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Abstract Cardiovascular disease remains the leading cause of morbidity and mortality, posing a significant challenge to healthcare systems worldwide. Transitional care interventions, which ensure coordination and continuity of care as patients move between different levels of healthcare, have been shown to reduce unnecessary healthcare utilization and improve patient outcomes. While much attention has been given to transitional care in heart failure, this review aims to map the interventions implemented for patients following an acute myocardial infarction (AMI). A scoping review was conducted following the Joanna Briggs Institute (JBI) methodology, with literature searches performed in the Cochrane, CINAHL, MEDLINE, JBI, and SciELO databases, focusing on publications from 2013 onwards in both Portuguese and English. Seventy‐five studies were included, with most combining multiple interventions that contributed to improved cardiovascular health outcomes, including increased adherence to healthy lifestyle behaviors, enhanced medication compliance, and better healthcare self‐management. These interventions were effective in reducing cardiovascular‐related Emergency Department visits, unplanned 30‐day readmissions, and mortality following a first‐time myocardial infarction. Key strategies identified included discharge planning, digital health solutions, outpatient care, and healthcare coordination. The findings of this review underscore the need for developing methodologies that enhance the transition of care from hospital to primary care following an AMI. There is an urgent need to design and implement new healthcare programs that integrate discharge interventions, digital health, outpatient care, and healthcare coordination to ensure continuity of care and optimize patient outcomes post‐discharge.

Abstract Aims Zinc‐finger protein 418 (ZNF418) has been confirmed to be expressed in myocardial tissue. However, the role and mechanism of ZNF418 in pathological myocardial remodelling after myocardial infarction (MI) have not been reported. This study was to elucidate the effect and mechanism of ZNF418 on ventricular remodelling after MI in mice. Methods and results MI mice and H9c2 cardiomyocytes were used to conduct in vivo and in vitro experiments, respectively. ZNF418 expression was regulated by adeno‐associated virus 9 and adenovirus vectors. Pathological analysis, echocardiography, and molecular analysis were performed. ZNF418 was down‐regulated in the left ventricular tissues of post‐MI mice. In contrast, ZNF418 overexpression decreased mortality and improved cardiac function in MI mice. The MI mice exhibited a significantly increased cross‐sectional area of myocardial cells and elevated protein expression levels of myocardial hypertrophy markers ANP, BNP, and β‐MHC (all P

Abstract Aims We aim to integrate the parameters of two‐dimensional (2D) echocardiography and identify the high‐risk population for all‐cause mortality in patients with acute ST‐segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Methods The study involved a retrospective cohort population with STEMI who were admitted to Yongchuan Hospital of Chongqing Medical University between January 2016 and January 2019. Baseline data were collected, including 2D echocardiography parameters and left ventricular ejection fraction (LVEF). The parameters of 2D echocardiography were subjected to cluster analysis. Logistic regression models were employed to assess univariate and multivariate adjusted odds ratios (ORs) of cluster information in relation to all‐cause mortality. Four logistic regression models were generated, utilizing cluster information, clinical variables, clinical variables in conjunction with LVEF, and clinical variables in conjunction with LVEF and cluster information as predictive variables, respectively. The area under the curve (AUC) were utilized to evaluate the incremental risk stratification value of cluster information. Results The study included 633 participants with 28.8% female, a mean age of 65.68 ± 11.98 years. Over the course of a 3‐year follow‐up period, 108 (17.1%) patients experienced all‐cause mortality. Utilizing cluster analysis of 2D echocardiography parameters, the patients were categorized into two distinct clusters, with statistically significant differences observed in most clinical variables, echocardiography, and survival outcomes between the clusters. Multivariate regression analysis revealed that cluster information was independently associated with the risk of all‐cause mortality with adjusted OR 7.33 (95% confidence interval [CI] 3.99–14.06, P

Abstract Aims Congestive heart failure (HF) is a common complication in patients with acute myocardial infarction (AMI). The estimated plasma volume status [ePVS = (100 − haematocrit)/haemoglobin] is used as the blood plasma volume index to determine the presence of congestion in patients with HF. However, the clinical impact of ePVS at discharge in patients with AMI remains unclear. This study aimed to investigate whether ePVS at discharge could determine the long‐term prognosis in patients with AMI. Methods and results We retrospectively identified patients with AMI with ePVS measured at discharge between January 2012 and December 2020. The primary endpoint was post‐discharge all‐cause death. The patients were divided into two groups according to an ePVS cut‐off value of 5.5%, which is commonly used in HF. In total, 1012 patients with AMI were included. The median age was 70 years (range, 61–78 years), and 76.4% of the patients were male. The ePVS > 5.5% (high‐ePVS) group included 365 patients (36.1%), and the all‐cause mortality rate in the total cohort was 17.7%. The log‐rank test revealed that the high‐ePVS group had a significantly higher rate of all‐cause death than the ePVS ≤ 5.5% (low‐ePVS) group (P

Abstract Aims The Selvester scoring system has been derived from ECG parameters for estimating infarct size. However, there is still a lack of evidence for Selvester score as an alternative to cardiac magnetic resonance (CMR) myocardial injury makers for risk stratification and prediction of left ventricular function (LVF) recovery among patients with ST‐segment elevation myocardial infarction (STEMI). Methods and results This multicentre observational study enrolled 328 STEMI patients (88.4% men, 57.3 ± 10.6 years of age) undergoing CMR examination 1 week post‐reperfusion therapy. Patients with baseline left ventricular ejection fraction (LVEF) 0.05). A Selvester score >10 doubled the risk of MACEs in patients with systolic dysfunction (1.91 [1.02 to 3.58], P = 0.04). Additionally, Selvester score, baseline LVEF, transmural infarction, and peak CK‐MB were independent predictors of recovered LVF, with Selvester score providing incremental predictive value to peak CK‐MB in predicting recovered LVF (∆AUC = 0.07, P

Abstract Aims Type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular disease (CVD) risk, but whether T2DM directly causes adverse cardiac remodelling is uncertain. We performed a comprehensive Mendelian randomization (MR) analysis to investigate the causal relevance of T2DM to CVD outcomes and cardiac structure/function. Methods and results Bidirectional two‐sample MR was conducted using summary‐level data from European‐ancestry genome‐wide association studies. The T2DM GWAS data included 80 154 cases and 853 816 controls from the DIAGRAM consortium. Outcomes included coronary artery disease (CAD), myocardial infarction (MI), stroke, heart failure, atrial fibrillation, and various quantitative cardiac imaging traits assessed by magnetic resonance imaging. MR analysis revealed causal associations between genetic predisposition to T2DM and increased risk of CAD (odds ratio [OR] 1.104, 95% confidence interval [CI] 1.078–1.130, P = 2.59e‐16), MI (OR 1.129, 95% CI 1.094–1.166, P = 6.02e‐14) and stroke (OR 1.086, 95% CI 1.064–1.109, P = 1.02e‐14). These associations were validated in the FinnGen cohort (CAD: OR 1.117, 95% CI 1.075–1.158, P = 1.56e‐9; MI: OR 1.132, 95% CI 1.083–1.184, P = 4.27e‐8; stroke: OR 1.138, 95% CI 1.107–1.170, P = 3.52e‐20). Multivariable MR show consistent findings (CAD: OR 1.063, 95% CI 1.031–1.097, P = 1.11e‐4; MI: OR 1.088, 95% CI 1.042–1.135, P = 1.12e‐4; stroke: OR 1.066, 95% CI 1.032–1.101, P = 1.18e‐4) after adjusting for cardiometabolic traits. T2DM was causally associated with higher left ventricular mass index (β = 0.473, 95% CI 0.193 to 0.752, P = 0.001), lower indexed right atrial minimum (β = −0.048, 95% CI −0.073 to −0.022, P = 2.1e‐5), and maximum (β = −0.042, 95% CI −0.065 to −0.019, P = 4.12e‐5) areas. The effects on right atrial size remained significant after adjusting for risk factors (minimum area: β = −0.041, 95% CI −0.072 to −0.010, P = 0.009; maximum area: β = −0.039, 95% CI −0.069 to −0.008, P = 0.012). Both apolipoprotein A1 and SBP are important mediators in the causal relationship between T2DM and left ventricular mass index. No reverse causal associations were identified. Conclusions Our MR study demonstrates that genetic liability to T2DM plays causal roles in CAD, MI, stroke, and cardiac structure changes including left ventricular hypertrophy and reduced right atrial dimensions. These findings provide genetic evidence supporting glycaemic control in T2DM to mitigate cardiovascular complications and adverse cardiac remodelling.

Abstract Background Myocardial infarction (MI) is an acute condition in which the heart muscle dies due to the lack of blood supply. Previous research has suggested that autophagy and angiogenesis play vital roles in the prevention of heart failure after MI, and miR‐106a is considered to be an important regulatory factor in MI. But the specific mechanism remains unknown. In this study, using cultured venous endothelial cells and a rat model of MI, we aimed to identify the potential target genes of miR‐106a and discover the mechanisms of inhibiting autophagy and angiogenesis. Methods We first explored the biological functions of miR‐106a on autophagy and angiogenesis on endothelial cells. Then we identified ATG7, which was the downstream target gene of miR‐106a. The expression of miR‐106a and ATG7 was investigated in the rat model of MI. Results We found that miR‐106a inhibits the proliferation, cell cycle, autophagy and angiogenesis, but promoted the apoptosis of vein endothelial cells. Moreover, ATG7 was identified as the target of miR‐106a, and ATG7 rescued the inhibition of autophagy and angiogenesis by miR‐106a. The expression of miR‐106a in the rat model of MI was decreased but the expression of ATG7 was increased in the infarction areas. Conclusion Our results indicate that miR‐106a may inhibit autophagy and angiogenesis by targeting ATG7. This mechanism may be a potential therapeutic treatment for MI.

Abstract Aims Patients with a reduced left ventricular ejection fraction (LVEF) following an acute myocardial infarction (MI) are at risk of progressive adverse cardiac remodelling that can lead to the development of heart failure and death. The early addition of a sodium‐glucose cotransporter 2 (SGLT2) inhibitor to standard treatment may delay or prevent progressive adverse remodelling in these patients. Methods and results EMpagliflozin to PREvent worSening of left ventricular volumes and Systolic function after Myocardial Infarction (EMPRESS‐MI) is a randomized, double‐blind, placebo‐controlled, multi‐centre trial designed to assess the effect of empagliflozin on cardiac remodelling evaluated using cardiovascular magnetic resonance (CMR) in 100 patients with left ventricular systolic dysfunction following MI. Eligible patients were those ≥12 h and ≤14 days following acute MI, with an LVEF

Abstract Mesenchymal stem cell (MSC)‐derived extracellular vesicles (EVs) are a promising treatment for myocardial infarction (MI), but their therapeutic efficacy is limited by inefficient accumulation at the target site. A minimally invasive MSC EV therapy that enhances EV accumulation at the disease site and extends EV retention could significantly improve post‐infarct cardiac regeneration. Here, we show that EVs decorated with the next‐generation of high‐affinity (HiA) heterodimerizing leucine zippers, termed HiA Zippersomes, amplify targetable surface areas through in situ crosslinking and exhibited ~7‐fold enhanced accumulation within the infarcted myocardium in mice after 3 days and continued to be retained up to Day 21, surpassing the performance of unmodified EVs. After MI in mice, HiA Zippersomes increase the ejection fraction by 53% and 100% compared with unmodified EVs and phosphate‐buffered saline (PBS), respectively. This notable improvement in cardiac function played a crucial role in restoring healthy heart performance. HiA Zippersomes also robustly decrease infarct size by 52% and 60% compared with unmodified EVs and PBS, respectively, thus representing a promising platform for minimally invasive vesicle delivery to the infarcted heart compared to intramyocardial injections.

Background European guidelines recommend the use of a 0h/1h hs‐cTn (high‐sensitivity cardiac troponin) protocol in patients with acute chest pain. We aimed to determine the performance of this protocol in routine care when supplemented with patient history and ECG and a recommendation to refrain from noninvasive testing in low‐risk patients. Methods and Results This was a pre‐ and postimplementation study with concurrent controls. Patients with chest pain were enrolled at 5 Swedish emergency departments (EDs) during a 10‐month period in both 2017 and 2018. All hospitals used a 0h/3h hs‐cTnT protocol in 2017 and 3 EDs implemented a 0h/1h hs‐cTnT protocol during 10 months in 2018. The 2 coprimary outcomes were the incidence of acute myocardial infarction and all‐cause death within 30 days and ED length of stay. The study included 26 040 consecutive patients. In the intervention hospitals, 21 (0.40%) of the discharged patients had an acute myocardial infarction/death event during the control period (0h/3h testing) and 22 (0.45%) in the intervention period (0h/1h testing), which met the criteria for noninferiority. There was no significant difference in ED length of stay (ratio 0.99, P=0.48) or ED discharge rate between the periods in the intervention versus the control hospitals. A total of 3142 patients met low‐risk 0h/1h hs‐cTnT criteria and were discharged, of whom 2 had an acute myocardial infarction/death event. Conclusions A 0h/1h hs‐cTnT protocol incorporating patient history and ECG was as safe as using a 0h/3h protocol but did not reduce ED length of stay or increase the discharge rate. Refraining from noninvasive testing in patients identified as low risk was safe. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03421873.

Background The proliferative capacity of cardiomyocytes in adult mammalian hearts is far too low to replace the cells that are lost to myocardial infarction. Both cardiomyocyte proliferation and myocardial regeneration can be improved via the overexpression of a constitutively active variant of YAP5SA (Yes‐associated protein, 5SA [active] mutant), but persistent overexpression of proliferation‐inducing genes could lead to hypertrophy and arrhythmia, whereas off‐target expression in fibroblasts and macrophages could increase fibrosis and inflammation. Methods and Results Transient overexpression of YAP5SA or GFP (green fluorescent protein; control) was targeted to cardiomyocytes via our cardiomyocyte‐specific modified mRNA translation system (YAP5SACM‐SMRTs or GFPCM‐SMRTs, respectively). YAP5SA‐cardiomyocyte specificity was confirmed via in vitro experiments in cardiomyocytes and cardiac fibroblasts that had been differentiated from human induced‐ pluripotent stem cells and in human umbilical‐vein endothelial cells, and the regenerative potency of YAP5SACM‐SMRTs was evaluated in a mouse myocardial infarction model. In cultured human induced‐pluripotent stem cells‐cardiomyocytes, YAP was abundantly expressed for 3 days after YAP5SACM‐SMRTs administration and was accompanied by increases in the expression of markers for proliferation, before declining to near‐background levels after day 7, whereas GFP fluorescence remained high from days 1 to 3 after GFPCM‐SMRTs treatment and then slowly declined. GFP fluorescence was also observed in human induced‐pluripotent stem cells‐cardiac fibroblasts and human umbilical‐vein endothelial cells on day 1 after GFPCM‐SMRTs administration but declined substantially by day 3. In the mouse myocardial infarction model, echocardiographic assessments of left‐ventricular ejection fraction and fractional shortening were significantly greater, whereas infarct sizes were significantly smaller in YAP5SACM‐SMRTs–treated mice than in vehicle‐treated control animals, and YAP5SACM‐SMRTs appeared to promote cardiomyocyte proliferation. Conclusions The CM‐SMRTs can be used to transiently and specifically overexpress YAP5SA in cardiomyocytes, and this treatment strategy significantly promoted cardiomyocyte proliferation and myocardial regeneration in a mouse myocardial infarction model.

Abstract Myocardial infarction accompanied by diabetes mellitus is accepted as the most serious type of coronary heart disease, and among the current treatment strategies, the precise delivery of protective drugs for inhibiting cardiomyocyte apoptosis is still a challenge. In this study, we developed a biodegradable nanoparticles‐based delivery system with excellent macrophage escape, cardiac targeting, and drug release properties to achieve targeted therapy of myocardial infarction. Specifically, a copolymer of p(DMA–MPC–CD) combining self‐adhesion, hydration lubrication, and targeting peptide binding site was successfully prepared by free radical copolymerization, and it was self‐assembled on the surface of melatonin‐loaded dendritic mesoporous silica nanoparticles (bMSNs) following the integration of adamantane‐modified cardiac homing peptide (CHP) based on supramolecular host–guest interaction. Importantly, a hydration layer formed around the zwitterionic phosphorylcholine groups of the multifunctional nanoparticles, which was confirmed by the enhancement in hydration lubrication and reduction in coefficient of friction, prevented the nanoparticles from phagocytosis by the macrophages. The in vivo bioluminescence imaging test indicated that the nanoparticles were endowed with satisfied cardiac targeting capability, and the in vivo mice study demonstrated that the intravenous injection of drug‐loaded nanoparticles (namely bMSNs–Mel@PDMC–CHP) effectively reduced cardiomyocyte apoptosis, alleviated myocardial interstitial fibrosis, and enhanced cardiac function.

Background The percentage of women

Background Neighborhood‐level income is inversely associated with cardiovascular events; however, it is uncertain whether this association varies with immigration status. Methods and Results We conducted a population‐based cohort study of 5.2 million (53% women, 19% immigrants) urban‐dwelling people aged ≥40 years without a prior history of cardiovascular disease in Ontario, Canada. Neighborhood‐level income was measured in quintiles from quintile 1 (lowest) to quintile 5 (highest), and immigrants were defined as those born outside of Canada who moved to Canada after 1985. We estimated the association between neighborhood‐level income and the rate of incident cardiovascular events (hospitalization for stroke or myocardial infarction, or cardiovascular death) using multivariable cause‐specific hazards models and added an interaction term to see if the association varies by immigration status. The absolute difference in the rate of cardiovascular events across income quintiles was less pronounced in immigrants than in long‐term residents: age‐ and sex‐adjusted rate per 1000 person‐years in quintile 1 versus quintile 5: 5.69 versus 4.10 in immigrants and 8.37 versus 5.87 in long‐term residents. In adjusted models, the interaction between immigration status and neighborhoodl evel was significant (Pinteraction

Background RANTES (regulated upon activation, normal T cell expressed, and secreted) or CCL5 (CC chemokine ligand 5) is a chemokine that mediates chemotaxis and activation of T cells, monocytes, mast cells, and dendritic cells. It is involved in the pathogenesis of several diseases, including atherosclerosis, but its role at the acute phase of myocardial infarction (MI) is unclear. Our objective is to determine whether the serum level of RANTES is a marker of the severity of acute MI. Methods and Results The study included 250 consecutive patients with ST‐segment–elevation MI who underwent percutaneous coronary intervention in a prospective cohort. Peripheral venous blood samples were taken at 5 time points and ELISA was performed. Major adverse cardiovascular events were prospectively recorded over the 12‐month follow‐up. Serum RANTES level raised from 12.9 (8.0–20.7) ng/mL at H0 to 13.9 (7.4–22.4) ng/mL at H4 and decreased gradually until 1 month at 9.7 (5.4–13.6) ng/mL (P

Abstract Myocardial infarction (MI) triggers a poor ventricular remodeling response, but the underlying mechanisms remain unclear. Here, the authors show that sentrin‐specific protease 1 (SENP1) is downregulated in post‐MI mice and in patients with severe heart failure. By generating cardiomyocyte‐specific SENP1 knockout and overexpression mice to assess cardiac function and ventricular remodeling responses under physiological and pathological conditions. Increased cardiac fibrosis in the cardiomyocyte‐specific SENP1 deletion mice, associated with increased fibronectin (Fn) expression and secretion in cardiomyocytes, promotes fibroblast activation in response to myocardial injury. Mechanistically, SENP1 deletion in mouse cardiomyocytes increases heat shock protein 90 alpha family class B member 1 (HSP90ab1) SUMOylation with (STAT3) activation and Fn secretion after ventricular remodeling initiated. Overexpression of SENP1 or mutation of the HSP90ab1 Lys72 ameliorates adverse ventricular remodeling and dysfunction after MI. Taken together, this study identifies SENP1 as a positive regulator of cardiac repair and a potential drug target for the treatment of MI. Inhibition of HSP90ab1 SUMOylation stabilizes STAT3 to inhibit the adverse ventricular remodeling response.

ABSTRACT Background Sodium‐glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular (CV) outcomes in patients with or without Type 2 diabetes and heart failure (HF). However, studies have shown conflicting evidence regarding their efficacy in patients following acute myocardial infarction (MI). We conducted a pilot systematic review and meta‐analysis to synthesise the available evidence regarding the effectiveness of SGLT2 inhibitors in MI. Methods A systematic literature search was conducted using PubMed/MEDLINE, the Cochrane Library and Embase databases to identify randomised controlled trials (RCTs) that compared clinical outcomes of SGLT2 inhibitors with placebo following MI. We conducted the statistical analysis using RevMan, version 5.4 and pooled risk ratios (RRs) along the corresponding 95% confidence interval (CI) for all outcomes. Results Five RCTs reporting data for 11,211 patients were included in our study. The mean follow‐up duration was 43.8 weeks. Our pooled analysis showed that SGLT2 inhibitors significantly reduced the risk of hospitalisations for heart failure (HHF) (RR = 0.76, 95% CI: 0.61–0.88, p = 0.001) in patients with MI. However, the risk of all‐cause mortality (RR = 1.05, 95% CI: 0.78–1.41, p = 0.76), CV mortality (RR = 1.04, 95% CI = 0.84–1.29, p = 0.73) and all‐cause hospitalisations (RR = 1.06, 95% CI: 0.96–1.17, p = 0.25) remained comparable across the two groups. Conclusion SGLT2 inhibitors reduce HHF without affecting all‐cause mortality, CV mortality and all‐cause hospitalisations. However, further evidence is required to reach a definitive conclusion.

Abstract Despite the proceeds in the management of acute myocardial infarction (AMI), the current therapeutic landscape still suffers from limited success in the clinic. Exaggerated inflammatory immune response and excessive oxidative stress are key pathological features aggravating myocardium damage. Herein, catalytic immunomodulatory nanocomplexes as anti‐AMI therapeutics to resolve reactive oxygen species (ROS)‐proinflammatory neutrophils‐specific‐inflammation is engineered. The nanocomplexes contain lyophilic S100A8/9 inhibitor ABR2575 in the core of nanoemulsions, which effectively disrupts the neutrophils‐S100A8/A9‐inflammation signaling pathway in the AMI microenvironment. Additionally, ROS scavenger ultrasmall CuxO nanoparticles are incorporated into the nanoemulsions via coordinating with SH groups of poly(ethylene glycol) (PEG)‐conjugated lipids, which mimic multiple enzymes, dramatically alleviating the oxidative stress damage to myocardial tissue. This combination strategy significantly suppresses the infiltration of pro‐inflammatory monocytes, macrophages, and neutrophils, as well as the secretion of inflammatory cytokines. Additionally, it potentially triggers cardiac Tert activation, which promotes myocardial function and decreases infarction size in preclinical murine AMI models. This approach offers a new nanomedicine for treating AMI, resulting in a dramatically enhanced therapeutic outcome.

Key Clinical Message Cerebrovascular events are closely related to cardiac events. Chronic inflammatory diseases, such as rheumatoid arthritis (RA), increase the risk of cardiovascular and cerebrovascular stroke. The link between RA, myocardial infarction, and resulting neurological issues highlights the case's complexity, stressing the need for a comprehensive, interdisciplinary medical approach.

Background Mineralocorticoid receptor (MR) induces cardiac inflammation cooperatively with nuclear factor‐κB and signal transducer and activator of transcription 3 (STAT3); MR blockers exert anti‐inflammatory effects. However, the underlying mechanism remains unclear. We investigated the anti‐inflammatory effect of esaxerenone, a novel MR blocker, in experimental myocardial infarction (MI) and its underlying mechanisms. Methods and Results Male C57BL/6J mice subjected to ligation of the left anterior descending artery were randomly assigned to either the vehicle or esaxerenone group. Esaxerenone was provided with a regular chow diet. The mice were euthanized at either 4 or 15 days after MI. Cardiac function, fibrosis, and inflammation were evaluated. Esaxerenone significantly improved cardiac function and attenuated cardiac fibrosis at 15 days after MI independently of its antihypertensive effect. Inflammatory cell infiltration, inflammatory‐related gene expression, and elevated serum interleukin‐6 levels at 4 days after MI were significantly attenuated by esaxerenone. In vitro experiments using mouse macrophage‐like cell line RAW264.7 cells demonstrated that esaxerenone‐ and spironolactone‐attenuated lipopolysaccharide‐induced interleukin‐6 expression without altering the posttranslational modification and nuclear translocation of p65 and STAT3. Immunoprecipitation assays revealed that MR interacted with both p65 and STAT3 and enhanced the p65–STAT3 interaction, leading to a subsequent increase in interleukin‐6 promoter activity, which was reversed by esaxerenone. Conclusions Esaxerenone ameliorated postinfarct remodeling in experimental MI through its anti‐inflammatory properties exerted by modulating the transcriptional activity of the MR–p65–STAT3 complex. These results suggest that the MR–p65–STAT3 complex can be a novel therapeutic target for treating MI.

Abstract Aims Acute mitral regurgitation (MR) in the setting of myocardial infarction (MI) may be the result of papillary muscle rupture (PMR). This condition is associated with high morbidity and mortality. We aim to evaluate the feasibility of transcatheter edge‐to‐edge mitral valve repair (TEER) in this acute setting. Methods and results We analysed data from the International Registry of MitraClip in Acute Mitral Regurgitation following acute Myocardial Infarction (IREMMI) of 30 centres in Europe, North America, and the middle east. We included patients with post‐MI PMR treated with TEER as a salvage procedure, and we evaluated immediate and 30‐day outcomes. Twenty‐three patients were included in this analysis (9 patients suffered complete papillary muscle rupture, 9 partial and 5 chordal rupture). The patients' mean age was 68 ± 14 years. Patients were at high surgical risk with median EuroSCORE II 27% (IQR 16, 28) and 20 out of 23 (87% were in cardiogenic shock). All patients were treated with vasopressors, and 17 out of 23 patients required mechanical support. TEER procedure was performed on the median 6 days after the index MI date IQR (3, 11). Procedural success was achieved in 87% of patients. The grade of MR was significantly decreased after the procedure. MR reduction to 0 or 1 + was achieved in 13 patients (57%), to 2 + in 7 patients (30%), P

Abstract Hypoglycemia is common in people with type 1 diabetes. Sometimes, severe hypoglycemia can be fatal. The underlying mechanisms by which severe hypoglycemia can lead to death are unclear. The sympathetic nervous system is thought to be proarrhythmic. We hypothesized that norepinephrine is the main mediator of severe hypoglycemia‐induced fatal cardiac arrhythmias. To test this hypothesis, adult, non‐diabetic Sprague–Dawley rats were subjected to hyperinsulinemic‐severe hypoglycemic clamps (3 h, 10–15 mg/dL) during two different experiments: (1) intracerebroventricular (ICV) norepinephrine (n = 26) or artificial cerebrospinal fluid (aCSF) (n = 20) infusion or (2) blockade of norepinephrine release by intraperitoneal reserpine (n = 20) or control (n = 29). In experiment 1, brain norepinephrine infusion during severe hypoglycemia led to a 2.5‐fold increase in third‐degree heart block and a 24% incidence of ST elevation compared to no ST elevation in aCSF controls. In experiment 2, reserpine successfully reduced plasma and cardiac norepinephrine levels. During severe hypoglycemia, reserpine completely prevented second and third‐degree heart block and T wave increases, a marker of myocardial infarction, compared to controls. In conclusion, norepinephrine increases while reserpine, used to reduce norepinephrine nerve terminal release, reduces heart block and markers of myocardial infarction during severe hypoglycemia.

Key Clinical Message Coronary occlusion due to large thrombus is frequently encountered during ST‐elevation myocardial infarction (STEMI). Despite guidelines discourage this practice, often thrombus aspiration is necessary to reduce thrombotic burden and to prevent embolization. We report a case of mechanical thrombectomy with a Neurovascular Catheter from radial artery during inferior STEMI.

Abstract Background Patients with myocardial infarction (MI) frequently experience a heightened incidence of depression, thereby increasing the risk of adverse cardiovascular events. Consequently, early detection and intervention in depressive symptoms among patients with MI are imperative. Shexiang Baoxin Pills (SBP), a Chinese patent medicine employed for the treatment of MI, exhibits diverse mechanisms targeting this condition. Nevertheless, its therapeutic efficacy on postmyocardial infarction depressive symptoms remains unclear. The aim of this study is to investigate the effectiveness and mechanism of SBP in managing depression during acute myocardial infarction (AMI). Methods A rat model combining MI and depression was established, and the rats were randomly divided into four groups: the model (MOD) group, SBP group, Fluoxetine (FLX) group, and Sham group. After 28 days of drug intervention, cardiac function was assessed using echocardiography while behavior was evaluated through sucrose preference test (SPT), forced swimming test (FST), and open‐field test (OFT). Additionally, levels of inflammatory factors in serum and hippocampus were measured along with NLRP3 inflammasome‐related protein expression via Western blotting and immunofluorescence. Results SBP can enhance cardiac function in rats with AMI and depression, while significantly ameliorating depressive‐like behavior. Compared to the Sham group, levels of IL‐1β, IL‐18, TNF‐α, and other inflammatory factors were markedly elevated in the MOD group. However, expressions of these inflammatory factors were reduced to varying degrees following treatment with SBP or FLX. Analysis of NLRP3 inflammasome‐related proteins in the hippocampus revealed a significant upregulation of IL‐1β, IL‐18, NLRP3, ASC, caspase‐1, and GSDMD in the MOD group; conversely, these measures were significantly attenuated after SBP intervention. Conclusion We have observed a significant amelioration in depression‐like behavior upon SBP administration during the treatment of AMI, suggesting that this effect may be attributed to the inhibition of NLRP3‐mediated pyroptosis. (The main findings are summarized in the graphical abstract in the supplementary file.)

Abstract Objective Coronary artery disease (CAD) is a debilitating condition that can lead to myocardial infarction (MI). Exosomal miRNAs (exo‐miRNA) can be diagnostic biomarkers for detecting MI. Here, we conduct a study to evaluate the efficacy of exo‐miRNA‐21‐5p/3p for early detection of MI. Methods A total of 135 CAD patients and 150 healthy subjects participated in this study. Additionally, we randomly divided 26 male Wistar rats (12 weeks old) into two groups: control and induced MI. Angiographic images were used to identify patients and healthy individuals of all genders. In the following, serum exosomes were obtained, and exo‐miRNA‐21‐5p/3p was measured by reverse‐transcriptase polymerase chain reaction. Results We observed an upregulation of exo‐miRNA‐21‐5p/3p in CAD patient and MI‐induced animal groups compared to controls. Analysis of the ROC curves defined 82% and 88% of the participants' exo‐miRNA‐21‐5p and exo‐miRNA‐21‐3p diagnostic power, respectively, which in the animal model was 92 and 82. Conclusion This study revealed that the mean expression levels of exo‐miRNA‐21‐5p/3p were significantly increased in CAD patients and animal models of induced MI. Also, these results are associated with the atherogenic lipid profile of CAD patients, which may play an important role in the progression of the disease. Therefore, they can be considered as novel biomarkers.

Key Clinical Message Clinicians should consider spontaneous coronary artery dissection in middle‐aged women presenting with acute coronary syndromes and a history of tamoxifen use, to ensure timely diagnosis, and appropriate management strategies. Abstract Spontaneous coronary artery dissection (SCAD) is characterized by a non‐iatrogenic, nontraumatic separation of the coronary artery wall, contributing to acute coronary syndromes (ACS), and sudden cardiac death. SCAD predominantly affects the left anterior descending artery (LAD) and is frequently observed in middle‐aged women. This condition has been associated with cancer treatment and exogenous hormones exposure. The diagnostic gold standard remains coronary angiography, management strategies include conservative measures, percutaneous coronary intervention (PCI), and coronary artery bypass graft surgery (CABG). We describe a case of a 54‐year‐old woman with breast cancer and a history of tamoxifen use, presenting with SCAD in the posterolateral branch (PLB) originating from the left circumflex artery (LCX), and right coronary artery (RCA) and managed conservatively.

Abstract Myocardial infarction (MI), a consequence of coronary artery occlusion, triggers the degradation of ferritin, resulting in elevated levels of free iron in the heart and thereby inducing ferroptosis. Targeting myocardial ferroptosis through the chelation of excess iron has therapeutic potential for MI treatment. However, iron chelation in post ischemic injury areas using conventional iron‐specific chelators is hindered by ineffective myocardial intracellular chelation, rapid clearance, and high systemic toxicity. A chitosan‐desferrioxamine nanosponge (CDNS) is designed by co‐crosslinking chitosan and deferoxamine through noncovalent gelation to address these challenges. This architecture facilitates direct iron chelation regardless of deferoxamine (DFO) release due to its sponge‐like porous hydrogel structure. Upon cellular internalization, CDNS can effectively chelate cellular iron and facilitate the efflux of captured iron, thereby inhibiting ferroptosis and associated oxidative stress and lipid peroxidation. In MI mouse models, myocardial injection of CDNS promotes sustainable retention and the suppression of ferroptosis in the infarcted heart. This intervention improves cardiac function and alleviates adverse cardiac remodeling post‐MI, leading to decreased oxidative stress and the promotion of angiogenesis due to ferroptosis inhibition by CDNS in the infarcted heart. This study reveals a nanosponge‐based nanomedicine targeting myocardial ferroptosis with efficient iron chelation and efflux, offering a promising MI treatment.

Abstract Aim To compare the cardiovascular preventive effect associated with glucagon‐like‐peptide‐1 receptor agonists (GLP‐1 RA) versus dipeptidyl peptidase‐4 inhibitors (DPP‐4i) according to the achieved target level of glycated hemoglobin (HbA1c). Methods We used retrospective Danish registries to include type 2 diabetes patients already in metformin treatment initiating GLP‐1 RA or DPP‐4i between 2007 and 2021. Patients were included 6 months after GLP‐1 RA or DPP‐4i initiation. The last available HbA1c measurement before inclusion was collected. The achieved HbA1c level was categorized according to a target level below or above 53 mmol/mol (7%). The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, and all‐cause death. We used a multivariable Cox proportional hazard model to estimate the effect of HbA1c levels on the outcome among GLP‐1 RA users compared to DPP‐4i users. Results The study included 13 634 GLP‐1 RA users (median age 56.9, interquartile range [IQR]: 48.5–65.5; 53% males) and 39 839 DPP‐4i users (median age 63.4, IQR: 54.6–71.8; 61% males). The number of GLP‐1 RA and DPP‐4i users according to achieved HbA1c levels were as follows: HbA1c ≤ 53 mmol/mol (≤7.0%): 3026 (22%) versus 4824 (12%); HbA1c > 53 mmol/mol (>7.0%): 6577 (48%) versus 17 508 (44%); missing HbA1c: 4031 (30%) versus 17 507 (44%). During a median follow‐up of 5 years (IQR: 2.6–5.0), 954 GLP‐1 RA users experienced the primary outcome compared to 7093 DPP‐4i users. The 5‐year risk (95% confidence interval [CI]) of the outcome associated with GLP1‐RA versus DPP‐4i according to HbA1c categories was as follows: HbA1c ≤ 53 mmol/mol: 10.3% (8.2–12.3) versus 24.3% (22.7–25.8); HbA1c > 53 mmol/mol: 16.0% (14.3–17.6) versus 21.1% (20.3–21.9); missing HbA1c: 17.1% (15.7–18.5) versus 25.6% (24.9–26.3). The preventive effect associated with GLP‐1 RA versus DPP‐4i was significantly enhanced when achieving lower HbA1c levels: HbA1c ≤ 53 mmol/mol: 0.65 (0.52–0.80); HbA1c > 53 mmol/mol: 0.92 (0.83–1.03); missing HbA1c: 0.92 (0.84–1.02) (p value for interaction

Cardiac troponin is extensively used as a biomarker in modern medicine due to its diagnostic capability for myocardial injury, as well as its predictive and prognostic value for cardiac diseases. However, heterophile antibodies, antitroponin antibodies, and macrotroponin complexes can be observed both in seemingly healthy individuals and patients with cardiac diseases, potentially leading to false positive or disproportionate elevation of cTn (cardiac troponin) assay results and introducing discrepancies in clinical interpretations with impact on medical management. In this review article, we describe the possible mechanisms of cTn release and the sources of variations in the assessment of circulating cTn levels. We also explore the pathophysiological mechanisms underlying antitroponin antibody development and discuss the influence exerted by macrotroponin complexes on the results of immunoassays. Additionally, we explore approaches to detect these complexes by presenting various clinical scenarios encountered in routine clinical practice. Finally, unsolved questions about the development, prevalence, and clinical significance of cardiac autoantibodies are discussed.

Abstract Myocardial infarction (MI) is a leading cause of death worldwide. Few drugs hold the ability to depress cardiac electrical and structural remodeling simultaneously after MI, which is crucial for the treatment of MI. The aim of this study is to investigate an effective therapy to improve both electrical and structural remodeling of the heart caused by MI. Here, an “ion cocktail therapy” is proposed to simultaneously reverse cardiac structural and electrical remodeling post‐MI in rats and minipigs by applying a unique combination of silicate, strontium (Sr) and copper (Cu) ions due to their specific regulatory effects on the behavior of the key cells involved in MI including angiogenesis of endothelial cells, M2 polarization of macrophages and apoptosis of cardiomyocyte. The results demonstrate that ion cocktail treatment attenuates structural remodeling post‐MI by ameliorating infarct size, promoting angiogenesis in both peri‐infarct and infarct areas. Meantime, to some extent, ion cocktail treatment reverses the deteriorative electrical remodeling by reducing the incidence rate of early/delayed afterdepolarizations and minimizing the heterogeneity of cardiac electrophysiology. This ion cocktail therapy reveals a new strategy to effectively treat MI with great clinical translation potential due to the high effectiveness and safety of the ion cocktail combination.

Abstract Myocardial infarction (MI) is a critical global health challenge, with current treatments limited by the complex MI microenvironment, particularly the excessive oxidative stress and intense inflammatory responses that exacerbate cardiac dysfunction and MI progression. Herein, a mannan‐based nanomedicine, Que@MOF/Man, is developed to target the inflammatory infarcted heart and deliver the antioxidative and anti‐inflammatory agent quercetin (Que), thereby facilitating a beneficial myocardial microenvironment for cardiac repair. The presence of mannan on the nanoparticle surface enables selective internalization by macrophages rather than cardiomyocytes. Que@MOF/Man effectively neutralizes reactive oxygen species in macrophages to reduce oxidative stress and promote their differentiation into a reparative phenotype, reconciling the inflammatory response and enhancing cardiomyocyte survival through intercellular communication. Owing to the recruitment of macrophages into inflamed myocardium post‐MI, in vivo, administration of Que@MOF/Man in MI rats revealed the specific distribution into the injured myocardium compared to free Que. Furthermore, Que@MOF/Man exhibited favorable results in resolving inflammation and protecting cardiomyocytes, thereby preventing further myocardial remodeling and improving cardiac function in MI rats. These findings collectively validate the rational design of an inflammation‐targeted delivery strategy to mitigate oxidative stress and modulate the inflammation response in the injured heart, presenting a therapeutic avenue for MI treatment.

Abstract The tissue‐specific heart decellularized extracellular matrix (hdECM) demonstrates a variety of therapeutic advantages, including fibrosis reduction and angiogenesis. Consequently, recent research for myocardial infarction (MI) therapy has utilized hdECM with various delivery techniques, such as injection or patch implantation. In this study, a novel approach for hdECM delivery using a wet adhesive paintable hydrogel is proposed. The hdECM‐containing paintable hydrogel (pdHA_t) is simply applied, with no theoretical limit to the size or shape, making it highly beneficial for scale‐up. Additionally, pdHA_t exhibits robust adhesion to the epicardium, with a minimal swelling ratio and sufficient adhesion strength for MI treatment when applied to the rat MI model. Moreover, the adhesiveness of pdHA_t can be easily washed off to prevent undesired adhesion with nearby organs, such as the rib cages and lungs, which can result in stenosis. During the 28 days of in vivo analysis, the pdHA_t not only facilitates functional regeneration by reducing ventricular wall thinning but also promotes neo‐vascularization in the MI region. In conclusion, the pdHA_t presents a promising strategy for MI treatment and cardiac tissue regeneration, offering the potential for improved patient outcomes and enhanced cardiac function post‐MI.

Background Individuals with both atrial fibrillation (AF) and myocardial infarction (MI) have higher mortality compared with individuals with only 1 condition. Whether mortality differs according to the temporal order of AF and MI is unclear. Methods and Results We included participants from the FHS (Framingham Heart Study) from 1960 and onwards. We assessed the hazard ratio (HR) of new‐onset AF and MI, and mortality according to MI and AF status (prevalent and interim) using multivariable‐adjusted Cox proportional hazards models. Interim diseases were modeled as time‐varying variables. For the analysis of new‐onset AF, 10 923 participants (55% women; mean±SD age, 54±8 years) were included. For new‐onset MI, 10 804 participants (55% women; mean±SD age, 54±8 years) were included. Compared with no MI, the hazard of new‐onset AF was higher in participants with prevalent (HR, 1.60 [95% CI, 1.32–1.94]) and interim MI (HR, 3.96 [95% CI, 3.18–4.91]). Both ST‐segment–elevation MI and non–ST‐segment–elevation MI were associated with new‐onset AF. Interim AF, not prevalent AF, was associated with higher hazard rate of new‐onset MI (HR, 2.21 [95% CI, 1.67–2.92]). Interim AF was associated with both ST‐segment–elevation MI and non–ST‐segment–elevation MI. Mortality was significantly greater among participants with AF and MI compared with participants with 1 of the 2, regardless of temporal order. Conclusions We report a bidirectional association between AF and MI, which was observed for both non–ST‐segment–elevation MI and ST‐segment–elevation MI. Participants with both AF and MI had considerably higher mortality compared with participants with only 1 of the 2 conditions, regardless of order.

Background Aspirin, an effective, low‐cost pharmaceutical, can significantly reduce mortality if used promptly after acute myocardial infarction (AMI). However, many AMI survivors do not receive aspirin within a few hours of symptom onset. Our aim was to quantify the mortality benefit of self‐administering aspirin at chest pain onset, considering the increased risk of bleeding and costs associated with widespread use. Methods and Results We developed a population simulation model to determine the impact of self‐administering 325 mg aspirin within 4 hours of severe chest pain onset. We created a synthetic cohort of adults ≥ 40 years old experiencing severe chest pain using 2019 US population estimates, AMI incidence, and sensitivity/specificity of chest pain for AMI. The number of annual deaths delayed was estimated using evidence from a large, randomized trial. We also estimated the years of life saved (YOLS), costs, and cost per YOLS. Initiating aspirin within 4 hours of severe chest pain onset delayed 13 016 (95% CI, 11 643–14 574) deaths annually, after accounting for deaths due to bleeding (963; 926–1003). This translated to an estimated 166 309 YOLS (149391–185 505) at the cost of $643 235 (633 944–653 010) per year, leading to a cost‐effectiveness ratio of $3.70 (3.32–4.12) per YOLS. Conclusions For

Abstract Aims We aim to characterize the clinical and proteomic profiles of patients at risk of developing heart failure (HF), with and without coronary artery disease (CAD) or prior myocardial infarction (MI). Methods and results HOMAGE evaluated the effect of spironolactone on plasma and serum markers of fibrosis over 9 months of follow‐up in participants with (or at risk of having) CAD, and raised natriuretic peptides. In this post hoc analysis, patients were classified as (i) neither CAD nor MI; (ii) CAD; or (iii) MI. Proteomic between‐group differences were evaluated through logistic regression and narrowed using backward stepwise selection and bootstrapping. Among the 527 participants, 28% had neither CAD or MI, 31% had CAD, and 41% had prior MI. Compared with people with neither CAD nor MI, those with CAD had higher baseline plasma concentrations of matrix metalloproteinase‐7 (MMP‐7), galectin‐4 (GAL4), plasminogen activator inhibitor 1 (PAI‐1), and lower plasma peptidoglycan recognition protein 1 (PGLYRP1), whilst those with a history of MI had higher plasma MMP‐7, neurotrophin‐3 (NT3), pulmonary surfactant‐associated protein D (PSPD), and lower plasma tumour necrosis factor‐related activation‐induced cytokine (TRANCE). Proteomic signatures were similar for patients with CAD or prior MI. Treatment with spironolactone was associated with an increase of MMP7, NT3, and PGLYRP1 at 9 months. Conclusions In patients at risk of developing HF, those with CAD or MI had a different proteomic profile regarding inflammatory, immunological, and collagen catabolic processes.

Abstract Aims The present analysis from the multicentre prospective Altshock‐2 registry aims to better define clinical features, in‐hospital course, and management of cardiogenic shock complicating acutely decompensated heart failure (ADHF‐CS) as compared with that complicating acute myocardial infarction (AMI‐CS). Methods and results All patients with AMI‐CS or ADHF‐CS enrolled in the Altshock‐2 registry between March 2020 and February 2022 were selected. The primary objective was the characterization of ADHF‐CS patients as compared with AMI‐CS. In‐hospital length of stay and mortality were secondary endpoints. One‐hundred‐ninety of the 238 CS patients enrolled in the aforementioned period were considered for the present analysis: 101 AMI‐CS (80% ST‐elevated myocardial infarction and 20% non‐ST‐elevated myocardial infarction) and 89 ADHF‐CS. As compared with AMI‐CS, ADHF‐CS patients were younger [63 (IQR 59–76) vs. 67 (IQR 54–73) years, P = 0.01], but presented with higher creatinine [1.6 (IQR 1.0–2.6) vs. 1.2 (IQR 1.0–1.4) mg/dL, P

Abstract Aims Left ventricular remodelling subsequent to myocardial infarction (MI) constitutes a pivotal underlying cause of heart failure. Intervention with the nontoxic endogenous aryl hydrocarbon receptor (AHR) agonist 2‐(1′H‐indole‐3′‐carbonyl)‐thiazole‐4‐carboxylic acid methyl ester (ITE) in the acute phase of MI has been shown to ameliorate cardiac function, but its role in the chronic phase remains obscured. This study explores the beneficial role of ITE in delaying the progression of heart failure in the chronic phase of MI. Methods and results MI rats established by ligating the left anterior descending coronary artery were treated with the indicated concentration of the AHR agonist ITE or vehicle alone. Echocardiography was performed to determine cardiac structure and function; myocardial morphology and fibrosis were observed by haematoxylin and eosin and Masson's trichrome staining; serum biochemical indices, BNP, and inflammatory cytokine levels were detected by enzyme‐linked immunosorbent assay; F4/80+iNOS+M1 macrophages and F4/80+CD206+M2 macrophages were detected by immunofluorescence; the terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling assay was used to detect the apoptosis of cardiomyocytes; ultrastructural changes in myocardial tissue were observed by transmission electron microscopy; and Cyp1a1, Akt, P‐Akt, p70S6K, P‐p70S6K, Bcl‐2, Bax, caspase‐3, and cleaved caspase‐3 protein levels were determined via Western blotting. We found that therapy with the AHR agonist ITE rescued cardiac remodelling and dysfunction in rats with MI and attenuated myocardial fibrosis, inflammation, and mitochondrial damage. Further studies confirmed that ITE dose‐dependently improved myocardial cell apoptosis after MI, as demonstrated by reduced levels of the apoptosis‐related proteins cleaved caspase‐3 and Bax but increased expression levels of Bcl‐2. These effects were attributed to ITE‐induced activation of AHR receptors, leading to the down‐regulation of Akt and p70S6K phosphorylation. Conclusions The AHR agonist ITE alleviates cardiomyocyte apoptosis through the Akt/p70S6K signalling pathway, thereby rescuing left ventricular adverse remodelling and cardiac dysfunction after MI.

Abstract Aims We aim to explore the role and mechanism of vagus nerve stimulation (VNS) in coronary endothelial cells and angiogenesis in infarcted hearts. Methods and results Seven days after rat myocardial infarction (MI) was prepared by ligation of the left anterior descending coronary artery, the left cervical vagus nerve was treated with electrical stimulation 1 h after intraperitoneal administration of the α7‐nicotinic acetylcholine inhibitor mecamylamine or the mAChR inhibitor atropine or 3 days after local injection of Ad‐shSDF‐1α into the infarcted heart. Cardiac tissue acetylcholine (ACh) and serum ACh, tumour necrosis factor α (TNF‐α), interleukin 1β (IL‐1β) and interleukin 6 (IL‐6) levels were detected by ELISA to determine whether VNS was successful. An inflammatory injury model in human coronary artery endothelial cells (HCAECs) was established by lipopolysaccharide and identified by evaluating TNF‐α, IL‐1β and IL‐6 levels and tube formation. Immunohistochemistry staining was performed to evaluate CD31‐positive vessel density and stromal cell‐derived factor‐l alpha (SDF‐1α) expression in the MI heart in vivo and the expression and distribution of SDF‐1α, C‐X‐C motif chemokine receptor 4 and CXCR7 in HCAECs in vitro. Western blotting was used to detect the levels of SDF‐1α, V‐akt murine thymoma viral oncogene homolog (AKT), phosphorylated AKT (pAKT), specificity protein 1 (Sp1) and phosphorylation of Sp1 in HCAECs. Left ventricular performance, including left ventricular systolic pressure, left ventricular end‐diastolic pressure and rate of the rise and fall of ventricular pressure, should be evaluated 28 days after VNS treatment. VNS was successfully established for MI therapy with decreases in serum TNF‐α, IL‐1β and IL‐6 levels and increases in cardiac tissue and serum ACh levels, leading to increased SDF‐1α expression in coronary endothelial cells of MI hearts, triggering angiogenesis of MI hearts with increased CD31‐positive vessel density, which was abolished by the m/nAChR inhibitors mecamylamine and atropine or knockdown of SDF‐1α by shRNA. ACh promoted SDF‐1α expression and its distribution along with the branch of the formed tube in HCAECs, resulting in an increase in the number of tubes formed in HCAECs. ACh increased the levels of pAKT and phosphorylation of Sp1 in HCAECs, resulting in inducing SDF‐1α expression, and the specific effects could be abolished by mecamylamine, atropine, the PI3K/AKT blocker wortmannin or the Sp1 blocker mithramycin. Functionally, VNS improved left ventricular performance, which could be abolished by Ad‐shSDF‐1α. Conclusions VNS promoted angiogenesis to repair the infarcted heart by inducing SDF‐1α expression and redistribution along new branches during angiogenesis, which was associated with the m/nAChR‐AKT‐Sp1 signalling pathway.

Abstract Cardiac function is under neural regulation; however, brain regions in the cerebral cortex responsible for regulating cardiac function remain elusive. In this study, retrograde trans‐synaptic viral tracing is used from the heart to identify a specific population of the excitatory neurons in the primary motor cortex (M1) that influences cardiac function in mice. Optogenetic activation of M1 glutamatergic neurons increases heart rate, ejection fraction, and blood pressure. By contrast, inhibition of M1 glutamatergic neurons decreased cardiac function and blood pressure as well as tyrosine hydroxylase (TH) expression in the heart. Using viral tracing and optogenetics, the median raphe nucleus (MnR) is identified as one of the key relay brain regions in the circuit from M1 that affect cardiac function. Then, a mouse model of cardiac injury is established caused by myocardial infarction (MI), in which optogenetic activation of M1 glutamatergic neurons impaired cardiac function in MI mice. Moreover, ablation of M1 neurons decreased the levels of norepinephrine and cardiac TH expression, and enhanced cardiac function in MI mice. These findings establish that the M1 neurons involved in the regulation of cardiac function and blood pressure. They also help the understanding of the neural mechanisms underlying cardiovascular regulation.

Background The aim of this study was to investigate temporal trends in survival and subsequent cardiovascular events in a nationwide myocardial infarction population with and without diabetes. Methods and Results Between 2006 and 2020, we identified 2527 individuals with type 1 diabetes, 48 321 individuals with type 2 diabetes and 243 170 individuals without diabetes with first myocardial infarction in national health care registries. Outcomes were trends in all‐cause death after 30 and 365 days, cardiovascular death and major adverse cardiovascular events (ie, nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, and heart failure hospitalization). Pseudo‐observations were used to estimate the mortality risk, with 95% CIs, using linear regression, adjusted for age and sex. Individuals with type 1 diabetes were younger (62±12.2 years) and more often women (43.6%) compared with individuals with type 2 diabetes (75±10.8 years; women, 38.1%), and individuals without diabetes (73±13.2 years; women, 38.4%). Early death decreased in people without diabetes from 23.1% to 17.5%, (annual change −0.48% [95% CI, −0.52% to −0.44%]) and in people with type 2 diabetes from 22.6% to 19.3% (annual change, −0.33% [95% CI, −0.43% to −0.24%]), with no such significant trend in people with type 1 diabetes from 23.8% to 21.7% (annual change, −0.18% [95% CI, −0.53% to 0.17%]). Similar trends were observed with regard to 1‐year death, cardiovascular death, and major adverse cardiovascular events. Conclusions During the past 15 years, the trend in survival and major adverse cardiovascular events in people with first myocardial infarction without diabetes and with type 2 diabetes have improved significantly. In contrast, a similar improvement was not seen in people with type 1 diabetes.

Background The implementation of preventive therapies among patients with stroke remains inadequately explored, especially when compared with patients with myocardial infarction (MI), despite sharing similar vascular risk profiles. We tested the hypothesis that participants with a history of stroke have a worse cardiovascular prevention profile in comparison to participants with MI. Methods and Results In cross‐sectional analyses within the UK Biobank and All of Us Research Program, involving 14 760 (9193 strokes, 5567 MIs) and 7315 (2948 strokes, 4367 MIs) participants, respectively, we evaluated cardiovascular prevention profiles assessing low‐density lipoprotein (

Background The purpose of this study was to investigate a therapeutic approach targeting the inflammatory response and consequent remodeling from ischemic myocardial injury. Methods and Results Coronary thrombus aspirates were collected from patients at the time of ST‐segment–elevation myocardial infarction and subjected to array‐based proteome analysis. Clinically indistinguishable at myocardial infarction (MI), patients were stratified into vulnerable and resilient on the basis of 1‐year left ventricular ejection fraction and death. Network analysis from coronary aspirates revealed prioritization of tumor necrosis factor‐α signaling in patients with worse clinical outcomes. Infliximab, a tumor necrosis factor‐α inhibitor, was infused intravenously at reperfusion in a porcine MI model to assess whether infliximab‐mediated immune modulation impacts post‐MI injury. At 3 days after MI (n=7), infliximab infusion increased proregenerative M2 macrophages in the myocardial border zone as quantified by immunofluorescence (24.1%±23.3% in infliximab versus 9.29%±8.7% in sham; P

Background Cardiac troponins are the preferred biomarkers for the diagnosis of acute myocardial infarction. Although sex‐specific 99th percentile thresholds of troponins are recommended in international guidelines, the clinical effect of their use is poorly investigated. The DANSPOT Study (The Danish Study of Sex‐ and Population‐Specific 99th percentile upper reference limits of Troponin) aims to evaluate the clinical effect of a prospective implementation of population‐ and sex‐specific diagnostic thresholds of troponins into clinical practice. Methods This study is a nationwide, multicenter, stepped‐wedge cluster‐randomized trial of the implementation of population‐ and sex‐specific thresholds of troponins in 22 of 23 clinical centers in Denmark. We established sex‐specific thresholds for 5 different troponin assays based on troponin levels in a healthy Danish reference population. Centers will sequentially cross over from current uniform manufacturer‐derived thresholds to the new population‐ and sex‐specific thresholds. The primary cohort is defined as patients with symptoms suggestive of acute coronary syndrome having at least 1 troponin measurement performed within 24 hours of arrival with a peak troponin value between the current uniform threshold and the new sex‐specific female and male thresholds. The study will compare the occurrence of the primary outcome, defined as a composite of nonfatal myocardial infarction, unplanned revascularization, and all‐cause mortality within 1 year, separately for men and women before and after the implementation of the new sex‐specific thresholds. Conclusions The DANSPOT Study is expected to show the clinical effects on diagnostics, treatment, and clinical outcomes in patients with myocardial infarction of implementing sex‐specific diagnostic thresholds for troponin based on a national Danish reference population. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05336435.

Abstract Background and Aims Fibrotic tissue formed after myocardial infarction (MI) can be as detrimental as MI itself. However, current in vitro cardiac fibrosis models fail to recapitulate the complexities of post‐MI tissue. Moreover, although MI and subsequent fibrosis is most prominent in the aged population, the field suffers from inadequate aged tissue models. Herein, an aged human post‐MI tissue model, representing the native microenvironment weeks after initial infarction, is engineered using three‐dimensional bioprinting via creation of individual bioinks to specifically mimic three distinct regions: remote, border, and scar. Methods The aged post‐MI tissue model is engineered through combination of gelatin methacryloyl, methacrylated hyaluronic acid, aged type I collagen, and photoinitiator at variable concentrations with different cell types, including aged human induced pluripotent stem cell‐derived cardiomyocytes, endothelial cells, cardiac fibroblasts, and cardiac myofibroblasts, by introducing a methodology which utilizes three printheads of the bioprinter to model aged myocardium. Then, using cell‐specific proteins, the cell types that comprised each region are confirmed using immunofluorescence. Next, the beating characteristics are analyzed. Finally, the engineered aged post‐MI tissue model is used as a benchtop platform to assess the therapeutic effects of stem cell‐derived extracellular vesicles on the scar region. Results As a result, high viability (>74%) was observed in each region of the printed model. Constructs demonstrated functional behavior, exhibiting a beating velocity of 6.7 μm/s and a frequency of 0.3 Hz. Finally, the effectiveness of hiPSC‐EV and MSC‐EV treatment was assessed. While hiPSC‐EV treatment showed no significant changes, MSC‐EV treatment notably increased cardiomyocyte beating velocity, frequency, and confluency, suggesting a regenerative potential. Conclusion In conclusion, we envision that our approach of modeling post‐MI aged myocardium utilizing three printheads of the bioprinter may be utilized for various applications in aged cardiac microenvironment modeling and testing novel therapeutics.

Key Clinical Message In acute thrombotic thrombocytopenic purpura (TTP), apart from urgent treatment, assessing the patient's medical history, especially conditions like systemic lupus erythematosus that could trigger TTP, is crucial. Rarely, TTP patients may experience cardiac conditions as severe as a myocardial infarction. Abstract A 45‐year‐old woman manifested severe and acute thrombotic thrombocytopenic purpura (TTP) of unknown origin. The patient's symptoms, the laboratory data, the detection of the reduction in ADAMTS13 activity, and the presence of schistocytes on the peripheral smear confirmed the diagnosis. The patient was then planned for therapeutic plasma exchange (TPE). Prior to the scheduled TPE, she suddenly experienced extreme shortness of breath and chest pain. An electrocardiogram was obtained immediately after reporting signs of an inferior myocardial infarction. Further examinations to acquire information about the patient's underlying medical conditions in order to study the secondary causes of TTP, combined with the results of the laboratory tests, resulted in the patient being diagnosed with systemic lupus erythematosus.

Background Increasing evidence suggests a higher propensity for acute myocardial infarction (MI) in patients with psoriasis. However, the shared mechanisms underlying this comorbidity in these patients remain unclear. This study aimed to explore the shared genetic features of psoriasis and MI and to identify potential biomarkers indicating their coexistence. Methods and Results Data sets obtained from the gene expression omnibus were examined using a weighted gene coexpression network analysis approach. Hub genes were identified using coexpression modules and validated in other data sets and through in vitro cellular experiments. Bioinformatics tools, including the Human microRNA Disease Database, StarBase, and miRNet databases, were used to construct a ceRNA network and predict potential regulatory mechanisms. By applying weighted gene coexpression network analysis, we identified 2 distinct modules that were significant for both MI and psoriasis. Inflammatory and immune pathways were highlighted by gene ontology enrichment analysis of the overlapping genes. Three pivotal genes—Src homology and collagen 1, disruptor of telomeric silencing 1‐like, and feline leukemia virus subgroup C cellular receptor family member 2—were identified as potential biomarkers. We constructed a ceRNA network that suggested the upstream regulatory roles of these genes in the coexistence of psoriasis and MI. Conclusions As potential therapeutic targets, Src homology and collagen 1, feline leukemia virus subgroup C cellular receptor family member 2, and disruptor of telomeric silencing 1‐like provide novel insights into the shared genetic features between psoriasis and MI. This study paves the way for future studies focusing on the prevention of MI in patients with psoriasis.

Abstract Background and Aim Myocardial infarction is a common cause of hospitalization, and nutritional behaviors are risk factors in such patients. The present study aimed to determine the effect of education based on the health belief model on nutritional behavior and indices in patients with myocardial infarction. Methods The present experimental study examined patients with myocardial infarction in 2021. Seventy‐two patients with myocardial infarction were randomly divided into intervention and control groups. The intervention group received educational interventions based on the health belief model in four 60‐min sessions for 3 months. The constructs of the health belief model, nutritional behavior, and indices were measured using a valid questionnaire before, 1, and 3 months after the intervention. At the end, the study data was analyzed using SPSS version 22 software. Results There was a significant difference between the two groups in the mean scores of knowledge, perceived susceptibility, perceived severity, perceived benefits, self‐efficacy, nutritional behaviors, and body mass index after the intervention (p 0.05). Biochemical factors also had a significant difference after the intervention (p