Comparison of Pressure vs Volume Overload Ventricular Wall Stress in Patients With Valvular Heart Disease.

BACKGROUND: Aortic stenosis (AS) and mitral regurgitation (MR) result in different patterns of left ventricular remodeling and hypertrophy. OBJECTIVES: We characterized left ventricular wall stress (LVWS) profiles in pressure and volume-overloaded systems, examined the relationship between baseline LVWS and cardiac remodeling, and assessed the acute effects of valve intervention on LVWS using invasive pressures combined with cardiac magnetic resonance (CMR) imaging measures of left ventricular volumes/mass. METHODS: A total of 47 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR) and 15 patients with severe MR undergoing MitraClip (MC) underwent a 6-minute walk test (6MWT), transthoracic echocardiogram, and CMR before their procedures. Catheters in the left ventricle were used to record hemodynamic changes before and after valve/clip deployment. This was integrated with CMR data to calculate LVWS before and after intervention. RESULTS: The TAVR group demonstrated significant reductions in systolic LVWS post procedure (median 24.7 Pa [IQR: 14 Pa] pre vs median 17.3 Pa [IQR: 12 Pa] post; P < 0.001). The MC group demonstrated significant reductions in diastolic LVWS (median 6.4 Pa [IQR: 5 Pa] pre vs median 4.3 Pa [IQR: 4.1 Pa] post; P = 0.021) with no significant change in systolic LVWS (30.6 ±1.61 pre vs 33 ±2.47 Pa post; P = 0.16). There was an inverse correlation between baseline systolic LVWS and 6MWT in the TAVR group (r = -0.31; P = 0.04). CONCLUSIONS: TAVR results in significant reductions in systolic LVWS acutely. MC results in significant reductions in diastolic LVWS. Higher baseline systolic LVWS in TAVR is associated with shorter 6MWT suggesting that in AS, LVWS may be a useful marker of early decompensation.

CSANZ and RANZCR Position Statement on Initial Certification and Maintenance of Recognition for Cardiac Magnetic Resonance Imaging (CMRI).

The CSANZ/RANZCR Position Statement on Cardiac Magnetic Resonance Imaging (CMRI) is intended to support and foster the provision of quality, safe CMRI services in Australia and New Zealand. This document specifically pertains to CMRI in adults, as distinct from general vascular MRI or paediatric imaging, and provides certification and recertification requirements.

Early Use of Aspirin for Coronary Allograft Prophylaxis in Heart Transplant Recipients.

BACKGROUND: Coronary allograft vasculopathy (CAV) remains a significant cause of morbidity and mortality after heart transplantation. The use of aspirin for CAV prophylaxis has recently garnered interest as a possible therapeutic adjunct in this setting. METHODS: This 2-center retrospective cohort study included 372 patients who underwent heart transplantation between January 2009 and March 2018 and were stratified according to the commencement of aspirin during their index transplant admission. The primary outcome was the development of moderate or severe CAV (International Society for Heart and Lung Transplantation grade ≥2) at surveillance coronary angiography. Secondary endpoints included mortality at follow-up. RESULTS: There were no differences in age, sex, and cause of heart failure. In the early aspirin group, the preponderant risk factors included use of ventricular assist devices, pretransplant smoking, and mild or moderate rejection. Multivariable analyses to assess for independent predictors of CAV development and mortality demonstrated that aspirin was associated with reduced mortality (adjusted hazard ratio = 0.19; 95% confidence interval, 0.08-0.47, P < 0.01) and a trend toward a protective effect against the development of moderate or severe CAV (adjusted hazard ratio = 0.24; 95% confidence interval, 0.54-1.19; P = 0.08). CONCLUSIONS: In this retrospective risk-adjusted 2-center cohort study, early aspirin administration was associated with reduced risk of death and a trend toward a protective effect against CAV development. These findings warrant validation in prospective randomized trials.

Halogen bonding aza-BODIPYs for anion sensing and anion binding-modulated singlet oxygen generation.

Two novel aza-BODIPY based anion sensors, decorated with halogen bonding recognition sites, are capable of detecting halide anions at biologically-relevant near-IR wavelengths. With potential application for improving the selectivity of photodynamic therapy agents, unprecedented supramolecular host-guest anion binding-modulated singlet oxygen generation is demonstrated.

HeartMate 3 implantation with an emphasis on the biventricular configuration.

OBJECTIVES: Right ventricular failure following implantation of a durable left ventricular assist device (LVAD) is a major driver of mortality. Reported survival following biventricular (BiVAD) or total artificial heart (TAH) implantation remains substantially inferior to LVAD alone. We report our outcomes with LVAD and BiVAD HeartMate 3 (HM3). METHODS: Consecutive patients undergoing implantation of an HM3 LVAD between November 2014 and December 2021, at The Alfred, Australia were included in the study. Comparison was made between the BiVAD and LVAD alone groups. RESULTS: A total of 86 patients, 65 patients with LVAD alone and 21 in a BiVAD configuration underwent implantation. The median age of the LVAD and BiVAD groups was 56 years (Interquartile range 46-62) and 49 years (Interquartile range 37-55), respectively. By 4 years after implantation, 54% of LVAD patients and 43% of BiVAD patients had undergone cardiac transplantation. The incidence of stroke in the entire experience was 3.5% and pump thrombosis 5% (all in the RVAD). There were 14 deaths in the LVAD group and 1 in the BiVAD group. The actuarial survival for LVAD patients at 1 year was 85% and BiVAD patients at 1 year was 95%. CONCLUSIONS: The application of HM 3 BiVAD support in selected patients appears to offer a satisfactory solution to patients requiring biventricular support.

No-Reflow Prediction in Acute Coronary Syndrome During Percutaneous Coronary Intervention: The NORPACS Risk Score.

BACKGROUND: Suboptimal coronary reperfusion (no reflow) is common in acute coronary syndrome percutaneous coronary intervention (PCI) and is associated with poor outcomes. We aimed to develop and externally validate a clinical risk score for angiographic no reflow for use following angiography and before PCI. METHODS: We developed and externally validated a logistic regression model for prediction of no reflow among adult patients undergoing PCI for acute coronary syndrome using data from the Melbourne Interventional Group PCI registry (2005-2020; development cohort) and the British Cardiovascular Interventional Society PCI registry (2006-2020; external validation cohort). RESULTS: A total of 30 561 patients (mean age, 64.1 years; 24% women) were included in the Melbourne Interventional Group development cohort and 440 256 patients (mean age, 64.9 years; 27% women) in the British Cardiovascular Interventional Society external validation cohort. The primary outcome (no reflow) occurred in 4.1% (1249 patients) and 9.4% (41 222 patients) of the development and validation cohorts, respectively. From 33 candidate predictor variables, 6 final variables were selected by an adaptive least absolute shrinkage and selection operator regression model for inclusion (cardiogenic shock, ST-segment-elevation myocardial infarction with symptom onset >195 minutes pre-PCI, estimated stent length ≥20 mm, vessel diameter <2.5 mm, pre-PCI Thrombolysis in Myocardial Infarction flow <3, and lesion location). Model discrimination was very good (development C statistic, 0.808; validation C statistic, 0.741) with excellent calibration. Patients with a score of ≥8 points had a 22% and 27% risk of no reflow in the development and validation cohorts, respectively. CONCLUSIONS: The no-reflow prediction in acute coronary syndrome risk score is a simple count-based scoring system based on 6 parameters available before PCI to predict the risk of no reflow. This score could be useful in guiding preventative treatment and future trials.

A Halogen Bonding [2]Rotaxane Shuttle for Chloride-Selective Optical Sensing.

The first example of a [2]rotaxane shuttle capable of selective optical sensing of chloride anions over other halides is reported. The rotaxane was synthesised via a chloride ion template-directed cyclisation of an isophthalamide macrocycle around a multi-station axle containing peripheral naphthalene diimide (NDI) stations and a halogen bonding (XB) bis(iodotriazole) based station. Proton NMR studies indicate the macrocycle resides preferentially at the NDI stations in the free rotaxane, where it is stabilised by aromatic donor-acceptor charge transfer interactions between the axle NDI and macrocycle hydroquinone moieties. Addition of chloride ions in an aqueous-acetone solvent mixture induces macrocycle translocation to the XB anion binding station to facilitate the formation of convergent XB⋅⋅⋅Cl- and hydrogen bonding HB⋅⋅⋅Cl- interactions, which is accompanied by a reduction of the charge-transfer absorption band. Importantly, little to no optical response was induced by addition of bromide or iodide to the rotaxane, indicative of the size discriminative steric inaccessibility of the interlocked cavity to the larger halides, demonstrating the potential of using the mechanical bond effect as a potent strategy and tool in chloride-selective chemo-sensing applications in aqueous containing solvent environments.

Anion Sensing through Redox-Modulated Fluorescent Halogen Bonding and Hydrogen Bonding Hosts.

Anion sensing via either optical or electrochemical readouts has separately received enormous attention, however, a judicious combination of the advantages of both modalities remains unexplored. Toward this goal, we herein disclose a series of novel, redox-active, fluorescent, halogen bonding (XB) and hydrogen bonding (HB) BODIPY-based anion sensors, wherein the introduction of a ferrocene motif induces remarkable changes in the fluorescence response. Extensive fluorescence anion titration, lifetime and electrochemical studies reveal anion binding-induced emission modulation through intramolecular photoinduced electron transfer (PET), the magnitude of which is dependent on the nature of both the XB/HB donor and anion. Impressively, the XB sensor outperformed its HB congener in terms of anion binding strength and fluorescence switching magnitude, displaying significant fluorescence turn-OFF upon anion binding. In contrast, redox-inactive control receptors display a turn-ON response, highlighting the pronounced impact of the introduction of the redox-active ferrocene on the optical sensing performance. Additionally, the redox-active ferrocene motif also serves as an electrochemical reporter group, enabling voltammetric anion sensing in competitive solvents. The combined advantages of both sensing modalities were further exploited in a novel, proof-of-principle, fluorescence spectroelectrochemical anion sensing approach, enabling simultaneous and sensitive read out of optical and electrochemical responses in multiple oxidation states and at very low receptor concentration.

Chest pain epidemiology and care quality for Aboriginal and Torres Strait Islander peoples in Victoria, Australia: a population-based cohort study from 2015 to 2019.

Background: This study examined chest pain epidemiology and care quality for Aboriginal and Torres Strait Islander ('Indigenous') patients presenting to hospital via emergency medical services (EMS) with chest pain. Methods: State-wide population-based cohort study of consecutive patients attended by ambulance for acute chest pain with individual linkage to emergency, hospital admission and mortality data in the state of Victoria, Australia from January 2015 to June 2019. Multivariable models were used to assess for differences in pre-hospital and hospital adherence to care quality, process measures and clinical outcomes. Findings: From 204,969 EMS attendances for chest pain, 3890 attendances (1.9%) identified as Aboriginal or Torres Strait Islander. Age-standardized incidence rates were higher overall for Indigenous people (3128 vs. 1147 per 100,000 person-years, incidence rate ratio 2.73, 95% CI 2.72-2.74), this difference being particularly striking for younger patients, women, and those residing in outer regional areas. In multivariable models, adherence to care quality and process measures was lower for attendances involving Indigenous people. In the pre-hospital setting, Indigenous people were less likely to be provided intravenous access or analgesia. In the hospital setting, Indigenous people were less likely to be seen by emergency clinicians within target time and less likely to transferred following myocardial infarction to a revascularization capable centre. Interpretation: Incidence of acute chest pain presentations is high among Indigenous people in Victoria, Australia. Opportunities to improve the quality of care for Indigenous Australians presenting with acute chest pain are identified. Funding: National Health and Medical Research Council, National Heart Foundation.

Assessing atrial myopathy with cardiac magnetic resonance imaging in embolic stroke of undetermined source.

BACKGROUND: Left atrial myopathy has been implicated in atrial fibrillation (AF)-related stroke and embolic stroke of undetermined source (ESUS). OBJECTIVE: To use advanced cardiac magnetic resonance (CMR) imaging techniques, including left atrial (LA) strain and 4D flow CMR, to identify atrial myopathy in patients with ESUS. METHODS: 20 patients with ESUS and no AF or other cause for stroke, and 20 age and sex-matched controls underwent CMR with 4D flow analysis. Markers of LA myopathy were assessed including LA size, volume, ejection fraction, and strain. 4D flow CMR was performed to measure novel markers of LA stasis such as LA velocities and the LA residence time distribution time constant (RTDtc). These markers of LA myopathy were compared between the two groups. RESULTS: There was no significant difference in: CMR-calculated LA velocities or LA total, passive or active ejection fractions between the groups. There was no significant difference in CMR-derived reservoir, conduit or contractile average longitudinal strain between the ESUS and control groups (22.9 vs 22.6%, p=0.379, 11.2 ± 3.5 vs 12.4 ± 2.6% p=0.224, 10.8 ± 3.2 vs 10.4 ± 2.3%, p=0.625 respectively). Similarly, RTDtc was not significantly longer in ESUS patients compared to controls (1.3 ± 0.2 vs 1.2 ± 0.2, p=0.1). CONCLUSIONS: There were no significant differences in any CMR marker of atrial myopathy in ESUS patients compared to healthy controls, likely reflecting the multiple possible aetiologies of ESUS suggesting that the role LA myopathy plays in ESUS is smaller than previously thought.

Variation in Health Care Processes, Quality and Outcomes According to Day and Time of Chest Pain Presentation via Ambulance.

BACKGROUND: Previous studies examining temporal variations in cardiovascular care have largely been limited to assessing weekend and after-hours effects. We aimed to determine whether more complex temporal variation patterns might exist in chest pain care. METHODS: This was a population-based study of consecutive adult patients attended by emergency medical services (EMS) for non-traumatic chest pain without ST elevation in Victoria, Australia between 1 January 2015 and 30 June 2019. Multivariable models were used to assess whether time of day and week stratified into 168 hourly time periods was associated with care processes and outcomes. RESULTS: There were 196,365 EMS chest pain attendances; mean age 62.4 years (standard deviation [SD] 18.3) and 51% females. Presentations demonstrated a diurnal pattern, a Monday-Sunday gradient (Monday peak) and a reverse weekend effect (lower rates on weekends). Five temporal patterns were observed for care quality and process measures, including a diurnal pattern (longer emergency department [ED] length of stay), an after-hours pattern (lower angiography or transfer for myocardial infarction, pre-hospital aspirin administration), a weekend effect (shorter ED clinician review, shorter EMS off-load time), an afternoon/evening peak period pattern (longer ED clinician review, longer EMS off-load time) and a Monday-Sunday gradient (ED clinician review, EMS offload time). Risk of 30-day mortality was associated with weekend presentation (Odds ratio [OR] 1.15, p=0.001) and morning presentation (OR 1.17, p<0.001) while risk of 30-day EMS reattendance was associated with peak period (OR 1.16, p<0.001) and weekend presentation (OR 1.07, p<0.001). CONCLUSIONS: Chest pain care demonstrates complex temporal variation beyond the already established weekend and after-hours effect. Such relationships should be considered during resource allocation and quality improvement programs to improve care across all days and times of the week.

Atrial Fibrillation Ablation for Heart Failure With Preserved Ejection Fraction: A Randomized Controlled Trial.

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) frequently develop atrial fibrillation (AF). There are no randomized trials examining the effects of AF ablation on HFpEF outcomes. OBJECTIVES: The aim of this study is to compare the effects of AF ablation vs usual medical therapy on markers of HFpEF severity, including exercise hemodynamics, natriuretic peptide levels, and patient symptoms. METHODS: Patients with concomitant AF and HFpEF underwent exercise right heart catheterization and cardiopulmonary exercise testing. HFpEF was confirmed with pulmonary capillary wedge pressure (PCWP) of 15 mm Hg at rest or ≥25 mm Hg on exercise. Patients were randomized to AF ablation vs medical therapy, with investigations repeated at 6 months. The primary outcome was change in peak exercise PCWP on follow-up. RESULTS: A total of 31 patients (mean age: 66.1 years; 51.6% females, 80.6% persistent AF) were randomized to AF ablation (n = 16) vs medical therapy (n = 15). Baseline characteristics were comparable across both groups. At 6 months, ablation reduced the primary outcome of peak PCWP from baseline (30.4 ± 4.2 to 25.4 ± 4.5 mm Hg; P < 0.01). Improvements were also seen in peak relative VO2 (20.2 ± 5.9 to 23.1 ± 7.2 mL/kg/min; P < 0.01), N-terminal pro-B-type natriuretic peptide levels (794 ± 698 to 141 ± 60 ng/L; P = 0.04), and MLHF (Minnesota Living with Heart Failure) score (51 ± -21.9 to 16.6 ± 17.5; P < 0.01). No differences were detected in the medical arm. Following ablation, 50% no longer met exercise right heart catheterization-based criteria for HFpEF vs 7% in the medical arm (P = 0.02). CONCLUSIONS: AF ablation improves invasive exercise hemodynamic parameters, exercise capacity, and quality of life in patients with concomitant AF and HFpEF.

Sex Differences in Epidemiology, Care, and Outcomes in Patients With Acute Chest Pain.

BACKGROUND: Discrepancies in cardiovascular care for women are well described, but few data assess the entire patient journey for chest pain care. OBJECTIVES: This study aimed to assess sex differences in epidemiology and care pathways from emergency medical services (EMS) contact through to clinical outcomes following discharge. METHODS: This is a state-wide population-based cohort study including consecutive adult patients attended by EMS for acute undifferentiated chest pain in Victoria, Australia (January 1, 2015, to June 30, 2019). EMS clinical data were individually linked to emergency and hospital administrative datasets, and mortality data and differences in care quality and outcomes were assessed using multivariable analyses. RESULTS: In 256,901 EMS attendances for chest pain, 129,096 attendances (50.3%) were women, and mean age was 61.6 years. Age-standardized incidence rates were marginally higher for women compared with men (1,191 vs 1,135 per 100,000 person-years). In multivariable models, women were less likely to receive guideline-directed care across most care measures including transport to hospital, prehospital aspirin or analgesia administration, 12-lead electrocardiogram, intravenous cannula insertion, and off-load from EMS or review by emergency department clinicians within target times. Similarly, women with acute coronary syndrome were less likely to undergo angiography or be admitted to a cardiac or intensive care unit. Thirty-day and long-term mortality was higher for women diagnosed with ST-segment elevation myocardial infarction, but lower overall. CONCLUSIONS: Substantial differences in care are present across the spectrum of acute chest pain management from first contact through to hospital discharge. Women have higher mortality for STEMI, but better outcomes for other etiologies of chest pain compared with men.

Incidence and severity of cytomegalovirus infection in seropositive heart transplant recipients.

BACKGROUND: The frequency and significance of cytomegalovirus (CMV) infection in seropositive (R+) heart transplant recipients (HTR) is unclear, with preventative recommendations mostly extrapolated from other groups. We evaluated the incidence and severity of CMV infection in R+ HTR, to identify risk factors and describe outcomes. METHODS: R+ HTR from 2010 to 2019 were included. Antiviral prophylaxis was not routinely used, with clinically guided monitoring the local standard of care. The primary outcome was CMV infection within one-year post-transplant; secondary outcomes included other herpesvirus infections and mortality. RESULTS: CMV infection occurred in 27/155 (17%) R+ HTR. Patients with CMV had a longer hospitalization (27 vs. 20 days, unadjusted HR 1.02, 95% CI 1.00-1.02, p = .01), higher rate of intensive care readmission (26% vs. 9%, unadjusted HR 3.46, 1.46-8.20, p = .005), and increased mortality (33% vs. 8%, unadjusted HR 10.60, 4.52-24.88, p < .001). The association between CMV and death persisted after adjusting for multiple confounders (HR 24.19, 95% CI 7.47-78.30, p < .001). Valganciclovir prophylaxis was used in 35/155 (23%) and was protective against CMV (infection rate 4% vs. 27%, adjusted HR .07, .01-.72, p = .025), even though those receiving it were more likely to have received thymoglobulin (adjusted OR 10.5, 95% CI 2.01-55.0, p = .005). CONCLUSIONS: CMV infection is common in R+ HTR and is associated with a high burden of disease and increased mortality. Patients who received valganciclovir prophylaxis were less likely to develop CMV infection, despite being at higher risk. These findings support the routine use of antiviral prophylaxis following heart transplantation in all CMV R+ patients.

Chest Pain Management Using Prehospital Point-of-Care Troponin and Paramedic Risk Assessment.

Importance: Prehospital point-of-care troponin testing and paramedic risk stratification might improve the efficiency of chest pain care pathways compared with existing processes with equivalent health outcomes, but the association with health care costs is unclear. Objective: To analyze whether prehospital point-of-care troponin testing and paramedic risk stratification could result in cost savings compared with existing chest pain care pathways. Design, Setting, and Participants: In this economic evaluation of adults with acute chest pain without ST-segment elevation, cost-minimization analysis was used to assess linked ambulance, emergency, and hospital attendance in the state of Victoria, Australia, between January 1, 2015, and June 30, 2019. Interventions: Paramedic risk stratification and point-of-care troponin testing. Main Outcomes and Measures: The outcome was estimated mean annualized statewide costs for acute chest pain. Between May 17 and June 25, 2022, decision tree models were developed to estimate costs under 3 pathways: (1) existing care, (2) paramedic risk stratification and point-of-care troponin testing without prehospital discharge, or (3) prehospital discharge and referral to a virtual emergency department (ED) for low-risk patients. Probabilities for the prehospital pathways were derived from a review of the literature. Multivariable probabilistic sensitivity analysis with 50 000 Monte Carlo iterations was used to estimate mean costs and cost differences among pathways. Results: A total of 188 551 patients attended by ambulance for chest pain (mean [SD] age, 61.9 [18.3] years; 50.5% female; 49.5% male; Indigenous Australian, 2.0%) were included in the model. Estimated annualized infrastructure and staffing costs for the point-of-care troponin pathways, assuming a 5-year device life span, was $2.27 million for the pathway without prehospital discharge and $4.60 million for the pathway with prehospital discharge (incorporating virtual ED costs). In the decision tree model, total annual cost using prehospital point-of-care troponin and paramedic risk stratification was lower compared with existing care both without prehospital discharge (cost savings, $6.45 million; 95% uncertainty interval [UI], $0.59-$16.52 million; lower in 94.1% of iterations) and with prehospital discharge (cost savings, $42.84 million; 95% UI, $19.35-$72.26 million; lower in 100% of iterations). Conclusions and Relevance: Prehospital point-of-care troponin and paramedic risk stratification for patients with acute chest pain could result in substantial cost savings. These findings should be considered by policy makers in decisions surrounding the potential utility of prehospital chest pain risk stratification and point-of-care troponin models provided that safety is confirmed in prospective studies.

Allosteric and Electrostatic Cooperativity in a Heteroditopic Halogen Bonding Receptor System.

A halogen bonding (XB) heteroditopic receptor, consisting of a 1,3-bis-iodo-triazole benzene XB anion binding site covalently appended via a flexible methylene group with two benzo-15-crown-5 (B15C5) cation binding moieties, and its hydrogen bonding receptor analogue, are used to delineate the mechanisms of cooperativity for alkali metal halide ion-pair recognition. Extensive cation, anion and ion-pair 1 H NMR titration investigations demonstrate the combination of allosteric pre-organisation, via 1 : 1 stoichiometric intramolecular potassium and rubidium metal cation bis-B15C5 sandwich complexation, in concert with favourable electrostatics and XB potency, results in a remarkable enhancement of halide anion binding affinity by a factor of at least 700. By contrast, a notably diminished halide anion affinity enhancement factor of just 15 is observed with the corresponding 1 : 1 stoichiometric sodium cation complexed receptor system, where the smaller sized cation singly occupies one B15C5 unit and only an electrostatic contribution to cooperativity is possible. These observations serve to illustrate that allosteric pre-organisation capability, electrostatic attraction and XB mediated anion recognition are important strategic design features to incorporate in future high-fidelity heteroditopic ion-pair receptor development.

LidocAine Versus Opioids In MyocarDial infarction: the AVOID-2 randomized controlled trial.

AIMS: Opioid analgesia has been shown to interfere with the bioavailability of oral P2Y12 inhibitors prompting the search for safe and effective non-opioid analgesics to treat ischaemic chest pain. METHODS AND RESULTS: The lidocAine Versus Opioids In MyocarDial infarction trial was a prospective, Phase II, prehospital, open-label, non-inferiority, randomized controlled trial enrolling patients with suspected STEACS with moderate to severe pain [numerical rating scale (NRS) at least 5/10]. Intravenous lidocaine (maximum dose 300 mg) or intravenous fentanyl (up to 50 µg every 5 min) were administered as prehospital analgesia. The co-primary end points were prehospital pain reduction and adverse events requiring intervention. Secondary end points included peak cardiac troponin I, cardiac MRI (cMRI) assessed myocardial infarct size and clinical outcomes to 30 days. A total of 308 patients were enrolled. The median reduction in pain score (NRS) was 4 vs. 3 in the fentanyl and lidocaine arms, respectively, for the primary efficacy end point [estimated median difference -1 (95% confidence interval -1.58, -0.42, P = 0.5 for non-inferiority, P = 0.001 for inferiority of lidocaine)]. Adverse events requiring intervention occurred in 49% vs. 36% of the fentanyl and lidocaine arms which met non-inferiority and superiority favouring lidocaine (P = 0.016 for superiority). No significant differences in myocardial infarct size and clinical outcomes at 30 days were seen. CONCLUSION: IV Lidocaine did not meet the criteria for non-inferiority with lower prehospital pain reduction than fentanyl but was safe and better tolerated as analgesia in ST-elevation myocardial infarction (STEMI). Future trials testing non-opioid analgesics in STEMI and whether opioid avoidance improves clinical outcomes are needed. TRIAL REGISTRATION: CTRN12619001521112p.

Risk-standardized mortality metric to monitor hospital performance for chest pain presentations.

AIMS: Risk-standardized mortality rates (RSMR) have been used to monitor hospital performance in procedural and disease-based registries, but limitations include the potential to promote risk-averse clinician decisions and a lack of assessment of the whole patient journey. We aimed to determine whether it is feasible to use RSMR at the symptom-level to monitor hospital performance using routinely collected, linked, clinical and administrative data of chest pain presentations. METHODS AND RESULTS: We included 192 978 consecutive adult patients (mean age 62 years; 51% female) with acute chest pain without ST-elevation brought via emergency medical services (EMS) to 53 emergency departments in Victoria, Australia (1/1/2015-30/6/2019). From 32 candidate variables, a risk-adjusted logistic regression model for 30-day mortality (C-statistic 0.899) was developed, with excellent calibration in the full cohort and with optimism-adjusted bootstrap internal validation. Annual 30-day RSMR was calculated by dividing each hospital's observed mortality by the expected mortality rate and multiplying it by the annual mean 30-day mortality rate. Hospital performance according to annual 30-day RSMR was lower for outer regional or remote locations and at hospitals without revascularisation capabilities. Hospital rates of angiography or transfer for patients diagnosed with non-ST elevation myocardial infarction (NSTEMI) correlated with annual 30-day RSMR, but no correlations were observed with other existing key performance indicators. CONCLUSION: Annual hospital 30-day RSMR can be feasibly calculated at the symptom-level using routinely collected, linked clinical, and administrative data. This outcome-based metric appears to provide additional information for monitoring hospital performance in comparison with existing process of care key performance measures.

Anti-Hofmeister Anion Selectivity via a Mechanical Bond Effect in Neutral Halogen-Bonding [2]Rotaxanes.

Exceptionally strong halogen bonding (XB) donor-chloride interactions are exploited for the chloride anion template synthesis of neutral XB [2]rotaxane host systems which contain perfluoroaryl-functionalised axle components, including a remarkably potent novel 4,6-dinitro-1,3-bis-iodotriazole motif. Halide anion recognition properties in aqueous-organic media, determined via extensive 1 H NMR halide anion titration experiments, reveal the rotaxane host systems exhibit dramatically enhanced affinities for hydrophilic Cl- and Br- , but conversely diminished affinities for hydrophobic I- , relative to their non-interlocked axle counterparts. Crucially, this mechanical bond effect induces a binding selectivity which directly opposes Hofmeister bias. Free-energy analysis of this mechanical bond enhancement demonstrates anion recognition by neutral XB interlocked host systems as a rare and general strategy to engineer anti-Hofmeister bias anion selectivity in synthetic receptor design.