Risk Of Events Research Articles

Prevalence of subclinical hypothyroidism in local adult obese population.

Objective: To find out the frequency of subclinical hypothyroidism (SCH) in local adult obese population and to determine the risk of cardiovascular events in patients with SCH using the 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk calculator. Study Design: Cross Sectional & Descriptive study design. Setting: Medicine Ward, PAF Hospital, Islamabad. Period: 20th July 2023 to 20th January 2024. Methods: A total of 200 patients of both gender with Body Mass Index (BMI) greater than 28kg/m2 were included in the study. Blood samples were Collected from all patients and sent to the hospital laboratory for performing thyroid function tests and fasting lipid profile. Patients found to have SCH (TSH levels more than reference range with normal T3 and T4 levels) had their ten-year risk of cardiovascular events determined using the ASCVD Risk Calculator. A calculated 10 year ASCVD risk of ≥7.5% was concluded significant. Results: Age range in this study was from 20 to 65 years with mean age of 43.295±8.85 years, mean BMI 30.960±1.53 Kg/m2, mean TSH 2.904±1.29 mIU/L (normal range 0.27 to 4.2 mIU/ml), mean T3 103.230±6.86 ng/dL (normal range 94 to 170 ng/dL) and mean T4 was 10.092±1.26 μg/dL (normal range 5 to 11 μg/dL). Subclinical hypothyroidism was observed in 16% patients. Amongst these patients, increased cardiovascular event risk was present in 25% patients. Conclusion: Our study has concluded a high prevalence of subclinical hypothyroidism among obese adult patients and increased risk of cardiovascular events in patients with SCH.

Oakland score to identify low-risk patients with lower gastrointestinal bleeding performs well among emergency department patients

BackgroundThe Oakland Score predicts risk of 30-day adverse events among hospitalized patients with lower gastrointestinal bleeding (LGIB) possibly identifying patients who may be safe for discharge. The Oakland Score has not been studied among emergency department (ED) patients with LGIB. The Oakland Score composite outcome includes re-bleeding, defined as additional blood transfusion requirements and/or a further decrease in hematocrit (Hct) >/= 20% after 24 h in clinical stability; red blood cell transfusion; therapeutic intervention to control bleeding, including surgery, mesenteric embolization, or endoscopic hemostasis; in-hospital death, all cause; and re-admission with further LGIB within 28 days. Prediction variables include age, sex, previous LGIB admission, systolic blood pressure, heart rate, and hemoglobin concentration, and scores range from 0 to 35 points, with higher scores indicating greater risk.MethodsRetrospective cohort study of adult (≥ 18 years old) patients with a primary ED diagnosis of LGIB across 21 EDs from March 1st, 2018, through March 1st, 2020. We excluded patients who were more likely to have upper gastrointestinal bleeding (esophago-gastroduodenoscopy without LGIB evaluation), patients who left against medical advice or prior to ED provider evaluation, ED patients without active health plan membership, and patients with incomplete Oakland Score variables. We assessed predictive accuracy by reporting the area under the receiver operator curve (AUROC) and sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios at multiple clinically relevant thresholds.ResultsWe identified 8,283 patients with LGIB, 52% were female, mean age was 68, 49% were non-White, and 27% had an adverse event. The AUROC for predicting an adverse event was 0.85 (95% CI 0.84–0.86). There were 1,358 patients with an Oakland Score of </=8; 4.9% had an adverse event, and sensitivity of the Oakland Score at this threshold was 97% (95% CI 96%−98%).ConclusionThe Oakland Score had high predictive accuracy among ED patients with LGIB. Prospective evaluation is needed to understand if the risk score could augment ED decision-making and improve outcomes and resource utilization.

Excess cardiometabolic risk in children and adolescents initiating antipsychotic treatment compared to young adults: results from a nationwide cohort study.

Antipsychotic treatment is associated with cardiometabolic risks that may be especially detrimental to children and adolescents. In this Danish population-based cohort study, we included individuals with psychiatric diagnoses who initiated antipsychotics in 2000-2021 at age 6-31 years. We assessed the risk of cardiometabolic adverse events up to 10 years following incident exposure to antipsychotics, compared to age- and sex-matched unexposed individuals with psychiatric diagnoses. Cox regression models were used to calculate hazard ratios (HRs) after adjustment using high-dimensional propensity scores, including age, sex, calendar time, hospital diagnoses, and prescription drug use. HRs were compared between incident exposure in youths (6-17 years) and young adults (18-31 years), and between incident exposure in children (6-11 years) and adolescents (12-17 years). The total cohort consisted of 335,093 individuals, including 36,092 subjects exposed to antipsychotics (children and adolescents: 8,547, mean follow-up: 6.8±3.2 years; young adults: 27,545, mean follow-up: 6.5±3.4 years) and 299,001 age-, sex- and calendar-matched unexposed subjects. The incidence rate of cardiometabolic events was higher for young adults initiating antipsychotics than for children and adolescents (23.2 vs. 14.1 events/1,000 person-years). However, the adjusted excess risk of cardiometabolic events was significantly higher in exposed compared to unexposed children and adolescents (HR=1.87, 95% CI: 1.71-2.05) than in exposed compared to unexposed young adults (HR=1.46, 95% CI: 1.40-1.51) (p<0.001). The excess risk of cardiometabolic events was even higher when antipsychotic treatment was initiated before age 12 years (HR=2.44; 95% CI: 1.99-2.98) than at age 12-17 years (HR=1.69, 95% CI: 1.52-1.87) (p=0.012). Concerning specific cardiometabolic outcomes, there was an effect of age at antipsychotic initiation on the risks of metabolic syndrome (p=0.011) and obesity (p<0.001), that were higher among children and adolescents than young adults. Thus, initiation of antipsychotic treatment before age 18 years is associated with an excess risk of cardiometabolic events compared to age- and sex-matched youths with psychiatric disorders but unexposed to antipsychotics. The excess cardiometabolic risk is significantly higher than that of individuals who start antipsychotic treatment in early adulthood, and significantly higher for treatment onset in childhood compared to adolescence. On the basis of these findings, recommendations are provided about the use of antipsychotics in children and adolescents.

The incidence and risk of cardiovascular events among gastroesophageal cancer patients receiving immune-checkpoint inhibitors.

374 Background: Immune checkpoint inhibitors (ICIs) have been associated with an increased risk of cardiovascular events. However, these data were mostly derived from patients with lung cancer or melanoma. To date, there is limited data describing the incidence and risk of cardiovascular adverse events associated with the use of ICIs among patients with gastroesophageal cancers. Methods: We performed a propensity score-matched cohort study using the TriNetX Analytics Network database, which comprises de-identified data from over 120 participating institutions and 101 million individuals. We defined the ICI cohort as patients who received any of the ICIs and chemotherapy. We defined the control cohort as patients who received only chemotherapy but not an ICI. We matched 2 cohorts based on predetermined variables including age, race, gastroesophageal cancer-directed therapy, cardiovascular agents, underlying comorbidities, and surgical history. The outcomes were myocarditis, pericarditis, myocardial infarction, heart failure, cerebral ischemia/infarction, atrial fibrillation, conduction disorders, and venous thromboembolism (VTE). All outcomes were captured within 1-year of the start of ICI therapy and identified using the International Classification of Diseases (ICD)-10 codes. Results: We identified 2005 patients who received ICI and chemotherapy (ICI cohort) and 14048 patients who received chemotherapy only (control cohort). We matched 952 patients in 2 cohorts. The mean age was 62.8 ± 12.7 and 62.8 ± 12.3 for the ICI and chemotherapy cohorts, respectively. We observed a significant increase in cardiovascular events in the ICI cohort compared to the chemotherapy cohort. In particular, the risk of myocarditis (4 cases in the ICI cohort and no cases in the chemotherapy cohort), pericarditis (Hazard ratio (HR), 2.53 [95% CI: 1.52-4.19]), conduction disorders (HR, 1.64 [95% CI: 1.04-2.59]), and VTE (HR, 1.56 [95% CI: 1.17-2.10]) were higher in the ICI cohort than the chemotherapy cohort. Conclusions: The use of ICI was associated with an increased risk of cardiovascular events, particularly myocarditis, pericarditis, conduction disorders, and VTE among patients with gastroesophageal cancer. Further studies are needed to identify strategies to stratify patients at high risk of developing ICI-associated cardiovascular events. Outcomes ICI + Chemotherapy(ICI cohort) Chemotherapy only(Control cohort) Hazard ratio(95% CI) Cases At risk patients Cases At risk patients Myocarditis 4 952 0 952 - Pericarditis 52 952 21 952 2.53 (1.52-4.19) Myocardial infarction 18 952 12 952 1.49 (0.72-3.11) Cerebral Ischemia/Infarction 22 952 17 952 1.30 (0.69-2.44) Atrial fibrillation 56 952 48 952 1.16 (0.79-1.71) Conduction disorder 49 952 30 952 1.64 (1.04-2.59) Venous thromboembolism 112 952 73 952 1.56 (1.16-2.10) Heart Failure 118 952 114 952 1.04 (0.80-1.34)

Incidence and Risk of Thromboembolic and Cardiovascular Adverse Events with PARP Inhibitor Treatment in Patients with Metastatic Castration-resistant Prostate Cancer: A Systematic Review and Safety Meta-analysis.

PARP inhibitor (PARPi) treatment is an effective option for patients with metastatic castration-resistant prostate cancer (mCRPC). There are few data on the cardiovascular and thromboembolic safety of these agents in mCRPC, as cardiovascular and thromboembolic adverse events (AEs) are uncommon. Our aim was to analyze the incidence and risk of major adverse cardiovascular events (MACEs), thromboembolic events, and hypertension with PARPi therapy in mCRPC. We conducted a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We systematically searched the PubMed, EMBASE, and Cochrane databases and the American Society of Clinical Oncology and European Society of Medical Oncology meeting abstracts for clinical trials on PARPi use in mCRPC up to March 31, 2024. We analyzed the pooled incidence of all-grade and high-grade MACEs, thromboembolic events, and hypertension, and calculated risk ratios (RRs) for PARPi versus non-PARPi treatment. We included 11 phase 2 or 3 trials in our meta-analysis. Hypertension was the most common AE for both any-grade (17.2%) and high-grade (9.3%) events. In comparison to other treatments, PARPi was associated with significantly higher risk of high-grade MACEs (RR 2.03; p=0.03) and thromboembolic events (RR 2.15; p=0.002), especially venous thromboembolism (VTE; RR 2.13; p=0.004) and pulmonary embolism (RR 3.60; p=0.001). The risk of hypertension, any-grade MACEs, and thromboembolic AEs was not significantly higher, apart from VTE (RR 2.17; p=0.01). There is higher risk of high-grade cardiovascular and thromboembolic toxicity with PARPi use in comparison to other treatments in mCRPC, although these toxicities are rare. Clinicians should be aware of this risk, especially in a population that often has comorbidities and concomitant treatments, for correct monitoring and management of these AEs. Drugs called PARP inhibitors are very effective in the treatment of metastatic prostate cancer that does not respond to hormone treatment. However, their use is associated with some cardiovascular adverse events, although these are rare. Our study shows that these events seem to be more frequent with PARP inhibitors than with other treatments, especially for severe grades. Doctors and patients should be aware of this risk to help in preventing, recognizing, and managing the occurrence of these rare complications.

Meta-analysis of randomized controlled trials (RCTs) to evaluate the incidence of hemorrhage and venous thromboembolism (VTE) events in patients with gastrointestinal (GI) cancers treated with fruquintinib.

118 Background: Fruquintinib is a novel cancer therapy that was recently approved by the US FDA as a third-line treatment for metastatic colorectal cancer (mCRC). It works by inhibiting the vascular endothelial growth factor receptors, that leads to blocking of angiogenesis which is essential for the tumor proliferation. Close monitoring is always crucial in order to promptly detect and manage any adverse events. This study aims to assess the risk of hemorrhagic and VTE events in patients with GI cancers treated with fruquintinib. Methods: A comprehensive literature search was conducted using MEDLINE, EMBASE, and COCHRANE databases from inception through August 12th, 2024. Phase II/III RCTs utilizing fruquintinib in GI cancers reporting hemorrhage or VTE events as an adverse event were included. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q-statistic. Random effects model was applied. Results: A total of 1872 patients were included. Data were pooled from three phase III RCTs (FRESCO, FRESCO-2, FRUTIGA) and one phase II RCT, all reporting VTE events including deep vein thrombosis and pulmonary embolism and hemorrhage. FRESCO, FRESCO-2, and the phase II trials involved patients with mCRC, comparing fruquintinib to placebo. FRUTIGA trial incorporated patients with gastric or gastroesophageal junction adenocarcinoma, comparing fruquintinib + paclitaxel to placebo + paclitaxel. High-grade hemorrhage incidence was higher in the fruquintinib arm compared to the control arm (29.00% vs 21.18%, RR 1.62; 95% CI: 1.26-2.08, P=0.0001). In the mCRC subgroup, high-grade hemorrhage rate was also higher and statistically significant in the fruquintinib arm 20.87% vs 11.22% (RR 1.84; 95% CI: 1.25-2.70; P=0.002). Incidence of any grade or high grade VTE events was neither statistically significant in GI cancer population or mCRC subgroup. Incidence of any grade VTE events in GI cancer group and mCRC subgroup was 2.74% vs 2.15% (RR, 1.23; 95% CI: 0.53-2.88; P=0.63) and 2.68% vs 1.53% (RR, 0.95; 95% CI: 0.09-9.67; P=0.97), respectively. Rate of high grade VTE events in GI cancer cohort was 1.67% vs 0.67% (RR, 1.96; 95% CI: 0.52-7.36; P=0.32), while in mCRC subgroup was 1.79% vs 0.76% (RR, 1.08; 95% CI: 0.06-19.98; P=0.96). Conclusions: This meta-analysis demonstrates that patients with GI cancers, including mCRC, treated with fruquintinib have higher incidence of high-grade hemorrhage. These findings underscore the importance of individualized risk assessment, especially for patients predisposed to hemorrhagic complications. No increased risk of VTE events was noted in patients treated with fruquintinib compared to placebo.

Abstract 32: Ischemic and hemorrhagic risks of patients with Basal Ganglia Perivascular Spaces on Antithrombotic Therapy

Background: Enlarged perivascular spaces (PVS), a marker of cerebral small vessel disease (SVD), are considered to increase the risk of stroke. However, there is limited data on the benfits and harms of antithrombotic agents in patients with PVS. We assessed the association of PVS with the risk of hemorrhagic or ischemic events in patients receiving antithrombotic agents. Methods: This is an investigator-initiated, prospective, multicenter observational study that enrolled patients with cerebrovascular or cardiovascular diseases who were taking oral antithrombotic agents from 52 hospitals across Japan between 2016 and 2019. All participants underwent baseline multimodal MRI. The MRI scans were centrally evaluated for radiologic indicators related to SVD, including white matter hyperintensities (WMH), cerebral microbleeds (CMBs), lacunes, basal ganglia enlarged-perivascular spaces (BGPVS), cortical superficial siderosis, using a visual scale. The outcomes included major bleeding, intracranial hemorrhage, ischemic events, ischemic stroke, and mortality. Results: Of the analyzed 5,250 patients (1,736 women; median age 73 [IQR 66–79] years), antiplatelets and anticoagulants were administered at baseline in 3,948 (75.2%) and 1,565 (29.8%), respectively. During a median 2 (IQR1.8–2.0) years, 278 ischemic events, 197 ischemic strokes, 93 major bleeding, 55 intracranial hemorrhage, and 217 deaths were observed. The distribution of BGPVS was as follows: 0 BGPVS in 475 patients (9.4%), 1-10 BGPVS in 2615 patients (51.6%), and 11+ BGPVS in 1975 patients (39.9%). A higher BGPVS burden was associated with older age, a lower proportion of women, higher rates of hypertension and smoking, lower eGFR values, and a higher prevalence of lacunes, CMBs, and WMH. A higher burden of BGPVS was associated with a higher risk of major bleeding (1–10 BGPVS: adjusted hazard ratio (aHR) 1.49, [95% confidence interval CI 0.76–7.92], 11+ BGPVS: aHR 3.27 [1.09–11.57] versus 0 BGPVS; p trend = 0.035) and ischemic stroke (1–10 BGPVS: aHR 1.79 [0.90–3.57], 11+ BGPVS: aHR 2.39 [1.19–4.81]; p trend = 0.014). In contrast, higher BGPVS burden was not significantly associated with an increased risk of ischemic events, intracranial hemorrhage, or mortality. Conclusions: A higher burden of BGPVS was associated with an increased risk of ischemic stroke and major bleeding in patients taking antithrombotic medication and might be useful in clinical decision making.

Exploring ChatGPT's potential in ECG interpretation and outcome prediction in emergency department.

Approximately 20% of emergency department (ED) visits involve cardiovascular symptoms. While ECGs are crucial for diagnosing serious conditions, interpretation accuracy varies among emergency physicians. Artificial intelligence (AI), such as ChatGPT, could assist in ECG interpretation by enhancing diagnostic precision. This single-center, retrospective observational study, conducted at Merano Hospital's ED, assessed ChatGPT's agreement with cardiologists in interpreting ECGs. The primary outcome was agreement level between ChatGPT and cardiologists. Secondary outcomes included ChatGPT's ability to identify patients at risk for Major Adverse Cardiac Events (MACE). Of the 128 patients enrolled, ChatGPT showed good agreement with cardiologists on most ECG segments, excluding T wave (kappa=0.048) and ST segment (kappa=0.267). Significant discrepancies arose in the assessment of critical cases, as ChatGPT classified more patients as at risk for MACE than were identified by physicians. ChatGPT demonstrates moderate accuracy in ECG interpretation, yet its current limitations, especially in assessing critical cases, restrict its clinical utility in ED settings. Future research and technological advancements could enhance AI's reliability, potentially positioning it as a valuable support tool for emergency physicians.

The relationship between depression and cardiovascular disease in older people: results from a large-scale epidemiological cohort study in Japan.

Depression is known to be associated with a greater risk of developing cardiovascular disease (CVD) in middle-aged people. However, it is not certain how depression would influence incident CVD in older people aged ≥ 75years. We investigated the association between depression and CVD in older people. We analyzed 146,085 individuals aged ≥ 75years including 7581 individuals (5.2%) with depression registered in the DeSC database from April 2014 to November 2022. We excluded those with a prior history of CVD. The incidence of composite CVD events, comprising ischemic heart disease (IHD), heart failure, and stroke was documented. A Cox proportional hazard regression analysis was conducted to estimate hazard ratios (HR) associated with the presence of depression. The median age was 79years and 41.0% were men. During the mean follow-up period of 3.4 ± 1.5years, 39,552 composite CVD events (IHD: n = 10,916; heart failure: n = 26,719; stroke: n = 13,090) were recorded. Multivariable Cox regression analyses showed that older individuals with depression had a greater risk of composite CVD events than those without (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.24-1.34). The HR (95% CI) of depression was 1.26 (1.17-1.37) for IHD, 1.25 (1.19-1.31) for heart failure, and 1.30 (1.21-1.39) for stroke, respectively. While considering the limitations of real-world data, we conducted multiple sensitivity analyses, which confirmed the results of the primary analysis. The presence of depression was independently associated with a greater risk of developing CVD even in older individuals.

Optimizing the life of vascular access during follow-up.

Optimizing the longevity of vascular access in hemodialysis patients remains a critical aspect of patient care, given the significant role of arteriovenous fistulas (AVFs) and arteriovenous grafts (AVGs) in enabling effective dialysis. Vascular access complications, such as stenosis, thrombosis, and cannulation-related damage, continue to challenge both the functionality and the sustainability of these access points. Recent advancements underscore the importance of a robust follow-up strategy, integrating clinical evaluations with diagnostic tools like color Doppler ultrasound (CDU) and emerging interventional approaches such as drug-coated balloon (DCB) angioplasty. Regular CDU surveillance has shown promise in identifying asymptomatic stenosis, providing an opportunity for early intervention and reducing the risk of thrombotic events. This non-invasive imaging modality allows for detailed evaluation of hemodynamic changes within the vascular access, enabling timely detection and monitoring of stenotic lesions. Furthermore, the use of DCBs - angioplasty balloons coated with antiproliferative agents such as paclitaxel - offers a targeted approach to manage intimal hyperplasia and reduce restenosis rates in vascular access sites. Studies indicate that DCBs can mitigate neointimal proliferation, prolonging patency and enhancing long-term access outcomes. In this paper, we explore the synergistic role of clinical follow-up, ultrasound-based diagnostics, and drug-coated technologies in the preservation of vascular access. By examining the impact of these strategies, we aim to provide a comprehensive approach to vascular access maintenance, emphasizing the need for structured surveillance protocols and interventional techniques to optimize the lifespan of hemodialysis access points.

Analysis of serum natalizumab concentrations obtained during routine clinical care in patients with multiple sclerosis: A cross-sectional study.

Natalizumab is a humanized monoclonal antibody administered at a fixed dose of 300 mg intravenously or subcutaneously every 4-6 weeks to treat relapsing-remitting multiple sclerosis. In this prospective cross-sectional study, natalizumab serum concentrations obtained during routine healthcare were measured, and the relationships between different routes of administration, sampling times, body characteristics, changes in blood count, and presence of anti-natalizumab antibodies were evaluated. Ninety-two patients were included in this study. Blood samples were collected 0-48 days after administration, and natalizumab serum and anti-natalizumab antibody concentrations, as well as blood counts were measured. Subsequently, patients were divided into three groups according to the collection time after natalizumab administration. During the entire monitored period, serum natalizumab concentrations ranged from 1.8 to 193.3 µg/mL and 1.8 to 100.3 µg/mL after intravenous and subcutaneous administrations, respectively. A significant inverse correlation was found between serum natalizumab concentrations and differential and absolute peripheral blood neutrophil counts, erythrocyte counts, and hemoglobin concentrations. Although all patients were treated with the same dose, a 30-fold difference in serum natalizumab concentrations was observed. This wide inter-individual variability can potentially lead to an increased risk of natalizumab adverse events or, conversely, suboptimal therapeutic concentrations with the risk of further worsening of multiple sclerosis.

Abstract TP207: Cerebral Amyloid Angiopathy Prevalence and Risk of Future Cerebrovascular Events and Mortality in Patients Presenting with Possible Transient Ischemic Attack

Abstract TP207: Cerebral Amyloid Angiopathy Prevalence and Risk of Future Cerebrovascular Events and Mortality in Patients Presenting with Possible Transient Ischemic Attack

Effect of Triple Therapy on Cardiovascular and Severe Cardiopulmonary Events in Chronic Obstructive Pulmonary Disease: A Post Hoc Analysis of a Randomized, Double-Blind, Phase 3 Clinical Trial (ETHOS).

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of cardiovascular and cardiopulmonary events. In the phase III, 52-week ETHOS trial (NCT02465567), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF) reduced rates of moderate/severe exacerbations and all-cause mortality compared with dual therapy with glycopyrrolate/formoterol fumarate (GFF) or budesonide/formoterol fumarate (BFF). However, the effect of BGF on cardiovascular events versus GFF remains unevaluated. Furthermore, the effect of BGF on time to first severe exacerbation has not been reported. Objectives: To assess the effects of BGF 320/18/9.6 μg (BGF 320) and other inhaled corticosteroid-containing arms on cardiovascular and severe cardiopulmonary endpoints versus GFF in patients with COPD from the ETHOS trial. Methods: Patients with moderate to very severe COPD and a history of exacerbations were randomized to twice-daily BGF 320, BGF 160/18/9.6 μg, BFF 320/9.6 μg, or GFF 18/9.6 μg (GFF). Time to first severe COPD exacerbation was a prespecified endpoint; post hoc cardiovascular and severe cardiopulmonary endpoints included time to first major adverse cardiac event, time to first cardiovascular adverse event (AE) of special interest, time to first cardiac AE, and time to the composite endpoint of first severe cardiopulmonary event. Measurements and Main Results: BGF 320 reduced the rate of first occurrence (hazard ratio [95% confidence interval]) of cardiovascular and severe cardiopulmonary events versus GFF, including for time to first cardiovascular adverse event of special interest (0.63 [0.48, 0.82]), cardiac AE (0.60 [0.48, 0.76]), and severe cardiopulmonary event (0.80 [0.67, 0.95]). Conclusions: BGF had a benefit on cardiovascular endpoints and severe cardiopulmonary events versus GFF in patients with moderate to very severe COPD.

Spontaneous echo contrast in the left atrial appendage is linked to a higher risk of thromboembolic events and mortality in patients with atrial fibrillation.

Cardioversion, a rhythm control treatment for atrial fibrillation (AF), requires ruling out cardiac embolic sources, often originating from the left atrial appendage (LAA). Transesophageal echocardiography (TEE) is used for LAA evaluation, but it is invasive and not widely available. This study aimed to identify cardiovascular risk factors linked to LAA abnormalities and predictors of thromboembolic events and all-cause mortality. A single-center retrospective analysis included AF patients admitted to the University Hospital Würzburg between 2009 and 2018 undergoing TEE. Among 2400 AF patients (median age 72; 36% women), 469 (20%) had LAA abnormalities: 282 (60%) had spontaneous echo contrast (SEC), 72 (15%) had thrombus formation (THR), and 115 (25%) had both. Predictors of LAA abnormalities included age (OR 1.04; p=0.002), congestive heart failure (OR 1.70; p=0.009), diabetes (OR 1.74; p=0.007), stroke history (OR 3.36; p=0.001), vascular disease (OR 1.57; p=0.026), elevated alkaline phosphatase (OR 1.15; p=0.003), prior VKA intake (OR 1.53; p=0.002), and DOAC intake (OR 0.57; p=0.038). SEC with or without THR independently predicted thromboembolic events (HR 1.74, p=0.031 and HR 1.53, p=0.006) and all-cause mortality (HR 1.77, p=0.011 and HR 1.57, p=0.002), adjusted for cardiovascular risk factors, anticoagulation, and laboratory data. In AF patients undergoing TEE, SEC, often overlooked in cardioversion decisions, independently predicted thromboembolic events and mortality.

High-sensitivity C-reactive protein, plaque vulnerability and adverse events in patients with stable coronary disease: An optical coherence tomography study.

Higher levels of high-sensitivity C-reactive protein (hsCRP) are associated with increased risk of cardiovascular events in patients with coronary artery disease (CAD). To elucidate the characteristics of coronary plaques in patients with CAD with high hsCRP levels. A total of 793 consecutive patients with stable CAD who underwent optical coherence tomography (OCT) of the culprit vessel during percutaneous coronary intervention were included. Patients were classified into the higher hsCRP group (hsCRP ≥0.2mg/dL, n=247) or lower hsCRP group (hsCRP <0.2mg/dL, n=546). OCT characteristics and clinical outcomes were investigated according to hsCRP levels. The prevalence of thin-cap fibroatheroma (TCFA) (32.0% vs. 20.9%, p<0.001) was significantly higher in the higher hsCRP group than in the lower hsCRP group. The incidence of myocardial infarction was significantly higher in the higher hsCRP group than in the lower hsCRP group (log-rank p=0.006) during a median follow-up of 938days, although the incidence of major adverse cardiac events was comparable (log-rank p=0.282). Among the four groups classified by hsCRP level and the presence of TCFA, the incidence of myocardial infarction was highest in the group with both higher hsCRP levels and TCFA (log-rank p=0.017). Higher hsCRP levels were associated with a higher prevalence of vulnerable characteristics of coronary plaques and worse clinical outcomes in patients with stable CAD. The risk of recurrent myocardial infarction in patients with high hsCRP levels was further increased in the presence of TCFA.

Obesity portends an increased risk of thromboembolic events in severely injured geriatric trauma, a retrospective study.

Obesity is a known risk factor for thromboembolic complications in trauma patients. The aim of our study is to evaluate the prevalence of thrombotic complications in obese geriatric patients. We performed a retrospective analysis of TQIP (2017-2019). A total of 119,906 patients≥65 years who sustained severe trauma were included. Primary outcomes were thrombotic complications including stroke/cerebrovascular accidents (CVA), myocardial infarction (MI), deep vein thrombosis (DVT) and pulmonary embolism (PE). Outcomes were compared between patients with obesity (BMI≥30​kg∖m2) and overweight (25​kg∖m2≤BMI<30​kg∖m2) and normal weight (19​kg∖m2≤BMI<25​kg∖m2) patients. A total number of 30,356 (26.8​%) patients were obese. All clotting complications (stroke/CVA, MI, DVT and PE) were significantly more frequent among obese patients (p​<​0.001for all). Multivariate logistic regression showed that obese patients had significantly increased odds of stroke/CVA (OR​=​1.207), MI (OR​=​1.301), DVT (OR​=​1.311) and PE (OR​=​1.241) (p​<​0.001 for all). Obese geriatric patients who sustain severe traumatic injuries are at increased risk of thromboembolic complications compared to non-obese patients. Level III retrospective study.

Association of iliofemoral calcium score and major vascular complications within the first year after lower limb endovascular revascularization

The accumulation of calcium load in peripheral lower extremity arteries has been associated with increased severity of peripheral artery disease (PAD) and mortality. While calcium scores are commonly calculated from non-contrast computed tomography (CT) scans, patients with PAD often undergo contrast-enhanced CT scans. This study aims to explore the association between a length-adjusted calcium score (LACS) of the iliofemoral arteries, determined through pre-intervention contrast-enhanced CT, and major adverse events in patients with chronic limb-threatening ischemia (CLTI). A cohort of CLTI patients subjected to endovascular revascularization between 2005 and 2017 at a tertiary referral center were categorized into 2 groups. The complication group experienced one of the composite outcomes (reintervention, above-the-ankle amputation, and/or all-cause mortality within 1year of the primary endovascular procedure), while control patients did not encounter this composite endpoint. Patients from the complication group were matched one-to-one with controls based on sex and Fontaine classification. LACS was calculated (Ca volume[mm3]/length[cm]) at 3 arterial segments; 1. the common iliac artery (CIA), 2. the external iliac artery and common femoral artery (EIA+CFA), and 3. the superficial femoral artery plus the popliteal artery (SFA+PA). Binary logistic regression analysis was conducted to investigate the association between LACS in the different arterial segments and the occurrence of the composite binary outcome (complication and control) and LACS of the different segments, adjusting influences of age, sex, BMI >25, Fontaine classification, diabetes mellitus type 1 & 2, chronic kidney disease stage, and hemodialysis treatment. Sixty-four CLTI patients were included in this study (complication group [n=32], and control group [n=32]). A significant difference (higher LACS was found for the complication group in the CIA, the SFA+PA, as well as the total trajectory. CLTI patients with high LACS in the SFA+PA or the total trajectory were more likely to suffer adverse events (SFA+PA: OR: 1.010, 95% CI: 1.000-1.020, P=0.04; Total LACS: OR: 1.008, 95% CI: 1.000-1.017, P=0.05). Patients with a high calcium load in the ilio-femoral arteries are at increased risk of major adverse events during 1year after endovascular revascularization. The calcium score, derived from contrast-enhanced CT scans, holds potential utility in decision making for CLTI patients.

Concomitant Use of Etrasimod With Opioids or Antidepressants in Patients With Ulcerative Colitis-A Safety Analysis.

Etrasimod is an oral, once-daily (q.d.), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Unlike the S1P receptor modulator ozanimod, etrasimod does not have a molecular structure to inhibit monoamine oxidase (MAO). Coadministration of drugs that inhibit MAO with opioids and antidepressants may increase the risk of adverse events (AEs). This post hoc analysis evaluated the incidence of AEs potentially related to serotonin syndrome in patients taking etrasimod and concomitant opioids or antidepressants in the Phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials. Safety data pooled from both trials were analysed in subgroups of patients receiving etrasimod 2mg q.d. (up to 52weeks of exposure) with/without concomitant opioids or antidepressants. We report the proportions of patients who had≥1 concurrent AE potentially associated with serotonin syndrome, including hypertension-related events. Among 527 patients receiving etrasimod, 77 (14.6%) and 35 (6.6%) were taking concomitant opioids or antidepressants, respectively. The incidence of AEs potentially related to serotonin syndrome, including hypertension-related AEs, was low (≤8.6%) and generally comparable in all subgroups. No reported AEs were serious or led to treatment discontinuation among patients taking these concomitant medications. The incidence of AEs was low and comparable in patients receiving etrasimod with or without concomitant opioids or antidepressants. This analysis further supports the low likelihood of clinically relevant drug-drug interactions between etrasimod and medications commonly prescribed to patients with UC, such as opioids or antidepressants. (ClinicalTrials.gov: NCT03945188; NCT03996369).

Clinical impact of circulating biomarkers in prediction of adverse cardiac events in patients with congenital heart disease. A systematic review

IntroductionPatients with congenital heart disease (ConHD) are at increased risk for adverse cardiac events. Predicting long-term outcomes and guidance of patient management might benefit from a range of (new) biomarkers. This is a rapidly evolving field with potentially large consequences for clinical decision making. With a systematic review of available biomarkers in ConHD we identified the clinical role of these markers, knowledge gaps and future research directions. MethodsWe systematically reviewed the literature on associations between blood biomarkers and outcome measures (mortality or composite adverse outcomes in patients with ConHD. ResultsThe inclusion criteria were met by 102 articles. Biomarkers assessed in more than studies are discussed in the main text, those studied in 3 or less studies are summarized in the supplement. Thus, we discuss 15 biomarkers from 92 studies. These biomarkers were studied in 32,399 / 10,735 patients for the association with mortality and composite adverse outcomes, respectively. Biomarkers that were studied most and had statistically significant associations with mortality or composite adverse outcomes were (NT-pro)BNP, MELD-XI score, Hs-CRP, creatinine, albumin and sodium. Most of these biomarkers are involved in intracardiac processes associated with inflammation or are markers of renal function. ConclusionFor (NT-pro)BNP, clinical value for prediction of mortality and composite adverse outcomes in adult and paediatric ConHD has been shown. For MELD-XI, hs-CRP, albumin, creatinine, sodium, RDW, and GDF-15, correlations with mortality and composite adverse outcomes have been demonstrated in patient groups with mixed types of ConHD, but clinical utility needs additional exploration.

Multiorgan Dysfunction and its Association With Congestion and Outcome in Aortic Stenosis Treated WithTAVI.

Degenerative severe aortic stenosis (AS) is treated by valve replacement to improve outcome. Despite diagnostic advancements, many AS patients are still diagnosed late with advanced heart failure. The aim of the study was to assess multiorgan dysfunction in severe AS using blood biomarkers and their association with quantitative fluid levels and clinical outcomes after transcatheter aortic valve implantation (TAVI). Consecutive AS patients undergoing TAVI received comprehensive preinterventional assessment with serum biomarker profiles reflecting organ dysfunction and quantitative fluid overload (FO) using bioelectrical impedance spectroscopy. FO by bioelectrical impedance spectroscopy was defined according to a previously established cut-off (≥1.0 L). Time to first heart failure hospitalization or death served as composite primary endpoint. Among 880 patients (age 81 ± 7years, 47% female), 41% had FO and 89% had biomarker abnormalities of at least one domain. Ascending fluid levels were independently associated with distorted biomarkers across domains of myocyte stress, hepatic dysfunction, renal dysfunction, inflammation, and anemia. After 2.4±1.0years of follow-up, 27% had reached the primary endpoint (29 heart failure hospitalization, 194 deaths, 13 both). Biomarkers across all domains were individually and independently associated with outcomes. In a multidomain approach, every affected extra-cardiac domain was associated with a 71% increase in event hazard (adjusted HR: 1.71; 95%CI: 1.39-2.11). Also, for each domain, the combination of distorted biomarkers and FO had the highest event risk. Biomarker abnormalities are highly prevalent in severe AS, influenced by congestion, and associated with impaired prognosis post-TAVI. Multiorgan dysfunction faces a particularly dismal outcome.