Empagliflozin in patients post myocardial infarction rationale and design of the EMPACT-MI trial

Background : Patients with acute myocardial infarction (MI) are at risk for developing heart failure (HF) and subsequently are at an increased risk of mortality. Sodium-glucose cotransporter-2 inhibitors have been proven to improve outcomes in patients with HF with reduced ejection fraction, and, in the case of empagliflozin, in HF with preserved ejection fraction even without diabetes, but their efficacy and safety in the post-MI population has not yet been evaluated. Methods : The EMPACT-MI trial will evaluate the safety and efficacy of empagliflozin compared with placebo in patients hospitalized for MI with or at high risk of new onset HF, in addition to standard care. EMPACT-MI is a streamlined, multinational, randomized, double-blind, placebo-controlled trial randomizing 5,000 participants at approximately 480 centers in 22 countries. Eligible patients presenting with spontaneous MI must have new signs or symptoms of pulmonary congestion requiring treatment or new left ventricular dysfunction (LVEF<45%), and at least one additional risk factor for development of future HF. Eligible and consenting patients are randomized to empagliflozin 10mg or placebo daily in addition to standard of care within 14 days of hospital admission for MI. The primary composite endpoint is time to first hospitalization for HF or all-cause mortality. Conclusions : EMPACT-MI will inform clinical practice regarding the role of empagliflozin in patients after an MI with high risk for the development of future HF and mortality

Impact of Empagliflozin in Heart Failure With Reduced Ejection Fraction in Patients With Ischemic Versus Nonischemic Cause

Background Outcomes and treatment effects of therapy may vary according to the cause of heart failure (HF). Methods and Results In this post hoc analysis of the EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction) trial, the effect of empagliflozin on cardiovascular and renal outcomes was assessed according to the cause of HF. The cause of HF was investigator reported and stratified as ischemic or nonischemic. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs. Of the 3730 patients enrolled, 1929 (51.7%) had ischemic cause. In the placebo arm, patients with ischemic cause of HF did not have a significantly higher risk of cardiovascular mortality (HR, 1.21 [95% CI, 0.90-1.63]) and hospitalization for HF (HR, 0.90 [95% CI, 0.72-1.12]) compared with nonischemic cause. Empagliflozin compared with placebo significantly reduced the risk of cardiovascular death or hospitalization for HF in patients with ischemic and nonischemic cause (HR, 0.82 [95% CI, 0.68-0.99] for ischemic and HR, 0.67 [95% CI, 0.55-0.82] for nonischemic cause; P interaction=0.15). The benefit of empagliflozin on HF hospitalization, the renal composite end point, estimated glomerular filtration slope changes, and health status scores were also consistent in both groups without treatment by cause modification. Conclusions Empagliflozin offers cardiovascular and renal benefits in patients with heart failure with reduced ejection fraction regardless of the cause of HF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977

Prognostic Importance of NT-proBNP and Effect of Empagliflozin in the EMPEROR-Reduced Trial

BACKGROUND: The relationship between the benefits of empagliflozin in heart failure with reduced ejection fraction (HFrEF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) has not been reported. OBJECTIVES: The authors sought to evaluate the relationship between NT-proBNP and empagliflozin effects in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction). METHODS: Patients with HFrEF were randomly assigned to placebo or empagliflozin 10 mg daily. NT-proBNP was measured at baseline, 4 weeks, 12 weeks, 52 weeks, and 100 weeks. Patients were divided into quartiles of baseline NT-proBNP. RESULTS: Incidence rates for each study outcome were 4- to 6-fold higher among those in the highest versus lowest NT-proBNP quartiles (≥3,480 vs <1,115 pg/mL). Study participants with higher NT-proBNP had 2- to 3-fold total hospitalizations higher than the lowest NT-proBNP quartile. Empagliflozin reduced risk for major cardiorenal events without heterogeneity across NT-proBNP quartiles (primary endpoint Pinteraction = 0.94; renal composite endpoint Pinteraction = 0.71). Empagliflozin treatment significantly reduced NT-proBNP at all timepoints examined; by 52 weeks, the adjusted mean difference from placebo was 13% (P < 0.001). An NT-proBNP in the lowest quartile (<1,115 pg/mL) 12 weeks after randomization was associated with lower risk for subsequent cardiovascular death or heart failure hospitalization regardless of baseline concentration. Treatment with empagliflozin resulted in 27% higher adjusted odds of an NT-proBNP concentration of <1,115 pg/mL by 12 weeks compared with placebo (P = 0.01). CONCLUSIONS: In EMPEROR-Reduced, higher baseline NT-proBNP concentrations were associated with greater risk for adverse heart failure or renal outcomes, but empagliflozin reduced risk regardless of baseline NT-proBNP concentration. The NT-proBNP concentration after treatment with empagliflozin better informs subsequent prognosis than pretreatment concentrations. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977)

Health status across major subgroups of patients with heart failure and preserved ejection fraction

AIMS: There are limited data on health status and changes in it over time across major subgroups of patients with heart failure and preserved ejection fraction (HFpEF), including ejection fraction spectrum, age, sex, region, body mass index (BMI), and comorbidities including diabetes, chronic kidney disease (CKD), anaemia, and atrial fibrillation/flutter. METHODS AND RESULTS: In the EMPEROR-Preserved trial, the Kansas City Cardiomyopathy Questionnaire (KCCQ) was assessed at baseline, 12, 32 and 52 weeks. Determinants of baseline KCCQ score and change over time, and the impact of empagliflozin on KCCQ scores were studied in specified subgroups. A Cox model was used to assess the association between 5- and 10-point increase and 5-point decrease in KCCQ score from baseline to week 12 and later outcomes. Among 2979 participants in the placebo arm, mean KCCQ clinical summary score (CSS) was 70.7 (20.8). Older age, female sex, BMI, anaemia, and a history of diabetes, and CKD were associated with worse scores. KCCQ-CSS score improved during follow-up; patients with atrial fibrillation/flutter at enrollment (p trend = 0.014) and CKD (p trend < 0.001) had less improvement. A 5-point increase in KCCQ-CSS at week 12 was associated with lower risk of cardiovascular death or heart failure hospitalization (5%), cardiovascular death (8%), and first heart failure hospitalization (4%) subsequently. A similar trend was seen with KCCQ total symptom score (TSS) and overall summary score (OSS). Empagliflozin improved KCCQ-CSS, -TSS and -OSS scores similarly across subgroups studied except for greater improvement in patients with the highest BMI (p trend = 0.153, 0.08 and 0.078, respectively). CONCLUSION: Health status in patients with HFpEF is impaired, especially in elderly, women, and those with obesity and comorbidities. Empagliflozin improved health status among all key subgroups studied with a greater effect in obese patients

Empagliflozin, Health Status, and Quality of Life in Patients With Heart Failure and Preserved Ejection Fraction: The EMPEROR-Preserved Trial

Background: Patients with heart failure with preserved ejection fraction have significant impairment in health-related quality of life. In the EMPEROR-Preserved trial (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction), we evaluated the efficacy of empagliflozin on health-related quality of life in patients with heart failure with preserved ejection fraction and whether the clinical benefit observed with empagliflozin varies according to baseline health status. Methods: Health-related quality of life was measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and 12, 32, and 52 weeks. Patients were divided by baseline KCCQ Clinical Summary Score (CSS) tertiles, and the effect of empagliflozin on outcomes was examined. The effect of empagliflozin on KCCQ-CSS, Total Symptom Score, and Overall Summary Score was evaluated. Responder analyses were performed to compare the odds of improvement and deterioration in KCCQ related to treatment with empagliflozin. Results: The effect of empagliflozin on reducing the risk of time to cardiovascular death or heart failure hospitalization was consistent across baseline KCCQ-CSS tertiles (hazard ratio, 0.83 [95% CI, 0.69–1.00], 0.70 [95% CI, 0.55–0.88], and 0.82 [95% CI, 0.62–1.08] for scores <62.5, 62.5–83.3, and ≥83.3, respectively; P trend=0.77). Similar results were seen for total heart failure hospitalizations. Patients treated with empagliflozin had significant improvement in KCCQ-CSS versus placebo (+1.03, +1.24, and +1.50 at 12, 32, and 52 weeks, respectively; P<0.01); similar results were seen for Total Symptom Score and Overall Summary Score. At 12 weeks, patients on empagliflozin had higher odds of improvement ≥5 points (odds ratio, 1.23 [95% CI, 1.10–1.37]), ≥10 points (odds ratio, 1.15 [95% CI, 1.03–1.27]), and ≥15 points (odds ratio, 1.13 [95% CI, 1.02–1.26]) and lower odds of deterioration ≥5 points in KCCQ-CSS (odds ratio, 0.85 [95% CI, 0.75–0.97]). A similar pattern was seen at 32 and 52 weeks, and results were consistent for Total Symptom Score and Overall Summary Score. Conclusions: In patients with heart failure with preserved ejection fraction, empagliflozin reduced the risk for major heart failure outcomes across the range of baseline KCCQ scores. Empagliflozin improved health-related quality of life, an effect that appeared early and was sustained for at least 1 year

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Capillary and venous lactate measurements with a handheld device compared to venous blood-gas analysis for emergency patients

Abstract Background/aim Early identification of lactate levels may have a large impact on triage classification and assist in identifying critically ill patients. A handheld device provides a rapid and timesaving measurement of lactate levels adapted to work in a prehospital care setting. I.e., the device is small, fast, and easy-to-use. The aim of this study was to evaluate the Accutrend Plus handheld lactate analyzer in comparison to the reference in-hospital method. Methods Patients triaged as minimum yellow according to the RETTS System (Rapid Emergency Triage and Treatment System) and transported to hospital by ambulance were selected and a written consent to participate was obtained prior to inclusion in the study. Capillary (CAP) and venous (VEN) blood were analyzed with Accutrend Plus (AP). Venous blood samples were analyzed at the local hospital laboratory (GEM premier 4000) within 20 min from sampling. All sampling was conducted by two registered nurses specially trained in prehospital care. Results 480 lactate measurements were performed in 160 patients. The mean difference between measurements in capillary blood compared with the reference method was 0.7 mmol/L and for venous blood 0.9 mmol/L. The limits of agreement from the Bland-Altman plot was − 0.9 to + 2.5 mmol/L and and − 0.1 to + 1.9 mmol/L, for CAP and VEN compared with GEM. Conclusion Our results shows low accuracy and low precision with VEN / CAP measurements of lactate compared to reference GEM

The epidemiology of and management of pediatric patients with head trauma : a hospital-based study from Southern Sweden

Background: Traumatic brain injury (TBI) is a common cause of morbidity and mortality in children worldwide. In Scandinavia, the epidemiology of pediatric head trauma is poorly documented. This study aimed to investigate and compare the epidemiology and management of pediatric patients with isolated head trauma (IHT) and head trauma in connection with multitrauma (MHT). Methods: We conducted a retrospective review of medical records of patients < 18 years of age who attended any of the five emergency departments (ED) in Scania County in Sweden in 2016 due to head trauma. Clinical data of patients with IHT were analyzed and compared with those of patients with MHT. Results: We identified 5046 pediatric patients with head trauma, 4874 with IHT and 186 with MHT, yielding an incidence of ED visits due to head trauma of 1815/100,000 children/year. There was male predominance, and the median age was four years. Falls were the dominating trauma mechanism in IHT patients, while motor vehicle accidents dominated in MHT patients. The frequencies of CT head-scans, ward admissions and intracranial injuries (ICI) were 5.4%, 11.1% and 0.7%, respectively. Four patients (0.08%) required neurosurgical intervention. The relative risks for CT-scans and admissions to a hospital ward and ICI were 10, 4.5 and 19 times higher for MHT compared with IHT patients. Conclusion: Head trauma is a common cause of ED visits in our study. Head-CTs and ICIs were less frequent than in previous studies. MHT patients had higher rates of CT-scans, admissions, and ICIs than IHT patients, suggesting that they are separate entities that should ideally be managed using different guidelines to optimize the use of CT-scans of the head

Effects of surgical specialization and surgeon resection volume on postoperative complications and mortality rate after emergent colon cancer resection

Background: The aim of this study was to evaluate the effect of surgical specialization and surgeon resection volume on short-term outcome after emergent colon cancer resections. Methods: A retrospective analysis of all patients who underwent resections for colon cancer between 2011 and 2020 at Helsingborg Hospital, Sweden was performed. The senior surgeon participating in each procedure was classified as a colorectal surgeon or a non-colorectal surgeon. Non-colorectal surgeons were further divided into acute care surgeons or surgeons with other specialties. Surgeons were also divided into three groups based on median yearly resection volumes. Postoperative complications and 30- or 90-day mortality rate after emergent colon cancer resections were compared in patients operated on by surgeons with different specializations and yearly resection volumes. Results: Of 1121 patients resected for colon cancer, 235 (21.0 per cent) had emergent procedures. The complication rate of emergent resections was similar in patients operated on by colorectal surgeons and non-colorectal surgeons (54.1 versus 51.1 per cent respectively), and the subgroup of acute care surgeons (45.8 per cent), whereas resections performed by general surgeons were significantly associated with more frequent complications (odds ratio (OR) 2.5 (95 per cent c.i. 1.1 to 6.1)). The complication rate was numerically highest in patients operated on by surgeons with the highest resection volumes, which differed significantly from that of surgeons with intermediate resection volumes (OR 4.2 (95 per cent c.i. 1.1 to 16.0)). There was no difference in the mortality rate of patients operated on by surgeons with different specializations or yearly resection volumes. Conclusion: This study documented similar morbidity and mortality rates after emergent colon resection performed by colorectal and acute care surgeons, but patients operated on by general surgeons had more frequent complications