Coronary coding in dTGA pre- and post-ASO-verification and necessary corrections following adult CMR.

Aims: In adult patients with transposition of the great arteries (dTGA) after arterial switch operation (ASO), the coronary artery circulation after neonatal surgical transfer remains a major culprit for long-term sequelae, including myocardial ischaemia and sudden cardiac death. As coronary imaging in paediatric age is often incomplete and classification mainly relies on the surgeon's description in the operation report, we intended to develop a systematic, understandable pattern of the coronary status for each young patient, combining unambiguous coding with non-invasive imaging. Methods and results: The monocentric prospective study evaluated 89 young adults (mean 23 years) after ASO for dTGA including cardiac magnetic resonance (CMR) coronary angiography. Following 'The Leiden Convention coronary coding system', we describe the systematic transformation process and provide a graphical illustration considering surgical and imaging views for the six main coronary types, followed by a comparison with adult CMR. Discordance between surgeon's and CMR classification is evaluated.In seven (7.9%) patients, a discordance between the surgeon's post-operative and the CMR classification was found; therefore, the initial classification had to be corrected according to adult CMR. Three cases (3.4%) with particularly challenging coronary variants (intramural and interarterial course, functional common ostium) are presented. Conclusion: Considering the risks of a possible neonatal coronary misclassification and of increasing additional acquired coronary artery disease with age, reliable cooperation between surgeons, cardiologists, and imaging specialists must be ensured. Therefore, after completion of growth, a systematic pattern of the coronary artery status, combining unambiguous coding with CMR imaging, should be established for each patient.

Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Kidney Outcomes across Baseline Cardiovascular-Kidney-Metabolic Conditions: A Systematic Review and Meta-Analyses.

BACKGROUND: The effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on kidney outcomes in patients with varying combinations of heart failure, chronic kidney disease, and type 2 diabetes mellitus have not been quantified. METHODS: PubMed and Scopus were queried up to December 2023 for primary and secondary analysis of placebo-controlled trials of SGLT2i in patients with heart failure, chronic kidney disease, or type 2 diabetes mellitus. Outcomes of interest were composite kidney endpoint (combination of estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2, sustained doubling of serum creatinine, varying percent change in eGFR, and need for kidney replacement therapy), rate of eGFR slope decline and albuminuria progression. Hazard ratios (HR) and mean differences with their 95% confidence intervals (CI) were extracted onto an excel sheet, and the results were then pooled using a random-effect model through Review Manager (version 5.3, Cochrane Collaboration). RESULTS: Eleven trials (n=80,928 patients) were included. Compared with the placebo, SGLT2i reduced the risk of the composite kidney endpoint by 41% (hazard ratio 0.59; 95%CI 0.42-0.83) in heart failure with reduced ejection fraction, 36% (hazard ratio 0.64;95%CI 0.55-0.73) in chronic kidney disease, and 38% (hazard ratio 0.62;95%CI 0.56-0.69) in type 2 diabetes mellitus. A similar pattern of benefit was observed in combinations of these comorbidities, as well as patients without baseline heart failure, chronic kidney disease, or type 2 diabetes mellitus. SGLT2i slowed the rate of eGFR slope decline and reduced the risk of sustained doubling of serum creatinine by 36% (hazard ratio 0.64; 95%CI 0.56-0.72) in the overall population, and a consistent effect on kidney outcomes was observed in most subpopulations with available data. CONCLUSIONS: SGLT2i improved kidney outcomes in cohorts with heart failure, chronic kidney disease, and type 2 diabetes mellitus, and these effects were consistent across patients with different combinations of these comorbidities.

Targeting Cyclophilin A in the Cardiac Microenvironment Preserves Heart Function and Structure in Failing Hearts.

BACKGROUND: Cardiac hypertrophy is characterized by remodeling of the myocardium, which involves alterations in the ECM (extracellular matrix) and cardiomyocyte structure. These alterations critically contribute to impaired contractility and relaxation, ultimately leading to heart failure. Emerging evidence implicates that extracellular signaling molecules are critically involved in the pathogenesis of cardiac hypertrophy and remodeling. The immunophilin CyPA (cyclophilin A) has been identified as a potential culprit. In this study, we aimed to unravel the interplay between eCyPA (extracellular CyPA) and myocardial dysfunction and evaluate the therapeutic potential of inhibiting its extracellular accumulation to improve heart function. METHODS: Employing a multidisciplinary approach encompassing in silico, in vitro, in vivo, and ex vivo experiments we studied a mouse model of cardiac hypertrophy and human heart specimen to decipher the interaction of CyPA and the cardiac microenvironment in highly relevant pre-/clinical settings. Myocardial expression of CyPA (immunohistology) and the inflammatory transcriptome (NanoString) was analyzed in human cardiac tissue derived from patients with nonischemic, noninflammatory congestive heart failure (n=187). These analyses were paralleled by a mouse model of Ang (angiotensin) II-induced heart failure, which was assessed by functional (echocardiography), structural (immunohistology, atomic force microscopy), and biomolecular (Raman spectroscopy) analyses. The effect of inhibiting eCyPA in the cardiac microenvironment was evaluated using a newly developed neutralizing anti-eCyPA monoclonal antibody. RESULTS: We observed a significant accumulation of eCyPA in both human and murine-failing hearts. Importantly, higher eCyPA expression was associated with poor clinical outcomes in patients (P=0.043) and contractile dysfunction in mice (Pearson correlation coefficient, -0.73). Further, myocardial expression of eCyPA was critically associated with an increase in myocardial hypertrophy, inflammation, fibrosis, stiffness, and cardiac dysfunction in vivo. Antibody-based inhibition of eCyPA prevented (Ang II)-induced myocardial remodeling and dysfunction in mice. CONCLUSIONS: Our study provides strong evidence of the pathogenic role of eCyPA in remodeling, myocardial stiffening, and dysfunction in heart failure. The findings suggest that antibody-based inhibition of eCyPA may offer a novel therapeutic strategy for nonischemic heart failure. Further research is needed to evaluate the translational potential of these interventions in human patients with cardiac hypertrophy.

Pioglitazone treatment mitigates cardiovascular bioprosthetic degeneration in a chronic kidney disease model.

Aims: Chronic kidney disease (CKD) is a risk factor for the development of cardiovascular diseases, e.g., atherosclerosis and calcific aortic valve disease, leading inevitably to valve replacement surgery. CKD patients with bioprosthetic cardiovascular grafts, in turn, have a higher risk of premature graft degeneration. Peroxisome proliferator-activated receptor gamma (PPARγ) activation by pioglitazone has cardio-renal protective properties, and research using a heterotopic valve implantation model has shown anti-degenerative effects of PPARγ activation on bioprosthetic valved grafts (BVG) in rats. The present work aims to analyze a potential protective effect of pioglitazone treatment on BVG in an adenine-induced rat model of CKD. Methods and Results: BVG of Sprague Dawley rats were heterotopically implanted in Wistar rats in an infrarenal position for 4 and 8 weeks. Animals were distributed into three groups for each time point: 1) control group receiving standard chow, 2) CKD group receiving 0.25% adenine and 3) CKD + pioglitazone group (300 mg per kg of 0.25% adenine chow). BVG function was analyzed by echocardiography. Plasma analytes were determined and explanted grafts were analyzed by semi-quantitative real-time PCR, Western blot analysis, histology and immunohistology.PPARγ activation significantly reduced CKD-induced calcification of aortic and valvular segments of BVG by 44% and 53%, respectively. Pioglitazone treatment significantly also reduced CKD-induced intima hyperplasia by 60%. Plasma analysis revealed significantly attenuated potassium and phosphate levels after pioglitazone treatment. Moreover, PPARγ activation led to significantly decreased interleukin-6 gene expression (by 57%) in BVG compared to CKD animals. Pioglitazone treatment leads to functional improvement of BVG. Conclusion: This study broadens the understanding of the potential value of PPARγ activation in cardio-renal diseases and delineates pioglitazone treatment as a valuable option to prevent bioprosthetic graft failure in CKD. Further mechanistic studies, e.g., using small molecules activating PPARγ signaling pathways, are necessary for the evaluation of involved mechanisms. Additionally, the translation into pre-clinical studies using large animals is intended as the next research project.

Obesity and cardiovascular disease: an ESC clinical consensus statement.

The global prevalence of obesity has more than doubled over the past four decades, currently affecting more than a billion individuals. Beyond its recognition as a high-risk condition that is causally linked to many chronic illnesses, obesity has been declared a disease per se that results in impaired quality of life and reduced life expectancy. Notably, two-thirds of obesity-related excess mortality is attributable to cardiovascular disease. Despite the increasingly appreciated link between obesity and a broad range of cardiovascular disease manifestations including atherosclerotic disease, heart failure, thromboembolic disease, arrhythmias, and sudden cardiac death, obesity has been underrecognized and sub-optimally addressed compared with other modifiable cardiovascular risk factors. In the view of major repercussions of the obesity epidemic on public health, attention has focused on population-based and personalized approaches to prevent excess weight gain and maintain a healthy body weight from early childhood and throughout adult life, as well as on comprehensive weight loss interventions for persons with established obesity. This clinical consensus statement by the European Society of Cardiology discusses current evidence on the epidemiology and aetiology of obesity; the interplay between obesity, cardiovascular risk factors and cardiac conditions; the clinical management of patients with cardiac disease and obesity; and weight loss strategies including lifestyle changes, interventional procedures, and anti-obesity medications with particular focus on their impact on cardiometabolic risk and cardiac outcomes. The document aims to raise awareness on obesity as a major risk factor and provide guidance for implementing evidence-based practices for its prevention and optimal management within the context of primary and secondary cardiovascular disease prevention.

Obesity and cardiovascular disease: an ESC clinical consensus statement.

The global prevalence of obesity has more than doubled over the past four decades, currently affecting more than a billion individuals. Beyond its recognition as a high-risk condition that is causally linked to many chronic illnesses, obesity has been declared a disease per se that results in impaired quality of life and reduced life expectancy. Notably, two-thirds of obesity-related excess mortality is attributable to cardiovascular disease. Despite the increasingly appreciated link between obesity and a broad range of cardiovascular disease manifestations including atherosclerotic disease, heart failure, thromboembolic disease, arrhythmias, and sudden cardiac death, obesity has been underrecognized and sub-optimally addressed compared with other modifiable cardiovascular risk factors. In the view of major repercussions of the obesity epidemic on public health, attention has focused on population-based and personalized approaches to prevent excess weight gain and maintain a healthy body weight from early childhood and throughout adult life, as well as on comprehensive weight loss interventions for persons with established obesity. This clinical consensus statement by the European Society of Cardiology discusses current evidence on the epidemiology and aetiology of obesity; the interplay between obesity, cardiovascular risk factors and cardiac conditions; the clinical management of patients with cardiac disease and obesity; and weight loss strategies including lifestyle changes, interventional procedures, and anti-obesity medications with particular focus on their impact on cardiometabolic risk and cardiac outcomes. The document aims to raise awareness on obesity as a major risk factor and provide guidance for implementing evidence-based practices for its prevention and optimal management within the context of primary and secondary cardiovascular disease prevention.

Systemic inflammation and health outcomes in patients receiving treatment for atherosclerotic cardiovascular disease.

BACKGROUND AND AIMS: The burden and outcomes of inflammation in patients with atherosclerotic cardiovascular disease (ASCVD) are not well defined beyond the controlled settings of trials and research cohorts. METHODS: This was an observational study of ASCVD adults undergoing C-reactive protein testing in Stockholm's healthcare (2007-21). After excluding C-reactive protein tests associated with acute illness or medications/conditions that bias C-reactive protein interpretation, systemic inflammation was evaluated over a 3-month ascertainment window. Determinants of C-reactive protein ≥ 2 mg/L were explored with logistic regression. C-reactive protein categories were compared via negative-binomial/Cox regression for subsequent healthcare resource utilization and occurrence of major adverse cardiovascular events, heart failure hospitalization, and death. RESULTS: A total of 84 399 ASCVD adults were included (46% female, mean age 71 years, 59% with C-reactive protein ≥ 2 mg/L). Female sex, older age, lower kidney function, albuminuria, diabetes, hypertension, and recent anaemia were associated with higher odds of C-reactive protein ≥ 2 mg/L. The use of renin-angiotensin system inhibitors, antiplatelets, and lipid-lowering therapy was associated with lower odds. Over a median of 6.4 years, compared with C-reactive protein < 2 mg/L, patients with C-reactive protein ≥ 2 mg/L had higher rates of hospitalizations, days spent in hospital, outpatient consultations, and dispensed medications (P < .05 for all). They also had a higher rate of major adverse cardiovascular events [hazard ratio (HR) 1.30; 95% confidence interval (CI) 1.27-1.33], heart failure (HR 1.24; 95% CI 1.20-1.30), and death (HR 1.35; 95% CI 1.31-1.39). Results were consistent across subgroups and granular C-reactive protein categories and robust to the exclusion of extreme C-reactive protein values or early events. CONCLUSIONS: Three in five adults with ASCVD have systemic inflammation, which is associated with excess healthcare resource utilization and increased rates of cardiovascular events and death.

IL-6 and hsCRP predict cardiovascular mortality in patients with heart failure with preserved ejection fraction.

AIMS: Inflammation accompanies heart failure (HF) and elevated levels of inflammatory biomarkers are linked to new onset of HF. However, whether the prognostic relevance of inflammatory biomarkers is different in HF with reduced (HFrEF) and preserved ejection fraction (HFpEF) is unclear. The aim of the current study is to explore the role of inflammation on the mortality risk in patients with HF. METHODS: We analysed interleukin-6 and hsCRP levels by ELISA and immunonephelometry, respectively, in HFpEF and HFrEF patients referred for coronary angiography and assessed the prognostic value in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. RESULTS: HF was present in 1086 patients (N = 506 HFpEF; N = 580 HFrEF; mean age 65 ± 10 years; 28% female). Increasing IL-6 levels were significantly associated with increased CV mortality in HFpEF [1.5 (95% CI: 1.1-2.2), P = 0.018] but not HFrEF [HR 1.3 (95% CI: 1.0-1.7), P = 0.06] patients. High-sensitive CRP followed a similar pattern but failed to reach statistical significance after full-adjustment (HFpEF: HR 1.4 95%C I: 1.0-2.0; P = 0.065; HFrEF HR: 1.0 95% CI: 0.7-1.3; P = 0.800). Interaction analysis in patients stratified by IL-6 and N terminal pro brain natriuretic peptide (NT-proBNP) above and below the median revealed a stepwise increase in CV-mortality in HFpEF (P = 0.036) but not HFrEF patients (P = 0.220). To investigate the relationship between IL-6 and NT-proBNP, we assessed the genetic IL6-Receptor variant p.Asp358Ala (rs2228145) which is linked to impaired IL-6 receptor signalling. Homozygous carriers with HFpEF but not HFrEF exhibited significantly lower NT-pro-BNP levels compared with wildtype carriers (HFpEF 779 pg/mL ± 787 vs. 1180 pg/ mL ± 1532; P = 0.008; HFrEF 2289 pg/ mL ± 3439 vs. 2326 pg/ mL ± 3386; P = 0.94), raising the hypothesis that IL-6 signalling may play a pathophysiological role in HFpEF. CONCLUSIONS: These data suggest a predictive value of elevated IL-6 for CV-mortality in HFpEF but not in HFrEF patients.

Evaluation of the Truncated Cone-Rhomboid Pyramid Formula for Simplified Right Ventricular Quantification: A Cardiac Magnetic Resonance Study.

Background/Objective: Cardiac magnetic resonance (CMR) is the reference method for right ventricular (RV) volume and function analysis, but time-consuming manual segmentation and corrections of imperfect automatic segmentations are needed. This study sought to evaluate the applicability of an echocardiographically established truncated cone-rhomboid pyramid formula (CPF) for simplified RV quantification using CMR. Methods: A total of 70 consecutive patients assigned to RV analysis using CMR were included. As standard method, the manual contouring of RV-short axis planes was performed for the measurement of end-diastolic volume (EDV) and end-systolic volume (ESV). Additionally, two linear measurements in four-chamber views were obtained in systole and diastole: basal diameters at the level of tricuspid valve (Dd and Ds) and baso-apical lengths from the center of tricuspid valve to the RV apex (Ld and Ls) were measured for the calculation of RV-EDV = 1.21 × Dd2 × Ld and RV-ESV = 1.21 × Ds 2 × Ls using CPF. Results: RV volumes using CPF were slightly higher than those using standard CMR analysis (RV-EDV index: 86.2 ± 29.4 mL/m2 and RV-ESV index: 51.5 ± 22.5 mL/m2 vs. RV-EDV index: 81.7 ± 24.1 mL/m2 and RV-ESV index: 44.5 ± 23.2 mL/m2) and RV-EF was lower (RV-EF: 41.1 ± 13.5% vs. 48.4 ± 13.7%). Both methods had a strong correlation of RV volumes (ΔRV-EDV index = -4.5 ± 19.0 mL/m2; r = 0.765, p < 0.0001; ΔRV-ESV index = -7.0 ± 14.4 mL/m2; r = 0.801, p < 0.0001). Conclusions: Calculations of RV volumes and function using CPF assuming the geometrical model of a truncated cone-rhomboid pyramid anatomy of RV is feasible, with a strong correlation to measurements using standard CMR analysis, and only two systolic and diastolic linear measurements in four-chamber views are needed.

Disparities in prevalence and treatment of diabetes, cardiovascular and chronic kidney diseases - Recommendations from the taskforce of the guideline workshop.

There is a mounting clinical, psychosocial, and socioeconomic burden worldwide as the prevalence of diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD) continues to rise. Despite the introduction of therapeutic interventions with demonstrated efficacy to prevent the development or progression of these common chronic diseases, many individuals have limited access to these innovations due to their race/ethnicity, and/or socioeconomic status (SES). However, practical guidance to providers and healthcare systems for addressing these disparities is often lacking. In this article, we review the prevalence and impact of healthcare disparities derived from the above-mentioned chronic conditions and present broad-based recommendations for improving access to quality care and health outcomes within the most vulnerable populations.

Application of wearables for remote monitoring of oncology patients: A scoping review.

Objective: This review aims to systematically map and categorize the current state of wearable applications among oncology patients and to identify determinants impeding clinical implementation. Methods: A Medline, Embase and clinicaltrials.gov search identified journal articles, conference abstracts, letters, reports, dissertations and registered studies on the use of wearables in patients with malignancies published up to 10 November 2021. Results: Of 2509 records identified, 112 met the eligibility criteria. Of these, 9.8% (11/112) were RCTs and 47.3% (53/112) of publications were observational. Wearables were investigated pre-treatment (2.7%; 3/112), during treatment (34.8%; 39/112), post-treatment (17.9%; 20/112), in survivors (27.7%; 31/112) and in non-specified or multiple treatment phases (17.0%; 19/112). Medical-grade wearables were applied in 22.3% (25/112) of publications. Primary objectives ranged from technical feasibility (8.0%; 9/112), user feasibility (42.9%; 48/112) and correlational analysis (40.2%; 45/112) to outcome change analysis (8.9%; 10/112). Outcome change was mostly investigated regarding physical activity improvement (80.0%; 8/10). Most publications (42.9%; 48/112) and registered studies (39.3%; 24/61) featured multiple cancer types, with breast cancer as the most prevalent specific type (22.3% in publications, 16.4% in registered studies). Conclusions: Most studies among oncology patients using wearables are focused on assessing the user feasibility of consumer-grade wearables, whereas rates of RCTs assessing clinical efficacy are low. Substantial improvements in clinically relevant endpoints by the use of wearables, such as morbidity and mortality are yet to be demonstrated.

CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes.

The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5-6, 2024 ( http://www.cvot.org ).

Increased levels of a mycophenolic acid metabolite in patients with kidney failure negatively affect cardiomyocyte health.

Chronic kidney disease (CKD) significantly increases cardiovascular risk and mortality, and the accumulation of uremic toxins in the circulation upon kidney failure contributes to this increased risk. We thus performed a screening for potential novel mediators of reduced cardiovascular health starting from dialysate obtained after hemodialysis of patients with CKD. The dialysate was gradually fractionated to increased purity using orthogonal chromatography steps, with each fraction screened for a potential negative impact on the metabolic activity of cardiomyocytes using a high-throughput MTT-assay, until ultimately a highly purified fraction with strong effects on cardiomyocyte health was retained. Mass spectrometry and nuclear magnetic resonance identified the metabolite mycophenolic acid-ß-glucuronide (MPA-G) as a responsible substance. MPA-G is the main metabolite from the immunosuppressive agent MPA that is supplied in the form of mycophenolate mofetil (MMF) to patients in preparation for and after transplantation or for treatment of autoimmune and non-transplant kidney diseases. The adverse effect of MPA-G on cardiomyocytes was confirmed in vitro, reducing the overall metabolic activity and cellular respiration while increasing mitochondrial reactive oxygen species production in cardiomyocytes at concentrations detected in MMF-treated patients with failing kidney function. This study draws attention to the potential adverse effects of long-term high MMF dosing, specifically in patients with severely reduced kidney function already displaying a highly increased cardiovascular risk.

GLP-1 in patients with myocardial infarction complicated by cardiogenic shock-an IABP-SHOCK II-substudy.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) is a gut-derived peptide secreted in response to nutritional and inflammatory stimuli. Elevated GLP-1 levels predict adverse outcome in patients with acute myocardial infarction or sepsis. GLP-1 holds cardioprotective effects and GLP-1 receptor agonists reduce cardiovascular events in high-risk patients with diabetes. In this study, we aimed to investigate the capacity of GLP-1 to predict outcome in patients with cardiogenic shock (CS) complicating myocardial infarction. METHODS: Circulating GLP-1 levels were serially assessed in 172 individuals during index PCI and day 2 in a prospectively planned biomarker substudy of the IABP-SHOCK II trial. All-cause mortality at short- (30 days), intermediate- (1 year), and long-term (6 years) follow-up was used for outcome assessment. RESULTS: Patients with fatal short-term outcome (n = 70) exhibited higher GLP-1 levels [86 (interquartile range 45-130) pM] at ICU admission in comparison to patients with 30-day survival [48 (interquartile range 33-78) pM; p < 0.001] (n = 102). Repeated measures ANOVA revealed a significant interaction of GLP-1 dynamics from baseline to day 2 between survivors and non-survivors (p = 0.04). GLP-1 levels above vs. below the median proved to be predictive for short- [hazard ratio (HR) 2.43; 95% confidence interval (CI) 1.50-3.94; p < 0.001], intermediate- [HR 2.46; 95% CI 1.62-3.76; p < 0.001] and long-term [HR 2.12; 95% CI 1.44-3.11; p < 0.001] outcome by multivariate Cox-regression analysis. CONCLUSION: Elevated plasma levels of GLP-1 are an independent predictor for impaired prognosis in patients with myocardial infarction complicated by CS. The functional relevance of GLP-1 in this context is currently unknown and needs further investigations. TRIAL REGISTRATION: www. CLINICALTRIALS: gov Identifier: NCT00491036.

Diabetes mellitus and presentation, care and outcomes of patients with NSTEMI: the Association for Acute Cardiovascular Care-European Association of Percutaneous Cardiovascular Interventions EURObservational Research Programme NSTEMI Registry of the European Society of Cardiology.

AIM: Diabetes mellitus (diabetes) is common amongst patients with NSTEMI. We describe presentation, care and outcomes of patients admitted with NSTEMI by diabetes status. METHODS: Prospective cohort study including 2928 patients (1104 with prior diabetes, 1824 without) admitted to hospital with NSTEMI from 287 centres in 59 countries. Quality of care was evaluated based on 12 guideline-recommended care interventions. Outcomes included in-hospital acute heart failure, cardiogenic shock, repeat myocardial infarction, stroke/transient ischaemic attack (TIA), BARC Type ≥ 3 bleeding and death, as well as 30-day mortality. RESULTS: Patients with diabetes had higher comorbidity burden and more frequently presented with Killip Class II-IV heart failure (10.2% vs 3.7%, P < 0.001), haemodynamic instability (7.1% vs 3.7%, P < 0.001) and ongoing chest pain (43.1% vs 37.0%, P < 0.001), than those without diabetes. Overall, care quality received was similar by diabetes status (60.0% vs 60.5% received ≥ 80% of eligible care interventions, P = 0.786), but patients with diabetes experienced higher rates of in-hospital acute heart failure (15.3% vs 6.8% P < 0.001), cardiogenic shock (4.5% vs 2.5%, P = 0.002), stroke/TIA (2.0% vs 0.8%, P = 0.006) and death (2.5% vs 1.4%, P = 0.022), and higher 30-day mortality (3.3% vs 2.0%, P = 0.025). Of NSTEMI with diabetes, only 1.9% and 9.0% received prescription for GLP-1 RAs and SGLT2 inhibitors, respectively, on discharge, and only 45.9% were referred for cardiac rehabilitation. CONCLUSION: NSTEMI patients with diabetes, compared to those without, present more clinically unwell and have worse outcomes despite receiving equal quality of care. Prescription of cardiovascular-protective glycaemic agents is an actionable target to reduce risk of further events.

Platelets from patients with chronic inflammation have a phenotype of chronic IL-1ß release.

Background: Chronic inflammation is a cardiovascular risk factor, and interleukin-1ß (IL-1ß) is central to the inflammatory host response. Platelets contain the NLRP3 inflammasome and are able to translate IL-1ß messenger RNA (mRNA) and secrete mature IL-1ß upon activation. However, the role of a chronic inflammatory environment in platelet IL-1ß mRNA and protein content remains unclear. Objectives: The aim of the current study was to investigate intracellular platelet IL-1ß and IL-1ß mRNA in a chronic inflammatory state. Methods: Sixty-five patients with stable inflammation (ie, high-sensitivity C-reactive protein within predefined margins in 2 separate measurements) were stratified according to high-sensitivity C-reactive protein levels in low (0.0-0.9 mg/L), medium (1.0-2.9 mg/L), and high (3.0-9.9 mg/L) risk groups. Platelet reactivity as well as platelet IL-1ß protein synthesis were studied. Results: The highest risk group was characterized by a distinct cardiovascular risk profile and approximately 20% higher platelet counts. While platelet reactivity was not different, a reduction in intracellular platelet IL-1ß mRNA and IL-1ß protein levels was observed in the highest risk group and was linked to decreased platelet size and granularity. This signature suggests a phenotype of chronic IL-1ß secretion and could be experimentally phenocopied by stimulation of platelets from healthy volunteers with either TRAP-6 or collagen related peptide (CRP-XL). Conclusion: Our data suggest a phenotype of chronic IL-1ß secretion by platelets in patients with chronic sterile inflammation.