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Myocardial infarction (MI) is a life-threatening medical condition that necessitates both timely and precise diagnosis. The enhancement of automated method to detect MI diseases from Normal patients can play a crucial role in healthcare. This paper presents a novel approach that utilizes the Discrete Wavelet Transform (DWT) for the detection of myocardial signals. The DWT is employed to break down ECG signals into distinct frequency components and subsequently to selectively filter out noise by thresholding the high-frequency details, resulting in denoised ECG signals for myocardial signal detection. These denoised signals are fed into lightweight one-dimensional Convolutional Neural Networks (CNN) for binary classification into Myocardial Infarction (MI) and Normal categories. The paper explores three distinct approaches: utilizing all signals, incorporating under-sampling and up-sampling to address class imbalances, with both noised and denoised signals. Evaluation of the suggested model is done with the help of two publicly available datasets: PTB-XL, a large publicly available electrocardiography dataset and PTB Diagnostic ECG Database. Results obtained through 5-fold cross-validation on the trained model show that the model has achieved an accuracy of 96%, precision of 97% and F1 score of 95%. On cross-validation with the PTB-ECG dataset, this paper achieved an accuracy of 91.18%. [ABSTRACT FROM AUTHOR]

Recent advancements in disease modeling for myocardial infarction (MI) and coronary artery disease (CAD) have significantly enhanced our understanding of cardiovascular pathology and therapeutic development. This review comprehensively reviews the integration of in vivo and in vitro approaches to better model and study these conditions. We specifically focus on cutting-edge in vitro techniques, such as cardiac organoids, engineered heart tissues, and patient-derived induced pluripotent stem cells (iPSCs), which allow for detailed exploration of cellular and molecular mechanisms involved in MI and CAD. These models provide insights into ischemic injury, myocardial remodeling, and the effects of potential therapeutic interventions at a cellular level. In parallel, we discuss advances in the in vivo models, including genetically modified mice and large animal models, which offer valuable information on disease progression, cardiac function, and response to treatments within a more complex physiological context. By bridging these in vivo and in vitro approaches, researchers can gain a more comprehensive understanding of disease mechanisms, validate experimental findings, and accelerate the development of effective therapies. This review highlights recent progress, identifies current limitations, and proposes strategies for future research to enhance the translation of model-based discoveries into clinical practice for MI and CAD. [ABSTRACT FROM AUTHOR]

Background: The development of coronary artery disease (CAD) is influenced by sex and genetic factors. Genome-wide association studies (GWAS) have linked genetic loci to CAD, mostly in European populations. The study aims to find sex-related genetic differences in the Iranian population. Research design and methods: We conducted a sex-stratified GWAS with 4519 subjects (1832 males and 2687 females) in the discovery group and 922 subjects (495 males and 427 females) in the confirmation group of an Iranian cohort. We analyzed 9,141,124 variants using a genome-wide complex trait analysis (GCTA) tool. Results: We detected distinct genetic variants associated with CAD in males: rs34952209 [OR = 1.79; p = 5.216E–8], rs1432687863 [OR = 1.95; p = 8.477E–8], and in females, rs7314741 [OR = 1.67; p = 7.142-8E] positively influenced CAD risk. The CAD-associated SNPs that were obtained have been confirmed using independent samples. Rs3495229 May impact histone mark and Pou2f2 motifs, while rs7314741 in the LEM Domain Containing 3 (LEMD3) promoter may affect a regulatory motif for the STAT transcription factor. According to Roadmap and ENCODE data, Rs1432687863 is a new variant affecting CAD in males, potentially through H3K9me3 in the heart. Conclusions: Our findings highlight the role of sex-specific genetic differences in CAD development, providing novel insights into disease pathways which is not appropriate using a sex-combined strategy. [ABSTRACT FROM AUTHOR]

Abstract Myocardial infarction (MI) is a life-threatening medical condition that necessitates both timely and precise diagnosis. The enhancement of automated method to detect MI diseases from Normal patients can play a crucial role in healthcare. This paper presents a novel approach that utilizes the Discrete Wavelet Transform (DWT) for the detection of myocardial signals. The DWT is employed to break down ECG signals into distinct frequency components and subsequently to selectively filter out noise by thresholding the high-frequency details, resulting in denoised ECG signals for myocardial signal detection. These denoised signals are fed into lightweight one-dimensional Convolutional Neural Networks (CNN) for binary classification into Myocardial Infarction (MI) and Normal categories. The paper explores three distinct approaches: utilizing all signals, incorporating under-sampling and up-sampling to address class imbalances, with both noised and denoised signals. Evaluation of the suggested model is done with the help of two publicly available datasets: PTB-XL, a large publicly available electrocardiography dataset and PTB Diagnostic ECG Database. Results obtained through 5-fold cross-validation on the trained model show that the model has achieved an accuracy of 96%, precision of 97% and F1 score of 95%. On cross-validation with the PTB-ECG dataset, this paper achieved an accuracy of 91.18%.

Background and objectives. Myocardial infarction (MI) is a severe cardiac event associated with plaque formation in arteries, leading to reduced blood flow to the heart. Arrhythmias, such as bradyarrhythmia or tachyarrhythmia, commonly accompany MI, contributing to its morbidity and mortality. Electrolyte disturbances, particularly potassium and magnesium imbalances, can exacerbate arrhythmic risks in MI patients. This study aimed to assess the incidence of alterations in serum potassium and magnesium levels during acute MI and their correlation with rhythm disturbances. Material and methods. A prospective analytical study was conducted with 150 patients diagnosed with acute MI based on ECG changes and elevated cardiac markers. Serum potassium and magnesium levels were measured, and rhythm disturbances were assessed using continuous cardiac monitoring and standard ECG. Spearman correlation analysis was performed to evaluate the association between serum potassium, serum magnesium, and rhythm changes. Results. The study investigated then demographic and clinical characteristics of participants and the potential relationship between serum electrolyte levels and arrhythmic changes. The mean age of the participants was 54.3 years, with a male predominance (76% male, 24% female). Among the participants, 50.67% had diabetes, 52% had hypertension, and 28% had both conditions. Serum electrolyte analysis showed elevated magnesium levels in 6.66% and elevated potassium levels in 12.66% of patients. Notably, arrhythmic changes in ECG were present in 62% of patients, with sinus tachycardia being the most prevalent (17%). However, statistical analysis revealed no significant correlation between serum magnesium, serum potassium, and rhythm changes (p >0.05). These findings suggest that while arrhythmic changes are common, they are not directly associated with elevated levels of these electrolytes, indicating the need for further investigation into other potential factors influencing arrhythmias in this population. Conclusion. Despite the prevalence of electrolyte disturbances in acute MI patients, this study found no significant association between serum magnesium, serum potassium levels, and rhythm disturbances. Further research is warranted to elucidate the complex interplay between electrolyte imbalances and arrhythmias in MI.

Introduction: Acute Coronary Syndrome (ACS) is a significant cause of morbidity and mortality worldwide, characterized by a spectrum of conditions ranging from unstable angina to myocardial infarction. Traditionally perceived as a disease predominantly affecting older adults, ACS is increasingly being recognized in younger populations, raising concerns about its etiology, presentation, and management in this age group. Aims: The findings will highlight the distinctive characteristics and needs of the very young CAD patients, underlining the necessity for targeted interventions in this emerging subset. This study is especially essential for India, given its significant and growing young population vulnerable to CVD. Materials and Methods: his study was an investigator-initiated, single-center, retrospective observational study aimed at examining the clinico-demographic, risk factors, and angiographic profiles of Acute Coronary Syndrome (ACS) in young adults at a tertiary Cardiology Institute in Central India. Approved by the local ethical committee and conducted according to ICH Harmonized Guidelines for Good Clinical Practice, the study involved a review of medical records from 550 young adults (aged 18 to = 45 years) diagnosed with ACS between January 2018 and July 2023. Result: The comparative analysis of coronary angiographic profiles by age group. Among the cases with single-vessel disease, 22 (8.9%) were under 30 years, while 226 (91.1%) were over 30 years. In cases of double-vessel disease, 1 (0.7%) was under 30 years, and 140 (99.3%) were over 30 years. Notably, no patients under 30 years had triple-vessel disease, whereas all 92 (100%) cases of triple-vessel disease occurred in patients over 30 years. Conclusion: Our study provides valuable insights into the clinicodemographic characteristics, risk factors, and angiographic profiles of ACS in young adults. Young ACS patients exhibit a strong male predominance. Although Obesity and hypertension emerged as the most common risk factor, affecting around 40% of participants, conventional risk factors, such as diabetes and hypertension, are significantly less prevalent in patients younger than 30 years compare to older young patients. [ABSTRACT FROM AUTHOR]

To uncover the possible role of TRAF3IP3 in the progression of myocardial infarction (MI), clarify its role in mitophagy and mitochondrial function, and explore the underlying mechanism. GEO chip analysis, RT-qPCR, and LDH release assay were used to detect the expression of TRAF3IP3 in tissues and cells and its effects on cell damage. Immunostaining and ATP product assays were performed to examine the effects of TRAF3IP3 on mitochondrial function. Co-IP, CHX assays, Immunoblot and Immunostaining assays were conducted to determine the effects of TRAF3IP3 on mitophagy. TRAF3IP3 was highly expressed in IR rats and HR-induced H9C2 cells. TRAF3IP3 knockdown can alleviate H/R-induced H9C2 cell damage. In addition, TRAF3IP3 knockdown can induce mitophagy, thus enhancing mitochondrial function. We further revealed that TRAF3IP3 can promote the degradation of NEDD4 protein. Moreover, TRAF3IP3 knockdown suppressed myocardial injury in I/R rats. TRAF3IP3 blocks mitophagy to exacerbate myocardial injury induced by I/R via mediating NEDD4 expression. [ABSTRACT FROM AUTHOR]

Scavenger receptor type B (SR-BI) is a receptor that binds both native and altered lipoproteins. It was revealed to facilitate utilization of high-density lipoprotein HDL and significantly affect the reverse transport of cholesterol. Therefore, the objectives were to identify the possible role of the genetic variant rs4238001 in patients with myocardial infarction (MI) on serum lipid level, and how this variant could impact the response of rosuvastatin drug. The genotyping of the rs4238001 genetic polymorphism of the SR-B1 gene was performed in 300 participants, including 150 MI patients treated with 20mg/day/4 weeks of rosuvastatin and 150 healthy control using Taq man probes (FAM and VIC) by Real-time PCR technique. The concentrations of the lipid profile were evaluated. The significance of the anthropometric data was revealed in the ejection fraction and smoking status (p < 0.05) between groups. The lipid profile shows either significant differences between control and MI patients (pre-treatment) or between pre-and post-treatment of MI patients (p < 0.05), but not HDL-c (p > 0.05). The minor allele frequency MAF% of the T allele and TT genotype were more frequent in MI patients than in controls (P = 0.173; OR = 3.62; 95% CI = 0.74–17.64). CC genotype was found to be associated with response to rosuvastatin therapy with a change of % (29.08 ± 53.2; p = 0.021). In the Iraqi population, the rs4238001 polymorphism of the SR-B1 gene is associated with variations in serum lipids, and the CC genotype of the SNP is related to higher HDL-C in the lipid-lowering rosuvastatin response. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases, including myocardial infarction (MI), constitute the leading cause of morbidity and mortality worldwide. Protein-aggregate deposition is a hallmark of aging and neurodegeneration. Our previous study reported that aggregation is strikingly elevated in hearts of hypertensive and aged mice; however, no prior study has addressed MI effects on aggregation in heart or brain. Here, we present novel data on heart and brain aggregation in mice following experimental MI, induced by left coronary artery (LCA) ligation. Infarcted and peri-infarcted heart tissue, and whole cerebra, were isolated from mice at sacrifice, 7 days following LCA ligation. Sham-MI mice (identical surgery without ligation) served as controls. We purified detergent-insoluble aggregates from these tissues, and quantified key protein constituents by high-resolution mass spectrometry (LC–MS/MS). Infarct heart tissue had 2.5- to 10-fold more aggregates than non-infarct or sham-MI heart tissue (each P = 0.001). Protein constituents from MI cerebral aggregates overlapped substantially with those from human Alzheimer's disease brain. Prior injection of mice with mesenchymal stem cell (MSC) exosomes, shown to limit infarct size after LCA ligation, reduced cardiac aggregation ~ 60%, and attenuated markers of endoplasmic reticulum (ER) stress in heart and brain (GRP78, ATF6, P-PERK) by 50–75%. MI also elevated aggregate constituents enriched in Alzheimer's disease (AD) aggregates, such as proteasomal subunits, heat-shock proteins, complement C3, clusterin/ApoJ, and other apolipoproteins. These data provide novel evidence that aggregation is elevated in mouse hearts and brains after myocardial ischemia, leading to cognitive impairment resembling AD, but can be attenuated by exosomes or drug (CDN1163) interventions that oppose ER stress. [ABSTRACT FROM AUTHOR]

Cold‐inducible RNA‐binding protein (CIRP) is a stress–response protein that has been shown to protect cardiomyocytes under a variety of stress conditions from apoptosis. Our recent study showed that the expression of CIRP protein in the heart was downregulated in patients with heart failure and an animal model of ischaemia heart failure, but its role in heart failure is still unknown. The present study aimed at evaluating the potential role of CIRP on the heart in an animal model of myocardial infarction (MI). MI model of rats was induced by the ligation of the left coronary artery. CIRP overexpression was mediated by direct intracardiac injection of adeno‐associated virus serotype 9 (AAV9) vectors carrying a CIRP coding sequence with a cardiac‐specific promoter before the induction of the MI model. The effects of CIRP elevation on MI‐induced heart were analysed through echocardiographic, pathological and molecular analysis. Our results showed that the intracardiac injection of AAV9 successfully mediated CIRP upregulation in cardiomyocytes. Upregulation of cardiac CIRP prevented MI‐induced cardiac dysfunction and adverse remodelling, coupled with the reduced inflammatory response in the heart. Collectively, these results demonstrated the beneficial role of intracellular CIRP on the heart and suggest that CIRP may be a therapeutic target in ischaemic heart disease. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (MI) is a sudden, severe cardiac ischemic event that results in the death of up to one billion cardiomyocytes (CMs) and subsequent decrease in cardiac function. Engineered cardiac tissues (ECTs) are a promising approach to deliver the necessary mass of CMs to remuscularize the heart. However, the hypoxic environment of the heart post-MI presents a critical challenge for CM engraftment. Here, we present a high-throughput, systematic study targeting several physiological features of human induced pluripotent stem cell-derived CMs (hiPSC-CMs), including metabolism, Wnt signaling, substrate, heat shock, apoptosis, and mitochondrial stabilization, to assess their efficacy in promoting ischemia resistance in hiPSC-CMs. The results of 2D experiments identify hypoxia preconditioning (HPC) and metabolic conditioning as having a significant influence on hiPSC-CM function in normoxia and hypoxia. Within 3D engineered cardiac tissues (ECTs), metabolic conditioning with maturation media (MM), featuring high fatty acid and calcium concentration, results in a 1.5-fold increase in active stress generation as compared to RPMI/B27 control ECTs in normoxic conditions. Yet, this functional improvement is lost after hypoxia treatment. Interestingly, HPC can partially rescue the function of MM-treated ECTs after hypoxia. Our systematic and iterative approach provides a strong foundation for assessing and leveraging in vitro culture conditions to enhance the hypoxia resistance, and thus the successful clinical translation, of hiPSC-CMs in cardiac regenerative therapies. [ABSTRACT FROM AUTHOR]

Cardiac fibroblasts (CFs) are of vital importance for post-myocardial infarction (MI) remodeling. This study explored the role of Placenta specific 8 (Plac8) in MI on the basis of single-cell RNA-Seq (scRNA-Seq) data (GSE136088) and micro-array data (GSE153485). Through bioinformatics analysis, Plac8 was finally identified as a key gene related to fibroblasts. In addition, primary CFs of the neonatal mice were isolated, cultured and treated with hypoxia for in vitro cell model construction. Hydroxyproline assay demonstrated enhanced collagen production in hypoxic CFs, and qRT-PCR revealed increased relative contents of type I and type III collagen (Col1a1 and Col3a1). Western blot showed increased protein expression level of α-smooth muscle actin (α-SMA), and transwell assay and wound-healing assay collectively suggested enhanced cell migration. Moreover, Plac8 was found to be upregulated in hypoxic CFs. Then, after transfection with siNC or siPlac8, it was revealed that down-regulating Plac8 protein expression in hypoxic CFs reduced the levels of collagen secretion, the number of activated CFs and the degree of cell migration, indicating the regulation of Plac8 on hypoxic CFs’ transformation into myofibroblasts, cell migration and collagen deposition. Excessive myocardial fibrosis can cause adverse cardiac remodeling, leading to malignant arrhythmia and even heart failure.

The present study outlines the many risk variables of myocardial infarction (MI) in the patient population. Blood lipid profiles were normolipidemic in the study’s subjects. Myocardial infarction patients and controls were compared concerning their lipid, lipoprotein, and apolipoprotein profiles. Materials & methods: In this study, 84 participants had their blood cholesterol, Apolipoprotein-A, LDL, VLDL, HDL, triacylglycerols, and malondialdehyde studied. Out of the total number of participants, 42 were individuals who had suffered a myocardial infarction (MI). In contrast, the other 42 were controls matched for age and sex. Results: Acute myocardial infarction (MI) patients had significantly elevated levels of total cholesterol and triacylglycerols (TAGs) (p <0.05) despite the presence of low-density lipoprotein (LDL) in their blood. A significant difference was seen between the levels of apolipoprotein-A and low-density lipoprotein in the MI group and those in the control group. Researchers found that those who had a rapid heart attack exhibited significantly higher levels of malondialdehyde (p<0.05). Conclusion: For individuals diagnosed with risk factors, lipid profile monitoring, dietary antioxidant consumption, and measurement of inflammatory markers can all help lower the risk of myocardial infarction (MI). Furthermore, early detection can prevent MI. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are the leading cause of global mortality among non-communicable diseases. Current cardiac regeneration treatments have limitations and may lead to adverse reactions. Hence, innovative technologies are needed to address these shortcomings. Messenger RNA (mRNA) emerges as a promising therapeutic agent due to its versatility in encoding therapeutic proteins and targeting "undruggable" conditions. It offers low toxicity, high transfection efficiency, and controlled protein production without genome insertion or mutagenesis risk. However, mRNA faces challenges such as immunogenicity, instability, and difficulty in cellular entry and endosomal escape, hindering its clinical application. To overcome these hurdles, lipid nanoparticles (LNPs), notably used in COVID-19 vaccines, have a great potential to deliver mRNA therapeutics for CVDs. This review highlights recent progress in mRNA-LNP therapies for CVDs, including Myocardial Infarction (MI), Heart Failure (HF), and hypercholesterolemia. In addition, LNP-mediated mRNA delivery for CAR T-cell therapy and CRISPR/Cas genome editing in CVDs and the related clinical trials are explored. To enhance the efficiency, safety, and clinical translation of mRNA-LNPs, advanced technologies like artificial intelligence (AGILE platform) in RNA structure design, and optimization of LNP formulation could be integrated. We conclude that the strategies to facilitate the extra-hepatic delivery and targeted organ tropism of mRNA-LNPs (SORT, ASSET, SMRT, and barcoded LNPs) hold great prospects to accelerate the development and translation of mRNA-LNPs in CVD treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. The success of modRNA-based COVID-19 vaccines has demonstrated that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases, including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options, and MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and mitigates cardiac dysfunction. However, it remains unclear whether early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. We hypothesized that CCN5 would alleviate the adverse effects of myocardial infarction (MI) through its anti-fibrotic properties under stress conditions. To induce the rapid expression of CCN5, ModRNA-CCN5 was synthesized and administrated directly into the myocardium in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: (1) preventive intervention and (2) therapeutic intervention. Functional analyses, including echocardiography and magnetic resonance imaging (MRI), along with molecular assays, demonstrated that modRNA-mediated CCN5 gene transfer significantly attenuated cardiac fibrosis and improved cardiac function in both preventive and therapeutic models, without causing left ventricular rupture or any adverse cardiac remodeling. In conclusion, early intervention in CF by ModRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure. [ABSTRACT FROM AUTHOR]

Abstract Background Myocardial infarction (MI) poses a global public health challenge, often associated with elevated mortality rates and a grim prognosis. A crucial aspect of the inflammatory injury and healing process post-MI involves the dynamic differentiation of macrophages. A promising strategy to alleviate myocardial damage after MI is by modulating the inflammatory response and orchestrating the shift from pro-inflammatory (M1) to anti-inflammatory (M2) macrophages, aiming to achieve a reduced M1/M2 ratio. Nuanxinkang (NXK), a simplified herbal decoction, has demonstrated noteworthy cardioprotective, inflammation-regulating, and myocardial energy metabolism-regulating properties. Methods In this study, we constructed an MI model by ligating coronary arteries to investigate the efficacy of NXK in improving ventricular remodeling and cardiac function. Mice were administered NXK (1.65 g/kg/d) or an equivalent volume of regular saline via gavage for 28 consecutive days, commencing the day after surgery. Then, we conducted echocardiography to assess the cardiac function, Masson staining to illustrate the extent of myocardial fibrosis, TUNEL staining to reveal myocardial apoptosis, and flow cytometry to analyze the polarization of M1 and M2 macrophages in the hearts. Besides, a lipopolysaccharide (LPS)-induced pro-inflammatory macrophage (M1) polarization model was implemented in RAW264.7 cells to elucidate the underlying mechanism of NXK in regulating macrophage polarization. RAW264.7 cells were pre-treated with or without NXK-containing serum. Oxidative stress was detected by MitoSox staining, followed by Seahorse energy metabolism assay to evaluate alterations in mitochondrial metabolic patterns and ATP production. Both In vivo and in vitro, HIF-1α and PDK1 were detected by fluorescent quantitative PCR and Western blotting. Results In vivo, MI mice exhibited a decline in cardiac function, adverse ventricular remodeling, and an increase in glycolysis, coupled with M1-dominant polarization mediated by the HIF-1α/PDK1 axis. Notably, robust responses were evident with high-dose NXK treatment (1.65 g/kg/day), leading to a significant enhancement in cardiac function, inhibition of cardiac remodeling, and partial suppression of macrophage glycolysis and the inflammatory phenotype in MI mice. This effect was achieved through the modulation of the HIF-1α/PDK1 axis. In vitro, elevated levels of mitochondrial ROS production and glycolysis were observed in LPS-induced macrophages. Conversely, treatment with NXK notably reduced the oxidative stress damage induced by LPS and enhanced oxidative phosphorylation (OXPHOS). Furthermore, NXK demonstrated the ability to modify the energy metabolism and inflammatory characteristics of macrophages by modulating the HIF-1α/PDK1 axis. The influence of NXK on this axis was partially counteracted by the HIF-1α agonist DMOG. And NXK downregulated PDK1 expression, curtailed glycolysis, and reversed LPS-induced M1 polarization in macrophages, similar to the PDK1 inhibitor DCA. Conclusion In conclusion, NXK protects against MI-induced cardiac remodeling by inducing metabolic reprogramming and phenotypic differentiation of macrophages, achieved through the modulation of the HIF-1α/PDK1 axis. This provides a novel and promising strategy for the treatment of MI.

Abstract Worldwide, myocardial infarction (MI) is the leading cause of death and disability-adjusted life years lost. Recent researches explored new methods of detecting biomarkers that can predict the risk of developing myocardial infarction, which includes identifying genetic markers associated with increased risk. We induced myocardial infarction in mice by occluding the left anterior descending coronary artery and performed TTC staining to assess cell death. Next, we performed ChIP assays to measure the enrichment of histone modifications at the promoter regions of key genes involved in mitochondrial fission. We used qPCR and western blot to measure expression levels of relative apoptotic indicators. We report that miR-181a inhibits myocardial ischemia-induced apoptosis and preserves left ventricular function after MI. We show that programmed cell death protein 4 (PDCD4) is the target gene involved in miR-181a-mediated anti-ischemic injury, which enhanced BID recruitment to the mitochondria. In addition, we discovered that p53 inhibits the expression of miR-181a via transcriptional regulation. Here, we discovered for the first time a mitochondrial fission and apoptosis pathway which is controlled by miR-181a and involves PDCD4 and BID. This pathway may be controlled by p53 transcriptionally, and we presume that miR-181a may lead to the discovery of new therapeutic and preventive targets for ischemic heart diseases.

Background: Myocardial infarction (MI) poses a global public health challenge, often associated with elevated mortality rates and a grim prognosis. A crucial aspect of the inflammatory injury and healing process post-MI involves the dynamic differentiation of macrophages. A promising strategy to alleviate myocardial damage after MI is by modulating the inflammatory response and orchestrating the shift from pro-inflammatory (M1) to anti-inflammatory (M2) macrophages, aiming to achieve a reduced M1/M2 ratio. Nuanxinkang (NXK), a simplified herbal decoction, has demonstrated noteworthy cardioprotective, inflammation-regulating, and myocardial energy metabolism-regulating properties. Methods: In this study, we constructed an MI model by ligating coronary arteries to investigate the efficacy of NXK in improving ventricular remodeling and cardiac function. Mice were administered NXK (1.65 g/kg/d) or an equivalent volume of regular saline via gavage for 28 consecutive days, commencing the day after surgery. Then, we conducted echocardiography to assess the cardiac function, Masson staining to illustrate the extent of myocardial fibrosis, TUNEL staining to reveal myocardial apoptosis, and flow cytometry to analyze the polarization of M1 and M2 macrophages in the hearts. Besides, a lipopolysaccharide (LPS)-induced pro-inflammatory macrophage (M1) polarization model was implemented in RAW264.7 cells to elucidate the underlying mechanism of NXK in regulating macrophage polarization. RAW264.7 cells were pre-treated with or without NXK-containing serum. Oxidative stress was detected by MitoSox staining, followed by Seahorse energy metabolism assay to evaluate alterations in mitochondrial metabolic patterns and ATP production. Both In vivo and in vitro, HIF-1α and PDK1 were detected by fluorescent quantitative PCR and Western blotting. Results: In vivo, MI mice exhibited a decline in cardiac function, adverse ventricular remodeling, and an increase in glycolysis, coupled with M1-dominant polarization mediated by the HIF-1α/PDK1 axis. Notably, robust responses were evident with high-dose NXK treatment (1.65 g/kg/day), leading to a significant enhancement in cardiac function, inhibition of cardiac remodeling, and partial suppression of macrophage glycolysis and the inflammatory phenotype in MI mice. This effect was achieved through the modulation of the HIF-1α/PDK1 axis. In vitro, elevated levels of mitochondrial ROS production and glycolysis were observed in LPS-induced macrophages. Conversely, treatment with NXK notably reduced the oxidative stress damage induced by LPS and enhanced oxidative phosphorylation (OXPHOS). Furthermore, NXK demonstrated the ability to modify the energy metabolism and inflammatory characteristics of macrophages by modulating the HIF-1α/PDK1 axis. The influence of NXK on this axis was partially counteracted by the HIF-1α agonist DMOG. And NXK downregulated PDK1 expression, curtailed glycolysis, and reversed LPS-induced M1 polarization in macrophages, similar to the PDK1 inhibitor DCA. Conclusion: In conclusion, NXK protects against MI-induced cardiac remodeling by inducing metabolic reprogramming and phenotypic differentiation of macrophages, achieved through the modulation of the HIF-1α/PDK1 axis. This provides a novel and promising strategy for the treatment of MI. Highlights: Balancing the coordination between M1 and M2 macrophages emerges as a promising therapeutic strategy for addressing myocardial infarction. Metabolic reprogramming plays a crucial role in the activation and differentiation of macrophages. NXK formulation intricately regulates macrophage polarization through the HIF-1α/PDK1 axis within a metabolic-inflammatory network. [ABSTRACT FROM AUTHOR]

Worldwide, myocardial infarction (MI) is the leading cause of death and disability-adjusted life years lost. Recent researches explored new methods of detecting biomarkers that can predict the risk of developing myocardial infarction, which includes identifying genetic markers associated with increased risk. We induced myocardial infarction in mice by occluding the left anterior descending coronary artery and performed TTC staining to assess cell death. Next, we performed ChIP assays to measure the enrichment of histone modifications at the promoter regions of key genes involved in mitochondrial fission. We used qPCR and western blot to measure expression levels of relative apoptotic indicators. We report that miR-181a inhibits myocardial ischemia-induced apoptosis and preserves left ventricular function after MI. We show that programmed cell death protein 4 (PDCD4) is the target gene involved in miR-181a-mediated anti-ischemic injury, which enhanced BID recruitment to the mitochondria. In addition, we discovered that p53 inhibits the expression of miR-181a via transcriptional regulation. Here, we discovered for the first time a mitochondrial fission and apoptosis pathway which is controlled by miR-181a and involves PDCD4 and BID. This pathway may be controlled by p53 transcriptionally, and we presume that miR-181a may lead to the discovery of new therapeutic and preventive targets for ischemic heart diseases. [ABSTRACT FROM AUTHOR]

BackgroundMyocardial infarction (MI), a critical condition, substantially affects patient outcomes and mortality rates. Long non-coding RNAs (lncRNAs) play a critical role in the onset and progression of MI. This study aimed to explore the related research on MI-related lncRNAs from a bibliometric perspective, providing new clues and directions for researchers in the field.MethodsA comprehensive search was conducted on 7 August 2023, using the Web of Science Core Collection (WoSCC) database to compile a dataset of all English-language scientific journals. The search gathered all relevant publications from January 2000 to August 2023 that pertain to MI-related lncRNAs. Data on countries, institutions, journals, authors, and keywords were collected, sorted, statistically analyzed, and visualized using CiteSpace 6.2.R4, VOSviewer 1.6.19, an online bibliometric analysis platform (http://bibliometric.com), and the bibliometric package in R-Studio 4.3.1. Articles were screened by two independent reviewersResultsBetween January 2000 and August 2023, a total of 1,452 papers were published in the research field of MI-related lncRNAs. The year with the most publications was 2020, accounting for 256 papers. The publication volume displayed an exponential growth trend, fitting the equation y = 2.0215e0.2786x, R^2 = 0.97. In this domain, China leads in both the number of published papers (N = 1,034) and total citations, followed by the United States, Germany, Iran, and Italy. The most productive institution is Harbin Medical University (N = 144). The European Review for Medical and Pharmacological Sciences had the highest number of publications (N = 46), while Circulation Research had the most citations (TC = 4,537), indicating its irreplaceable standing in this field. Research mainly focuses on the cardiovascular system, cellular biology, physiology, etc. The most productive author is Zhang Y. Apart from “Myocardial Infarction” and “LncRNA,” the most frequent keywords include “expression,” “atherosclerosis,” and “apoptosis.” Cluster analysis suggests current research themes concentrate on cardiovascular diseases and gene expression, cardiac ischemia/reperfusion injury and protection, expression and proliferation, atherosclerosis and inflammatory response, among others. Keyword bursts indicate recent hot topics as targeting, autophagy, etc.ConclusionThis bibliometric analysis reveals that research on MI-related lncRNAs has rapidly expanded between January 2000 and August 2023, primarily led by China and the United States. Our study highlights the significant biological roles of lncRNAs in the pathogenesis and progression of MI, including their involvement in gene expression regulation, atherosclerosis development, and apoptosis. These findings underscore the potential of lncRNAs as therapeutic targets and biomarkers for MI. Additionally, our study provides insights into the features and quality of related publications, as well as the future directions in this research field. There is a long road ahead, highlighting the urgent need for enhanced global academic exchange.

Myocardial infarction (MI), widely referred to as a heart attack, is a leading reason for deaths worldwide. It is frequently caused by coronary artery occlusion, resulting in inadequate oxygen and blood supply, which damages the myocardial structure and function. Therefore, innovative diagnostic methods are required for reliable and timely identification of MI. The typical 12-lead electrocardiogram (ECG) technology causes patient discomfort and makes cardiac monitoring challenging. The frontal, sagittal, and transverse planes (3 orthogonal planes) are where vectorcardiogram (VCG) renders an edge over 12-lead ECG. This study, proposes a method for detecting MI utilising VCG signals of four seconds. Circulant singular spectrum analysis (CSSA) and four stage savitzky-golay (SG) filter were used in the filtering stage for the removal of power-line interference and base-line wander. The signal was time-invariantly decomposed using the CSSA, then features were extracted. The binary harry hawks-based feature selection method is employed on the extracted features to choose the optimal feature subspace which was followed by supervised machine learning based classification. The 10-fold cross validation, an even more practical leave-one-out (LOO) cross validation approach, and inter dataset cross validation (IDCV) were used to evaluate the reliability of the suggested method. Voting-based ensemble classification was used in LOO, IDCV validation, which improves the accuracy of this method. The proposed technique achieved an accuracy of 99.97%, 91.03%, and 99.41% for 10-fold, LOO cross validation, and IDCV, out-performing the state-of-the-art methods in the cross validation scenarios. The proposed technique results in an accurate detection of MI. Successful accomplishment of the LOO cross validation demonstrates the applicability and dependability of the suggested technique in the health care applications.

Myocardial infarction (MI) stands as a prominent contributor to global cardiovascular disease (CVD) mortality rates. Acute MI (AMI) can result in the loss of a large number of cardiomyocytes (CMs), which the adult heart struggles to replenish due to its limited regenerative capacity. Consequently, this deficit in CMs often precipitates severe complications such as heart failure (HF), with whole heart transplantation remaining the sole definitive treatment option, albeit constrained by inherent limitations. In response to these challenges, the integration of bio-functional materials within cardiac tissue engineering has emerged as a groundbreaking approach with significant potential for cardiac tissue replacement. Bioengineering strategies entail fortifying or substituting biological tissues through the orchestrated interplay of cells, engineering methodologies, and innovative materials. Biomaterial scaffolds, crucial in this paradigm, provide the essential microenvironment conducive to the assembly of functional cardiac tissue by encapsulating contracting cells. Indeed, the field of cardiac tissue engineering has witnessed remarkable strides, largely owing to the application of biomaterial scaffolds. However, inherent complexities persist, necessitating further exploration and innovation. This review delves into the pivotal role of biomaterial scaffolds in cardiac tissue engineering, shedding light on their utilization, challenges encountered, and promising avenues for future advancement. By critically examining the current landscape, we aim to catalyze progress toward more effective solutions for cardiac tissue regeneration and ultimately, improved outcomes for patients grappling with cardiovascular ailments.

Stimulating cardiomyocyte proliferation in the adult heart has emerged as a promising strategy for cardiac regeneration following myocardial infarction (MI). The NRG1-ERBB4 signaling pathway has been implicated in the regulation of cardiomyocyte proliferation. However, the therapeutic potential of recombinant human NRG1 (rhNRG1) has been limited due to the low expression of ERBB4 in adult cardiomyocytes. Here, we investigated whether a fusion protein of rhNRG1 and an ERBB3 inhibitor (rhNRG1-HER3i) could enhance the affinity of NRG1 for ERBB4 and promote adult cardiomyocyte proliferation. In vitro and in vivo experiments were conducted using postnatal day 1 (P1), P7, and adult cardiomyocytes. Western blot analysis was performed to assess the expression and activity of ERBB4. Cardiomyocyte proliferation was evaluated using Ki67 and pH 3 immunostaining, while fibrosis was assessed using Masson staining. Our results indicate that rhNRG1-HER3i, but not rhNRG1, promoted P7 and adult cardiomyocyte proliferation. Furthermore, rhNRG1-HER3i improved cardiac function and reduced cardiac fibrosis in post-MI hearts. Administration of rhNRG1-HER3i inhibited ERBB3 phosphorylation while increasing ERBB4 phosphorylation in adult mouse hearts. Additionally, rhNRG1-HER3i enhanced angiogenesis following MI compared to rhNRG1. In conclusion, our findings suggest that rhNRG1-HER3i is a viable therapeutic approach for promoting adult cardiomyocyte proliferation and treating MI by enhancing NRG1-ERBB4 signaling pathway. [Display omitted] • rhNRG1 has been limited due to the low expression of ERBB4 in adult cardiomyocytes. • Here, we find a fusion protein rhNRG1-HER3i could enhance the affinity for ERBB4. • rhNRG1-HER3i could promoted P7 and adult cardiomyocyte proliferation. [ABSTRACT FROM AUTHOR]

Background:The myocardial infarction, commonly known as heart attack, is caused by coronary artery disease, and it remains a major cause of mortality globally. Since MI is prevalent in both developed and developing countries, there is need for a simple and cost effective tool for screening. Hereby we shall study the north Indian population with its genetic disposition on myocardial infarction in co-relation with the dermatoglyphic pattern of palm and fingers. According to the available literature, there has been found a genetic correlation between the dermatoglyphics and myocardial infarction. The present study is also to test the same hypothesis to find out any correlation and its uses as a diagnostic tool. The present study was conducted after taking informed consent form from 150 patients of myocardial infarction as cases while 150 normal health individual were included in the study as controls. Fingerprints were taken using the method described by Cummin and Mildo [1,2]. The earlier studies shows that the important palmar dermatoglyphics pattern that are a-b ridge count and atd angle have a specific position and pattern which is markedly different in Myocardial infarction cases and control. On statistical analysis a small decrease in the mean value of ab ridge count was reported in Myocardial Infarction males and Myocardial Infarction (M+F), when compared with controls. On the contrary there was a small increase in mean value of ab ridge count in Myocardial Infarction females as compared to control females. In case of atd angle, it was reported that there is increase in the mean value of at angle in Myocardial infarction males and females as compared to controls. Similarly the increase was also found in both right and left hands in Myocardial Infarction when compared between the two groups. Dermatoglyphics and Myocardial infarction has shown a close correlation due to genetic disposition. Thus it can be used as one of the cost effective diagnostic tool for early diagnosis of pre disposition of Myocardial Infarction. [ABSTRACT FROM AUTHOR]

Cardiac fibroblasts (CFs) are of vital importance for post-myocardial infarction (MI) remodeling. This study explored the role of Placenta specific 8 (Plac8) in MI on the basis of single-cell RNA-Seq (scRNA-Seq) data (GSE136088) and micro-array data (GSE153485). Through bioinformatics analysis, Plac8 was finally identified as a key gene related to fibroblasts. In addition, primary CFs of the neonatal mice were isolated, cultured and treated with hypoxia for in vitro cell model construction. Hydroxyproline assay demonstrated enhanced collagen production in hypoxic CFs, and qRT-PCR revealed increased relative contents of type I and type III collagen (Col1a1 and Col3a1). Western blot showed increased protein expression level of α-smooth muscle actin (α-SMA), and transwell assay and wound-healing assay collectively suggested enhanced cell migration. Moreover, Plac8 was found to be upregulated in hypoxic CFs. Then, after transfection with siNC or siPlac8, it was revealed that down-regulating Plac8 protein expression in hypoxic CFs reduced the levels of collagen secretion, the number of activated CFs and the degree of cell migration, indicating the regulation of Plac8 on hypoxic CFs' transformation into myofibroblasts, cell migration and collagen deposition. Excessive myocardial fibrosis can cause adverse cardiac remodeling, leading to malignant arrhythmia and even heart failure. [ABSTRACT FROM AUTHOR]

Background: Multifaceted etiology of cardiovascular diseases (CVD), especially coronary heart disease, has been recognized for a long time. The Metabolic syndrome (METS) is a specific clustering of cardiovascular risk factors in the same person (abdominal obesity, atherogenic dyslipidemia, elevated blood pressure (BP), insulin resistance (IR), a prothrombotic and a proinflammatory state. Aims and Objectives: To evaluate the prognosis of Myocardial Infarction (STEMI & N-STEMI) in patients with Metabolic Syndrome in our tertiary care hospital. Materials And Methods: Total of 154 Patients have been reported for diagnosis in our hospital. A final diagnosis of Myocardial Infarction (MI) was made in the presence of serial increases in serum biochemical markers of cardiac necrosis, associated with typical electrocardiographic changes and/or typical symptoms as defined by the joint committee of the European society of cardiology and the American college of cardiology. A detailed case history was taken including the symptoms, history of diabetes mellitus, hypertension (HT), smoking and alcohol consumption. A careful physical examination was done with special reference to resting blood pressure (BP), waist circumference (WC), height and weight. Results and Observations: As we sampled a total of 154 Patients, 77 patients with MI and METS and 77 Patients without MI and METS into two groups 1 & 2. There were 39 (50.66%) cases of heart failure among patients of MI with METS compared to 18 (24.00%) cases of heart failure among patients of MI without METS, and the difference was statistically significant. Postoperative analgesic requirement was seen in 64 % of the patients of group 1 while it was seen in 16 % of the patients in group 2. Conclusion: The main finding of present study was that the Metabolic Syndrome was a meaningful predictor of in-hospital death in patients with STEMI. During one week of hospital stay there were significantly more deaths and heart failure among patients of MI with METS compared to patients of MI without METS (50.66% and 25.33% vs. 24% and 14.66%). Though the number of patients who developed other complications like recurrent MI, VT (Ventricular Tachycardia), VF (Ventricular Fibrillation) and Stroke were more in patients of MI with METS when compared to patients of MI without METS, The difference was not statistically significant. [ABSTRACT FROM AUTHOR]

Background: When it comes to identifying an acute myocardial infarction, ECG is both sensitive and specific. For a prompt evaluation of the effectiveness of reperfusion treatment in acute ST- elevation myocardial infarction (STEMI), simple and quick assessments are required. Although successful recanalization of the epicardial vessel is a prerequisite, micro vascular flow is the factor that most closely predicts the outcome. ST segment changes, which reflect myocardial rather than epicardial flow, provide prognostic information beyond that offered by a coronary angiogram alone. It has been demonstrated that failure to resolve ST segment alterations after thrombolysis is a predictor of a worse long-term result in comparison to the cohort with resolution. There hasn't been a lot of research on using ECG to gauge the state of LV function or ST segment changes following thrombolytic therapy for AMI. We thus conducted this study to evaluate the ECG changes in AMI patients treated with thrombolytic therapy at a tertiary care centre in eastern Gujarat. Methodology: This was a retrospective, descriptive, cross-sectional study at a tertiary care medical college and hospital in Eastern Gujarat. A baseline conventional 12 lead ECG was performed on admission and at 1 hr, 3 hr, 6 hr and 12 hr following thrombolysis and in between if the patient showed arrhythmias. Data was collected for each patient using hospital records. Demographic and clinical data was collected in a pre-structured proforma. All the data was tabulated in Microsoft Excel and Statistical analysis was done using SPSS program (version20). Results: Majority were from the age group of 51 to 70 years with 38 cases (38%). There were 68% males. We observed that the most common cases were from inferior wall MI with 42 cases (42%), Inferoposterior wall M.I. with 26 cases (26%). Out of 42 patients with Inferior wall MI, we observed that 26 patients had >50% regression at 1 hour. Out of 26 patients with Infero-posterior wall MI 9 patients had >50% regression in 1 hours. Antereoseptal wall M.I. there were 16 cases with Antereoseptal wall M.I. 7 patients had >50% regression in 1 hour post SK ECG. Conclusion: Premature recording of the ST segment and T wave after acute myocardial infarction is a sensitive, reasonably specific, and easily recognizable ECG manifestation. Also, reperfusion is associated with accelerated evolution and deepening of the T waves following acute myocardial infarction. So, efforts to improve the delivery of thrombolytic therapy in the emergency department should include a focus on electrocardiographic interpretation skills. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD) is a very common disease with an estimated 442 million cases worldwide. It is a well-documented independent risk factor for many gastrointestinal pathologies, however, its role in cardiovascular disease (CVD) is unclear, despite its high prevalence in patients with CVD. Although traditionally considered a causative agent of noncardiac chest pain, a common imitator of cardiac chest pain, or an incidentally shared comorbidity in patients with CVD, a number of studies have implicated GERD and its therapies as risk factors for CVD. This narrative review will explore the relationship between GERD and CVD, including medical and mechanical therapeutic approaches for GERD that could potentially impact the incidence, progression, and mortality of CVD. [ABSTRACT FROM AUTHOR]

Purpose: Heart failure (HF) remains a major cause of late morbidity and mortality after myocardial infarction (MI). To date, no clinically established 18F-labeled sympathetic nerve PET tracers for monitoring myocardial infarction are available. Therefore, in this study, we synthesized a series of 18F-labeled benzyl guanidine analogs and evaluated their efficacy as cardiac neuronal norepinephrine transporter (NET) tracers for myocardial imaging. We also investigated the preliminary diagnostic capabilities of these tracers in myocardial infarction animal models, as well as the structure-activity relationship of these tracers. Procedures: Three benzyl guanidine-NET tracers, including [18F]1, [18F]2, and [18F]3, were synthesized and evaluated in vivo as PET tracers in a myocardial infarction mouse model. [18F]LMI1195 was used as a positive control for the tracers. H&E staining of the isolated myocardial infarction heart tissue sections was performed to verify the efficacy of the selected PET tracer. Results: Our data show that [18F]3 had a moderate decay corrected labeling yield (~10%) and high radiochemical purity (>95%) compared to other tracers. The uptake of [18F]3 in normal mouse hearts was 1.7±0.1%ID/cc at 1 h post-injection (p. i.), while it was 2.4±0.1, 2.6±0.9, and 2.1±0.4%ID/cc in the MI mouse hearts at 1, 2, and 3 days after surgery, respectively. Compared with [18F]LMI1195, [18F]3 had a better myocardial imaging effect in terms of the contrast between normal and MI hearts. The area of myocardial infarction shown by PET imaging corresponded well with the infarcted tissue demonstrated by H&E staining. Conclusions: With an obvious cardiac uptake contrast between normal mice and the myocardial infarction mouse model, [18F]3 appears to be a potential tool in the diagnosis of myocardial infarction. Therefore, it is necessary to conduct further structural modification studies on the chemical structure of [18F]3 to improve its in vivo stability and diagnostic detection ability to achieve reliable and practical imaging effects. [ABSTRACT FROM AUTHOR]

Abstract Aims Lactate/albumin ratio (L/A) is a recognized prognostic index of patients with heart failure (HF) after myocardial infarction (MI). We aim to evaluate the prognostic value of L/A ratio in predicting in‐hospital mortality for those patients. Methods and results We enrolled qualified patients from Medical Information Mart for Intensive Care IV database for retrospective study. A receiver operating characteristic (ROC) curve of the subjects was applied to determine the predicted value and the best cut‐off value of L/A on admission. Univariate/multivariate Cox regression analysis and restricted cubic splines (RCS) were performed to identify the association between hospital admission and hospital mortality. The Kaplan–Meier (KM) method was used to draw the survival curve of the two groups with different L/A levels at admission. L/A values at admission were significantly higher in the death groups than the survival groups [1.36 (1.20) vs. 0.62 (0.36), P

BackgroundStent thrombosis (ST) is an uncommon but serious complication of stent implantation. This study aimed to explore factors associated with early, late, and very late ST to help guide risk assessment and clinical decision-making on ST.MethodsThe analysis included patients who received stent placement for the index acute coronary syndrome (ACS). Cumulative incidence of ST was assessed at 30 days (early ST), 31–360 days (late ST), 361–720 days (very late ST), and up to 720 days. Cox proportional hazards models were used to assess associations between ST and various factors, including patient characteristics [i.e., age, sex, ACS presentation, history of hypertension, smoking, diabetes, prior myocardial infarction (MI), heart failure, prior ischemic stroke, and cancer], laboratory tests [i.e., positive cardiac biomarker, hemoglobin, platelet count, white blood cell (WBC) count], and treatment [i.e., drug-eluting stent (DES) vs. bare-metal stent (BMS) and anticoagulant with rivaroxaban vs. placebo].ResultsAmong the 8,741 stented patients, 155 ST events (2.25%) occurred by Day 720. The cumulative incidences of early, late, and very late ST were 0.80%, 0.81%, and 0.77%, respectively. After multivariable adjustment, age ≥ 75 [hazard ratio (HR) = 2.13 (95% confidence interval, CI: 1.26–3.60)], a history of prior MI [HR = 1.81 (95% CI: 1.22–2.68)], low hemoglobin level [HR = 2.34 (95% CI: 1.59–3.44)], and high WBC count [HR = 1.58 (95% CI: 1.02–2.46)] were associated with a greater risk of overall ST, whereas DES [HR = 0.56 (95% CI: 0.38–0.83)] and rivaroxaban therapy [HR = 0.63 (95% CI: 0.44–0.88)] were associated with a lower risk of overall ST up to 720 days. Low hemoglobin level and high WBC count were associated with early ST (low hemoglobin: HR = 2.35 [95% CI: 1.34–4.12]; high WBC count: HR = 2.11 [95% CI: 1.17–3.81]). Low hemoglobin level and prior MI were associated with a greater risk of late ST (low hemoglobin: HR = 2.32 [95% CI: 1.26–4.27]; prior MI: HR = 2.98 [95% CI: 1.67–5.31]), whereas DES was associated with a lower risk of late ST [HR = 0.33 (95% CI: 0.16–0.67)]. Age ≥75 years was associated with very late ST.ConclusionThe study identified positive and negative associations with early, late, and very late ST. These variables may be useful in constructing risk assessment models for ST.Clinical Trial Registrationhttp://www.clinicaltrials.gov, identifier NCT00809965.

Objective: This prospective cohort study aimed to investigate the relationship between changes in proteinuria and the risk of myocardial infarction (MI) in individuals with diabetes or pre-diabetes. Methodology: The prospective study was conducted involving 200 participants in India, with data collection occurring during routine medical examinations from 2020 to 2022. The participants were followed up, and data collection concluded in 2023. Results: Among the participants, those with persistent proteinuria exhibited a significantly higher risk of MI, with a 2.5-fold increased hazard compared to those without proteinuria. Furthermore, a reduction in proteinuria over time was associated with a 21% decrease in MI incidence. This relationship was not observed in individuals without proteinuria, highlighting the importance of persistent proteinuria in influencing MI risk. Conclusion: The findings emphasize the critical role of persistent proteinuria as a predictor of elevated MI risk in individuals with diabetes and pre-diabetes. Monitoring and managing proteinuria could potentially mitigate the risk of future heart attacks in this population. Recommendations: Healthcare professionals should consider routine monitoring of proteinuria levels in outpatient settings for individuals with diabetes and pre-diabetes. Exploring interventions to lower proteinuria levels for heart attack prevention is recommended, including lifestyle modifications, medications, or targeted therapies. Improved comprehension of the mechanisms connecting proteinuria to the risk of MI is essential for the formulation of efficient preventive approaches. This study underscores the significance of early detection and management of proteinuria in diabetic patients and pre-diabetics to reduce the risk of myocardial infarction.

Key Clinical Message: Left coronary artery embolism from aortic valve leaflet tissue mass is a rare but potentially life‐threatening complication following transcatheter aortic valve replacement. It is important for interventional cardiologists to be aware of this rare complication for rapid identification and prompt treatment which is the key to a successful outcome. An 81‐year‐old female presented for elective transcatheter aortic valve replacement (TAVR) for severe low‐flow low‐gradient aortic stenosis. Immediately post‐procedure, she developed unexplained, persistent hypotension. There was no bleeding. There was no aortic injury. Activated clotting time was in therapeutic range. Coronary angiography revealed hazy filling defects in left anterior descending and left circumflex. Intravascular ultrasound showed heterogeneous, hypoechoic mass with mild calcification consistent with embolized valve leaflet tissue. This was treated with emergent percutaneous coronary intervention with excellent results. Left coronary artery embolism from aortic valve leaflet tissue is a rare, but potentially life‐threatening complication following TAVR. Prompt recognition is key to a successful outcome. [ABSTRACT FROM AUTHOR]

There has been a proliferation of machine learning (ML) electrocardiogram (ECG) classification algorithms reaching > 85% accuracy for various cardiac pathologies. Although the accuracy within institutions might be high, models trained at one institution might not be generalizable enough for accurate detection when deployed in other institutions due to differences in type of signal acquisition, sampling frequency, time of acquisition, device noise characteristics and number of leads. In this proof-of-concept study, we leverage the publicly available PTB-XL dataset to investigate the use of time-domain (TD) and frequency-domain (FD) convolutional neural networks (CNN) to detect myocardial infarction (MI), ST/T-wave changes (STTC), atrial fibrillation (AFIB) and sinus arrhythmia (SARRH). To simulate interinstitutional deployment, the TD and FD implementations were also compared on adapted test sets using different sampling frequencies 50 Hz, 100 Hz and 250 Hz, and acquisition times of 5 s and 10s at 100 Hz sampling frequency from the training dataset. When tested on the original sampling frequency and duration, the FD approach showed comparable results to TD for MI (0.92 FD – 0.93 TD AUROC) and STTC (0.94 FD – 0.95 TD AUROC), and better performance for AFIB (0.99 FD – 0.86 TD AUROC) and SARRH (0.91 FD – 0.65 TD AUROC). Although both methods were robust to changes in sampling frequency, changes in acquisition time were detrimental to the TD MI and STTC AUROCs, at 0.72 and 0.58 respectively. Alternatively, the FD approach was able to maintain the same level of performance, and, therefore, showed better potential for interinstitutional deployment. [ABSTRACT FROM AUTHOR]

Abstract 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.

The South African flag sign (SAFS) is an acute, dynamic electrocardiographic (ECG) finding typically associated with first diagonal (D1) artery occlusion. We report the case of a 47-year-old woman who exhibited this pattern but subsequently revealed the dreaded "widow-maker" lesion (100% occluded proximal left anterior descending [LAD] artery) and severe multivessel disease (90% stenosis of the posterior left ventricular [PLV] artery and 80% stenosis of the left circumflex artery [LCx]). [ABSTRACT FROM AUTHOR]

Adverse cardiac remodeling, including cardiac fibrosis, after myocardial infarction (MI) is a major cause of long-term heart failure. 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), an enzyme that regulates glucose metabolism, also plays an important role in various fibrotic and cardiovascular diseases. However, its effects on MI remain unknown. Here, PFKFB3 inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) and a permanent left anterior descending ligation mouse model were used to explore the functional role of PFKFB3 in MI. We showed that PFKFB3 expression increased significantly in the area of cardiac infarction during the early phase after MI, peaking on day 3. 3PO treatment markedly improved cardiac function, accompanied by decreased infarction size and collagen density in the infarct area. Meanwhile, 3PO attenuated cardiac fibrosis after MI by reducing the expression of collagen and fibronectin in murine hearts. Notably, 3PO reduced PFKFB3 expression and inhibited the transforming growth factor-beta 1/mothers against the decapentaplegic homolog 2/3 (TGF-β1/SMAD2/3) signaling pathway to inhibit cardiac fibrosis after MI. Moreover, PFKFB3 expression in neonatal rat cardiac fibroblasts (NRCFs) increased significantly after MI and under hypoxia, whereas 3PO alleviated the migratory capacity and activation of NRCFs induced by TGF-β1. In conclusion, 3PO effectively reduced fibrosis and improved adverse cardiac remodeling after MI, suggesting PFKFB3 inhibition as a novel therapeutic strategy to reduce the incidence of chronic heart failure following MI. [ABSTRACT FROM AUTHOR]

Connexin 43 (Cx43) is expressed in the left and right ventricles and is primarily responsible for conducting physiological responses in microvasculature. Studies have demonstrated that NADPH oxidase (NOX) enzymes are essential in cardiac redox biology and are responsible for the generation of reactive oxygen species (ROS). NOX2 is linked to left ventricular remodeling following myocardial infarction (MI). It was hypothesized that conjugated linoleic acid (cLA) treatment increases NOX-2 levels in heart tissue and disrupts connexins between the myocytes in the ventricle. Data herein demonstrate that cLA treatment significantly decreases survival in a murine model of MI. The observance of cLA-induced ventricular tachyarrhythmia's (VT) led to the subsequent investigation of the underlying mechanism in this MI model. Mice were treated with cLA for 12 h, 24 h, 48 h, or 72 h to determine possible time-dependent changes in NOX and Cx43 signaling pathways in isolated left ventricles (LV) extracted from cardiac tissue. The results suggest that ROS generation, through the stimulation of NOX2 in the LV, triggers a decrease in Cx43 levels, causing dysfunction of the gap junctions following treatment with cLA. This cascade of events may initiate VT and subsequent death during MI. Taken together, individuals at risk of MI should use caution regarding cLA consumption. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarction (MI) is a common cardiac condition with a high incidence of morbidity and mortality. Despite extensive medical treatment for MI, the development and outcomes of post-MI heart failure (HF) continue to be major factors contributing to poor post-MI prognosis. Currently, there are few predictors of post-MI heart failure. Methods: In this study, we re-examined single-cell RNA sequencing and bulk RNA sequencing datasets derived from the peripheral blood samples of patients with myocardial infarction, including patients who developed heart failure and those who did not develop heart failure after myocardial infarction. Using marker genes of the relevant cell subtypes, a signature was generated and validated using relevant bulk datasets and human blood samples. Results: We identified a subtype of immune-activated B cells that distinguished post-MI HF patients from non-HF patients. Polymerase chain reaction was used to confirm these findings in independent cohorts. By combining the specific marker genes of B cell subtypes, we developed a prediction model of 13 markers that can predict the risk of HF in patients after myocardial infarction, providing new ideas and tools for clinical diagnosis and treatment. Conclusion: Sub-cluster B cells may play a significant role in post-MI HF. We found that the STING1, HSPB1, CCL5, ACTN1, and ITGB2 genes in patients with post-MI HF showed the same trend of increase as those without post-MI HF. [ABSTRACT FROM AUTHOR]

Aims: Lactate/albumin ratio (L/A) is a recognized prognostic index of patients with heart failure (HF) after myocardial infarction (MI). We aim to evaluate the prognostic value of L/A ratio in predicting in‐hospital mortality for those patients. Methods and results: We enrolled qualified patients from Medical Information Mart for Intensive Care IV database for retrospective study. A receiver operating characteristic (ROC) curve of the subjects was applied to determine the predicted value and the best cut‐off value of L/A on admission. Univariate/multivariate Cox regression analysis and restricted cubic splines (RCS) were performed to identify the association between hospital admission and hospital mortality. The Kaplan–Meier (KM) method was used to draw the survival curve of the two groups with different L/A levels at admission. L/A values at admission were significantly higher in the death groups than the survival groups [1.36 (1.20) vs. 0.62 (0.36), P < 0.05], and area under the ROC curve [0.780 (95% confidence interval, 0.772–0.827)] was better than other indicators, and the best the cut‐off value was 0.671. Data of Cox regression analysis showed that higher L/A value supposed to be an independent risk factor for in‐hospital mortality. RCS analysis showed evidence of an increasing trend and a non‐linear relationship between L/A and in‐hospital mortality (P value was non‐linear <0.05). KM survival curves were significantly lower in the high L/A group than the low L/A group (P < 0.001), and the former group had an increased risk of in‐hospital mortality compared with the latter one (log rank P < 0.001). Conclusions: Elevated L/A ratio on admission is an independent predictor of high in‐hospital mortality in post‐MI heart failure patients, which proved to be better than lactate, Sequential Organ Failure Assessment score and other related indicators. [ABSTRACT FROM AUTHOR]