in the first 5 minutes of resuscitation. We suggest that attention to team training, rapid application of the device to minimize interruption, and feedback from defibrillator and video recordings may be useful to improve resuscitation team performance.

Outcomes of Patients Presenting with Primary or Secondary Atrial Fibrillation with Rapid Ventricular Rate to the Emergency Department.

INTRODUCTION: Atrial fibrillation (AF) with rapid ventricular rate (RVR) is a common diagnosis in the Emergency Department (ED) requiring evaluation and treatment. We present the characteristics and outcomes of patients presenting with primary or secondary AF in a tertiary hospital ED. MATERIALS AND METHODS: This retrospective cohort study included consecutive patients ≥21 years old, with a primary or secondary diagnosis of AF with RVR in the ED over a 1-year period from 1 January 2016 to 31 December 2016. Primary AF is defined as AF with no precipitating cause and secondary AF as AF secondary to a precipitating cause. RESULTS: A total of 464 patients presented to the ED from 1 January to 31 December 2016 with primary and secondary diagnosis of AF with RVR; 44.8% had primary diagnosis of AF whereas 55.2% had secondary AF. Overall admission rate from ED was high at 91.8% (primary 84.6% vs secondary 97.7%). Patients with primary AF were younger (68 vs 74 years, P <0.001), had lower rates of cardiovascular risk factors, and shorter length of stay (median 4 vs 5 days). Within 30 days of discharge, they had lower ED reattendance (16.3% vs 25.8%, P <0.001) and lower readmission (16.3% vs 25.8%, P <0.001). There was no mortality in the primary AF group (0% vs 9.8%, P <0.001). CONCLUSION: Currently, majority of patients with AF with RVR are admitted from the ED. Other study suggests patients with uncomplicated primary AF have lower adverse outcomes and some could potentially be treated as outpatients.

Improving the quality of cardiopulmonary resuscitation by training dedicated cardiac arrest teams incorporating a mechanical load-distributing device at the emergency department.

OBJECTIVE: Determine if implementing cardiac arrest teams trained with a 'pit-crew' protocol incorporating a load-distributing band mechanical CPR device (Autopulse™ ZOLL) improves the quality of CPR, as determined by no-flow ratio (NFR) in the first 10min of resuscitation. METHODS: A phased, prospective, non-randomized, before-after cohort evaluation. Data collection was from April 2008 to February 2011. There were 100 before and 148 after cases. Continuous video and chest compression data of all study subjects were analyzed. All non-traumatic, collapsed patients aged 18 years and above presenting to the emergency department were eligible. Primary outcome was NFR. Secondary outcomes were return of spontaneous circulation (ROSC), survival to hospital admission and neurological outcome at discharge. MAIN RESULTS: After implementation, mean total NFR for the first 5min decreased from 0.42 to 0.27 (decrease=0.15, 95% CI 0.10-0.19, p<0.005), and from 0.24 to 0.18 (decrease=0.06, 95% CI 0.01-0.11, p=0.02) for the next 5min. The mean time taken to apply Autopulse™ decreased from 208.8s to 141.6s (decrease=67.2, 95% CI, 22.3-112.1, p<0.005). The mean CPR ratio increased from 46.4% to 88.4% (increase=41.9%, 95% CI 36.9-46.9, p<0.005) and the mean total NFR for the first 10min decreased from 0.33 to 0.23 (decrease=0.10, 95% CI 0.07-0.14, p<0.005). CONCLUSION: Implementation of cardiac arrest teams was associated with a reduction in NFR in the first 10min of resuscitation. Training cardiac arrest teams in a 'pit-crew' protocol may improve the quality of CPR at the ED.