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Myocardial infarction (MI) is a cardiovascular disease with high morbidity and mortality. Clinically, rehabilitation after massive MI often has a poor prognosis. Therefore, it is necessary to explore the therapeutic methods of myocardial protection after MI. As a first-line treatment for type 2 diabetes, metformin has been found to have a certain protective effect on myocardial tissue. However, its pharmacological mechanism remains unclear. In this study, we investigated key factors that reduced MI with metformin. Through in vivo, in vitro, and in silico analyses, we identified HSF1 as a key target for metformin. HSF1 could up-regulate the transcriptional level of AMPKα2 through transcriptional activation and stimulate the activity of the downstream AMPK/mTOR signaling pathway. Metformin stimulated cardiomyocytes to form stress granules (SGs), and knockdown of HSF1 reversed this process. Furthermore, HSF1 exhibited better in vitro affinity for metformin than AMPK, suggesting that HSF1 may be a more sensitive target for metformin.

Extracellular vesicles (EVs) generated from mesenchymal stem cells (MSCs) play an essential role in modulating cell—cell communication and tissue regeneration. The clinical translation of EVs is constrained by the poor yield of EVs. Extrusion has recently become an effective technique for producing a large scale of nanovesicles (NVs). In this study, we systematically compared MSC NVs (from extrusion) and EVs (from natural secretion). Proteomics and RNA sequencing data revealed that NVs resemble MSCs more closely than EVs. Additionally, microRNAs in NVs are related to cardiac repair, fibrosis repression, and angiogenesis. Lastly, intravenous delivery of MSC NVs improved heart repair and cardiac function in a mouse model of myocardial infarction. [ABSTRACT FROM AUTHOR]

Introduction: Myocardial infarction (MI), the end outcome of coronary artery disease (CAD), continues to be a major cause of mortality and morbidity worldwide. Over the past 50 years, it has been abundantly obvious that the series of thrombotic events that occur after an atherosclerotic plaque rupture obstructs the coronary artery, cutting off the oxygen and blood supply to the myocardial and leading to infarction. Aims: To assess the relationship between Nterminal pro-Brain natriuretic peptide levels on admission in ST elevation myocardial infarction (STEMI) and its short term complications, to determine the value of NT-pro-BNP in predicting short term outcome in patients with STEMI and compare the effectiveness of NT-pro BNP with cardiac troponin T and left ventricular ejection fraction in predicting the short term outcomes in STEMI. Materials and method: The present study was a cross-sectional study. This study was conducted from April 2021 to November 2022in Patna Medical College and Hospital, Patna were included as cases. Total 40 patients were included in this study. Result: Out of the 40 patients studied, 45 % of the patients had ALWMI, 15 % had ASMI, 32. 5 % with IWMI and 7. 5% with IWMI+RWMI. 23 (57. 5%) were smokers. The relation between smoking and NT-pro BNP was not statistically significant. NT- pro BNP levels in the full cohort ranged from 246 to 3000 pg/ml. The mean levels were 1585. 65± 999 .133 pg/ml with the median NT- pro BNP as 1483 .50 pg/ml. There was a significantly higher incidence of arrhyhmias (p - 0.001), cardiac failure (p- 0.043), lower ejection fraction (p-< 0.020) and deaths (p-0.024) in the group who had above median NTpro- BNP values. All 13 patients who had complications belonged to the above median NT pro BNP group. (p- <0.0001). The relation between the cardiac troponin T values, NT- pro BNP values, complications and deaths were not statistically significant. There was no statistical significance in the relation between LVEF < 50 % and the occurrence of complications, deaths. However there was strong correlation between LVEF < 50 % and NT- pro BNP above the median. (p - 0.020). Conclusion: NT-pro BNP is a superior short term prognostic indicator than cardiac troponin T and LVEF. It is a valuable tool for risk stratifying acute MI patients so that suitable treatment options may be developed and NT-pro BNP is a powerful predictor of short term prognosis in AMI, including mortality. [ABSTRACT FROM AUTHOR]

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Abstract Background Myocardial infarction (MI) is characterized by coronary artery occlusion, ischemia and hypoxia of myocardial cells, leading to irreversible myocardial damage. Therefore, it is urgent to explore the potential mechanism of myocardial injury during the MI process to develop effective therapies for myocardial cell rescue. Methods We downloaded the GSE71906 dataset from GEO DataSets, and the R software was used to identify the differentially expressed genes (DEGs) in mouse heart tissues of MI and sham controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed to understand the significantly activated signaling pathways in MI. Protein–protein interaction (PPI) network was constructed to highlight the hub genes in DEGs. The Western Blot, qRT-PCR and TUNEL staining were used to explore the function of hub gene in hypoxia-induced cardiomyocytes in vitro. Results A total of 235 DEGs were identified in GSE71906 dataset. Functional enrichment analysis revealed that the upregulated genes were primarily associated with the inflammatory response and apoptosis. 20 hub genes were identified in PPI network, and the early growth response 2 (EGR2) was highlighted. In vitro. We confirmed the EGR2 was upregulated induced by hypoxia and revealed the upregulated EGR2 aggravates pro-inflammation and pro-apoptotic genes expression. In addition, EGR2 knockout mitigates hypoxia-induced inflammation and apoptosis in cardiomyocytes. Conclusion The present study identified the EGR2 was a hub gene in myocardial damage during MI process, the excessive EGR2 aggravates hypoxia-induced myocardial damage by accelerating inflammation and apoptosis in vitro. Therefore, targeting EGR2 offers a potential pharmacological strategy for myocardial cell rescue in MI.

Therapeutic and/or preventive interventions using phytochemical constituents for ischemic heart disease have gained considerable attention worldwide, mainly due to their antioxidant activity. This study investigated the cardioprotective effect and possible mechanism of juglone, a major constituent of the walnut tree, using an isoproterenol (ISO)-induced myocardial infarction (MI) model in rats. Rats were pretreated for five (5) days with juglone (1, 3 mg/kg, i.p) and atenolol (1 mg/kg, i.p) in separate experiments before inducing myocardial injury by administration of ISO (80 mg/kg, s.c) at an interval of 24 h for 2 consecutive days (4th and 5th day). The cardioprotective effect of juglone was confirmed through a lead II electrocardiograph (ECG), cardiac biomarkers (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological study. The results of our present study suggest that prior administration of juglone (1 and 3 mg/kg) proved to be effective as a cardioprotective therapeutic agent in reducing the extent of myocardial damage (induced by ISO) by fortifying the myocardial cell membrane, preventing elevated T-waves, deep Q-waves in the ECG, heart to body weight ratio, infarction and also by normalizing cardiac marker enzymes (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological changes, such as inflammation, edema and necrosis. In conclusion, this study has identified phytochemical constituents, in particular juglone, as a potential cardioprotective agent.

Myocardial infarction (MI) is one of the most severe cardiovascular diseases (CVD). Traditional Chinese medicines have unique advantages in the treatment of CVD, with Xin-Ke-Shu (XKS) being a commonly used Chinese patent medicine for the prevention and treatment of MI patients. This study aimed to investigate the dynamic metabolic profiles of plasma and urine in left anterior descending coronary artery ligation (LAD) -induced MI rats at days 3, 12, and 21 after surgery, and to evaluate the regulatory effects of XKS at these time points using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) metabolomics. The metabolic profiles of plasma and urine in the LAD-induced MI rats showed significant variations at days 3, 12, and 21 after MI. We identified a total of 23 plasma metabolites and 12 urine metabolites as potential pathological markers related to MI progression. These metabolites were mainly involved in pathways such as TCA cycle, arachidonic acid metabolism, glutathione metabolism, glycerophospholipid metabolism, sphingolipid metabolism, and fatty acid metabolism, all of which were associated with imbalance of myocardial energy metabolism, oxidative stress, and calcium overload. Disturbances in the TCA cycle, arachidonic acid metabolism, glutathione metabolism, and purine metabolism in plasma and urine were observed as early as day 3 after MI. By day 12, we noted significant changes in fatty acid metabolism in plasma and urine, along with notable alterations in sphingolipid metabolism in plasma. Disorders in plasma glycerophospholipid metabolism were first evident at day 12 and reached their peak severity by day 21. Treatments with XKS significantly regulated the disturbances in the plasma and urine metabolic profiles of MI rats at days 3, 12, and 21, with medium dose of XKS displaying a particularly strong regulatory effect, especially at day 12. Our study demonstrates that host metabolism undergoes dynamical changes following MI with most metabolic disorders manifesting in the early stage of MI. XKS effectively regulates nearly all of these disturbances and can be administered as soon as possible after MI. These findings provide valuable insights into the metabolic progression of MI and highlight the therapeutic potential of XKS in the treatment of MI. [Display omitted] • Plasma and urine metabolic profiles in MI rats show different on days 3, 12 and 21. • TCA cycle and arachidonic acid metabolism in MI rats were disturbed earlier (day 3). • Fatty acid and lipid metabolisms in MI rats were disturbed later (day 12). • XKS dynamically regulated the metabolic disturbances in different stages of MI. [ABSTRACT FROM AUTHOR]

Adverse LV remodeling post–ST-segment elevation myocardial infarction (STEMI) is associated with a poor prognosis, but the underlying mechanisms are not fully understood. Diffusion tensor (DT)-cardiac magnetic resonance (CMR) allows in vivo characterization of myocardial architecture and provides unique mechanistic insight into pathophysiologic changes following myocardial infarction. This study evaluated the potential associations between DT-CMR performed soon after STEMI and long-term adverse left ventricular (LV) remodeling following STEMI. A total of 100 patients with STEMI underwent CMR at 5 days and 12 months post-reperfusion. The protocol included DT-CMR for assessing fractional anisotropy (FA), secondary eigenvector angle (E2A) and helix angle (HA), cine imaging for assessing LV volumes, and late gadolinium enhancement for calculating infarct and microvascular obstruction size. Adverse remodeling was defined as a 20% increase in LV end-diastolic volume at 12 months. A total of 32 patients experienced adverse remodeling at 12 months. Compared with patients without adverse remodeling, they had lower FA (0.23 ± 0.03 vs 0.27 ± 0.04; P < 0.001), lower E2A (37 ± 6° vs 51 ± 7°; P < 0.001), and, on HA maps, a lower proportion of myocytes with right-handed orientation (RHM) (8% ± 5% vs 17% ± 9%; P < 0.001) in their acutely infarcted myocardium. On multivariable logistic regression analysis, infarct FA (odds ratio [OR]: <0.01; P = 0.014) and E2A (OR: 0.77; P = 0.001) were independent predictors of adverse LV remodeling after adjusting for left ventricular ejection fraction (LVEF) and infarct size. There were no significant changes in infarct FA, E2A, or RHM between the 2 scans. Extensive cardiomyocyte disorganization (evidenced by low FA), acute loss of sheetlet angularity (evidenced by low E2A), and a greater loss of organization among cardiomyocytes with RHM, corresponding to the subendocardium, can be detected within 5 days post-STEMI. These changes persist post-injury, and low FA and E2A are independently associated with long-term adverse remodeling. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Electrical storm (ES) is a heterogeneous clinical emergency that can present with malignant ventricular arrhythmias such as ventricular fibrillation (VF), ventricular tachycardia (VT), requiring the need for cardiac defibrillation. ES is a life-threatening condition with a high mortality rate. Successfully managing ES in the setting of acute myocardial infarction (MI) is expected to be known by physicians on call to reduce in-hospital mortality. Case presentation: A 57-year-old man presenting with acute onset chest pain was found to have an infero-posterior ST-segment elevation myocardial infarction (STEMI) complicated by acute right ventricular MI secondary to total occlusion of the proximal right coronary artery (RCA). The patient developed ES in the form of recurrent VF that was managed successfully with electrical defibrillation, antiarrhythmic therapy with amiodarone and esmolol, endotracheal intubation, sedation, electrolyte replacement, volume resuscitation, comfort care, psychological intervention, and percutaneous coronary intervention (PCI) of the occluded epicardial artery. With these interventions used in quick succession and with the aspiration of a massive RCA thrombus, the patient was reversed to hemodynamic stability, did not have further episodes of VF, and survived the index hospitalization. Conclusion: ES is a rare but fatal complication of acute MI. Residents on night shifts should be better prepared and equipped to deal with this rare condition. We hope our successful experience can benefit physicians on call who take care of acute MI patients that deteriorate with ES. [ABSTRACT FROM AUTHOR]

Background: CAD is leading cause of Morbidity and Mortality in men and women. Various risk factors involved include hardening of coronary arteries, reduced blood flow, hypertension, smoking, deranged lipid profile, obesity, diabetes and stress. However, current research reveals that atherosclerosis is an inflammatory disease and not a simply due to accumulation of lipids in coronary arteries. Therefore, recent research in the developed countries is focused on new biochemical and inflammatory markers. Material and Methods: This is a case control study. The study was carried out at Department of Biochemistry, in collaboration with Dept. of Medicine Lady Hardinge Medical College & Dept. of Cardiology at G.B Pant Hospital. The study population consisted of 100 consecutive patients above 35 years of age with documented stable coronary artery disease. Control group consisted of 100 subjects age and sex matched with no clinical or ECG evidence of Coronary Artery Disease. Plasma levels of hsCRP interleukin-2, interleukin-6 were assayed by ELISA. Serum glucose, cholesterol, triacylglycerol, urea and creatinine were measured by using standard kits on fully automated auto analyzer. Multivariate analysis was performed to evaluate the associations between blood pressure and circulating levels of IL-2 and IL-6. Results: We compared the values of serum hsCRP, IL-6, IL-2, cholesterol and triacylglycerol of group B with control group-A and significance difference was found with p value < 0.001. Conclusion: Raised levels of hs C-reactive protein interleukin-2 and interleukin-6 may have a role in the development of coronary artery disease and can be makers for CAD. [ABSTRACT FROM AUTHOR]

The diagnosis and management of myocardial infarction with non-obstructive coronary arteries (MINOCA) presents a formidable challenge to clinicians due to its multifaceted etiologies and underlying pathophysiological mechanisms. Etiologies encompass a spectrum including myopericarditis, coronary vasospasm, microvascular diseases, coronary artery embolism, and takotsubo syndrome, among others. Despite its clinical significance, leading medical organizations need more consensus guidelines delineating the optimal approach to MINOCA diagnosis, treatment, and follow-up. In this case report, we elucidate a complex case of a 65-year-old male devoid of significant cardiovascular history who presented with characteristic chest pain, ST-segment elevation on electrocardiography, and markedly elevated troponin levels. Coronary angiography revealed non-obstructive coronary vessels, posing a diagnostic conundrum. Subsequent literature reviews of advanced imaging modalities such as cardiac magnetic resonance imaging (MRI) and coronary angiography with cardiac biopsy were noted to be pivotal in elucidating the specific etiology of MINOCA, which otherwise posed a diagnostic challenge. Ultimately, the patient was diagnosed with MINOCA secondary to myopericarditis, underscoring the importance of a comprehensive diagnostic approach in such cases. This case underscores the critical role of advanced imaging techniques in delineating the underlying pathology of MINOCA and emphasizes the necessity for individualized management strategies tailored to the specific etiology. Furthermore, we discuss potential strategies for optimizing the diagnostic workup and discharge planning following coronary angiography in patients with MINOCA., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Edpuganti et al.)

The rising incidences of myocardial infarction (MI), often affecting individuals without traditional risk factors, highlight the urgent need for improved early detection using personal health data. However, health surveys and electronic health records (EHRs) frequently suffer from class imbalances, leading to prediction biases and differences between specificity and sensitivity, which hinder reliable model development despite the valuable insights contained in these datasets. To address this, we have introduced a novel approach to enhance MI risk prediction using self-reported attributes from the Behavioral Risk Factor Surveillance System (BRFSS) and the National Health Interview Survey (NHIS) dataset. Our approach incorporates three innovative techniques: the Dual-Path Artificial Neural Network (DP-ANN) to mitigate biased decision making across imbalanced datasets, the Triple Criteria Selection (TCS) for unbiased feature selection, and Minority Weighted Sampling (MWS) to tackle challenges of uncontrolled minority class sampling. These methods collectively enhance MI prediction and feature relevance. The DP-ANN model has achieved balanced performance, with an average specificity of 80%, sensitivity of 82%, and AUC-ROC of 89.5%, improving imbalance variance by approximately 14.96% compared to prior studies. By outperforming other models across four heavily imbalanced datasets, our approach demonstrates robustness and generalizability. Additionally, SHapley Additive exPlanations (SHAP) analysis has revealed key predictors and risk factors for MI, such as coronary heart disease and bronchitis in females, and stroke among individuals aged 35-54. In conclusion, our study provides a robust model for healthcare professionals to assess MI risk through targeted factors, promoting early detection and potentially improving patient outcomes., Competing Interests: Declaration of competing interest No members of our team have any conflicts of interest related to this project., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Abstract Biological processes involving environmental and genetic factors drive the interplay between age- and sex-regulating lipid profile. The relation between variations in the LPA gene with increasing the risk of coronary heart disease is dependent on population differences, sex, and age. The present study tried to do a gene candidate association analysis in people with myocardial infarction (MI) in a 22 year cohort family-based longitudinal cohort study, Tehran Cardiometabolic Genetic Study (TCGS). After adjusting p value by the FDR method, only the association of rs6415084 with the MI probability and the age-of-CHD-onset was significant in males in their middle age (p

Background and Aims: Observational studies have indicated that sedentary behavior is associated with myocardial infarction (MI), heart failure (HF), and atrial fibrillation (AF). Nevertheless, whether these associations are causal remain controversial, due to confounding factors (e.g., physical activity) and reverse causality.Methods and Results: Instrumental variables were obtained from the largest genome-wide association studies of sedentary behavior (408,815 individuals) to date. We obtained summary statistics of MI from the CARDIoGRAMplusC4D consortium (171,875 individuals), HF from the HERMES Consortium (977,323 individuals), and AF from the Atrial Fibrillation Consortium (588,190 individuals). The inverse-variance weighted method was applied to obtain Mendelian randomization (MR) estimates, and other statistical methods were conducted in the sensitivity analyses. The main analyses were repeated using data from the FinnGen study. Multivariable MR analysis and mediation analysis were performed to evaluate the role of physical activity and other confounders. Genetically determined television watching was associated with MI (odds ratio [OR], 1.38; 95% CI, 1.19-1.59; p = 1.9 × 10-5) and HF (OR, 1.23; 95%CI, 1.09-1.38; p = 7.0 × 10-4) but not AF. The main results kept robust in most sensitivity analyses. The effect of sedentary behavior on MI and HF was partly mediated by body mass index (BMI). No consistent evidence was found for the causal effect of computer use and driving on MI, HF, or AF.Conclusions: Genetic liability to prolonged television watching is associated with higher risks of MI and HF. Interventions for reducing television watching time, such as public education and awareness campaigns, should be further investigated. [ABSTRACT FROM AUTHOR]

Abstract Background Exosomes are considered a substitute for stem cell-based therapy for myocardial infarction (MI). FNDC5, a transmembrane protein located in the cytoplasm, plays a crucial role in inflammation diseases and MI repair. Furthermore, our previous study found that FNDC5 pre-conditioning bone marrow-derived mesenchymal stem cells (BMMSCs) could secrete more exosomes, but little was known on MI repair. Methods Exosomes isolated from BMMSCs with or without FNDC5-OV were injected into infarcted hearts. Then, cardiomyocytes apoptosis and inflammation responses were detected. Furthermore, exosomes were administrated to RAW264.7 macrophage with LPS treatment to investigate its effect on inflammation and macrophage polarization. Results Compared with MSCs-Exo, FNDC5-MSCs-Exo had superior therapeutic effects on anti-inflammation and anti-apoptosis, as well as polarizing M2 macrophage in vivo. Meanwhile, the in vitro results also showed that FNDC5-MSCs-Exo decreased pro-inflammatory secretion and increased anti-inflammatory secretion under LPS stimulation, which partly depressed NF‐κB signaling pathway and upregulated Nrf2/HO-1 Axis. Conclusions FNDC5-BMMSCs-derived exosomes play anti-inflammation effects and promote M2 macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 Axis, which may develop a promising cell-free therapy for MI.

The no reflow phenomenon is a feared complication in Percutaneous Coronary Intervention (PCI) procedures including elective as well as primary PCI (Percutaneous Coronary Intervention), and results in worse prognosis. A number of etiological factors are involved in pathogenesis of no reflow phenomenon. These include distal athero embolization, ischemic and reperfusion injury, microvascular spasm and endothelial dysfunction. The treatment of no reflow depends on underlying mechanism and includes pharmacological as well as non-pharmacological interventions. Pharmacological agents include vasodilators like adenosine, sodium nitroprusside, verapamil, in addition to adrenaline (intracoronary) and, GpIIa/IIIb inhibitors. Non pharmacological measures include mechanical thrombus aspiration. Among pharmacological agents, Verapamil is usually the least preferred agent because of its negative ionotropic effect. Here, we describe a case of refractory no reflow in a patient undergoing primary PCI to right coronary artery (RCA), which was treated with a no. of pharmacological agents as well as aspiration thrombectomy but without much success and finally responded to intracoronary verapamil.

As a vital adipokine, Adipsin is closely associated with cardiovascular risks. Nevertheless, its role in the onset and development of cardiovascular diseases remains elusive. This study was designed to examine the effect of Adipsin on survival, cardiac dysfunction and adverse remodeling in the face of myocardial infarction (MI) injury. In vitro experiments were conducted to evaluate the effects of Adipsin on cardiomyocyte function in the face of hypoxic challenge and the mechanisms involved. Our results showed that Adipsin dramatically altered expression of proteins associated with iron metabolism and ferroptosis. In vivo results demonstrated that Adipsin upregulated levels of Ferritin Heavy Chain (FTH) while downregulating that of Transferrin Receptor (TFRC) in peri-infarct regions 1 month following MI. Adipsin also relieved post-MI-associated lipid oxidative stress as evidenced by decreased expression of COX2 and increased GPX4 level. Co-immunoprecipitation and immunofluorescence imaging prove a direct interaction between Adipsin and IRP2. As expected, cardioprotection provided by Adipsin depends on the key molecule of IRP2. These findings revealed that Adipsin could be efficiently delivered to the heart by exosomes derived from pericardial adipose tissues. In addition, Adipsin interacted with IRP2 to protect cardiomyocytes against ferroptosis and maintain iron homeostasis. Therefore, Adipsin-overexpressed exosomes derived from pericardial adipose tissues may be a promising therapeutic strategy to prevent adverse cardiac remodeling following ischemic heart injury.

Objective: Several microRNA (miRNA) polymorphisms have been associated with susceptibility to specific health disorders, including cardiovascular diseases. The aim of the present study was to investigate whether four well-studied miRNA polymorphisms in non-Caucasian populations, namely miR146a G>C (rs2910164), miR149 C>T (rs2292832), miR196a2 C>T (rs11614913) and miR499 A>G (rs3746444), contribute to the risk for the development of premature Coronary Artery Disease (CAD) in the Greek population. Methods: We used a case-control study to examine these associations in 400 individuals: 200 CAD patients [including a subgroup of myocardial infraction (MI) patients] and 200 healthy controls, all of Greek origin. MiRNA polymorphisms were genotyped using three different assays: Polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP), High resolution Melting (HRM) and Sanger sequencing. Results: Two of these polymorphisms, miR196a2 C>T (rs11614913) and miR499 A>G (rs3746444) were found to be strongly associated with increased risk for CAD (p=0.0388 and p=0.0013, respectively) and for MI (p=0.0281 and p=0.0273, respectively). Furthermore, miR146C-miR149C-miR196T-miR499G allele combination appeared to be significantly related to CAD (p=0.0185) and MI (p=0.0337) prevalence. Conclusions: Our results suggest that at least two of the studied polymorphisms, miR196a2 C>T (rs11614913) and miR499 A>G (rs3746444), as well as the miR146C-miR149C-miR196T-miR499G allele combination could represent useful biomarkers of CAD and/or MI susceptibility in the Greek population. These special genetic characteristics, in combination with environmental factors and personal habits, might contribute to CAD and/or MI prevalence.

Myocardial infarction (MI) is a prevalent and life-threatening cardiovascular ailment, diagnosed primarily through the twelve-lead electrocardiogram (ECG). These leads provide unique insights into electrical activity across diverse heart regions, crucial for MI differentiation and assessment. However, prior studies predominantly focus on single-perspective 12-lead ECG analysis, overlooking inter-lead disparities. Moreover, prevailing methods often lack versatility, being tailored to specific tasks. Therefore, this paper presents the Multi-Task Multi-View Knowledge Distillation Framework (MT-MV-KDF) for MI detection and localization. The framework combines multi-view learning, multi-task learning, and knowledge distillation to enhance model performance and efficiency. Specifically, The introduction of multi-view learning aims to learn ECG feature representations from different views. Additionally, multi-task learning enables the model to learn the similarities and differences of multiple related tasks simultaneously. Finally, knowledge distillation is used to transfer latent knowledge from the complex teacher model to the simpler student model to improve efficiency. The MT-MV-KDF consists of MT-MVT-net and MT-SVS-net, which use a multi-layer CNN architecture to extract ECG different scale features. An attention module is used to capture inter-channel information and spatial cues. Through knowledge distillation, the MT-DSVS-net (0.40M) inherits insights from MT-MVT-net while achieving comparable performance with fewer parameters. Evaluation on the PTB-XL database demonstrates MT-DSVS-net has an A c c , A U C of 93.78% and 92.23% for MI detection and 83.45% and 78.26% for MI localization, respectively. Additionally, Robustness validation on CPSC2018 and Chapman datasets further confirms the efficacy of MT-MV-KDF. This study highlights the MT-MV-KDF effectiveness in MI detection and localization, particularly in improving inter-patient MI localization. • MT-MV-KDF integrates multi-task learning and multi-view learning, and knowledge distillation. • Proposed lightweight network, MT-DSVS-net, transfers knowledge from MT-MVT-net to MT-SVS-net. • MT-DSVS-net (0.40M params) excels in inter-patient experiments across 3 DBs, outperforming SOTA. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarction (MI) is characterized by coronary artery occlusion, ischemia and hypoxia of myocardial cells, leading to irreversible myocardial damage. Therefore, it is urgent to explore the potential mechanism of myocardial injury during the MI process to develop effective therapies for myocardial cell rescue.Methods: We downloaded the GSE71906 dataset from GEO DataSets, and the R software was used to identify the differentially expressed genes (DEGs) in mouse heart tissues of MI and sham controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed to understand the significantly activated signaling pathways in MI. Protein-protein interaction (PPI) network was constructed to highlight the hub genes in DEGs. The Western Blot, qRT-PCR and TUNEL staining were used to explore the function of hub gene in hypoxia-induced cardiomyocytes in vitro.Results: A total of 235 DEGs were identified in GSE71906 dataset. Functional enrichment analysis revealed that the upregulated genes were primarily associated with the inflammatory response and apoptosis. 20 hub genes were identified in PPI network, and the early growth response 2 (EGR2) was highlighted. In vitro. We confirmed the EGR2 was upregulated induced by hypoxia and revealed the upregulated EGR2 aggravates pro-inflammation and pro-apoptotic genes expression. In addition, EGR2 knockout mitigates hypoxia-induced inflammation and apoptosis in cardiomyocytes.Conclusion: The present study identified the EGR2 was a hub gene in myocardial damage during MI process, the excessive EGR2 aggravates hypoxia-induced myocardial damage by accelerating inflammation and apoptosis in vitro. Therefore, targeting EGR2 offers a potential pharmacological strategy for myocardial cell rescue in MI. [ABSTRACT FROM AUTHOR]

ELECTROCARDIOGRAM (ECG) signals are reliable in identifying and monitoring patients with various cardiac diseases and severe cardiovascular syndromes, including arrhythmia and myocardial infarction (MI). Thus, cardiologists use ECG signals in diagnosing cardiac diseases. Machine learning (ML) has also proven its usefulness in the medical field and in signal classification. However, current ML approaches rely on hand-crafted feature extraction methods or very complicated deep learning networks. This paper presents a novel method for feature extraction from ECG signals and ECG classification using a convolutional neural network (CNN) with eXtreme Gradient Boosting (XBoost), ConvXGB. This model was established by stacking two convolutional layers for automatic feature extraction from ECG signals, followed by XGBoost as the last layer, which is used for classification. This technique simplified ECG classification in comparison to other methods by minimizing the number of required parameters and eliminating the need for weight readjustment throughout the backpropagation phase. Furthermore, experiments on two famous ECG datasets–the Massachusetts Institute of Technology–Beth Israel Hospital (MIT-BIH) and Physikalisch-Technische Bundesanstalt (PTB) datasets–demonstrated that this technique handled the ECG signal classification issue better than either CNN or XGBoost alone. In addition, a comparison showed that this model outperformed state-of-the-art models, with scores of 0.9938, 0.9839, 0.9836, 0.9837, and 0.9911 for accuracy, precision, recall, F1-score, and specificity, respectively. [ABSTRACT FROM AUTHOR]

Detection of abnormality in heart is of major importance for early and appropriate clinical medication. In this work, we have proposed two models for detection of abnormality in ECG signals. The normal ECG signals are closely repetitive in nature to a large extent, whereas ECG signals with abnormalities tend to differ from cycle to cycle. Hence, repetitive plot like the Poincare is efficient to detect such nonrepetitiveness of the signal; thereby, indicating abnormalities. Hence, we have used Poincare plot to develop the two proposed models. One of the models uses direct analysis of the binary image of the plot to detect the difference in retracing, between the healthy and unhealthy samples. The other model uses entropy of the Poincare plot to detect the difference in randomness of plots between the two classes. Most importantly, only lead II ECG signal is used here for analysis. This ensures ease of computation as it uses signal of only a single lead instead of the 12 leads of the complete ECG signal. We have validated the proposed models using ECG signals from the 'ptb database'. We have observed that the entropy analysis of the Poincare plots gives the best results with 90% accuracy of abnormality detection. This high accuracy of classification, combined with less computational burden enables its practical implementation for the development of a reallife abnormality detection scheme. [ABSTRACT FROM AUTHOR]

Objectives: This study belongs to the overview of three versatile cardiac biomarkers for specific diagnosis and prognosis in cardiac patients. Methods: A search performed in different search sites such as Web of Science, Pub Med, and Google scholar searches for relevant studies from 2015 to 2022. Search names included were "heart disease," "cardiac troponin," "acute coronary disease," "coronary artery disease," "new biomarker," "non-STelevation acute coronary syndrome," etc. Studies were included if they were prospective, retrospective, randomized controlled trials or reviews. Findings: Troponin I &T along with CPK-MB can increase the diagnostic sensitivity and specificity when used collectively in the diagnosis of Myocardial infarction either acute or chronic conditions. These cardiac versatile biomarkers can diagnose re-infarct also with serial testing. Whereas sensitivity and specificity of Troponins I &T ranges from 84 to 96 and 80 to 95% respectively. When all three cardiac markers were combined, sensitivity and specificity will reach up to approximately 100%. Novelty/Improvement: This article provides the best available three versatile specific cardiac biomarkers in the diagnosis of myocardial infarction and reinfarction with about 100% accuracy. [ABSTRACT FROM AUTHOR]

Bergenin is a phenolic glycoside that has been reported to occur naturally in several plant species, reported as a cardioprotective. However, bergenin, one of the important phytochemicals in these plants, is still not reported as a cardioprotective. The present study was designed to investigate the cardioprotective effects of bergenin on isoproterenol-induced myocardial infarction in rats. Bergenin and atenolol were administered through intraperitoneal (i.p.) injection to Sprague Dawley (SD) rats in separate experiments for five (5) days. At the end of this period, rats were administered isoproterenol (80 mg/kg s.c.) to induce myocardial injury. After induction, rats were anaesthetized to record lead II ECG, then sacrificed, blood was collected to analyze cardiac marker enzymes, and a histopathological study of the heart tissues was also performed. Pretreatment with bergenin showed a significant decrease in ST-segment elevation, deep Q-wave, infarct size, and also normalized cardiac marker enzymes (cTnI, CPK, CK-MB, LDH, ALT, and AST), particularly at 3 mg/kg, as compared to isoproterenol treated group. Our findings revealed, for the first time, the use of glycoside bergenin as a potential cardioprotective agent against the isoproterenol-induced MI in rats. [ABSTRACT FROM AUTHOR]

Yanan Zhang,1,2 Xiajing Chen,1,2 Lingjuan Liu,1,2 Jie Tian,1,2 Lan Hao,3 Hai-tao Ran3 1Department of Cardiology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China; 2Chongqing Key Laboratory of Pediatrics, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China; 3Chongqing Key Laboratory of Ultrasound Molecular Imaging & Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of ChinaCorrespondence: Jie TianDepartment of Cardiology, Children’s Hospital of Chongqing Medical University, 136 Zhongshan Er Road, Yu Zhong District, Chongqing, 400014, People’s Republic of ChinaTel +86 23 68486767Fax +86 23 68485111Email jietian@cqmu.edu.cnBackground and Purpose: Myocardial infarction (MI) is a serious threat to public health. The early identification of MI is important to promote appropriate treatment strategies for patients. Recently, strategies targeting extracellular matrix (ECM) components have gained attention. Fibrin is an ECM protein involved after MI. In this work, we constructed fibrin-targeted nanoparticles (NPs) by co-assembling a fibrin-targeted peptide (CREKA) and indocyanine green (ICG) and used them to enhance photoacoustic (PA) imaging for noninvasive detection of the infarct region to help diagnose MI.Methods: ICG NPs modified with CREKA were prepared (CREKA-ICG-LIP NPs). Then, the fundamental characteristics, stability, safety, and targeting ability of the NPs were detected. Finally, in an ischemia-reperfusion (IR) injury model, the performance of the NPs in detecting the infarct region in the model on PA imaging was evaluated.Results: CREKA-ICG-LIP NPs were successfully constructed and showed excellent basic characteristics, a high safety level, and an excellent targeting ability. After intravenous injection, the CREKA-ICG-LIP NPs accumulated in the injured region in the IR model. Then, the PA signal in the infarct region could be detected by the ultrasound transducer of the Vevo LAZR Photoacoustic Imaging System.Conclusion: This work provides new insights for non-invasive, real-time imaging techniques to detect the region of myocardial injury and help diagnose MI based on a PA imaging system with high sensitivity in optical imaging and deep penetration in ultrasound imaging.Keywords: PA imaging, MI, infarction region, diagnosis, CREKA, ICG

Background: The COVID-19 pandemic increased the complexity of the clinical management and pharmacological treatment of patients presenting with an Acute Coronary Syndrome (ACS). Aim: to explore the incidence and prognostic impact of in-hospital bleeding in patients presenting with ACS before and during the COVID-19 pandemic. Methods: We evaluated in-hospital Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding among 2851 patients with ACS from 17 Italian centers during the first wave of the COVID-19 pandemic (i.e., March–April 2020) and in the same period in the previous two years. Results: The incidence of in-hospital TIMI major and minor bleeding was similar before and during the COVID-19 pandemic. TIMI major or minor bleeding was associated with a significant threefold increase in all-cause mortality, with a similar prognostic impact before and during the COVID-19 pandemic. Conclusions: the incidence and clinical impact of in-hospital bleeding in ACS patients was similar before and during the COVID-19 pandemic. We confirmed a significant and sizable negative prognostic impact of in-hospital bleeding in ACS patients. [ABSTRACT FROM AUTHOR]

Mutations in the LDL receptor gene LDLR cause familial hypercholesterolemia (FH); however, the pharmacogenomics of specific LDLR mutations remains poorly understood. The goals of this study were to identify the genetic cause of a three-generation Chinese family affected with autosomal dominant FH, and to investigate the response of FH patients in the family to statin and evolocumab. Whole exome sequencing of the FH family with four patients and six unaffected members identified a heterozygous splicing mutation (c.1187-2A>G) in LDLR. The mutation co-segregated with FH in the family, providing strong genetic evidence to support its pathogenicity. The proband was a 48-year-old male FH patient who had an acute myocardial infarction (MI) and ventricular fibrillation (VF), and showed LDL-C of 5.23 mmol/L. A combination of life style modifications on food and exercise and treatment with rosuvastatin reduced his LDL-C to 2.05–2.80 mmol/L. Addition of ezetimibe did not improve rosuvastatin therapy, but addition of evolocumab further reduced LDL-C by 70% to 0.7 mmol/L at the first time and by 67% to 1.31 mmol/L at the second time. Rosuvastatin also reduced LDL-C for proband's father and sister by 40% and 43–63%, respectively. Lovastatin alone or addition to rosuvastatin treatment did not have any effect on LDL-C for the proband and his son. Both patients carry ApoE 3/4 genotype and SLCO1B1 rs4149056 TT genotype. These results suggest that combined treatment with rosuvastatin (but not lovastatin or ezetimibe) and evolocumab can control LDL-C to meet the LDL-C treatment goal for patients with LDLR splicing mutation c.1187-2A>G. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) produces acute changes in strain and stiffness within the infarct that can affect remote areas of the left ventricle (LV) and drive pathological remodeling. We hypothesized that intramyocardial delivery of a hydrogel within the MI region would lower wall stress and reduce adverse remodeling in Yorkshire pigs (n = 5). 99mTc-Tetrofosmin SPECT imaging defined the location and geometry of induced MI and border regions in pigs, and in vivo and ex vivo contrast cine computed tomography (cineCT) quantified deformations of the LV myocardium. Serial in vivo cineCT imaging provided data in hearts from control pigs (n = 3) and data from pigs (n = 5) under baseline conditions before MI induction, post-MI day 3, post-MI day 7, and one hour after intramyocardial delivery of a hyaluronic acid (HA)-based hydrogel with shear-thinning and self-healing properties to the central infarct area. Isolated, excised hearts underwent similar cineCT imaging using an ex vivo perfused heart preparation with cyclic LV pressurization. Deformations were evaluated using nonlinear image registration of cineCT volumes between end-diastole (ED) and end-systole (ES), and 3D Lagrangian strains were calculated from the displacement gradients. Post-MI day 3, radial, circumferential, maximum principal, and shear strains were reduced within the MI region (p < 0.04) but were unchanged in normal regions (p > 0.6), and LV end diastolic volume (LV EDV) increased (p = 0.004), while ejection fraction (EF) and stroke volume (SV) decreased (p < 0.02). Post-MI day 7, radial strains in MI border zones increased (p = 0.04) and dilation of LV EDV continued (p = 0.052). There was a significant negative linear correlation between regional radial and maximum principal/shear strains and percent infarcted tissue in all hearts (R2 > 0.47, p < 0.004), indicating that cineCT strain measures could predict MI location and degree of injury. Post-hydrogel day 7 post-MI, LV EDV was significantly reduced (p = 0.009), EF increased (p = 0.048), and radial (p = 0.021), maximum principal (p = 0.051), and shear strain (p = 0.047) increased within regions bordering the infarct. A smaller strain improvement within the infarct and normal regions was also noted on average along with an improvement in SV in 4 out of 5 hearts. CineCT provides a reliable method to assess regional changes in strains post-MI and the therapeutic effects of intramyocardial hydrogel delivery. [Display omitted] • Developed novel platform to assess left ventricle deformation in vivo and ex vivo. • Local cardiac strains decreased progressively over 7 days in infarcted regions. • Measured linear correlation between local degree of infarction and strain. • Hydrogel injection improved strain in regions bordering the infarct. • Hydrogel injection resulted in less ventricle dilation and larger ejection fraction. [ABSTRACT FROM AUTHOR]

Background: The prevalence of cardiovascular complications in COVID-19 infection varied in different studies. One of these complications is Myocardial Infarction. A disturbance of the blood supply can lead to Myocardial Infarction by clot formation in the arteries. However, no evidence of significant coronary stenosis has been found in more than 50% of patients with COVID-19 and ST elevation. Case presentation: 38 and 49 years old men (patients 1, 2) were admitted to our hospital with the complaint of typical chest pain and COVID-19 symptoms. The Real-time Polymerase Chain Reaction (RT-PCR) test confirmed COVID-19 in both. Patient 1 represented inferior posterior ST-Elevation Myocardial Infarction (STEMI) in his Electrocardiogram (ECG). Also, patient 2 has ST-elevation in high lateral and septal leads (I, Augmented Vector Left (AVL), V1, V2) and ST-segment depression in AVR and inferior leads (III, Augmented Vector Foot (AVF)). Their troponin was positive. The vital signs were normal in both of them. Patient 2 just had a history of Aortic Valve Replacement (AVR) 5 years ago. However, Patient 1 had no medical history. Trans-Thoracic Echocardiography (TTE) data demonstrated some disturbances in patient 1 severe hypokinesia of inferior, posterior, lateral, and septal walls. However, TTE data were unremarkable for patient 2. We prescribed recommended medications for them. Therefore, their ECG changes were corrected, and his condition improved. In addition, coronary angiography was done that demonstrated patent and normal coronary arteries in both of them. Conclusion: COVID-19 infection can cause normal coronary arteries Myocardial Infarction with probable two mechanisms prolonged vasospasm or intraluminal coronary thrombogenesis. [ABSTRACT FROM AUTHOR]

Accurate segmentation of the myocardial scar may supply relevant advancements in predicting and controlling deadly ventricular arrhythmias in subjects with cardiovascular disease. In this paper, we propose the architecture of inclusion and classification of prior information U-Net (ICPIU-Net) to efficiently segment the left ventricle (LV) myocardium, myocardial infarction (MI), and microvascular-obstructed (MVO) tissues from late gadolinium enhancement magnetic resonance (LGE-MR) images. Our approach was developed using two subnets cascaded to first segment the LV cavity and myocardium. Then, we used inclusion and classification constraint networks to improve the resulting segmentation of the diseased regions within the pre-segmented LV myocardium. This network incorporates the inclusion and classification information of the LGE-MRI to maintain topological constraints of pathological areas. In the testing stage, the outputs of each segmentation network obtained with specific estimated parameters from training were fused using the majority voting technique for the final label prediction of each voxel in the LGE-MR image. The proposed method was validated by comparing its results to manual drawings by experts from 50 LGE-MR images. Importantly, compared to various deep learning-based methods participating in the EMIDEC challenge, the results of our approach have a more significant agreement with manual contouring in segmenting myocardial diseases. [ABSTRACT FROM AUTHOR]

Abstract Background The beneficial functions of bone marrow mesenchymal stem cells (BM-MSCs) decline with decreased cell survival, limiting their therapeutic efficacy for myocardial infarction (MI). Irisin, a novel myokine which is cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), is believed to be involved in a cardioprotective effect, but little was known on injured BM-MSCs and MI repair yet. Here, we investigated whether FNDC5 or irisin could improve the low viability of transplanted BM-MSCs and increase their therapeutic efficacy after MI. Methods BM-MSCs, isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein positive (Fluc+–eGFP+) transgenic mice, were exposed to normoxic condition and hypoxic stress for 12 h, 24 h, and 48 h, respectively. In addition, BM-MSCs were treated with irisin (20 nmol/L) and overexpression of FNDC5 (FNDC5-OV) in serum deprivation (H/SD) injury. Furthermore, BM-MSCs were engrafted into infarcted hearts with or without FNDC5-OV. Results Hypoxic stress contributed to increased apoptosis, decreased cell viability, and paracrine effects of BM-MSCs while irisin or FNDC5-OV alleviated these injuries. Longitudinal in vivo bioluminescence imaging and immunofluorescence results illustrated that BM-MSCs with overexpression of FNDC5 treatment (FNDC5-MSCs) improved the survival of transplanted BM-MSCs, which ameliorated the increased apoptosis and decreased angiogenesis of BM-MSCs in vivo. Interestingly, FNDC5-OV elevated the secretion of exosomes in BM-MSCs. Furthermore, FNDC5-MSC therapy significantly reduced fibrosis and alleviated injured heart function. Conclusions The present study indicated that irisin or FNDC5 improved BM-MSC engraftment and paracrine effects in infarcted hearts, which might provide a potential therapeutic target for MI.

Abstract Thrombosis is frequently observed in COVID‐19, especially in critically ill patients. Management of such life‐threatening conditions is of high importance in the context of the current pandemic. Herein, we provide a case series of myocardial infarction in the clinical evolution of COVID‐19, emphasizing its importance and implications on the cardiovascular system.

Background: Ventricular septal rupture (VSR), a mechanical complication of myocardial infarction (MI), usually presents with rapid clinical deterioration with acute heart failure or cardiogenic shock. VSR may occur within 24 h to several days after MI and can occur in both anterior and inferior wall MI. Although guidelines recommend emergent surgery, this is associated with a high mortality rate of up to 40%. Intra-aortic balloon pump (IABP) and extracorporeal membrane oxygenation (ECMO) stabilize patients in preparation for angiography and surgery. Delayed surgery allows better septal repair in scarring tissue but also carries the risk of rupture extension and death while waiting. Percutaneous closure of the defect with appropriately designed devices results in better survival in the subacute phase. Aims: To study the indicators and predictors of VSR in the current era of primary percutaneous coronary interventions and mechanical circulatory support. Methods: Of total of 34,681 patients presenting with MI, the incidence of VSR was 0.45%. We sought to evaluate the predictors of survival and death in VSR. Coronary angiography (CAG) was performed, hemodynamic support provided to unstable patients, and consenting patients were referred to definitive therapy, either surgery or percutaneous device closure. The previously postulated hypotheses of triple vessel disease (TVD), diabetes mellitus (DM), and concentric left ventricular hypertrophy (LVH) due to Hypertension (HTN) being protective against VSR were explored. Results: Of the 169 patients with VSR, we found that the group that survived was mostly men and the mean age was 61.5 years; this was in contrast to the non-survivors, who were mainly women, and the mean age was 65.2 years (p = 0.025); higher Killip Class was 111-1V (p = 0.001), lower LVEF (p = 0.010), apical VSR and LV aneurysm (p = 0.015 and p = 0.002, respectively) were predictors of death. 48 patients underwent CAG, with single vessel disease (SVD) with lower-grade Rentrop collateral flow being most common in the death group. 25 patients were subjected to definitive therapy with surgical patch closure or percutaneous device closure. The patients who died were older by approximately 7 years. The risk factors for coronary artery disease, such as HTN, diabetes, and smoking, were not statistically different between the two groups. Conclusion: Prevention of myocardial infarction is more important than managing a VSR, which carries a high mortality despite advanced mechanical support and definitive interventional therapy such as emergent surgery and percutaneous device closure.

Forkhead box protein P1 (Foxp1) is a kind of tumor suppressor gene, and the role of Foxp1 in the macrophages of myocardial infarction (MI) has not been studied yet. Here, we verified the role of the transcription factor high mobility group box 1 (HMGB1) and its target gene Foxp1 in the inflammatory response. In this study, the key genes HMGB1 and Foxp1 in the macrophages of mouse MI model were screened out through single‐cell transcriptome analysis of GSE136088 (GEO database). In vitro experiment indicated that hypoxia induced the inflammatory response in RAW264.7 macrophages, promoted the secretion of inflammatory factors (tumor necrosis factor α [TNF‐α], interleukin 6 [IL‐6], and IL‐1β) and the activation of NLRP3 inflammasome (NLRP3, ASC, and pro‐caspase‐1). Meanwhile, HMGB1 increased while Foxp1 decreased in hypoxia‐treated RAW264.7 macrophages. HMGB1 bound to the upstream promoter region of Foxp1 as demonstrated by the dual‐luciferase reporter assay, chromatin immunoprecipitation (ChIP)‐quantitative polymerase chain reaction (qPCR) and agarose gel electrophoresis. As a transcription factor, HMGB1 regulated Foxp1 expression. The secretion of inflammatory factors and the expression of NLRP3 inflammasome protein were changed when the expression of HMGB1 and Foxp1 was regulated in the hypoxia‐treated RAW264.7 macrophages. This study verified that HMGB1 could aggravate the hypoxia‐treated inflammatory response of macrophages through downregulating Foxp1, which not only provides evidence to support the role of HMGB1/Foxp1 in macrophages but also offers another angle for the treatment of MI. [ABSTRACT FROM AUTHOR]

Biological processes involving environmental and genetic factors drive the interplay between age- and sex-regulating lipid profile. The relation between variations in the LPA gene with increasing the risk of coronary heart disease is dependent on population differences, sex, and age. The present study tried to do a gene candidate association analysis in people with myocardial infarction (MI) in a 22 year cohort family-based longitudinal cohort study, Tehran Cardiometabolic Genetic Study (TCGS). After adjusting p value by the FDR method, only the association of rs6415084 with the MI probability and the age-of-CHD-onset was significant in males in their middle age (p < 0.005). Surprisingly, a lack of association was observed for the rest of the markers (16 SNPs). These results revealed the moderator effects of age and sex on the association between the genetic variants (SNPs) of LPA and heart disease risk. Our observations may provide new insights into the biology that underlies lipid profile with age or the sexual dimorphism of Lp(a) metabolism. Finally, Lp(a) appears to be an independent risk factor; however, the role of sex and ethnicity is important. [ABSTRACT FROM AUTHOR]

Electrocardiography (ECG) is a noninvasive diagnostic tool used to diagnose coronary artery disease, myocardial infarction (MI), and other heart disorders. As MI is the death of cardiac muscle tissue owing to a coronary artery blockage. It should be diagnosed at an early stage to provide timely treatment and thereby save lives. This study proposes a novel efficient technique for MI detection and localization based on variational mode decomposition (VMD) and regularized neighborhood component analysis (RNCA). Statistical and nonlinear features calculated from intrinsic mode functions decomposed by VMD create the final feature set. These features are ranked using RNCA, a nonparametric feature ranking approach, and then fed into the k-nearest neighbors (KNN) and AdaBoost classifiers with minimum features. With 12-Lead ECG System, i.e., ten electrodes on the body for detection might be costly and restricts patient movement. The Physikalisch-Technische Bundesanstalt ECG diagnostic database consisting of all 12 leads data is studied to find the minimum number of leads needed for successful MI diagnosis and localizing infarcted artery. Using 33 features from lead 8 (V2) with the KNN, the proposed approach gave the best accuracy of 99.82% for detection compared to previous related studies. The technique also distinguished the 11 types of MI with 99.75% accuracy utilizing 22 features from lead 7 (V1) with the KNN. The study reveals that an automated diagnostic tool for the portable device may be built just by chest lead. As VMD provides a robust solution against noise, this algorithm is excellent for portable health devices. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) causes rapid and permanent damage to the heart muscle. Without timely diagnosis and treatment, it will deteriorate the myocardial structure and function. The precise localization of MI based on 12-lead electrocardiogram (ECG) signals still remains a great challenge. We, thus, present a novel algorithm for automatically localizing MI from multilead ECG signals. The image-based heartbeat tensorization establishes a third-order lead ${\times }$ time ${\times }$ amplitude tensor structure. This image tensor encompasses key information between leads and the correlation within the heartbeat, which are essential for the MI diagnosis. The Tucker2 decomposition-based feature extractor automatically extracts the morphological core tensor of the image tensor. The morphological core tensor includes crucial information among three dimensions. Localization of MI is evaluated as a multiclass problem. We use the bagged decision tree for multiclass classification. The 12-lead ECG signals from the benchmark Physikalisch-Technische Bundesanstalt (PTB) database are employed to verify the applicability of the proposed algorithm. The PTB database includes normal ECG, 11 types of MI: anterior, anterior lateral, anterior septal, anterior septal lateral, inferior, inferior lateral, inferior posterior, inferior posterior lateral, lateral, posterior, and posterior lateral. We demonstrated, with the morphological core features obtained from the image tensor, that 12 categories of ECG signals achieved a total accuracy of 99.67% and an F1 score of 0.9997. The area under the receiver operating characteristic curves and precision-recall curves of each kind of ECG signal has been found to be more than 0.88. The proposed algorithm effectively realizes the classification of normal ECG and 11 categories of MI, and our approach of using a 12-lead ECG signal herein holds great promise for helping the cardiologists localize MI. [ABSTRACT FROM AUTHOR]

Introduction: ST-elevation myocardial infarction (STEMI) is a major cause of mortality and morbidity worldwide, but fast and reliable diagnosis can reduce mortality. Therefore, this study aimed to assess the diagnostic value of serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) among patients with acute STEMI, and also its importance to monitor the response to percutaneous coronary intervention (PCI). A total of 30 healthy subjects and 150 acute STEMI patients treated by PCI were enrolled into our study. Besides the routine lab work, serum sLOX-1 level was measured using a commercial ELISA kit. Results: Our results revealed the increased serum sLOX-1 level among patients with acute STEMI (112.79 ± 10.76) than controls (47.75 ± 12.87). After the treatment of acute STEMI patients with the primary PCI, the level of serum sLOX-1 was not sigificantly decreased either after 12 hrs (111.04 ± 11.06) or 48 hrs (110.31 ± 11.24) from PCI management. Our results also showed that serum sLOX-1 level was positively correlated with cholesterol, LDL, troponin I, CK-MB, CRP, TG, and VLDL. Results obtained from ROC curve analysis showed that serum sLOX-1 is an excellent biomarker for acute STEMI disease, its AUC is one with 100% sensitivity and specificity. Conclusions: Finally, from these results, we can conclude that LOX-1 has a crucial role in the pathogenesis of acute STEMI; also, serum sLOX-1 could be a good diagnostic clinical biomarker for the detection of acute STEMI disease and to monitor the response to PCI. [ABSTRACT FROM AUTHOR]

Thrombosis is frequently observed in COVID‐19, especially in critically ill patients. Management of such life‐threatening conditions is of high importance in the context of the current pandemic. Herein, we provide a case series of myocardial infarction in the clinical evolution of COVID‐19, emphasizing its importance and implications on the cardiovascular system. Due to proinflammatory state in COVID‐19, myocardial infarction may occur. In addition to its fatal entity, the challenges at the way of acute management of myocardial infarction at the time of COVID‐19 pandemic have worsened the outcome of patients. [ABSTRACT FROM AUTHOR]

Background: Exosomes are considered a substitute for stem cell-based therapy for myocardial infarction (MI). FNDC5, a transmembrane protein located in the cytoplasm, plays a crucial role in inflammation diseases and MI repair. Furthermore, our previous study found that FNDC5 pre-conditioning bone marrow-derived mesenchymal stem cells (BMMSCs) could secrete more exosomes, but little was known on MI repair. Methods: Exosomes isolated from BMMSCs with or without FNDC5-OV were injected into infarcted hearts. Then, cardiomyocytes apoptosis and inflammation responses were detected. Furthermore, exosomes were administrated to RAW264.7 macrophage with LPS treatment to investigate its effect on inflammation and macrophage polarization. Results: Compared with MSCs-Exo, FNDC5-MSCs-Exo had superior therapeutic effects on anti-inflammation and anti-apoptosis, as well as polarizing M2 macrophage in vivo. Meanwhile, the in vitro results also showed that FNDC5-MSCs-Exo decreased pro-inflammatory secretion and increased anti-inflammatory secretion under LPS stimulation, which partly depressed NF‐κB signaling pathway and upregulated Nrf2/HO-1 Axis. Conclusions: FNDC5-BMMSCs-derived exosomes play anti-inflammation effects and promote M2 macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 Axis, which may develop a promising cell-free therapy for MI. [ABSTRACT FROM AUTHOR]

Purpose of Review: Cardiac rehabilitation (CR) referral is a Class I post-myocardial infarction (MI) recommendation from the American Heart Association and the American College of Cardiology, yet referral rates remain strikingly low, with cardiologists some of the worst under-referring offenders. This paper seeks to review the evolution of CR and its well-established benefits, as well as reasons behind the poor referral and utilization. Recent Findings: CR is a secondary prevention program for cardiovascular disease (CVD) that was first initiated in the 1970s as a hospital-based exercise program after an acute MI, but then evolved into a comprehensive multi-disciplinary program for patients with a wider range of cardiovascular diseases. CR mortality and morbidity benefits have endured over decades, even as interventional and pharmacological cardiovascular therapeutics have improved and as patients have become relatively more stable. Summary: Despite being an evidence-based clinical standard, referral and participation in CR are disconcertingly low. In efforts to combat poor referral rates, and improve care in the contemporary care environment, the approach to CR is evolving. Innovations include broadening CR beyond the hospital setting into remote- and hybrid-based formats, while still incorporating exercise training, risk factor reduction, and education, as well as behavioral and psychosocial support. Nonetheless, there still remain many challenges to overcome in order to increase participation of all ages, financials, races, and sexes. With new performance measures as well as an increasing number of NIH-funded studies on the horizon, there is hope that CR will become a relatively more valued and utilized component of cardiovascular preventative care. [ABSTRACT FROM AUTHOR]

Cardiac failure, such as myocardial infarction (MI), is one of the most serious causes of mortality worldwide. MI is the sign of cardiac cell damage as a result of decreased blood oxygen level, which causes some morphological changes in the form of 12‐lead electrocardiogram (ECG) waves including T‐wave, Q‐wave, and ST‐segment. The main goal of this study is to represent vectorcardiography (VCG) as a complementary diagnostic tool of the ECG method to discriminate the various type of MI from normal cases. The system proposed in this study was analysed on the Physikalisch‐Technische Bundesanstalt diagnostic ECG database and a recorded signal database for 80 MI and 52 healthy cases. Each record consists of 15 ECG and VCG signals. In this study, tridimensional morphological features were applied to the classification and regression tree (CART) and the feedforward neural network classifier. To classify MI cases from healthy control cases of our recorded database, classification and regression tree achieved the same results when VCG features or ECG features were applied with an accuracy of 99.4%, a sensitivity of 100%, and a specificity of 98.7%. Further, by using VCG Octant features with this current method, anterior‐MI and inferior‐MI were separated with an accuracy of 98.9%, a sensitivity of 98%, and a specificity of 100%. The outcomes prove that the VCG features performed more accurately than ECG features in MI localisation. [ABSTRACT FROM AUTHOR]

Objective: Atrial fibrillation (AF) and venous thromboembolism (VTE) share several risk factors related to arterial thromboembolism. No study has reported the differential contribution to arterial thromboembolic events and mortality between these two conditions in the same population. We therefore assessed the differential arterial thromboembolic events between AF and VTE.Methods: We included AF and VTE national cohorts derived from Taiwan National Health Insurance Research Database between 2001 and 2013. The eligible population was 314,861 patients in the AF cohort and 41,102 patients in the VTE cohort. The primary outcome was arterial thromboembolic events, including ischemic stroke, extracranial arterial thromboembolism (ECATE) and myocardial infarction (MI). Secondary outcomes were all-cause mortality and cardiovascular death.Results: After a 1:1 propensity matching, 32,688 patients in either group were analyzed. The risk of arterial thromboembolic events was lower in the VTE cohort than that in the AF cohort (subdistribution hazard ratio [SHR], 0.60; 95% confidence interval [CI], 0.57–0.62). The risk of ischemic stroke (SHR, 0.44; 95% CI, 0.42–0.46) and MI (SHR, 0.80; 95% CI, 0.72–0.89) were lower in the VTE cohort, while the risk of ECATE (SHR, 1.23; 95% CI, 1.14–1.33; particularly lower extremities) was higher in the VTE cohort. All-cause mortality rate was higher in the VTE cohort (HR, 1.18; 95% CI, 1.15–1.21) while the risk of cardiovascular death was lower in the VTE cohort (HR, 0.96; 95% CI, 0.93–0.995).Conclusions: Patients with AF had higher risks of arterial thromboembolic events compared to patients with VTE, despite having risk factors in common. The VTE cohort had higher risks of all-cause mortality and ECATE, particularly lower extremity events, compared to AF patients. The differential manifestations of thromboembolism sequelae and mortality between AF and VTE patients merit further investigation.

Coronary artery disease (CAD) and its main complication, myocardial infarction (MI), is a complex disease caused by environmental and genetic factors and their interaction. Family-based linkage analysis and genome-wide association studies have indicated many of genetic variations related to CAD and MI in recent years. Some are in the coding sequence, which mediates the coding protein, while others are in the non-coding region, which affects the expression of adjacent genes and forms differential gene expression. These variants and differential expressions will have varying degrees of impact on the development of the cardiovascular system and normal heart electrical activity function, subsequently leading to CAD and MI. Among these affected genes, some Transcription Factors (TFs), as important means of transcriptional regulation, have a key role in the pathogenesis of coronary artery disease and myocardial infarction. The GATAs binding protein 2 (GATA2) enhances monocyte adhesion and promoted vessel wall permeabilization through vascular EC adhesion molecule 1 (VCAM-1) upregulation, further revealing its atherosclerosis-promoting role. Myocyte enhancer factor 2 (MEF2) has a role in fostering many functions of the atherosclerotic endothelium and is a potential therapeutic target for atherosclerosis, thrombosis, and inflammation. Nuclear factor-kappa B (NF-κB) is an important promoter of vascular endothelial growth factor (VEGF)-driven angiogenesis, and its pathway has a key role in atherosclerosis-related complications such as angiogenesis, inflammation, apoptosis, and immune effects. Activating transcription factor 3 (ATF3) may be a novel prognostic biomarker and therapeutic target for atherosclerosis. The important role of signal transducer and activator of transcription 3 (STAT3) (especially in mitochondria) in endothelial cells (EC) dysfunction, inflammation, macrophage polarization and immunity in atherosclerosis.

Objective: After myocardial infarction (MI), the non-infarcted left ventricle (LV) ensures appropriate contractile function of the heart. Metabolic disturbance in this region greatly exacerbates post-MI heart failure (HF) pathology. This study aimed to provide a comprehensive understanding of the metabolic derangements occurring in the non-infarcted LV that could trigger cardiovascular deterioration.Methods and Results: We used a pig model that progressed into chronic HF over 3 months following MI induction. Integrated gene and metabolite signatures revealed region-specific perturbations in amino acid- and lipid metabolism, insulin signaling and, oxidative stress response. Remote LV, in particular, showed impaired glutamine and arginine metabolism, altered synthesis of lipids, glucose metabolism disorder, and increased insulin resistance. LPIN1, PPP1R3C, PTPN1, CREM, and NR0B2 were identified as the main effectors in metabolism dysregulation in the remote zone and were found differentially expressed also in the myocardium of patients with ischemic and/or dilated cardiomyopathy. In addition, a simultaneous significant decrease in arginine levels and altered PRCP, PTPN1, and ARF6 expression suggest alterations in vascular function in remote area.Conclusions: This study unravels an array of dysregulated genes and metabolites putatively involved in maladaptive metabolic and vascular remodeling in the non-infarcted myocardium and may contribute to the development of more precise therapies to mitigate progression of chronic HF post-MI.

Despite clinical use of late gadolinium enhancement (LGE) for two decades, an efficient, robust fat suppression (FS) technique still does not exist for this CMR mainstay. In ischemic and non‐ischemic heart disease, differentiating fibrotic tissue from infiltrating and adjacent fat is crucial. Multiple groups have independently developed an FS technique for LGE, double spectral attenuated inversion recovery (DSPAIR), but no comprehensive evaluation was performed. This study aims to fill this gap. DSPAIR uses two SPAIR pulses and one non‐selective IR pulse to enable FS LGE, including compatibility with phase sensitive inversion recovery (PSIR). We implemented a magnitude (MAGN) and a PSIR variant and compared them with LGE without FS (CONTROL) and with spectral presaturation with inversion recovery (SPIR) in simulations, phantoms, and patients. Fat magnetization by SPIR, MAGN DSPAIR, and PSIR DSPAIR was simulated as a function of pulse B1, readout (RO) pulse number, and fat TI. A phantom with fat, fibrosis, and myocardium compartments was imaged using all FS methods and modifying pulse B1, RO pulse number, and heart rate. Signal was measured in SNR units. Fat, myocardium, and fibrosis SNR and fibrosis‐to‐fat CNR were obtained. Patient images were acquired with all FS techniques. Fat, myocardium, and fibrosis SNR, fibrosis‐to‐fat CNR, and image and FS quality were assessed. In the phantom, both DSPAIR variants provided superior FS compared with SPIR, independent of heart rate and RO pulse number. MAGN DSPAIR reduced fat signal by 99% compared with CONTROL, PSIR DSPAIR by 116%, and SPIR by 67% (25 RO pulses). In patients, both DSPAIR variants substantially reduced fat signal (MAGN DSPAIR by 87.1% ± 10.0%, PSIR DSPAIR by 130.5% ± 36.3%), but SPIR did not (35.8% ± 25.5%). FS quality was good to excellent for MAGN and PSIR DSPAIR, and moderate to poor for SPIR. DSPAIR provided highly effective FS across a wide range of parameters. PSIR DSPAIR performed best. [ABSTRACT FROM AUTHOR]