Post-acute Myocardial Infarction Research Articles

Abstract 4138633: Infusion of human apolipoprotein A-I (CSL112) promotes several aspects of reverse cholesterol transport

Background: High-density lipoprotein (HDL)-cholesterol is inversely correlated with cardiovascular risk, but increasing its circulating concentration is insufficient to prevent adverse cardiovascular outcomes. Instead, the emerging paradigm is on increasing the function of HDL and its major protein constituent apolipoprotein A-I (apoA-I), to increase reverse cholesterol transport. Objective: To investigate the effect of apoA-I [human] (CSL112) infusion on HDL protein composition, and provide further insights into the mechanism of action of CSL112 administered post-acute myocardial infarction (AMI). Methods: A mass spectrometry (MS)-based proteomic approach was used to evaluate changes in HDL protein composition in patients (n=50) from the AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) study who received either placebo or CSL112 post AMI. HDL was immuno-isolated from patient plasma using anti-apoA-I antibodies. Cholesterol esterification rate (CER) was measured to determine lecithin-cholesterol acyl transferase (LCAT) activity. Cholesterol efflux capacity (CEC) and hepatocyte uptake were assessed using patient serum in ex vivo cell-based assays. Results: CSL112 induced extensive rearrangement of HDL proteins at 4 hours post-infusion. Levels of apolipoproteins A2, B, C, and E as well as the acute phase proteins serum amyloid A1 and A4 were significantly reduced. By contrast, apoA-I, apoM, and LCAT significantly increased. Elevated apoA-I and LCAT levels on HDL were associated with an increase in CEC, plasma HDL-C levels, and CER in CSL112-treated patients. Furthermore, enhanced CEC strongly correlated with cholesterol uptake by hepatic cells (r=0.95 p<0.001). Conclusion: CSL112 altered HDL composition and increased HDL functionality by promoting multiple steps of the reverse cholesterol transport pathway.

Abstract 4138486: Unplanned Readmissions Due to Post-Acute Myocardial Infarction Complications: Insights from the Nationwide Readmission Database

Introduction: Acute myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. Despite advances in treatment, readmissions within 30 days remain a significant concern, impacting both patient outcomes and healthcare costs. This study aims to analyze trends in 30-day readmission rates (30-dr) for patients discharged after an acute MI. Methods: We analyzed the 2016-2020 Nationwide Readmission Database for patients aged ≥ 18 years with initial admission of acute MI and were readmitted within 30 days. Variables were identified using ICD-10 codes. The primary outcome was trends in 30-dr; secondary outcomes included trends in complications, mortality rate, length of stay (LOS), and healthcare costs. Multivariate and descriptive bivariate analyses were conducted, with p-values <0.05 considered statistically significant. Results: There was a notable decrease in the acute MI index admissions total number from 507,608 in 2016 to 471,292, p trend < 0.01. The index admission mean age throughout the study years was 66.9 ± 13.5 years, with 62.7% male patient. Index admission inpatient mortality dropped reaching OR 0.92 (CI 0.88-0.96) by 2020 with a drop of 0.08 OR from 2016 with (p trend < 0.01) using logistic regression. The index admission LOS remained consistent with allover average 4.64 days (p trend = 0.25). The mean healthcare costs saw a significant increase from $22,456 in 2016 to $27,249 in 2020 (p trend < 0.01). The 30-dr trend decreased from 9.41% in 2016 to 7.8% in 2020 (p trend < 0.01). The top five readmission reasons in order included heart failure (14.94%of total readmission), myocardial reinfarction (13.59%), sepsis (4.49%), Acute kidney injury(2.4%), and chest pain(2.1%). The risk of readmission went up 1% for each year increase of age and 12% for female gender (using OR,logistic regression), despite initial admission was more male dominant. Conclusion: Our study demonstrates a declining initial admission, its mortality rate,and 30-dr. There was readmission healthcare costs increase. We noticed four top complications-driven readmission falling under cardiovascular diseases category with the top one as heart failure and myocardial reinfarction. This study tries to highlight relevant data to target interventions to reduce readmissions and complications, ultimately improving patient outcomes and reducing the healthcare economic burden.

New left ventricular thrombus and embolic events in left ventricular dysfunction postmyocardial infarction

Background: We aimed to assess the incidence and evolution of new left ventricular thrombus (LVT), and the incidence of manifest systemic embolism, in patients with severe left ventricular (LV) systolic dysfunction postacute anterior myocardial infarction (MI) who had been discharged on dual antiplatelet therapy. Methods: We prospectively included consecutive patients with postacute anterior MI and LV ejection fraction (LVEF) ≤35% or apical aneurysms or large infarctions with LVEF ≤40%. Transthoracic echocardiography (TTE) confirmed no LVT before hospital discharge, and a second TTE was performed at 30 days and a third one at 3 months. All TTE studies were prespecified to assess LVT, and the patients were screened for the development of clinically manifest systemic embolisms. Results: Two hundred and two consecutive patients (males 93%; mean age 55.2±6.4 years; mean LVEF 29.5±5.0%) were included. At 30 days (interquartile range: 2837 days), a new LVT was detected in 12 (5.9%) patients. Oral anticoagulant was added to all patients with LVT, and aspirin was continued in 5 (42.7%) patients for a month. The 3month TTE showed favorable evolution of LV size, LVEF and apical wall motion score index compared to the baseline. At 3 months, the LVT disappeared in 7 (58.3%) patients and 5 patients still had a mural LVT of smaller size, and none got new LVT. Among the group without LVT, one patient had a stroke, and another had a myocardial infarction and died. Conclusions: In contemporary practice, and using routine TTE, the incidence of new LVT in patients with severe LV dysfunction postacute anterior MI is low. They have a favorable LVT evolution with minor risk for clinically manifest systemic embolism.

Impact of coronary revascularization on clinical outcomes of post-acute myocardial infarction patients with left ventricular thrombus

Abstract Background Left ventricular thrombus (LVT) is an uncommon, but dangerous complication seen in post-acute myocardial infarction (AMI). With advances in percutaneous coronary intervention (PCI) techniques, the incidence of post-AMI LVT has declined in the contemporary era. However, a minority of patients do not undergo coronary revascularisation due to medical contraindications or patient preference. This study aimed to evaluate the clinical characteristics and outcomes of post-AMI LVT patients treated with and without coronary revascularisation. Methods This was a retrospective study of 263 consecutive post-AMI patients diagnosed with LVT from November 2012 to January 2021, retrieved from a echocardiography database. Patients were stratified by the presence or absence of revascularisation treatment. Baseline clinical characteristics, treatment and outcomes data were collected and analysed. Results The median follow-up duration was 2.9 years (IQR: 0.9 – 4.7). A majority of post-AMI LVT patients underwent revascularisation via PCI (71.5%, n = 188), CABG (4.2%, n = 11) or thrombolysis (0.4%, n = 1). Unrevascularised patients (24.0%, n = 63) were older (p <0.001), more likely to be female (p <0.001), and had more co-morbidities such as previous stroke (p <0.001), heart failure (p = 0.001), chronic kidney disease (p = 0.020), and malignancy (p = 0.021). More unrevascularised patient had NSTEMI (p < 0.001), and significantly fewer were treated with triple therapy (p < 0.001). Incidence of LVT resolution was lower (p < 0.001) while all-cause mortality was higher (p < 0.001) for unrevascularised patients on univariate survival analyses. On multivariable Cox regression, revascularisation status was not an independent predictor of LVT resolution, bleeding, stroke, or all-cause mortality outcomes. Conclusion While unrevascularised post-AMI LVT patients had poorer outcomes compared to revascularised patients overall, revascularisation status itself was not independently associated with poorer clinical outcomes. Optimising medical therapy such as triple therapy remains a key treatment goal for post-AMI LVT patients.

Exploring the long-term effects of dapagliflozin in patients with stable acute myocardial infarction and preserved ejection fraction through a propensity score matching study

Abstract Background and Aims The recent Emmy trial underscored notable improvements in cardiac structure and function among post-acute myocardial infarction (AMI) patients treated with Empagliflozin, compared to those receiving a placebo. However, limitations such as a small sample size and a short follow-up period hindered the assessment of potential differences in actual clinical events between the groups. Consequently, our study aimed to evaluate the long-term outcomes, survival rates, rates of major adverse cardiovascular events (MACE), and heart failure (HF) incidence in patients with preserved ejection fraction (EF) who experienced AMI and underwent successful percutaneous coronary intervention (PCI), comparing those who received early initiation of Dapagliflozin with those who did not. Methods Data from the Taipei Medical University Research Database in Taiwan identified 7,081 inpatients who met the criteria of AMI status post successful PCI, with a left ventricular ejection fraction (LVEF) greater than 50% and absence of clinical symptoms indicative of heart failure. Exclusion criteria included individuals with a pre-existing diagnosis of heart failure before the index AMI episode and those with an LVEF below 50%, resulting in the exclusion of 357 patients from our study. The study subjects were then divided into two groups: those treated with Dapagliflozin and those not treated with Dapagliflozin, with matching for age, diabetes mellitus, and chronic kidney disease in a 1:2 ratio. Results The cohort study included of 756 patients who met the criteria of this study, among whom 252 were Dapagliflozin users and 504 were not. Over a 7-year follow-up period, Kaplan-Meier survival analyses revealed a significant reduction in cardiovascular mortality and all-cause mortality among Dapagliflozin users compared to non-users (p < 0.01). However, no significant differences were observed in heart failure, recurrent AMI, or stroke during the follow-up. Multivariate Cox analysis indicated the use of Dapagliflozin (hazard ratio = 0.310, 95% confidence interval = 0.188-0.510, p < 0.001) and age of diagnosis (hazard ratio = 1.063, 95% confidence interval =1.045-1.081, p < 0.001) were both independent predictors of all cause death. Conclusions In patients with stabilized AMI, the use of Dapagliflozin was associated with a decreased risk of all-cause death, especially cardiovascular mortality. However, there were no significant differences observed in the rates of heart failure, recurrent AMI, or stroke over the seven-year follow-up period.Baseline characteristicsKaplan–Meier curves of all cause death

Sodium-Glucose Cotransporter-2 Inhibitors After Acute Myocardial Infarction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Cardiovascular disease is on the rise globally, with ischemic heart disease being the leading cause of mortality and morbidity. While sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to improve cardiovascular outcomes in patients with heart failure, evidence is limited in guiding initiation in post-acute myocardial infarction (post-AMI) patients. Hence, this study aimed to appraise the current literature on the effect of SGLT2i on the clinical outcomes of post-AMI patients. A comprehensive search of PubMed, EMBASE, SCOPUS, and ClinicalTrials.gov was conducted up to 1 May 2024. Only randomized controlled trials studying the use of SGLT2i in post-AMI patients were included. We included adult patients aged 18 years old and older diagnosed with AMI and initiated on SGLT2i in the acute post-AMI setting. SGLT2i studies solely in heart failure settingswere excluded. Eight clinical trials were included in the systematic review, comprising 11,436 patients. Compared with placebo, SGLT2i initiation in post-AMI patients significantly reduced total number of heart failure hospitalizations (risk ratio [RR] 0.74, 95% confidence interval [CI] 0.62-0.90) and was associated with a lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) level (- 26.67 pg/ml, 95% CI - 41.74 to - 11.59). There was no difference in all-cause mortality (RR 1.02, 95% CI 0.81-1.28), cardiovascular mortality (RR 1.03, 95% CI 0.83-1.28), change in left ventricular ejection fraction, and glycated hemoglobin (HbA1c), as compared with placebo. SGLT2i use in patients with AMI was associated with a reduction in heart failure hospitalizations and a decrease in NT-proBNP. There were no significant differences in mortality outcomes. PROSPERO identifier number CRD42024540843.

Nose-to-brain delivery of stem cells in stroke: the role of extracellular vesicles.

Stem cell transplantation offers a promising therapy that can be administered days, weeks, or months after a stroke. We recognize 2 major mitigating factors that remain unresolved in cell therapy for stroke, notably: (1) well-defined donor stem cells and (2) mechanism of action. To this end, we advance the use of ProtheraCytes, a population of non-adherent CD34+ cells derived from human peripheral blood and umbilical cord blood, which have been processed under good manufacturing practice, with testing completed in a phase 2 clinical trial in post-acute myocardial infarction (NCT02669810). We also reveal a novel mechanism whereby ProtheraCytes secrete growth factors and extracellular vesicles (EVs) that are associated with angiogenesis and vasculogenesis. Our recent data revealed that intranasal transplantation of ProtheraCytes at 3 days after experimentally induced stroke in adult rats reduced stroke-induced behavioral deficits and histological damage up to 28 days post-stroke. Moreover, we detected upregulation of human CD63+ EVs in the ischemic brains of stroke animals that were transplanted with ProtheraCytes, which correlated with increased levels of DCX-labeled neurogenesis and VEGFR1-associated angiogenesis and vasculogenesis, as well as reduced Iba1-marked inflammation. Altogether, these findings overcome key laboratory-to-clinic translational hurdles, namely the identification of well-characterized, clinical grade ProtheraCytes and the elucidation of a potential CD63+ EV-mediated regenerative mechanism of action. We envision that additional translational studies will guide the development of clinical trials for intranasal ProtheraCytes allografts in stroke patients, with CD63 serving as a critical biomarker.

COVID-19 Is a Coronary Artery Disease Risk Equivalent and Exhibits a Genetic Interaction With ABO Blood Type.

COVID-19 is associated with acute risk of major adverse cardiac events (MACE), including myocardial infarction, stroke, and mortality (all-cause). However, the duration and underlying determinants of heightened risk of cardiovascular disease and MACE post-COVID-19 are not known. Data from the UK Biobank was used to identify COVID-19 cases (n=10 005) who were positive for polymerase chain reaction (PCR+)-based tests for SARS-CoV-2 infection (n=8062) or received hospital-based International Classification of Diseases version-10 (ICD-10) codes for COVID-19 (n=1943) between February 1, 2020 and December 31, 2020. Population controls (n=217 730) and propensity score-matched controls (n=38 860) were also drawn from the UK Biobank during the same period. Proportional hazard models were used to evaluate COVID-19 for association with long-term (>1000 days) risk of MACE and as a coronary artery disease risk equivalent. Additional analyses examined whether COVID-19 interacted with genetic determinants to affect the risk of MACE and its components. The risk of MACE was elevated in COVID-19 cases at all levels of severity (HR, 2.09 [95% CI, 1.94-2.25]; P<0.0005) and to a greater extent in cases hospitalized for COVID-19 (HR, 3.85 [95% CI, 3.51-4.24]; P<0.0005). Hospitalization for COVID-19 represented a coronary artery disease risk equivalent since incident MACE risk among cases without history of cardiovascular disease was even higher than that observed in patients with cardiovascular disease without COVID-19 (HR, 1.21 [95% CI, 1.08-1.37]; P<0.005). A significant genetic interaction was observed between the ABO locus and hospitalization for COVID-19 (Pinteraction=0.01), with risk of thrombotic events being increased in subjects with non-O blood types (HR, 1.65 [95% CI, 1.29-2.09]; P=4.8×10-5) to a greater extent than subjects with blood type O (HR, 0.96 [95% CI, 0.66-1.39]; P=0.82). Hospitalization for COVID-19 represents a coronary artery disease risk equivalent, with post-acute myocardial infarction and stroke risk particularly heightened in non-O blood types. These results may have important clinical implications and represent, to our knowledge, one of the first examples of a gene-pathogen exposure interaction for thrombotic events.

Comprehensive analysis of macrophage-associated inflammatory genes in AMI based on bulk combined with single-cell sequencing data.

Previous studies have highlighted the crucial role of macrophages in the post-acute myocardial infarction (AMI) inflammatory response. This study specifically focused on investigating macrophage-related targets involved in the inflammatory response after AMI. Bioinformatics methods were applied for identifying differentially expressed genes (DEGs) in datasets GSE163465, GSE236374, and GSE183272 obtained from the Gene Expression Omnibus (GEO) database. Communication analysis was conducted to analyze macrophages in AMI. Subsequent analyses encompassed functional enrichment analysis of Co-DEGs using Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG). Gene set variation analysis (GSVA) and immune infiltration analysis were carried out for screening key genes. Validation of the bioinformatics analysis results involved original and GSE114695 datasets, supported by quantitative real time polymerase chain reaction (qRT-PCR). Animal experiments confirmed the upregulation of Saa3, Acp5, and Fcgr4 genes in AMI mouse myocardial tissues. A total of 80 and 1,907 DEGs were respectively identified by analyzing scRNA-seq and bulk RNA-seq data. The overlapping Co-DEGs were found to be closely associated with inflammation-associated pathways, specifically the PI3K-Akt-mTOR pathway. Screening based on GSVA scores and macrophage-associated scores highlighted four key genes (Saa3, Ms4a4c, Acp5, and Fcgr4). Immunoinfiltration analysis revealed their close association with macrophages. Dataset validation corroborated these findings. Experimental validation focused on Saa3, Ms4a4c, Acp5, and Fcgr4, demonstrating the upregulation of their expression in cardiac macrophages in the AMI group, consistent with previous reports. This study provides new perspectives on AMI treatment. In addition, Saa3, Acp5, and Fcgr4 exhibit potential as biomarkers for improving cardiac repair and slowing down the development of heart failure after AMI.

Direct Oral Anticoagulants Versus Vitamin K Antagonists for the Management of Left Ventricular Thrombus After Myocardial Infarction: A Meta-Analysis

Left ventricular (LV) thrombus formation remains a post-acute myocardial infarction (AMI) complication even in the modern era of early reperfusion. The optimal anticoagulation regimen in this clinical scenario is poorly defined. The present meta-analysis sought to investigate the efficacy and safety profile of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for the management of LV thrombus after AMI. A systematic literature review was conducted in electronic databases to identify studies reporting efficacy and safety outcome data regarding the use of DOACs versus VKAs for patients with LV thrombus after AMI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and random-effects meta-analyses were conducted to synthesize pooled ORs. Eight studies comprising a total of 605 patients were included. DOACs were associated with an almost twofold higher likelihood of thrombus resolution compared with VKAs (pooled OR 1.95 [1.25 to 3.04], p = 0.003, I2 = 0%), and decreased the risk of systemic embolism by 70% (pooled OR 0.30 [0.12 to 0.75]; p = 0.01, I2 = 0%). The use of DOACs was associated with a 54% lower risk of bleeding compared with VKAs (pooled OR 0.46 [0.26 to 0.84], p = 0.01, I2 = 0%). Overall, patients receiving DOACs had a 63% lower risk of reaching the composite outcome of safety and efficacy compared with patients using VKAs (pooled OR 0.37 [0.23 to 0.60], p <0.0001, I2 = 0%). In conclusion, DOACs appear to have a more favorable efficacy and safety profile compared with VKAs for the management of LV thrombus related to AMI.

Lipid-Lowering Treatment Gaps in Patients after Acute Myocardial Infarction: Using Global Database TriNetX.

Background and Objectives: Patients with previous acute myocardial infarction are at significantly higher risk of recurrent events. Early and intensive lipid-lowering therapy targeting low-density lipoprotein cholesterol is a key strategy for reducing cardiovascular risk in post-acute myocardial infarction patients worldwide. This study aimed to assess patients' real-life lipid-lowering treatment gaps after acute myocardial infarction using a global network, TriNetX, of anonymous, real-time patient data. The uniqueness of the study was the use of the novel, evolving, and constantly improving TriNetX platform and the evaluation of its feasibility for clinical research. Materials and Methods: A retrospective study was conducted on global repository patients in 2020, diagnosed with acute myocardial infarction, with a three-year follow-up. Results: After acute myocardial infarction, the prescribing rate of lipid-lowering medication (statins, ezetimibe and PCSK9I) was insufficient to reach target LDL-C values. The mean LDL-C level decreased from 2.7 mmol/L (103 mg/dL) as measured on the day of AMI to 1.97 mmol/L (76 mg/dL) between 31D and 3M. During the second and third years, the mean LDL-C value was stable (around 2.0 mmol/L (78 mg/dL)). LDL-C goals were not sufficiently reached, as only 7-12% of patients were reported to have LDL-C values < 55 mg/dL (1.4 mmol/L) and 13-20% of patients were reported to have LDL-C values < 70 mg/dL (1.8 mmol/L) during the follow-up periods. This means that a substantial number of patients remain at a very high risk for CV complications and mortality. Most cardiovascular complications happen within three months after acute myocardial infarction. Conclusions: Gaps remain between the recommendations for managing LDL-C in guidelines and what occurs in real life. The TriNetX platform is an innovative platform with significant potential and should be further developed for clinical research, as it enables the use of valuable interinstitutional data.

Treg-enhancing and immunomodulating microgel scaffold promotes cell ingrowth and heart function recovery post-acute myocardial infarction in vivo

The ingrowth of endogenous cells into tissue scaffolds and modulation of Treg population take a pivotal function in restoring the structure and function of heart post-acute myocardial infarction (MI). However, the traditional hydrogels are failed to achieve such functions due to their critically small mesh size and inherent bioinertness. In this study, a Treg-regulated microgel scaffold (GTK-TK-drug) was prepared by inter-microgels assembly of microgels having cyclodextrin (CD) or adamantane (Ad) with a particle size of about 220 μm. The raw materials to obtain the microgels included gelatin methacryloyl (GelMA), reactive oxygen species (ROS)-responsive crosslinking agent poly(ethylene glycol)-thioketal-poly(ethylene glycol) (PEG-TK-PEG), ROS-responsive release prodrug aminooxyacetic acid (PEG-TK-AOA), PEG-CD or PEG-Ad, and photoinitiator lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP). Quantitative real-time PCR (qPCR), cell counting kit-8, and immunofluorescence staining revealed the effectiveness of AOA for the differentiation of T cells into Treg and the ingrowth of cells in vitro and in vivo. During the short treatment of MI in vivo, the levels of plasma inflammatory factors, cardiomyocyte apoptosis and inflammatory cells were reduced significantly. In the long-term animal experiments, the recovery of cardiac function was significantly enhanced as characterized by echocardiography and the degree of myocardial fibrosis compared to the unassembled microgels control.

Novel Impact of Colchicine on Interleukin-10 Expression in Acute Myocardial Infarction: An Integrative Approach.

Background: Inflammation plays a critical role in myocardial infarction as a critical process in the development of heart failure, involving the development of cardiac fibrosis. Colchicine is a well-established anti-inflammatory drug, but its scientific application in controlling post-acute myocardial infarction (AMI) inflammatory processes has not been established. IL-10 is a key cytokine in modulating inflammatory responses, underscoring its potential as a crucial therapeutic target of colchicine. The objective was to explore the protective role of IL-10 modulated by colchicine in myocardial healing and repair following AMI, particularly cardiac fibrosis. Methods: The predicted protein of colchicine was assessed using WAY2DRUG PASS as probability active value. Proteins associated with colchicine, cardiac fibrosis, and acute myocardial infarction were analyzed with DisGeNET and Open Target databases. Analysis and visualization of protein-protein interactions were conducted using STRING and Cytoscape. A 3T3 cell line treated with CoCl2 was used to mimic hypoxic. HIF-1α and IL-10 expression were measured by flow cytometry and analyzed using a one-way ANOVA test. This observational clinical trial examined acute myocardial infarction patients undergoing immediate and delayed primary percutaneous coronary interventions. Subjects were randomized into control groups receiving placebo and intervention groups treated with colchicine. Assessments occurred at 24 h and five days after the intervention. IL-10 expression in the clinical trial was measured by ELISA and analyzed using a T-test. Results: Colchicine demonstrates promising bioactivity in treating acute myocardial infarction, with notably activity values highlighting its probable role as a tubulin antagonist (0.744), beta-tubulin antagonist (0.673), and NOS2 inhibitor (0.529). Its primary action targets IL-10, with the protein-protein interactions analysis indicating interactions between IL-10 and key inflammatory mediators-IL-1β, IFN-γ, CCL2, TNF, and TGF-β1-during acute myocardial infarction and cardiac fibrosis. Hypoxic conditions in the CoCl2-induced 3T3 cell model show significantly elevated HIF-1α compared to controls (p < 0.0001). Colchicine use significantly increased IL-10 expression in CoCl2-treated cells (p < 0.0001) and in AMI patients within five days (p < 0.05). Conclusions: Colchicine may bolster the anti-inflammatory response post-myocardial infarction by activating IL-10 pathways in fibroblasts and in clinical settings, potentially reducing inflammation after AMI. Further investigation into broader aspects of this pathway, particularly in cardiac fibroblasts, is required.

Dapagliflozin and sacubitril on myocardial microperfusion in patients with post-acute myocardial infarction heart failure and type 2 diabetes.

Coronary heart disease and type 2 diabetes mellitus (T2DM) frequently coexist, creating a complex and challenging clinical scenario, particularly when complicated with acute myocardial infarction (AMI). To examine the effects of dapagliflozin combined with sakubactrovalsartan sodium tablets on myocardial microperfusion. In total, 98 patients were categorized into control (n = 47) and observation (n = 51) groups. The control group received noxital, while the observation group was treated with dapagliflozin combined with noxital for 6 months. Changes in myocardial microperfusion, blood glucose level, cardiac function, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level, growth differentiation factor-15 (GDF-15) level, and other related factors were compared between the two groups. Additionally, the incidence of major adverse cardiovascular events (MACE) and adverse reactions were calculated. After treatment, in the observation and control groups, the corrected thrombolysis in myocardial infarction frame counts were 37.12 ± 5.02 and 48.23 ± 4.66, respectively. The NT-proBNP levels were 1502.65 ± 255.87 and 2015.23 ± 286.31 pg/mL, the N-terminal pro-atrial natriuretic peptide (NT-proANP) levels were 1415.69 ± 213.05 and 1875.52 ± 241.02 ng/mL, the GDF-15 levels were 0.87 ± 0.43 and 1.21 ± 0.56 g/L, and the high-sensitivity C-reactive protein (hs-CRP) levels were 6.54 ± 1.56 and 8.77 ± 1.94 mg/L, respectively, with statistically significant differences (P < 0.05). The cumulative incidence of MACEs in the observation group was significantly lower than that in the control group (P < 0.05). The incidence of adverse reactions was 13.73% (7/51) in the observation group and 10.64% (5/47) in the control group, with no statistically significant difference (P > 0.05). Dapagliflozin combined with nocinto can improve myocardial microperfusion and left ventricular remodeling and reduce MACE incidence in patients with post-AMI heart failure and T2DM. The underlying mechanism may be related to the reduction in the expression levels of NT-proANP, GDF-15, and hs-CRP.

Abstract Mo040: Enhanced neovascularisation does not account for preservation of cardiac function by 11βHSD1 inhibition in a pig model of myocardial infarction

While acute post-myocardial infarction (MI) survival has improved thanks to early intervention, the myocardium still sustains damage that increases the risk of heart failure. Adrenal glucocorticoids (GCs) protect cardiomyocytes immediately after MI, but inhibition of GC regeneration within the heart by 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) during infarct repair prevents subsequent deterioration of ventricular structure and function. In the 11βHSD1-knockout mouse this outcome is associated with enhancement of peri-infarct neovascularisation and prevention of infarct expansion. Here, we tested the hypothesis that pharmacological 11βHSD1 inhibition after MI can preserve function in a translational pig model and investigated the role of neovascularisation. MI was induced in female minipigs via temporary coronary occlusion. A standard clinical therapy (SCT, n =9) group received statin, anti-platelet, βadrenoreceptor antagonist and ACE inhibitor immediatley after MI, and a 11βHSD1i group (n=11) received SCT +11βHSD1 inhibitor (50mg/kg) from 48h after MI until the end of the study. Prior to 11βHSD1i treatment, short-axis cine and late gadolinium-enhanced MRI showed no difference in either infarct mass (4.2±0.4g SCT vs 4.0±0.6g 11βHSD1i) or ejection fraction (EF; 60.6±2.9% SCT vs 56.6±1.8% 11βHSD1i). However, by 28 days after MI, while EF was reduced in SCT pigs to 48±4%, it was maintained in pigs given additional 11βHSD1i treatment (57.9±1.8%, p &lt;0.05 vs SCT). Infarct mass did not differ between the two treatments, suggesting that inhibition of infarct expansion did not account for the improvement in function, this was confirmed by a similar area of infarct collagen in histological analysis. Angiogenesis, represented by an increase in CD31 +ve capillaries, was not enhanced in the infarct or the border zone (BZ) after 11βHSD1i treatment, relative to SCT. While vessel maturation (αSMA +ve vessels) was improved in the infarct compared to the remote myocardium, there was no difference between the two groups. Proteomic pathway analysis of the BZ indicated extracellular matrix organisation as the main pathway regulated by 11βHSD1i compared to SCT. In conclusion, 11βHSD1i after MI successfully preserves cardiac function and structure but the mechanism is independent of scar size reduction or enhanced neovascularisation. Instead, the beneficial effects of 11βHSD1i are likely to result from favourable regulation of collagen processing during scar formation.

Clinical phenotypes and outcomes of patients with left ventricular thrombus: an unsupervised cluster analysis

BackgroundLeft ventricular thrombus (LVT) can develop in a diverse group of patients with various underlying causes, resulting in divergent natural histories and trajectories with treatment. Our aim was to use cluster analysis to identify unique clinical profiles among patients with LVT and then compare their clinical characteristics, treatment strategies, and outcomes. MethodsWe conducted a retrospective study involving 472 patients with LVT whose data were extracted from a tertiary center's echocardiography database, from March 2011 to January 2021. We used the TwoStep cluster analysis method, examining 19 variables. ResultsOur analysis of the 472 patients with LVT revealed two distinct patient clusters. Cluster 1, comprising 247 individuals (52.3%), was characterized by younger patients with a lower incidence of traditional cardiovascular risk factors and relatively fewer comorbidities compared with Cluster 2. Most patients had LVT attributed to an underlying ischemic condition, with a larger proportion being due to post-acute myocardial infarction in Cluster 1 (68.8%), and due to ischemic cardiomyopathy in Cluster 2 (57.8%). Notably, patients in Cluster 2 exhibited a reduced likelihood of LVT resolution (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.44–0.77, p < 0.001) and a higher risk of all-cause mortality (HR 2.27, 95% CI 1.43–3.60, p = 0.001). These associations persisted even after adjusting for variables such as anticoagulation treatment, the presence of left ventricular aneurysms, and specific LVT characteristics such as mobility, protrusion, and size. ConclusionThrough TwoStep cluster analysis, we identified two distinct clinical phenotypes among patients with LVT, each distinguished by unique baseline clinical attributes and varying prognoses.

Functionalizing Sgc8-Paclitaxel Conjugates with F-Base Modifications: Targeted Drug Delivery with Optimized Cardiac Safety.

Recent advancements in cancer treatment have improved patient prognoses, but chemotherapy induced cardiotoxicity remains a prevalent concern. This study explores the potential of F-base-modified aptamers for targeted drug delivery, focusing on their impact on cardiotoxicity. From the phosphoramidite, F-base-functionalized Sgc8-F23 was prepared in an automated and programmable way, which was further reacted with paclitaxel (PTX) to give the F-base- modified aptamer Sgc8-paclitaxel conjugates (Sgc8-F23-PTX) efficiently. The conjugate exhibited prolonged circulation time and enhanced efficacy as a precision anticancer drug delivery system. Echocardiographic assessments revealed no exacerbation of cardiac dysfunction after myocardial infarction (MI) and no pathological changes or increased apoptosis in non-infarcted cardiac regions. Autophagy pathway analysis showed no discernible differences in Sgc8-F23-PTX-treated cardiomyocytes compared with controls, in contrast to the increased autophagy with nanoparticle albumin-bound-paclitaxel (Nab-PTX). Similarly, apoptosis analysis showed no significant differences. Moreover, Sgc8-F23-PTX exhibited no inhibitory effect on hERG, hNav1.5, or hCav1.2 channels. These findings suggest the safety and efficacy of F-base-modified Sgc8 aptamers for targeted drug delivery with potential clinical applications. Further research is warranted for clinical translation and exploration of other drug carriers.

Unraveling the Cardiac Matrix: From Diabetes to Heart Failure, Exploring Pathways and Potential Medications.

Myocardial infarction (MI) often leads to heart failure (HF) through acute or chronic maladaptive remodeling processes. This establishes coronary artery disease (CAD) and HF as significant contributors to cardiovascular illness and death. Therefore, treatment strategies for patients with CAD primarily focus on preventing MI and lessening the impact of HF after an MI event. Myocardial fibrosis, characterized by abnormal extracellular matrix (ECM) deposition, is central to cardiac remodeling. Understanding these processes is key to identifying new treatment targets. Recent studies highlight SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1-RAs) as favorable options in managing type 2 diabetes due to their low hypoglycemic risk and cardiovascular benefits. This review explores inflammation's role in cardiac fibrosis and evaluates emerging anti-diabetic medications' effectiveness, such as SGLT2i, GLP1-RAs, and dipeptidyl peptidase-4 inhibitors (DPP4i), in preventing fibrosis in patients with diabetes post-acute MI. Recent studies were analyzed to identify effective medications in reducing fibrosis risk in these patients. By addressing these areas, we can advance our understanding of the potential benefits of anti-diabetic medications in reducing cardiac fibrosis post-MI and improve patient outcomes in individuals with diabetes at risk of HF.

PCR151 Understanding the Patient Perspectives of Post-Discharge Care and Impact of Treatment in the First Year Post-Acute Myocardial Infarction

PCR151 Understanding the Patient Perspectives of Post-Discharge Care and Impact of Treatment in the First Year Post-Acute Myocardial Infarction

The impact of extracorporeal membrane oxygenation on mortality in patients with cardiogenic shock post acute myocardial infarction: a systematic review and meta-analysis

The impact of extracorporeal membrane oxygenation on mortality in patients with cardiogenic shock post acute myocardial infarction: a systematic review and meta-analysis