Cardiac rehabilitation and secondary prevention of CVD: time to think about cardiovascular health rather than rehabilitation.

During the past century, there have been major developments in the medical and surgical treatment of cardiovascular disease (CVD). These advancements have resulted in more people surviving initial events and having reduced length of stay in hospital; consequently, there is an increasing number of people in need of ongoing and lifelong cardiovascular risk management. The physical and emotional effects of living with CVD are ongoing with broad challenges ranging from the individual to system level. However, post-discharge care of people with coronary disease continues to follow a 50-year-old cardiac rehabilitation model which focuses on the sub-acute phase and is of a finite in duration. The aim of this paper is to consider the concept of supporting survivors to live well with CVD rather than 'rehabilitating' them and propose factors for consideration in reframing secondary prevention towards optimizing cardiovascular health. We discuss deeply-held potential considerations and challenges associated with the concept of supporting survivors achieve optimal cardiovascular health and live well with CVD rather than 'rehabilitating' them. We propose the concept of 5 x P's for reframing traditional cardiac rehabilitation towards the concept of cardiovascular health for survivors beyond 'rehabilitation'. These include the need for personalization, processes, patient-centered care, parlance, and partnership. Taken together, consideration of challenges at the systems and population level will ultimately improve engagement with secondary prevention as well as outcomes for all people who need it.

Corrigendum: Genome-wide association study identifying variants related to performance and injury in high-performance athletes.

[This corrects the article DOI: 10.1177/15353702231198068.].

The INTOXICATE study: methodology and preliminary results of a prospective observational study.

BACKGROUND: There is currently no practice-based, multicenter database of poisoned patients admitted to intensive care units (ICUs). The INTOXICATE study, endorsed by the ESICM and EAPCCT, aimed to determine the rate of eventful admissions among acutely intoxicated adult ICU patients. METHODS: Ethical approval was obtained for this multicenter, prospective observational study, and data-sharing agreements were signed with each participating center. An electronic case report form was used to collect data on patient demographics, exposure, clinical characteristics, investigations, treatment, and in-hospital mortality data. The primary outcome, 'eventful admission', was a composite outcome defined as the rate of patients who received any of the following treatments in the first 24 h after the ICU admission: oxygen supplementation with a FiO2 > 40%, mechanical ventilation, vasopressors, renal replacement therapy (RRT), cardiopulmonary resuscitation, antidotes, active cooling, fluid resuscitation (> 1.5 L of intravenous fluid of any kind), sedation, or who died in the hospital. RESULTS: Seventy-eight ICUs, mainly from Europe, but also from Australia and the Eastern Mediterranean, participated. A total of 2,273 patients were enrolled between November 2020 and June 2023. The median age of the patients was 41 years, 72% were exposed to intoxicating drugs. The observed rate of patients with an eventful ICU admission was 68% (n = 1546/2273 patients). The hospital mortality was 4.5% (n = 103/2273). CONCLUSIONS: The vast majority of patients survive, and approximately one third of patients do not receive any ICU-specific interventions after admission in an intensive care unit for acute intoxication. High-quality detailed clinical data have been collected from a large cohort of acutely intoxicated ICU patients, providing information on the pattern of severe acute poisoning requiring intensive care admission and the outcomes of these patients. TRIAL REGISTRATION: OSF registration ID: osf.io/7e5uy.

Dysglycaemia screening and its prognostic impact in patients with coronary artery disease: experiences from the EUROASPIRE IV and V cohort studies.

BACKGROUND: Glucose perturbations can be detected by fasting plasma glucose (FPG), HbA1c, and the oral glucose tolerance test (OGTT). The highest yield is provided by OGTT. HbA1c is considered more practical. We compare the diagnostic and predictive performance of these glycaemic indicators based on combined data from the EUROASPIRE IV (EAIV) and V (EAV) studies. METHODS: This cohort study was conducted in 79 centres in 24 European countries (EAIV) and 131 centres in 27 European countries (EAV). Eligible patients were aged 18-80 years, did not have diabetes, and were diagnosed with coronary artery disease 6-36 months (EAIV) or 6-24 months (EAV) before the investigation. Patients were investigated with OGTT (FPG and 2 h post-load glucose [2-hPG]) and HbA1c. Follow-up of subsequent cardiovascular events was done by means of a questionnaire at least 1 year after the baseline investigation. Analyses were done in patients with both OGTT and HbA1c data available. Outcome analysis in these patients was restricted to those with valid follow-up data available. FINDINGS: 16 259 patients were interviewed in EAIV (2012-13) and EAV (2016-17). 8364 patients had both OGTT and HbA1C data and were included in the analysis population (3932 in EAIV and 4432 in EAV). Information on cardiovascular events was available in 7892 patients. Follow-up was for a median 1·6 years (IQR 1·2-2·0). The average patient age was 63·3 years (SD 9·8), and 6346 (75·9%) of 8364 patients were men. At baseline, 1856 (22·5%) of 8263 patients were determined to have newly detected type 2 diabetes using OGTT alone, compared with 346 (4·2%) using HbA1c alone. New dysglycaemia, defined as newly detected type 2 diabetes or impaired glucose tolerance (IGT), was present in 3896 (47·1%) of the patients according to 2hPG. 2hPG 9 mmol/L or greater (162 mg/dL, adjusted hazard ratio [aHR] 1·58; 95% CI 1·27-1·95, p<0·0001), and HbA1c 5·9% or greater (41 mmol/mol, aHR 1·48, 1·19-1·84; p=0·0010) were the strongest predictors of cardiovascular events, while FPG did not predict. A multivariable model showed that the effect of HbA1c on cardiovascular events was mainly explained by 2hPG (aHR for 1 unit increase in HbA1c 1·13, 0·98-1·30; p=0·11; and aHR for 1 unit increase in Ln[2hPG] 1·37, 1·08-1·74; p=0·0042). INTERPRETATION: 2hPG appears better than HbA1c in detecting dysglycaemia and predicting its impact on future cardiovascular events in patients with coronary artery disease and should be recommended as the primary screening tool. FUNDING: Swedish Heart-Lung Foundation, Region Stockholm (ALF), the Erling Persson Foundation, the Baltic Child Foundation.

Complete vs. Culprit-Only Revascularization in Older Patients with ST-segment Elevation Myocardial Infarction: An Individual Patient Meta-Analysis.

Background: Complete revascularization is the standard treatment for patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. The Functional Assessment in Elderly MI Patients with Multivessel Disease (FIRE) trial confirmed the benefit of complete revascularization in a population of older patients, but the follow-up is limited to 1 year. Therefore, the long-term benefit ( > 1-year) of this strategy in older patients is debated. To address this, an individual patient data meta-analysis was conducted in STEMI patients aged 75 years or older enrolled in randomized clinical trials investigating complete vs. culprit-only revascularization strategies. Methods: PubMed, Embase, and the Cochrane database, were systematically searched to identify randomized clinical trials comparing complete vs. culprit-only revascularization. Individual patient-level data were collected from the relevant trials. The primary endpoint was death, myocardial infarction (MI), or ischemia-driven revascularization. The secondary endpoint was cardiovascular death or myocardial infarction. Results: Data from seven RCTs, encompassing 1733 patients (917 randomized to culprit-only and 816 to complete revascularization), were analyzed. The median age was 79 [77-83] years. Females were 595 (34%). Follow-up ranged from a minimum of six months to a maximum of 6.2 years (median 2.5 [1-3.8] years). Complete revascularization reduced the primary endpoint up to four years (HR 0.78, 95%CI 0.63-0.96), but not at the longest available follow-up (HR 0.83, 95%CI 0.69-1.01). Complete revascularization significantly reduced the occurrence of cardiovascular death or MI at the longest available follow-up (HR 0.76, 95%CI 0.58-0.99). This was observed even when censoring the follow-up at each year. Long-term rate of death did not differ between complete and culprit-only revascularization arms. Conclusions: In this individual patient data meta-analysis of older STEMI patients with multivessel disease, complete revascularization reduced the primary endpoint of death, MI or ischemia-driven revascularization up to 4-year. At the longest follow-up, complete revascularization reduced the composite of cardiovascular death or MI, but not the primary endpoint. Clinical Study Registration: PROSPERO CRD42022367898.

Feasibility and Utility of Anatomical and Physiological Evaluation of Coronary Disease With Cardiac CT in Severe Aortic Stenosis (FUTURE-AS Registry): Rationale and Design.

Background: Coronary artery disease (CAD) in patients with severe aortic stenosis (AS) is common and may be associated with worse outcomes. Computed tomography coronary angiography (CTCA) and fractional flow reserve derived from computed tomography (FFRCT) are tools for comprehensive coronary assessment. The utility and safety of CTCA and FFRCT in the work-up for transcatheter aortic valve replacement (TAVR) is not established, especially in an evolving landscape that involves younger TAVR patients. The FUTURE-AS Registry will assess the utility and safety of cardiac-optimized CTCA and FFRCT to evaluate CAD and guide referral for downstream invasive coronary angiography (ICA) in patients with severe AS being considered for TAVR. Methods: FUTURE-AS is an international, prospective, multicenter registry of patients with severe AS referred for TAVR being assessed for CAD with CTCA and FFRCT. The primary end point is the per-patient sensitivity and negative predictive value of CTCA and FFRCT for identifying anatomical and physiologically significant CAD compared to ICA and invasive FFR. The safety end point is the incidence of symptomatic hypotension or bradycardia requiring intervention following the administration of nitroglycerin or ß-blocker medications. Feasibility end points include the incidence of noninterpretable CTCA scans and CTCA scans not adequate for FFR analysis. Other utility end points include specificity, positive predictive value, and accuracy of CTCA and FFRCT. Lastly, the potential of a CTCA and FFRCT guided strategy to defer pre-TAVR ICA will be assessed. Conclusions: FUTURE-AS will characterize the utility, safety, and feasibility of CTCA and FFRCT for coronary assessment pre-TAVR.

The Impact of Parental Suicide Stigma on Youth Suicide Stigma in Mexico.

Suicide negatively impacts societies worldwide. A particular area of concern is the prevalence of suicide among Latinx youth, as research indicates that suicide behaviors among Latinx in the United States and youth in Latin America have increased drastically over the last decade. Reducing suicide stigma is a key factor in promoting youth help-seeking behaviors regarding suicidality. Previous research suggests that a relationship with a trusted adult may influence the likelihood of an adolescent contacting a suicide crisis line. Our study seeks to further the research of how parents can influence youth perceptions of suicide by studying the relationship between parent and child suicide stigma. Data were collected from parent-child dyads throughout Mexico. The Stigma of Suicide Scale Short Form was used to measure suicide stigma among adult and youth participants independently. Results suggest that parent suicide stigma was a significant predictor of youth suicide stigma, that male youth in our sample had higher suicide stigma than female youth, and that access to healthcare services was associated with lower suicide stigma. Results are discussed considering unique cultural factors in Mexico such as familismo. If future research reinforces the findings of this study, suicide stigma programs might be more effective if targeted at the entire family unit rather than just adolescents.

Variation in Secondary Prevention of Coronary Heart Disease: The INTERASPIRE Study.

BACKGROUND AND AIMS: INTERASPIRE is an international study of coronary heart disease (CHD) patients, designed to measure if guideline standards for secondary prevention and cardiac rehabilitation are being achieved in a timely manner. METHODS: Between 2020-2023, adults hospitalized in the preceding 6-24 months with incident or recurrent CHD were sampled in 14 countries from all 6 World Health Organization regions and invited for a standardized interview and examination. Direct age and sex standardization was used for country-level prevalence estimation. RESULTS: Overall, 4548 (21.1% female) CHD patients were interviewed a median of 1.05 (interquartile range 0.76-1.45) years after index hospitalization. Among all participants, 24% were obese (40% centrally). Only 38.5% achieved a blood pressure (BP) <130/80 mmHg and 19.2% a low-density lipoprotein cholesterol (LDL-C) of <1.4 mmol/l. Of those smoking at hospitalization, 48% persisted at interview. Of those with known diabetes, 56% achieved glycated hemoglobin (HbA1c) of <7.0%. A further 9.8% had undetected diabetes and 26.9% impaired glucose tolerance. Females were less likely to achieve targets: BP (females 37.4% males 38.6%), LDL-C (females 13.7% males 18.6%) and HbA1c in diabetes (females 47.7% males 57.5%). Overall, just 9.0% (inter-country range 3.8%-20.0%) reported attending cardiac rehabilitation and 1.0% (inter-country range 0.0%-2.4%) achieved the study definition of optimal guideline adherence. CONCLUSIONS: INTERASPIRE demonstrates inadequate and heterogeneous international implementation of guideline standards for secondary prevention in the first year after CHD hospitalization, with geographic and sex disparity. Investment aimed at reducing between-country and between-individual variability in secondary prevention will promote equity in global efforts to reduce the burden of CHD.

Improved self-cleaving precipitation tags for efficient column free bioseparations.

Current biological research requires simple protein bioseparation methods capable of purifying target proteins in a single step with high yields and purities. Conventional affinity tag-based approaches require specific affinity resins and expensive proteolytic enzymes for tag removal. Purification strategies based on self-cleaving aggregating tags have been previously developed to address these problems. However, these methods often utilize C-terminal cleaving contiguous inteins which suffer from premature cleavage, resulting in significant product loss during protein expression. In this work, we evaluate two novel mutants of the Mtu RecA ΔI-CM mini-intein obtained through yeast surface display for improved protein purification. When used with the elastin-like-polypeptide (ELP) precipitation tag, the novel mutants - ΔI-12 and ΔI-29 resulted in significantly higher precursor content, product purity and process yield compared to the original Mtu RecA ΔI-CM mini-intein. Product purities ranging from 68 % to 94 % were obtained in a single step for three model proteins - green fluorescent protein (GFP), maltose binding protein (MBP) and beta-galactosidase (beta-gal). Further, high cleaving efficiency was achieved after 5 h under most conditions. Overall, we have developed improved self-cleaving precipitation tags which can be used for purifying a wide range of proteins cheaply at laboratory scale.

Less Deformable Erythrocyte Subpopulations Biomechanically Induce Endothelial Inflammation in Sickle Cell Disease.

Sickle cell disease (SCD) is canonically characterized by reduced red blood cell (RBC) deformability leading to microvascular obstruction and inflammation. While the biophysical properties of sickle RBCs are known to influence SCD vasculopathy, the contribution of poor RBC deformability to endothelial dysfunction has yet to be fully explored. Leveraging interrelated in vitro and in silico approaches, we introduce a new paradigm of SCD vasculopathy in which poorly deformable sickle RBCs directly cause endothelial dysfunction via mechanotransduction, where endothelial cells sense and pathophysiologically respond to aberrant physical forces independently of microvascular obstruction, adhesion, or hemolysis. We demonstrate that perfusion of sickle RBCs or pharmacologically-dehydrated healthy RBCs into small venule-sized "endothelialized" microfluidics leads to pathologic physical interactions with endothelial cells that directly induce inflammatory pathways. Using a combination of computational simulations and large venule-sized endothelialized microfluidics, we observed that perfusion of heterogeneous sickle RBC subpopulations of varying deformability, as well as suspensions of dehydrated normal RBCs admixed with normal RBCs leads to aberrant margination of the less-deformable RBC subpopulations towards the vessel walls, causing localized, increased shear stress. Increased wall stress is dependent on the degree of subpopulation heterogeneity and oxygen tension and leads to inflammatory endothelial gene expression via mechanotransductive pathways. Our multifaceted approach demonstrates that the presence of sickle RBCs with reduced deformability leads directly to pathological physical (i.e., direct collisions and/or compressive forces) and shear-mediated interactions with endothelial cells and induces an inflammatory response, thereby elucidating the ubiquity of vascular dysfunction in SCD.

Analytically Confirmed Intentional Overdose of the Antidepressant Vortioxetine.

INTRODUCTION: Vortioxetine is an antidepressant with a multimodal mechanism of action. It is used as a treatment option for patients with major depressive episodes. There have only been two previously reported non-fatal overdoses of vortioxetine; neither of these were analytically confirmed There has also been one case of serotonin syndrome potentially related to vortioxetine and two deaths where vortioxetine was detected. We report here a non-fatal analytically confirmed case of vortioxetine overdose. CASE REPORT: A 32-year-old male presented to the emergency department (ED) 12-13 h after oral ingestion of 1,260 mg of vortioxetine and 350 mg of diazepam. A family member reported that he had been drowsy after the overdose, but his level of consciousness and observations (heart rate, blood pressure and temperature) were normal on review by the pre-hospital emergency services and on arrival to the ED. During a period of observation, he did not develop any features of serotonin syndrome or any other significant toxicity. Toxicological analysis of a blood sample taken in the ED detected vortioxetine (plasma concentration 457 ng/mL 10 h after ingestion) and sub-therapeutic concentrations of diazepam and pregabalin. DISCUSSION: Despite having a plasma vortioxetine concentration nearly 15-times therapeutic vortioxetine concentrations, this patient did not develop any significant toxicity. In particular he did not develop any clinical or biochemical features of serotonin toxicity that would be expected with this class of antidepressant. Additional reporting of analytically confirmed vortioxetine overdoses will allow clinicians and licensing authorities to further understand the safety of this medication in overdose.

Clinical and Radiological Outcomes at ≥10-Year Follow-up After Matrix-induced Autologous Chondrocyte Implantation in the Patellofemoral Joint.

BACKGROUND: Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging outcomes in the treatment of knee cartilage defects, although limited research is available on its longer term (≥10 years) sustainability in the patellofemoral joint. PURPOSE: To report the clinical and radiological outcomes at ≥10 years in a prospectively recruited cohort of patients undergoing MACI in the patellofemoral joint and compare outcomes in patients undergoing MACI on the patella versus the trochlea. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The current study prospectively enrolled 95 patients who underwent patellofemoral MACI, of whom 29 (13 patella, 16 trochlea) underwent concomitant tibial tubercle osteotomy. Patients were assessed preoperatively and at 2, 5, and ≥10 years using a range of patient-reported outcome measures (PROMs) including the Knee injury and Osteoarthritis Outcome Score, the 36-item Short Form Health Survey, and the frequency and severity of knee pain as well as patient satisfaction, full active knee flexion and extension, and peak isokinetic knee extensor and flexor torques. High-resolution magnetic resonance imaging (MRI) was performed to assess pertinent graft parameters, as well as determine an overall MRI composite score, per the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system. Results were analyzed according to the graft location (patella or trochlea). RESULTS: Of the 95 patients recruited, 82 patients (41 patella, 41 trochlea) were available for a clinical review at ≥10 years after surgery (mean follow-up, 11.9 years [range, 10-15 years]). For the whole patellofemoral MACI cohort, all PROMs significantly improved over time (P < .05), with no significant changes (P > .05) observed in any MRI-based score from 2 to ≥10 years after surgery. At ≥10 years, 90.2% (n = 74) were satisfied with MACI in relieving their knee pain, and 85.4% (n = 70) were satisfied with the improvement in their ability to participate in sports. No differences (P > .05) were observed in PROMs between those undergoing patellar MACI and those undergoing trochlear MACI, although a significant group effect was observed for limb symmetry indices of knee extensor (P = .009) and flexor (P = .041) strength, which were greater in those undergoing patellar (vs trochlear) MACI. No statistically significant differences (P > .05) were observed between patellar and trochlear grafts on any MRI-based measure. In the cohort assessed at ≥10 years after surgery, 4 patients (2 patella, 2 trochlea) demonstrated graft failure on MRI scans, although a further 3 patients (all trochlea) were omitted from the ≥10-year review for having already progressed to total knee arthroplasty. CONCLUSION: Good clinical scores, high levels of patient satisfaction, and adequate graft survivorship were observed at ≥10 years after MACI on the patella and trochlea.

Intravenous lipid emulsion interference in coagulation testing: an ex vivo analysis.

INTRODUCTION: Intravenous lipid emulsion is used in the rescue treatment of certain poisonings. A complication is interference with laboratory analyses. The aim of this study was to determine the impact of intravenous lipid emulsion on routine laboratory analysis of coagulation parameters ex vivo and determine if any of the analytical techniques remain reliable. METHODS: Samples were obtained from 19 healthy volunteers and divided in triplicate. One sample served as a control, and the other two were diluted to simulate the treatment of an average adult with Intralipid® 20 per cent Fresenius Kabi 100 mL (dilution-1) or 500 mL (dilution-2). Coagulation tests performed were prothrombin time, activated prothrombin time, D-dimer concentration and fibrinogen. Coagulation testing was performed by three techniques. Test-1 was performed on a Sysmex CN6000 analyzer. Test-2 was performed with a manual mechanical endpoint method using the semi-automated Stago KC4 Delta. Test-3 involved high-speed centrifugation before repeat testing on the Sysmex CN6000 analyzer. RESULTS: For test-1, only nine (47 per cent) samples in dilution-1 could be analyzed for coagulation tests, and no coagulation tests could be analyzed for dilution-2 because of lipaemia. For test-2 and test-3, all samples could be analyzed, and all results of both testing methods fell within the limits of the laboratory reference range. DISCUSSION: Difficulties in laboratory analysis of patients having received intravenous lipid emulsion are due to multiple factors. Most automated coagulation analyzers use optical measurements, which can be unreliable in the presence of a high intravenous lipid concentration. By altering the lipaemia in the testing solution using high-speed centrifugation or by using manual mechanical endpoint detection, we were able to obtain reliable results. These findings are limited by the use of an ex vivo method and healthy volunteers. CONCLUSIONS: This ex vivo model confirms that Intralipid® interferes with routine coagulation studies. It is important that clinicians are aware and inform their laboratories of its administration.

An Internet Snapshot Survey Assessing the sale of Synthetic Cannabinoid Receptor Agonists for use with Electronic Vaping Devices.

INTRODUCTION: Synthetic cannabinoid receptor agonists (SCRAs) are associated with significant toxicity and are increasingly used in electronic vaping devices. We assessed the availability of SCRA vaping products to UK purchasers on the surface web. METHODS: An internet snapshot survey was performed between October 2022 and January 2023 on 'google.com' using the search terms "buy c-liquid vape", "buy herbal incense vape liquid", "buy cannabis vape liquid", "buy hashish vape liquid", "buy K2 vape liquid". RESULTS: 62 websites selling 128 SCRA vaping brands were identified. Most were purportedly based in the USA (41 websites, 66%) and most sold other controlled substances. Purchase incentives offered included discreet packaging (38, 61%), discounts for bulk purchase (34, 55%) and tracked delivery (30, 48%). Many websites stated SCRA products were: not for human consumption (41, 66%), for research purposes only (15, 24%), or legal (28, 45%). Websites sold a median (IQR) of 16 (7-25) SCRA vaping brands. Almost all were bottles of vaping liquid (1220/1225, 99.6%). The most common bottle size was 5mL (60%), the median (IQR) total volume of SCRA liquid per sale was 50mL (10-200mL). Median (IQR) price was £3.39/mL (£2.01/mL- £5.29/mL). Price decreased with increasing volume purchased (£6.58/mL for ≤ 5mL, £1.60/mL for > 200mL). CONCLUSION: SCRA vaping products are easily obtainable online, in both small and bulk quantities. Information provided to purchasers on safety and legality is lacking or misleading. Further studies are needed to confirm the chemistry of these products. Policymakers should consider steps to limit the potential harm caused by the purchase and use of these products.

Hydrodynamic Assessment of Explanted Degenerated Transcatheter Aortic Valves: Novel Insights Into Noncalcific and Calcific Mechanisms.

BACKGROUND: The etiology of transcatheter aortic valve (TAV) degeneration is poorly understood, particularly noncalcific mechanisms. OBJECTIVES: The authors sought to investigate noncalcific and calcific mechanisms of TAV degeneration and evaluate their impact on leaflet function by bench testing, imaging, and histology. METHODS: TAV explants were obtained from the EXPLANT THV registry and clinical institutions. Hydrodynamic assessment was performed using a heart valve pulse duplicator system under physiological conditions. Micro-computed tomography, high-resolution photography, high speed video, and hematoxylin and eosin staining were used to evaluate the morphological appearance, leaflet kinematics, and calcium burden of TAVs. RESULTS: A total of 14 explants were evaluated: 10 self-expanding CoreValve/Evolut TAVs (Medtronic), 3 balloon-expandable SAPIEN 3 TAVs (Edwards Lifesciences), and 1 mechanically expandable Lotus TAV (Boston Scientific). The median patient age at explantation was 73.0 years (Q1-Q3: 64.5-80.0 years), with a time to explantation of 4 years 1 month (1 year 5 months to 4 years 11 months). Six TAV explants were found to have leaflet calcification (162.4 mm3; 58.8-603.0 mm3), and 8 had no calcification detectable by micro-computed tomography and histology. All samples had impaired leaflet kinematics. There was no significant difference in the hydrodynamic mean gradient between calcified (47.2 mm Hg; 26.6-74.1 mm Hg) and noncalcified (27.6 mm Hg; 15.2-36.7 mm Hg; P = 0.28) TAVs. Leaflet calcification had a weak but nonsignificant association with the hydrodynamic mean gradient (r = 0.42; P = 0.14). CONCLUSIONS: TAV function can be severely impacted by noncalcific and calcific mechanisms of tissue degeneration. Importantly, functional stenosis can occur in TAVs in the absence of obvious and significant calcification.

Joint RCEM and NPIS best practice guideline: assessment and management of acute opioid toxicity in adults in the emergency department.

The Royal College of Emergency Medicine Toxicology Special Interest Group in collaboration with the UK National Poisons Information Service and the Clinical Toxicology Department at Guy's and St Thomas' NHS Foundation Trust has produced guidance to support clinicians working in the ED with the assessment and management of adults with acute opioid toxicity.Considerations regarding identification of acute opioid toxicity are discussed and recommendations regarding treatment options and secondary prevention are made. There is a focus on making recommendations on the best available evidence.

Bicuspid valve CT registry of balloon-expandable TAVR: BETTER TAVR registry.

BACKGROUND: The anatomic substrate of bicuspid valves may lead to suboptimal TAVR stent expansion and geometry. AIM: We evaluated determinants of stent geometry in bicuspid valves treated with Sapien transcatheter aortic valve replacement (TAVR) valves. METHODS: A multicenter retrospective registry of patients (February 2019 to August 2022) who underwent post-TAVR computed tomography to determine stent area (vs. nominal valve area) and stent ellipticity (maximum diameter/minimum diameter). Predictors of relative stent expansion (minimum area/average of inflow + outflow area) and stent ellipticity were evaluated in a multivariable regression model, including valve calcium volume (indexed by annular area), presence of raphe calcium, sinus diameters indexed by area-derived annular diameter, and performance of pre-dilation and post-dilation. RESULTS: The registry enrolled 101 patients from four centers. The minimum stent area (vs. nominal area) was 88.1%, and the maximum ellipticity was 1.10, with both observed near the midframe of the valve in all cases. Relative stent expansion ≥90% was observed in 64/101 patients. The only significant predictor of relative stent expansion ≥90% was the performance of post-dilation (OR: 4.79, p = 0.018). Relative stent expansion ≥90% was seen in 86% of patients with post-dilation compared to 57% without (p < 0.001). The stent ellipticity ≥1.1 was observed in 47/101 patients. The significant predictors of stent ellipticity ≥1.1 were the indexed maximum sinus diameter (OR: 0.582, p = 0.021) and indexed intercommisural diameter at 4 mm (OR: 2.42, p = 0.001). Stent expansion has a weak negative correlation with post-TAVR mean gradient (r = -0.324, p < 0.001). CONCLUSION: Relative stent expansion ≥90% was associated with the performance of post-dilation, and stent ellipticity ≥1.1 was associated with indexed intercommisural diameter and indexed maximum sinus diameter. Further studies to determine optimal deployment strategies in bicuspid valves are needed.