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Objective To investigate the effects of basic fibro-blast growth factor (FGF-2) and Panax notoginseng saponins (PNS) alone or combined together on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into cardiomyocytes (CMs) and the mechanism of action of PNS and FGF-2 in the differentiation. Methods BMSCs were isolated from 3-week-old SD rats (20~30 g) by whole bone marrow adherence, and then the purity of BMSCs was identified by flow cytometry. After the purity was qualified, PNS and FGF-2 alone or in combination, or combined with LY294002 (phosphatidylinositol 3 kinase inhibitor), were used to induce BMSCs to differentiate. According to the corresponding culture time, the cells were divided into control group, PNS group, FGF-2 group, and PNS+FGF-2 group. The expression levels of Desmin and Cx43 after induction were detected by immunohistochemical assay. Western blotting was used to measure the expression levels of myocardium-specific proteins, related pathway proteins, and apoptosis-related proteins. RT-qPCR was conducted to detect the expression of myocardial transcription factors. Results The expression levels of myocardium-specific proteins and genes were increased in each single induction group (PNS group and FGF-2 group) and combined induction group (PNS+FGF-2 group, P < 0.05), and the highest expression levels were observed in the combined group. PNS and FGF-2 combined with LY294002 decreased the expression levels of myocardium-specific proteins and genes, decreased the phosphorylation of pathway-related protein Akt, decreased the level of Bcl-2, increased the level of Bax, and decreased the ratio of Bcl-2/Bax when compared with the 2 single induction groups (P < 0.05). Conclusion Both PNS and FGF-2 can induce BMSCs to differentiate into CMs after induction, and the combined induction is more effective in the differentiation. The PI3K/Akt signaling pathway is involved in the differentiation process by PNS and FGF-2, and PNS and FGF-2 play a role in reducing apoptosis.

Introduction: Myocardial ischemia-reperfusion injury is a set of cellular and molecular patho-mechanisms that lead to the death of living cardiomyocytes and compromised cardiac function. The aim of this study was to determine the effect of moderate intensity interval training on the expression of RIPK-1, RIPK-3 and MLKL genes in the heart of male heart attack model rats. Methods: In this experimental study, thirty 16-week-old male Wistar rats weighing 220 to 280 gr were randomly divided into three groups: control (healthy), myocardial infarction (MI), and moderate intensity interval training. Myocardial infarction was performed by direct intervention with occlusion in the left anterior descending artery (LAD) for 30 minutes. Interval training protocol was performed three days a week, for 8 weeks, with moderate intensity of 60 minutes of interval running on a treadmill, each interval including 4 minutes of running with an intensity of 65-70% of VO2max and 2 minutes of active recovery with an intensity of 50-60% of VO2max. qRT-PCR method was used to check the gene expression of research variables. Data were compared using SPSS software version 16, one-way analysis of variance and Tukey's post hoc test at a significance level of p

Abstract Background Although stem cell transplantation is a promising approach for the treatment of myocardial infarction (MI), there are still some problems faced such as the low survival rate of stem cells. Here, we investigated the role of Notoginsenoside R1 (NGR1) pretreatment in improving the effects of neonatal rat bone marrow mesenchymal stem cell (MSC) transplantation for treatment of MI. Methods Cardiac functions were detected by echocardiography and the myocardial infarct size was determined by Masson’s trichrome staining in a rat model of MI. The cardioprotective effects of NGR1/LY294002 co-pretreated MSCs was evaluated to explore the underlying mechanism. The angiogenesis was determined by vWF and α-SMA immunofluorescence staining and cell apoptosis was detected by TUNEL. In vitro, the effects of NGR1 on stem cell proliferation was examined by CCK-8 and levels of P-Akt, P-CREB, P-FoxO1 were detected by western blot. Apoptosis, ROS content, and cytokine levels were examined by DAPI and TUNEL staining, a ROS assay kit, and ELISA, respectively. Results NGR1 elevated the therapeutic effect of MSC transplantation on infarction by preserving cardiac function, increasing angiogenesis and expressions of IGF-1, VEGF, and SDF-1, and reducing cell apoptosis, whereas the addition of LY294002 prior to NGR1 treatment significantly counteracted the foregoing effects of NGR1. NGR1 pretreatment and SC79 pretreatment were similar in that both significantly increased P-Akt and P-FoxO1 levels in MSC and did not affect P-CREB levels. Besides, both NGR1 and SC79 promoted VEGF, SCF and bFGF levels in MSC cultures, and significantly reduced ROS accumulation and the attenuated cell apoptosis in MSC triggered by H2O2. Similarly, addition of LY294002 before NGR1 treatment significantly counteracted the aforementioned effects of NGR1 in vitro. Conclusions NGR1 pretreatment enhances the effect of MSC transplantation for treatment of MI through paracrine signaling, and the mechanism underlying this effect may be associated with PI3K/Akt/FoxO1 signaling pathways.

Abstract Background The efficiency of mesenchymal stem cells (MSCs) in treating myocardial infarction (MI) remains inconsistent, which limits their therapeutic applications. Therefore, exploring the mechanism for the inconsistent efficacy of MSCs and identification the criteria for screening MSCs are important for improving the efficiency of MSCs. Methods Mouse model after MI was utilized to test the role of MSCs from different donors and the functional subpopulation in improving cardiac function. Heterogeneity of MSCs was identified using single-cell RNA sequencing (scRNA-seq) of MSC-GY. GSEA and Scissor analyses were used to find the functional subpopulations of MSCs that promote angiogenesis. The role of functional subpopulations in promoting angiogenesis was verified by detecting the secretory proteins, the ratio of N-CADHERIN+/CD168− subpopulations in MSCs, and the tube formation, migration, and proliferation of HUVECs after treatment with conditional medium (CM) derived from different MSCs. Results We found that umbilical cord-derived MSCs (UC-MSCs) from different donors have varied therapeutic efficacy in MI mice and UC-MSCs with higher therapeutic effectiveness exhibited the most potent pro-angiogenic effects by secreting elevated levels of angiogenesis-related proteins, such as MYDGF, VEGFA, and FGF2. ScRNA-seq of 10,463 UC-MSCs revealed that the N-CADHERIN+/CD168− subpopulation was closely associated with pro-angiogenic effects, and the ratio of this cell subpopulation was positively correlated with the angiogenic potential of MSCs. We also found that the N-CADHERIN+/CD168− subpopulation was the functional subpopulation of MSCs in improving cardiac function of MI mice. Conclusions Our study identified that the N-CADHERIN+/CD168− subpopulation was the functional subpopulation of MSCs in treating MI, which was essential for the development and utilization of MSCs in MI treatment.

Abstract Myocardial infarction (MI) is a leading cause of heart failure, disability and mortality worldwide. In this study, the effects of intramyocardial injection of human platelet lysate (HPL), bone marrow mesenchymal stem cells pretreated with HPL (PMSCs), and PMSC lysate (lys), alone and in combination were investigated on MI-induced by LAD ligation in male Wistar rats. The experiment was carried out on sham, vehicle (Veh), HPL, PMSCs, PMSC lysate (PMSC lys), HPL + PMSCs, and HPL + PMSC lys groups. SBP, DBP, and ± dp/dt max were monitored by the PowerLab physiograph. The MSC characteristics and CD31, NKX2.5, and cardiac troponin I (cTnI) contents were determined by flow cytometry, immunohistochemistry, and immunofluorescence, respectively. SBP, DBP, and ± dp/dt max that decreased in the MI group were recovered by HPL, PMSC, PMSC lys, HPL + PMSC, and HPL + PMSC lys treatments. CD31 density was higher in all treated groups compared to the Veh group. CD31 density in the HPL + PMSCs and HPL + PMSC lys groups was higher than in the PMSCs group. The number of Dil+/NKX2.5 + and Dil+/cTnI + cells was higher in the HPL + PMSCs group compared to the PMSCs group. The HPL and PMSCs mitigates heart injuries and cardiac dysfunction after MI. HPL provides an appropriate environment for cardiomyocyte differentiation from PMSCs.

Abstract The relationship between the triglyceride-glucose (TyG) index and mortality among survivors of myocardial infarction (MI) remains understudied. This study aims to evaluate the association between the TyG index and mortality among adult MI patients in the US. Our study included 986 MI patients, sourced from the National Health and Nutrition Examination Survey conducted from 1999 to 2018. Employing a multivariate Cox proportional hazards model, we examined the association between the TyG index and mortality. To explore potential nonlinear relationships, we employed restricted cubic splines in our analysis. Additionally, we applied a two-piecewise Cox proportional hazards model for a more nuanced analysis of the data, using key turning points as boundaries. To validate the robustness of our research findings, we also performed subgroup analyses. During a 7,342 person-years follow-up period, 434 MI survivors succumbed to various causes, including 158 cardiovascular disease-related deaths. The study revealed a U-shaped pattern between the TyG index and mortality. At TyG index levels below the thresholds (8.85 for all-cause mortality and 9.02 for cardiovascular mortality), mortality exhibited a negative correlation with the TyG index (HR = 0.56, 95%CI 0.39–0.82; HR = 0.67, 95%CI 0.39–1.14). Conversely, mortality rates increased when the TyG index surpassed these thresholds (HR = 1.38, 95%CI 1.08–1.76; HR = 1.56, 95%CI 1.02–2.38). Furthermore, among diabetic patients, subgroup analyses demonstrated that the U-shaped pattern between the TyG index and cardiovascular mortality was particularly pronounced. Our research indicates that among MI survivors, a U-shaped pattern exists between the TyG index and mortality rates, which is particularly pronounced in the diabetic patient subgroup. The corresponding threshold values for all-cause and cardiovascular mortality are 8.85 and 9.02, respectively.

Abstract Background Circular RNAs (circRNAs) are differentially expressed in various cardiovascular diseases, including myocardial infarction (MI) injury. However, their functional role in necroptosis-induced loss of cardiomyocytes remains unclear. We identified a cardiac necroptosis-associated circRNA transcribed from the Cacna1c gene (circCacna1c) to investigate the involvement of circRNAs in cardiomyocyte necroptosis. Methods To investigate the role of circCacna1c during oxidative stress, H9c2 cells and neonatal rat cardiomyocytes were treated with hydrogen peroxide (H2O2) to induce reactive oxygen species (ROS)-induced cardiomyocyte death. The N 6-methyladenosine (m6A) modification level of circCacna1c was determined by methylated RNA immunoprecipitation quantitative polymerase chain reaction (MeRIP–qPCR) analysis. Additionally, an RNA pull-down assay was performed to identify interacting proteins of circCacna1c in cardiomyocytes, and the regulatory role of circCacna1c in target protein expression was tested using a western blotting assay. Furthermore, the MI mouse model was constructed to analyze the effect of circCacna1c on heart function and cardiomyocyte necroptosis. Results The expression of circCacna1c was found to be reduced in cardiomyocytes exposed to oxidative stress and in mouse hearts injured by MI. Overexpression of circCacna1c inhibited necroptosis of cardiomyocytes induced by hydrogen peroxide and MI injury, resulting in a significant reduction in myocardial infarction size and improved cardiac function. Mechanistically, circCacna1c directly interacts with heterogeneous nuclear ribonucleoprotein F (Hnrnpf) in the cytoplasm, preventing its nuclear translocation and leading to reduced Hnrnpf levels within the nucleus. This subsequently suppresses Hnrnpf-dependent receptor-interacting protein kinase 1 (RIPK1) expression. Furthermore, fat mass and obesity-associated protein (FTO) mediates demethylation of m6A modification on circCacna1c during necrosis and facilitates degradation of circCacna1c. Conclusion Our study demonstrates that circCacna1c can improve cardiac function following MI-induced heart injury by inhibiting the Hnrnpf/RIPK1-mediated cardiomyocyte necroptosis. Therefore, the FTO/circCacna1c/Hnrnpf/RIPK1 axis holds great potential as an effective target for attenuating cardiac injury caused by necroptosis in ischemic heart disease. Graphical Abstract

Abstract Background and objective Retinal vein occlusion (RVO) and acute myocardial infarction (MI) are significant vascular events that impact patient health and mortality. Both conditions share common risk factors, such as hypertension, diabetes, and atherosclerosis. This study investigated the potential connection between RVO and MI, particularly among younger individuals, to improve preventive measures and management protocols. Method A systematic review and meta-analysis were conducted, adhering to the PRISMA and MOOSE guidelines. Multiple databases, including PubMed, Scopus, MEDLINE, ScienceDirect, and ClinicalTrials.gov, were exhaustively searched until August 24, 2024. Studies were selected based on their reports of the association between RVO and MI risk. Quality assessment was performed using the Newcastle-Ottawa Quality Assessment Scale, and data were pooled using a random-effects model with hazard ratios and 95% confidence intervals. Result Twelve studies comprising 371,817 participants were included. Meta-analysis revealed a pooled hazard ratio of 1.324 (95% CI, 1.238–1.415), indicating a significant association between RVO and increased MI risk (p = 0.0001). Subgroup analysis for central retinal vein occlusion (CRVO) showed a hazard ratio of 1.691 (95% confidence interval [CI] 1.142, 2.502, p = 0.009) with moderate heterogeneity (I2 = 36%), whereas branch retinal vein occlusion (BRVO) yielded a non-significant hazard ratio of 1.167 (95% CI 0.843, 2.106, p = 0.444; I2 = 33%). Publication bias was identified (Egger’s test, p = 0.036) and addressed through trim-and-fill adjustment, maintaining statistical significance. Conclusion Our meta-analysis shows a strong association between CRVO and a 69.1% increased risk of MI, while BRVO shows no significant correlation. Overall, RVO is linked to a 32.4% elevated risk of MI. Despite slight publication bias, adjusted analyses confirm reliability, indicating that improved cardiovascular monitoring for RVO patients, especially those with CRVO, is essential to mitigate MI risk. Clinical trial number Not applicable.

Xing Zhou,1,&ast; Quan Lu,2,&ast; Qiu Wang,2,&ast; Wenxin Chu,2 Jianhao Huang,2 Jinming Yu,2 Yuechou Nong,2 Wensheng Lu2,&ast; 1Pharmacy Department, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of China; 2Department of Endocrinology and Metabolism, National Key Endocrine Clinical Construction Specialty, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wensheng Lu; Yuechou Nong, Department of Endocrinology and Metabolism, National Key Endocrine Clinical Construction Specialty, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, No. 6, Taoyuan Road, Nanning, Guangxi, 530021, People’s Republic of China, Email Lwswxqz@163.com; wslu@gxams.org.cn; yuechou_gx@163.comBackground: Mitochondrial calcium uptake-induced mitophagy may play an essential role in myocardial ischemia/reperfusion (MI/R) injury. Diltiazem hydrochloride (DIL), a traditional calcium channel blocker, can alleviate MI/R injury by blocking calcium overload. However, whether the protective mechanism of DIL involves mitophagy remains elusive. This study aimed to clarify the underlying molecular mechanism by which DIL ameliorates MI/R injury by downregulating mitophagy in vivo and in vitro.Methods: Thirty rats were randomized into three groups: the sham, MI/R, and MI/R+DIL (1 mg/kg) groups (n = 10/per group). MI/R injury was induced by ligating the left anterior descending (LAD) artery for 30 min followed by 60 min of reperfusion in vivo. H9C2 cells were selected to establish an oxygen-glucose deprivation/recovery (OGD/R) model to simulate MI/R injury in vitro. The potential mechanism by which DIL alleviates MI/R injury was analyzed based on tissue morphology, mitophagy-related gene transcription, and protein expression.Results: According to histological and immunohistochemical evaluations, DIL significantly alleviated myocardial damage in vivo. Moreover, DIL significantly increased cell viability, attenuated OGD/R-induced apoptosis, and inhibited mitochondrial autophagy in vitro. Mechanistically, DIL attenuated mitochondrial autophagy through the upregulation of dual-specificity protein phosphatase 1 (DUSP1) and the downregulation of c-Jun N-terminal kinase (JNK) and Bcl2 interacting protein 3-like (BNIP3L, also known as NIX) expression.Conclusion: Diltiazem hydrochloride protects against myocardial ischemia/reperfusion injury in a BNIP3L/NIX-mediated mitophagy manner in vivo and in vitro.Keywords: diltiazem hydrochloride, calcium channel blockers, myocardial infarction, myocardial ischemia/reperfusion injury, mitophagy

Fabricio Beltrame,1,2 Bianca Nascimento-Carlos,3 Jaqueline S da Silva,1,3 Rodolfo Couto Maia,4 Tadeu Lima Montagnoli,3,4 Eliezer J Barreiro3,4 ,† Gisele Zapata-Sudo1– 4 1Programa de Pós-Graduação em Medicina (Cardiologia), Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 2Instituto do Coração Edson Saad, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 3Programa de Pós-Graduação em Farmacologia e Química Medicinal, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 4Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil†Professor Eliezer Barreiro passed away on April 8, 2024Correspondence: Gisele Zapata-Sudo, Universidade Federal do Rio de Janeiro, Instituto do Coração Edson Saad, Faculdade de Medicina, Centro de Ciências da Saúde, Bloco J, Sala 11, Rio de Janeiro, RJ, 21941-902, Brasil, Tel/Fax +55-21-39386505, Email gsudo@icb.ufrj.br; gzsudo@gmail.comBackground and Purpose: Current treatments for acute myocardial infarction (AMI) include pain relief and attempts to improve survival. This study investigated the effects of two new ligands of the adenosine receptor, LASSBio-1027 and LASSBio-1860, on cardiac function in an experimental model of AMI.Methods: AMI was induced in Wistar rats by ligating the anterior descending coronary arteries. Infarcted animals were treated orally with vehicle (DMSO), LASSBio-1027 (30 and 70 μmol/kg), or LASSBio-1860 (70 μmol/kg) for seven days. Hemodynamic parameters were observed using echocardiography, whereas inflammation and fibrosis were detected using histological analysis.Results: MI increased the filling pressure from 23.0 ± 1.6 and 14.0 ± 2.0 to 37.0 ± 3.7 and 33.2 ± 8.0, respectively indicating diastolic dysfunction. However, treatment with LASSBio-1027 (70 μmol/kg) and LASSBio-1860 (70 μmol/kg) reduced this parameter to 23.9 ± 5.4 and 17.1 ± 6.7. An impairment in ejection fraction from 57.1 ± 3.2 to 36.6 ± 2.0% was observed after MI, partially recovered to 47.0 ± 7.4% by LASSBio-1027 and fully restored to 61.8 ± 4.3% after 7 days of treatment with LASSBio-1860. After MI, collagen deposition in LV free wall was increased to 31.4 ± 11.0% and treatment with LASSBio-1027 reduced to 23.4 ± 6.0 and 19.7 ± 8.0% at 30 and 70 μmol/kg, respectively. Similarly, LASSBio-1860 reduced collagen levels to 63.1 ± 2.0%.Conclusion: Fibrosis and inflammatory components of MI reduced following treatment with agonist of adenosine receptor subtype A2A. Cardiac remodeling induced by LASSBio-1027 and LASSBio-1860 may be responsible for the improvement in cardiac function in AMI through the activation of A2A adenosine receptors.Keywords: cardiac remodeling, inflammation, myocardial infarction, adenosine receptors

Kathryn Haran,1 Chandler E Johnson,1 Payton Smith,1 Zoë Venable,2 Allison Kranyak,1 Tina Bhutani,1 Caleb Jeon,2 Wilson Liao1,3 1Department of Dermatology, University of California San Francisco, San Francisco, CA, USA; 2Department of Dermatology, Golden State Dermatology, Berkeley, CA, USA; 3Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USACorrespondence: Wilson Liao, Department of Dermatology, University of California San Francisco, 2340 Sutter Street, Box 0808, San Francisco, CA, 94143, USA, Tel +1 415 476-8364, Email wilson.liao@ucsf.eduAbstract: Psoriasis is an immune-mediated skin disease known to be associated with a higher risk of cardiometabolic comorbidities such as hypertension, myocardial infarction, and stroke. GLP-1 receptor agonists (GLP-1RAs) are medications approved to treat type 2 diabetes mellitus and obesity and have been reported to improve psoriasis. As more psoriasis patients start GLP-1RAs for approved indications, it is of interest to understand the impact of GLP-1RAs on both psoriasis and associated cardiovascular risk. In this review, we examine the effect of GLP-1RAs on psoriasis and cardiovascular comorbidities—defined as hypertension, stroke, and myocardial infarction. The majority of case reports and prospective cohort studies found GLP-1RAs improved psoriasis, while two randomized controlled trials showed conflicting results. For cardiovascular disease, most studies found GLP-1RAs reduced systolic blood pressure, total stroke, and myocardial mortality. These results suggest that GLP-1RAs may be a particularly promising treatment for psoriasis patients with diabetes or obesity comorbidities, offering both cardioprotective benefits and potential improvement in psoriatic symptoms.Keywords: skin disease, oxidative stress, hypertension, stroke, myocardial infarction

Abstract Background The clinical application of mesenchymal stem cells (MSCs) in myocardial infarction (MI) is severely hampered by their poor survival. Pretreatment is a key strategy that has been adopted to promote their therapeutic efficacy. This study aimed to investigate the benefit of growth differentiation factor 15-pretreated MSCs (GDF15-MSCs) in enhancing cardiac repair following MI and to determine the underlying mechanisms. Methods MSCs with or without GDF15 pretreatment were exposed to serum deprivation and hypoxia (SD/H) challenge. Apoptosis of MSCs was assessed by TUNEL staining. The conditioned media (CM) of MSCs and GDF15-MSCs was collected by centrifugation. MSCs and GDF15-MSCs were transplanted into the peri-infarct region in a mouse model of MI. Cardiac function, fibrosis and MSC survival were examined 4 weeks after MSC transplantation. Results Pretreatment with GDF15 greatly reduced SD/H-induced apoptosis of MSCs via inhibition of reactive oxygen species (ROS) generation by attenuating mitochondrial fission. Mechanistically, GDF15 pretreatment ameliorated mitochondrial fission of MSCs under SD/H challenge by activating the AMPK pathway. These effects were partially abrogated by AMPK inhibitor. Pretreatment with GDF15 also promoted paracrine effects of MSCs in vitro, evidenced by improving tube formation of HUVECs, and inhibited the apoptosis of cardiomyocytes induced by SD/H. At 4 weeks after transplantation, compared with MSCs, GDF15 pretreatment strongly promoted the survival of MSCs in the ischemic heart with consequent enhanced cardiac function, reduced cardiac fibrosis and increased angiogenesis. Conclusions Our study showed that pretreatment with GDF15 promoted the cardioprotective effects of MSCs in MI via regulation of pro-survival signaling and paracrine actions. GDF15 pretreatment is an effective approach to enhance the therapeutic efficacy of MSCs in ischemic heart disease.

Abstract Background The effect of milk on the risk of ischemic heart disease (IHD) and acute myocardial infarction (MI) is unclear. We aimed to examine the association between non-fermented and fermented milk consumption on these endpoints and investigate the relationship between milk intake and cardiometabolic-related proteins in plasma. Methods Our study is based on two Swedish prospective cohort studies that included 59,998 women and 40,777 men without IHD or cancer at baseline who provided repeated measures of diet and lifestyle factors and plasma proteomics data in two subcohorts. Through registry linkage, 17,896 cases with IHD were documented during up to 33 years of follow-up, including 10,714 with MI. We used time-updated multivariable Cox regression analysis to examine non-fermented or fermented milk intake with time to IHD or MI. Using high-throughput multiplex immunoassays, 276 cardiometabolic plasma proteins were measured in two subcohorts. We applied multivariable-adjusted regression models using a discovery-replication design to examine protein associations with increasing consumption of non-fermented or fermented milk. Results The results for non-fermented milk differed by sex (p-value for interaction = 0.01). In women, we found a pattern of successively greater risk of IHD and MI at non-fermented milk intake levels higher than 1.5 glasses/day. Compared with an intake of 0.5 glass/day (100 mL/day), non-fermented milk intake of 2 glasses/day in women conferred a multivariable-adjusted hazard ratio (HR) of 1.05 (95% CI 1.01–1.08) for IHD, an intake of 3 glasses/day an HR of 1.12 (95% CI 1.06–1.19), and an intake of 4 glasses/day an HR of 1.21 (95% CI 1.10–1.32). Findings were similar for whole, medium-fat, and low-fat milk. We did not detect higher risks of IHD with increasing milk intakes in men. Fermented milk intake was unrelated to the risk of IHD or MI in either sex. Increasing non-fermented milk intake in women was robustly associated with a higher concentration of plasma ACE2 and a lower concentration of FGF21. Conclusions We show a positive association between high amounts of non-fermented milk intake and IHD in women but not men. We suggest metabolic pathways related to ACE2 and FGF21 potentially underlie the association. Graphical abstract Our analysis of two large cohort studies involving 100,775 participants and 17,896 clinically confirmed IHD events supports a dose–response positive association between non-fermented milk intake higher than 300 mL/day with higher rates of IHD (and acute MI specifically) in women, but not in men. The higher risk of IHD with high milk intake in women was evident, irrespective of the fat content of the milk. Fermented milk intake was unrelated to the risk of IHD in both women and men. Non-fermented milk intake was associated in different directions with circulating levels of ACE2 and FGF21 in women—two essential cardiometabolic proteins, also related to IHD in women in our study.

Abstract The study’s goals are to fabricate PLGA nanoparticles (PNPs) loaded with apigenin (AP) and adenosine (AD) using a microfluidic preparation method to a standard emulsification method and investigate the possible heart-protective effects of AP-AD PNPs made using the emulsification method. Compared to microfluidics, the emulsification method fabricated small-size nanoparticles, which are better at encapsulating drugs, retaining more drugs, and having a low viscosity for the myocardial infarction (MI) injection. TheMI model was developed using SD rats injected under the skin with 85 mg/kg doxorubicin (DOX) for 2 days. The metabolic results showed that our AP-AD PNPs accelerated the blood flow in rats with MI, which increased the amounts of AP and AD in the circulatory system. This led to significant improvements in the cardiac index and lower amounts of AST, LDH, and CK in the blood. A histopathological study using Hematoxylin&eosin, and TUNEL staining showed that cardiac function had improved and apoptosis had decreased. Moreover, tests that checked the amounts of IL-6, TNF-α, NO, GSH, MDA, and SOD showed that AP-AD PNPs may help treat MI by reducing oxidative stress and inflammation, making it a potentially useful therapeutic approach.

Thanatporn Threetong,1 Somchai Yongsiri,2 Kornkamol Annopawong3 1Department of Ophthalmology, Faculty of Medicine, Burapha University, Chonburi, Thailand; 2Department of Medicine, Faculty of Medicine, Burapha University, Chonburi, Thailand; 3Department of Ophthalmology, Rajavithi Hospital and College of Medicine, Rangsit University, Bangkok, ThailandCorrespondence: Kornkamol Annopawong, Department of Ophthalmology, Rajavithi Hospital and College of Medicine, Rangsit University, 2, PhayaThai Road, Thung PhayaThai, Ratchathewi, Bangkok, 10400, Thailand, Tel +66949951594, Email a.kornkamol@gmail.comPurpose: To evaluate the surgical outcomes and identify ocular and systemic prognostic factors of trabeculectomy with mitomycin C (MMC) in the eyes of patients with neovascular glaucoma (NVG) in Thailand.Patients and Methods: This retrospective study was conducted by reviewing records of Thai patients with NVG who underwent trabeculectomy with MMC between 2013 and 2022. Criterion failure was defined as intraocular pressure (IOP) > 21 mmHg or less than a 20% reduction below baseline on two consecutive study visits after 3 months, IOP ≤ 5 mmHg on two consecutive study visits after 3 months, reoperation for glaucoma, and loss of light perception. Kaplan–Meier survival curves were used to examine success rates, and risk factors were analyzed using Cox’s proportional hazard model.Results: The study included 106 eyes of 106 patients with a mean age of 57 years (range, 27– 87 years). The cause of NVG was proliferative diabetic retinopathy (PDR) in 63 eyes (59.43%), central retinal vein occlusion (CRVO) in 39 eyes (36.79%), and ocular ischemic syndrome (OIS) in 4 eyes (3.77%). The cumulative probability of success in the first year was 73.6% with anti-glaucoma medication and 54.7% without medication. The multivariate model demonstrated that major cardiovascular events (hazard ratio [HR], 2.778 p=0.001) and preoperative systemic antiglaucoma medication use (HR, 1.837, p=0.045) were prognostic factors for surgical failure among all NVG patients. Postoperative manipulation with a subconjunctival injection of MMC occurred significantly more frequently in the failure group (HR, 3.100; p< 0.001).Conclusion: Trabeculectomy with MMC effectively reduced the elevated IOP associated with NVG in Thailand. Underlying systemic diseases involving major vascular events and the use of adjunct systemic IOP-lowering medications were prognostic factors for surgical failure.Keywords: intraocular pressure, major vascular events, stroke, myocardial infarction, vascular endothelial growth factor

Samah I Abohamr,1,2 Mohammad O Kattea,3 Rami M Abazid,4 Mubarak A Aldossari,2 Nayef Al Asiri,2 Ayman Uthman Alhussini,2 Khalid I Al Hussaini,5 Glowi A Alasiri,6 Asghar Ali,7 Eman Elsheikh1,8 1Department of Cardiology, College of Medicine, Tanta University Hospital, Tanta, Egypt; 2Chairman of cardiology services, Mouwasat medical group, Al-Khobar, Saudi Arabia; 3Nassau University Medical Center, East Meadow, NY, USA; 4Internal Medicine Department, Sault Area Hospital, Sault Ste Marie, Northern Ontario Medical School University (NOSM), Sault Ste Marie, Ontario, Canada; 5Department of Internal Medicine, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 4233-13317, Saudi Arabia; 6Department of Biochemistry, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 4233-13317, Saudi Arabia; 7Clinical Biochemistry Laboratory, Department of Biochemistry, School of Chemical and Life Sciences (SCLS), Jamia Hamdard, New Delhi, 110062, India; 8Internal Medicine Department, King Faisal University, Alahsa, Saudi ArabiaCorrespondence: Khalid I Al Hussaini, Department of Internal Medicine, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 4233-13317, Saudi Arabia, Email kialhussaini@imamu.edu.sa Asghar Ali, Clinical Biochemistry Laboratory, Department of Biochemistry, School of Chemical and Life Sciences (SCLS), Jamia Hamdard, New Delhi, 110062, India, Email asgharali@jamiahamdard.ac.inPurpose: COVID-19 is a new disease caused by the recently discovered SARS-CoV-2 virus. The COVID-19 disease manifests in several ways and it may affect various systems, including the gastrointestinal, musculoskeletal, neurological, cardiovascular, and pulmonary systems. Individuals who have ad-additional health conditions, such as cardiovascular disorders, are particularly more likely to experience illness and death. This study aimed to assess the clinical effect of COVID-19 on myocardial injury, as measured by troponin elevation, and to determine if this effect has an impact on the outcome.Patients and Methods: This retrospective study was conducted at King Saud Medical City. The electronic medical records used to identify all admitted patients between March 23 and June 15, 2020, with a laboratory-confirmed positive COVID-19 diagnosis who had troponin I measured.Results: During the study period, 768 COVID-19-positive patients were hospitalized. Of those, 187 patients were excluded because the troponin level was not measured. The remaining 581 (75.7%) had troponin I measured. Overall, 89 of 581 (15.3%) patients died. Of those, 67.8% were in the markedly elevated cTnI group, 8.5% were in the mildly elevated cTnI group, whereas no deaths were reported in the group with normal cTnI levels.Conclusion: Myocardial injury was observed in COVID-19-admitted patients at a significant level that warrants attention to this consequence. In older individuals with pre-existing cardiovascular comorbidities, the diagnosis of myocardial injury was linked to a higher likelihood of being admitted to the intensive care unit, experiencing a worse prognosis, and ultimately, death.Keywords: myocardial infarction, cardiovascular comorbidities, ARDS, biomarker, cytokine storm, risk stratification

Background: Patients with myocardial infarction (MI) often experience sexual concerns, yet sexual counseling remains underutilized. This study explored barriers to sexual counseling for MI patients from the perspective of nurses working in southern Iraq. Methods: This cross-sectional study recruited 126 nurses (response rate 89%) from a specialized heart center in 2023. They were selected using convenience sampling. A valid adapted questionnaire assessed perceived barriers related to patients, nurses, and organizations. The obtained data were analyzed with descriptive statistics, analysis of variance, and independent t test using SPSS software, version 27. P≤0.05 was considered significant. Results: Religious issues (3.01±0.49), confidentiality concerns (2.92±0.55), and patient reluctance to discuss sex (2.87±0.54) were the most significant patient-related barriers. High workload (2.92±0.42), cultural beliefs (2.82±0.51), and nurse discomfort discussing sex (2.79±0.50) were the leading nurse-related barriers. Lack of administrative support (2.81±0.47), feedback mechanisms (2.77±0.51), and unsuitable consultation environment (2.76±0.53) were the primary organizational barriers. No significant relationships were found between the barriers and demographic data. Conclusion: Religious beliefs, confidentiality concerns, and patient reluctance, along with nurses’ high workload, cultural norms, and discomfort, pose significant barriers to sexual counseling for MI patients in this setting. Addressing these barriers through education, cultural sensitivity training, and organizational support could improve sexual counseling accessibility for MI patients.

Purpose: Here, we describe cardiac magnetic resonance imaging (CMR) findings in patients with proven COVID-19 infection and presenting with cardiac problems both at presentation and in convalescence from a tertiary care center, in North India. A pertinent review of the literature is also discussed. Materials and Methods: Retrospective analysis of patients with real-time reverse transcriptase-polymerase chain reaction proven COVID-19 infection either at presentation or convalescence referred for CMR at our facility from January 2021 to December 2023 was done. CMR was performed on a 3T system (Ingenia, Philips Healthcare, Best, The Netherlands) and examinations were customized according to the clinical indications. Results: Retrospective analysis yielded 14 patients (4 at presentation; 10 in convalescence). Patients at presentation 4/14 had clinically presented with chest pain with raised troponins and electrographic abnormalities, while 10/14 patients had presented with clinical features of heart failure with two-dimensional transthoracic echocardiography demonstrating systolic dysfunction with reduced left ventricular ejection fraction. Out of 14, 4 patients at presentation, CMR showed features of acute myocarditis in three patients, while one had inferior wall myocardial infarction (MI) (this patient on catheter angiogram had aneurysmally dilated coronary arteries with thrombus and stenosis in the mid right coronary artery which was successfully stented). Out of 14, 10 patients on CMR had features of dilated cardiomyopathy (DCMP). Conclusion: Cardiac involvement in COVID-19 can have vivid clinicoradiological presentations with features of myocarditis and MI at presentation or DCMP in convalescence. CMR in such cases is a problem-solving tool where myocarditis is candidly differentiated from MI. Moreover, follow-up CMR demonstrates temporal changes in COVID-19-associated myocarditis and evaluation of cardiac structure and function in patients presenting with DCMP.

Abstract Background Type 2 diabetes has traditionally been a risk factor for worse prognosis after myocardial infarction (MI), but major advances have been made in its treatment, and the use of secondary preventive measures has intensified. We evaluated the short- and long-term mortality rates of patients with type 2 diabetes after MI and explored the associations between the characteristics of patients with type 2 diabetes and MI mortality. Methods Mortality rates among consecutive MI patients with type 2 diabetes using oral antidiabetic medication (n = 13,152; 40% female; mean age 73.6 years) and MI patients without diabetes (n = 77,669) treated in Finland from 2004 to 2018 were retrospectively studied using a combination of national registries (median follow-up 5.7 years). Differences between groups were balanced with multivariable adjustments and propensity score matching. Results Mortality was higher in patients with type 2 diabetes than in the propensity score-matched controls without diabetes at 30 days (12.6% versus 12.0%: p = 0.013), at 1 year (22.4% versus 21.4%; p = 0.001), and at 15 years (83.2% vs. 73.4%; HR 1.20; 95% CI 1.17–1.24; p

Abstract Objective This study aimed to explore the association between electrophysiological markers of early recurrence after defibrillation in post-myocardial infarction ventricular fibrillation and the therapeutic effects of sympathetic renal denervation, as well as to investigate the potential underlying mechanisms. Methods Experimental research was conducted using an animal model. Myocardial infarction was induced, followed by defibrillation treatment for ventricular fibrillation cases, and the electrophysiological markers of early recurrence were recorded. Subsequently, a subset of animals underwent sympathetic renal denervation intervention, and the therapeutic effects were compared between the sympathetic renal denervation group and the control group. Electrocardiogram monitoring, histological analysis of myocardial tissue, and neurotransmitter measurements were also performed. Results Following defibrillation treatment, early recurrence was observed in ventricular fibrillation cases. The electrophysiological markers revealed significantly higher ST segment elevation and T wave changes in the early recurrence group. However, in the sympathetic renal denervation intervention group, the early recurrence rate was significantly reduced, and the electrocardiogram showed improved stability and regularity. Additionally, histological analysis of myocardial tissue demonstrated less cellular damage and lower levels of myocardial fibrosis in the sympathetic renal denervation group. Neurotransmitter measurements revealed a significant decrease in sympathetic nerve activity in the sympathetic renal denervation intervention group. Conclusion The results of this study indicate an association between electrophysiological markers of early recurrence after defibrillation in post-myocardial infarction ventricular fibrillation and the therapeutic effects of sympathetic renal denervation. Sympathetic renal denervation intervention can significantly reduce the early recurrence rate, improve electrocardiogram characteristics, and alleviate myocardial damage and fibrosis. Furthermore, the reduction in sympathetic nerve activity may be one of the potential underlying mechanisms of sympathetic renal denervation intervention.

Abstract Background Hyperuricemia is independently associated with a poor prognosis in patients with myocardial infarction (MI). Furthermore, MI induces activation of the repair response in local fibroblasts, resulting in extracellular matrix accumulation that generates a stable fibrotic scar in the infarcted area. However, researchers have not determined whether hyperuricemia affects fibroblast activation and its involvement in postinfarction cardiac remodeling. Objectives We aimed to trigger hyperuricemia by administering potassium oxonate in a mouse model of MI to evaluate the role of hyperuricemia in MI pathogenesis. Methods Microarray datasets and single-cell sequencing data from gout patients, heart failure patients, and model mice were used to identify the underlying mechanisms responsible for the effect of hyperuricemia on MI progression. A hyperuricemia-related MI mouse model was established. Cardiac function was assessed, followed by sample collection and a uric acid assay. We conducted an enzyme-linked immunosorbent assay, histological detection, immunofluorescence, sequencing data processing, single-cell RNA-seq, and functional enrichment analysis. We then isolated and cultured cardiac fibroblasts and performed Western blotting, quantitative real-time polymerase chain reaction, and shRNA-mediated lumican knockdown assays. Results Hyperuricemia decreased cardiac function, increased mortality, and aggravated adverse fibrosis remodeling in mice after MI. These outcomes were closely related to reduced levels of fibroblast-derived lumican. This reduction activated the TGF-β/SMAD signaling pathway to induce aberrant myofibroblast activation and extracellular matrix deposition in the infarcted area. Furthermore, lumican supplementation or uric acid-lowering therapy with allopurinol alleviated hyperuricemia-mediated abnormal cardiac remodeling. Conclusion Hyperuricemia aggravates postinfarction cardiac remodeling by reducing lumican expression and promoting fibroblast phenotype transition. We highlight the clinical importance of lowering uric acid levels in hyperuricemia-related MI to prevent adverse ventricular remodeling.

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

Xue-Qing Guan, Lin Guan, Gong Cheng, Zhi-Jun Sun, Chuan-He Wang Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, 110021, People’s Republic of ChinaCorrespondence: Zhi-Jun Sun; Chuan-He Wang, Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, 110021, People’s Republic of China, Tel/Fax +86 18940251218 ; Tel/Fax +86 18940252598, Email sunzhijunszj8@126.com; chuanhewangwch@126.comAim: In this study, the predictive value of soluble growth stimulation expressed gene 2 protein (sST2) for long-term clinical outcomes in patients with acute heart failure (AHF) is assessed. In addition, the influence of a history of myocardial infarction on the levels of sST2 in patients with HF, as well as its impact on outcome events, is explored. We also aim to establish a specific standard for sST2 levels in this subgroup.Methods: We conducted an ambispective cohort study involving hospitalized patients with AHF, measuring their sST2 levels and following their progress over three years. The primary endpoint was major adverse cardiovascular events (MACEs), encompassing heart failure readmission and all-cause mortality over three years. Cox regression analysis was used to evaluate the prognostic significance of sST2 levels, along with a subgroup analysis using propensity score matching (PSM) to adjust for confounding variables. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal sST2 threshold using Youden’s J statistics, and a sensitivity analysis included Kaplan–Meier survival curves.Results: The study included 149 patients with a median age of 68 years, of whom 57% were male. Both univariate and multivariate Cox regression analyses confirmed sST2 as an independent predictor of MACEs. Post-PSM analysis, 124 samples were grouped by MI history ROC curve analysis revealed an area under the curve of 0.726 for predicting MACEs in patients with MI, demonstrating a significant predictive value for sST2 levels above 34 ng/mL, which correlated with increased readmission and mortality rates. In contrast, sST2 levels in patients without MI history showed no significant predictive relevance.Conclusion: sST2 has significant long-term predictive value for clinical outcomes in patients with AHF, particularly for those with a prior MI history, indicating a need for heightened clinical attention and thorough follow-up to mitigate long-term adverse cardiovascular outcomes.Keywords: Acute heart failure, myocardial infarction, soluble growth-stimulated expression gene 2, ventricular remodeling

Abstract Histological analysis with 2,3,5-triphenyltetrazolium chloride (TTC) staining is the most frequently used tool to detect myocardial ischemia/reperfusion injury. However, its practicality is often challenged by poor image quality in gross histology, leading to an equivocal infarct-boundary delineation and potentially compromised measurement accuracy. Here, we introduce several crucial refinements in staining protocol and sample processing, which enable TTC images to be analyzed with light microscopy. The refined protocol involves a two-step TTC staining process (perfusion and immersion) and subsequent Zamboni fixation to differentiate myocardial viability and necrosis, and use of Coomassie brilliant blue to label area-at-risk. After the duo-staining steps were completed, the heart sample was embedded and sliced transversally by a cryostat into a series of thin sections (50 µm) for microscopic analysis. The refined TTC (redTTC) assay yielded remarkably high-quality images with striking color intensity and sharply defined boundaries, permitting unambiguous and reliable delineation of the infarct and area-at-risk. In the same animals, the redTTC assay showed good agreement with the in-vivo gold standard measurements (LGE and MEMRI). Meanwhile, redTTC imaging allows tracking of viable cardiomyocytes at cellular resolution, and with this enhanced capability, we convincingly demonstrated the pro-survival action of stem cells based-therapy. Therefore, the redTTC assay represents a significant technical advance that permits precise detection of the true extent of cardiac injury and cardiomyocyte viability. This approach is cost-effective and may be adapted for use in diverse applications, making it highly appealing to many laboratories performing ischemia/reperfusion injury experiments.

Acute coronary syndrome remains the leading cause of death in both patients with coronary artery disease and patients with other diseases (such as diabetes mellitus, chronic kidney disease, inflammatory diseases of various etiologies, and others). Early diagnosis of cardiomyocyte damage and necrosis opens up wide opportunities to improve the prognosis of patients with atherosclerotic lesions of the coronary arteries, and also makes it possible to discharge patients without acute cardiovascular pathology from intensive care units with a high degree of probability. The article discusses the evolution of the research and introduction into broad clinical practice of markers of myocardial damage and necrosis, which have largely improved modern clinical practice.

Zhuhong Lai, Tingqiao Ye, Mingjun Zhang, Ying Mu Department of Cardiology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of ChinaCorrespondence: Ying Mu, Department of Cardiology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China, Email muyingdr123@yeah.netAbstract: Exosomes have grown as promising carriers for noncoding RNAs (ncRNAs) in the treatment of inflammation, particularly in conditions like ischemic stroke and myocardial infarction. These ncRNAs, which include microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), play a crucial role in regulating inflammatory pathways, presenting new therapeutic opportunities. In both ischemic stroke and myocardial infarction, inflammation significantly influences disease progression and severity. Exosomes can deliver ncRNAs directly to specific cells and tissues, providing a targeted approach to modulate gene expression and reduce inflammation. Their biocompatibility and low risk of inducing immune responses make exosomes ideal therapeutic vehicles. Ongoing research is focused on optimizing the loading of ncRNAs into exosomes, ensuring efficient delivery, and understanding the mechanisms by which these ncRNAs mitigate inflammation. In ischemic stroke, exosome-derived ncRNAs originate from various cell types, including neurons, M2 microglia, patient serum, genetically engineered HEK293T cells, and mesenchymal stromal cells. In the case of myocardial infarction, these ncRNAs are sourced from mesenchymal stem cells, endothelial cells, and patient plasma. These exosome-loaded ncRNAs play a significant role in modulating inflammation in both ischemic stroke and myocardial infarction. As this research advances, therapies based on exosomes may completely change how diseases linked to inflammation are treated, offering new avenues for patient care and recovery. This review explores the latest advancements in understanding how exosomes impact specific inflammatory components, with a particular emphasis on the role of ncRNAs contained in exosomes. The review concludes by highlighting the clinical potential of exosome-derived ncRNAs as innovative therapeutic and diagnostic tools.Keywords: exosomes, noncoding RNA, inflammation, ischemic stroke, myocardial infarction

Abstract Background Stem cell transplantation has been regarded as a promising therapeutic strategy for myocardial regeneration after myocardial infarction (MI). However, the survival and differentiation of the transplanted stem cells in the hostile ischaemic and inflammatory microenvironment are poor. Recent studies have focused on enhancing the survival and differentiation of the stem cells, while strategies to suppress the senescence of the transplanted stem cells is unknown. Therefore, we investigated the effect of growth differentiation factor 11 (GDF11) on attenuating oxidative stress-induced senescence in the engrafted endothelial progenitor cells (EPCs). Methods Rat models of oxidative stress were established by hydrogen peroxide conditioning. Oxidative stress-induced senescence was assessed through senescence-associated β-galactosidase expression and lipofuscin accumulation. The effects of GDF11 treatment on senescence and autophagy of EPCs were evaluated 345, while improvement of myocardial regeneration, neovascularization and cardiac function were examined following transplantation of the self-assembling peptide (SAP) loaded EPCs and GDF11 in the rat MI models. Results Following hydrogen peroxide conditioning, the level of ROS in EPCs decreased significantly upon treatment with GDF11. This resulted in reduction in the senescent cells and lipofuscin particles, as well as the damaged mitochondria and rough endoplasmic reticula. Concurrently, there was a significant increase in LC3-II expression, LC3-positive puncta and the presence of autophagic ultrastructures were increased significantly. The formulated SAP effectively adhered to EPCs and sustained the release of GDF11. Transplantation of SAP-loaded EPCs and GDF11 into the ischaemic abdominal pouch or myocardium resulted in a decreased number of the senescent EPCs. At four weeks after transplantation into the myocardium, neovascularization and myocardial regeneration were enhanced, reverse myocardial remodeling was attenuated, and cardiac function was improved effectively. Conclusions This study provides novel evidence suggesting that oxidative stress could induce senescence of the transplanted EPCs in the ischemic myocardium. GDF11 demonstrates the ability to mitigate oxidative stress-induced senescence in the transplanted EPCs within the myocardium by activating autophagy.

Abstract Background Cardiovascular diseases are prevalent worldwide with any age, and it is characterized by sudden blockage of blood flow to heart and permanent damage to the heart muscle, whose cause and underlying molecular mechanisms are not fully understood. This investigation aimed to explore and identify essential genes and signaling pathways that contribute to the progression of MI. Methods The aim of this investigation was to use bioinformatics and next-generation sequencing (NGS) data analysis to identify differentially expressed genes (DEGs) with diagnostic and therapeutic potential in MI. NGS dataset (GSE132143) was downloaded from the Gene Expression Omnibus (GEO) database. DEGs between MI and normal control samples were identified using the DESeq2 R bioconductor tool. The gene ontology (GO) and REACTOME pathway enrichment analyses of the DEGs were performed using g:Profiler. Next, four kinds of algorithms in the protein–protein interaction (PPI) were performed to identify potential novel biomarkers. Next, miRNA-hub gene regulatory network analysis and TF-hub gene regulatory network were constructed by miRNet and NetworkAnalyst database, and Cytoscape software. Finally, the diagnostic effectiveness of hub genes was predicted by receiver operator characteristic curve (ROC) analysis and AUC more than 0.800 was considered as having the capability to diagnose MI with excellent specificity and sensitivity. Results A total of 958 DEGs were identified, consisting of 480 up-regulated genes and 478 down-regulated genes. The enriched GO terms and pathways of the DEGs include immune system, neuronal system, response to stimulus and multicellular organismal process. Ten hub genes (namely cftr, cdk1, rps13, rps15a, rps27, notch1, mrpl12, nos2, ccdc85b and atn1) were obtained via protein–protein interaction analysis results. MiRNA-hub gene regulatory network and TF-hub gene regulatory network showed that hsa-mir-409-3p, hsa-mir-3200-3p, creb1 and tp63 might play an important role in the MI. Conclusions Analysis of next-generation sequencing dataset combined with global network information and validation presents a successful approach to uncover the risk hub genes and prognostic markers of MI. Our investigation identified four risk- and prognostic-related gene signatures, including cftr, cdk1, rps13, rps15a, rps27, notch1, mrpl12, nos2, ccdc85b and atn1. This gene sets contribute a new perspective to improve the diagnostic, prognostic, and therapeutic outcomes of MI.

Yijuan Feng,1,&ast; Yan Wang,1,&ast; Li Li,1,&ast; Yan Yang,1 Xiaoqiu Tan,1– 3 Tangting Chen1,2 1Key Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Department of Cardiology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Department of Physiology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tangting Chen; Xiaoqiu Tan, Key Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Email ctt@swmu.edu.cn; tanxiaoqiu@swmu.edu.cnAbstract: Recanalization therapy can significantly improve the prognosis of patients with acute myocardial infarction (AMI). However, infarction or reperfusion-induced cardiomyocyte death, immune cell infiltration, fibroblast proliferation, and scarring formation lead to cardiac remodeling and gradually progress to heart failure or arrhythmia, resulting in a high mortality rate. Due to the inability of cardiomyocytes to regenerate, the healing of infarcted myocardium mainly relies on the formation of scars. Cardiac fibroblasts, as the main effector cells involved in repair and scar formation, play a crucial role in maintaining the structural integrity of the heart after MI. Recent studies have revealed that exosome-mediated intercellular communication plays a huge role in myocardial repair and signaling transduction after myocardial infarction (MI). Exosomes can regulate the biological behavior of fibroblasts by activating or inhibiting the intracellular signaling pathways through their contents, which are derived from cardiomyocytes, immune cells, endothelial cells, mesenchymal cells, and others. Understanding the interactions between fibroblasts and other cell types during cardiac remodeling will be the key to breakthrough therapies. This review examines the role of exosomes from different sources in the repair process after MI injury, especially the impacts on fibroblasts during myocardial remodeling, and explores the use of exosomes in the treatment of myocardial remodeling after MI.Keywords: exosomes, myocardial infarction, myocardial fibrosis, cardiac fibroblasts

This article discusses the problem of underuse, low availability of modern imaging techniques such as magnetic resonance imaging of the heart (MRI). This technique is characterized by high accuracy and uniqueness in the diagnosis of myocardial lesions of various genesis. The widespread introduction of this technique in emergency cardiology departments can improve the accuracy of diagnosis and the effectiveness of patient therapy. Despite the high costs of implementation and current use, modern diagnostic methods can save healthcare resources by reducing hospital stays and improving treatment outcomes.

Abstract Background Troponin elevation is frequently observed in various scenarios in the Emergency Department (ED), yet there is a paucity of studies investigating simultaneously measured high-sensitivity cardiac troponin T (hs-cTnT) and troponin I (hs-cTnI) within a diverse cohort in a clinical setting. Methods All patients who underwent troponin testing at a single center were eligible for this study. Only patients with simultaneous samples with hs-cTnI (Siemens) and hs-cTnT (Roche) were included, regardless of chief complaint. Results Analysis of 1987 samples from 1134 patients showed a significant correlation between hs-cTnT and hs-cTnI (r = 0.86, p

Abstract Background A growing interest in using Nigella sativa oil (NSO) in the prevention or treatment of several cardiovascular diseases has prompted this study. The research aims to investigate the effect of NSO on cardiac damage prevention after long-term administration in induced myocardial infarction (MI) in rats. Methods NSO was analyzed for its fatty acids composition using gas chromatography-mass spectrometry (GC-MS) analysis and administered in rats before and after isoproterenol (45 mg/kg body weight) induced myocardial infarction. The following parameters were assessed: electrocardiograms, histopathological examination, serum biochemical aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase-myocardial band (CK-MB), serum and heart inflammation (tumor necrosis factor-alpha (TNF), interleukin 1 beta (IL-1b), and interleukin 6 (IL-6)), and tissue oxidative stress (total antioxidant capacity (TAC), total oxidative stress (TOS), nitric oxide (NO), malondialdehyde (MDA), and the total thiols (THIOL)). Results Linoleic acid (C18:2n-6) and oleic acid (C18:1n-9) were approximately 89% of total fatty acids while palmitic acid (C16:0) was 6.10%. Administration of NSO for 28 days helped in preventing QT and QTc interval prolongation and reduced heart rate (HR), after MI induction. The histological assessment showed improvement in myofibrillary degeneration and necrosis and also better reduced inflammatory process in the groups treated with NSO. In serum, pro-inflammatory cytokines IL-1b and IL-6 were downregulated in chronic conditions (for IL-1b, NSO vs. control was 86.09vs 150.39 pg/mL, and for IL-6 NSO vs. control was 78.00 vs. 184.98 pg/ml). In the heart tissue, the downregulation was observed only for TNF in both acute and chronic conditions (acute NSO vs. control was 132.37 vs. 207.63 pg/mL, and chronic NSO vs. control was 135.83 vs. 183.29 pg/ml). The pro-oxidant parameters TOS, NO, MDA, and OSI, were reduced in the groups treated with NSO only after 14 days of treatment, suggesting that the NSO antioxidant effect is time-dependent. Conclusions NSO administration might have a favourable impact on the regulation of oxidative stress and inflammation processes after MI induction in rats, and it is worth considering its administration as an adjuvant treatment.

Abstract Acute coronary syndromes, such as myocardial infarction (MI), lack effective therapies beyond heart transplantation, which is often hindered by donor scarcity and postoperative complications. Human induced pluripotent stem cells (hiPSCs) offer the possibility of myocardial regeneration by differentiating into cardiomyocytes. However, hiPSC-derived cardiomyocytes (hiPSC-cardiomyocytes) exhibit fetal-like calcium flux and energy metabolism, which inhibits their engraftment. Several strategies have been explored to improve the therapeutic efficacy of hiPSC-cardiomyocytes, such as selectively enhancing energy substrate utilization and improving the transplantation environment. In this review, we have discussed the impact of altered mitochondrial biogenesis and metabolic switching on the maturation of hiPSC-cardiomyocytes. Additionally, we have discussed the limitations inherent in current methodologies for assessing metabolism in hiPSC-cardiomyocytes, and the challenges in achieving sufficient metabolic flexibility akin to that in the healthy adult heart.

Abstract Background: Histone deacetylase 4 (HDAC4) and histone deacetylase 5 (HDAC5) are two isoforms of class IIa HDACs, and LMK235 is an HDAC inhibitor with higher selectivity for HDAC4/5. This study aimed to explore the expression and subcellular localization of HDAC4/5 and determine the mechanisms underlying the impact of LMK235 on ventricular remodelling post-MI. Methods: The MI model was established by left anterior descending branch (LAD) ligation, and LMK235 or vehicle was intraperitoneally injected daily for 21 days. Cardiac function was determined by echocardiography. Inflammation was evaluated by HE staining and measuring inflammatory cytokine expression, and fibrosis was evaluated by Masson staining and measuring fibrotic biomarker expression. Results: We found that LMK235 ameliorated cardiac dysfunction post-MI by suppressing inflammation and fibrosis, and LMK235 inhibited upregulation of lysine-specific demethylase 1 (LSD1) expression post-MI. In macrophages, LMK235 attenuated lipopolysaccharide (LPS) - induced inflammatory cytokine expression and inhibited LSD1 expression, while overexpression of LSD1 abrogated the anti-inflammatory effect of LMK235. In cardiac fibroblasts, LMK235 attenuated transforming growth factor-β1 (TGF-β1) - induced fibrotic biomarker expression and inhibited LSD1 expression, while overexpression of LSD1 abrogated the antifibrotic effect of LMK235. Conclusion: LMK235 attenuates chronic inflammation and fibrosis post-MI, leading to improved cardiac function. The anti-inflammatory effect of LMK235 may result from inhibition of the LSD1-NF-κB pathway in macrophages. The antifibrotic effect of LMK235 may result from inhibition of the LSD1-Smad2/3 pathway in cardiac fibroblasts.

Aim. To determine the relationships between serum concentrations of growth and differentiation factor 15 (GDF 15) and NTproBNP and features of heart remodeling in patients with heart failure and preserved ejection fraction (HFPEF) depending on the history of Q-myocardial infarction (MI). Materials and methods. The study was performed on the basis of the Cardiology Department of the Municipal non-profit Enterprise “City Hospital of Urgent and Emergency Medical Care” of Zaporizhzhia City Council. 72 patients (mean age 62.1 ± 1.7 years) with HFPEF after MI were enrolled. The patients were divided into two groups depending on the time of previous MI. The patients were examined using two-dimensional echocardiography on a MyLab50 device (Esaote, Italy) according to the recommendations of the American Society of Echocardiography. Serum concentrations of GDF 15 and NTproBNP were measured by enzyme immunoassay using Elabscience reagent kits (USA). Results. In the 1st and 2nd groups of patients who suffered MI within a year, a significant increase in GDF 15 has been found (by 66.1 % and 74.7 %, respectively; p < 0.05) compared to the control group. The level of GDF 15 was significantly higher (by 41.8 %, p < 0.05) in the group of patients who had MI over a one-to-two-year period as compared to those who had MI within one year. The serum concentration of NTproBNP was also significantly higher in HFPEF groups compared to the control group (by 84.7 % and 87.2 %, respectively, p < 0.05). In the 2nd group of patients with the history of MI between 1 and 2 years, a significant increase in end-systolic volume (by 11.8 %, p < 0.05), end-diastolic volume (by 22.3 %, p < 0.05), left ventricular myocardial mass index (by 19.1 %, p < 0.05) and the E/e’ ratio (by 20.9 %, p < 0.05) has been revealed as compared to the 1st patient group. A strong direct correlation has been shown between the time of MI occurrence and the concentration of GDF 15 (r = 0.58, p < 0.05), the interventricular septum thickness at diastole (r = 0.61, p < 0.05) and the left ventricular myocardial mass index (r = 0.63, p < 0.05), GDF 15 and E/e’ (r = 0.37, p < 0.05), GDF 15 and the left atrial volume index (r = 0.41, p < 0.05), GDF 15 and NTproBNP (r = 0.56, p < 0.05). Conclusions. Progression of left ventricular myocardial hypertrophy and diastolic dysfunction with dilatation of the heart chambers has been observed in HFPEF patients with a longer history of MI. The time period of MI in patients with HFPEF was associated with the serum concentration of GDF 15, the interventricular septum thickness and the mass index of the left ventricular myocardium. The serum concentration of GDF 15 was significantly correlated with the deterioration of the left ventricular diastolic function, such as an increase in the E/e’ ratio and the left atrial volume index.

Abstract Background Nuts consumption is related to cardioprotective effects on primary cardiovascular prevention, but studies conducted in secondary prevention are small, scarce and controversial. The objective of this trial was to evaluate the effects of a regional and sustainable cardioprotective diet added or not with an affordable mixed nuts on cardiometabolic features in patients with previous myocardial infarction. Methods DICA-NUTS study is a national, multi-center, and superiority-parallel randomized clinical trial. Males and females over 40 years old diagnosed with previous myocardial infarction in the last 2 to 6 months were included. Patients were allocated into two groups: the Brazilian Cardioprotective diet (DICA Br) supplemented with 30 g/day of mixed nuts (10 g of peanuts; 10 g of cashew; 10 g of Brazil nuts) (intervention group, n = 193); or only DICA Br prescription (control group, n = 195). The primary outcome was low-density lipoprotein cholesterol means (in mg/dL) after 16 weeks. Secondary outcomes were other lipid biomarkers, glycemic and anthropometric data and diet quality. Results After adjustment for baseline values, participating study site, time since myocardial infarction and statin treatment regimen (high potency, moderate and low potency/no statins), no significant difference was found between the groups in low-density lipoprotein cholesterol concentrations (intervention-control difference: 3.48 mg/dL [-3.45 to 10.41], P = 0.32). Both groups improved their overall diet quality at the end of the study without differences between them after 16 weeks (intervention-control difference: 1.05 (-0.9 to 2.99); P = 0.29). Other lipids, glycemic profile and anthropometrics were also not different between study groups at the end of the study. Conclusion Adding 30 g/day of mixed nuts to the DICA Br for 16 weeks did not change lipid, glycemic and anthropometric features in the post-myocardial infarction setting. Trial registration This study is registered on ClinicalTrials.gov website under number NCT03728127 and its World Health Organization Universal Trial Number (WHO-UTN) is U1111-1259–8105.

Abstract Background Myocardial infarction (MI) induces complex transcriptional changes across diverse cardiac cell types. Single-cell RNA sequencing (scRNA-seq) provides an unparalleled ability to discern cellular diversity during infarction, yet the veracity of these discoveries necessitates confirmation. This investigation sought to elucidate MI mechanisms by integrating scRNA-seq and bulk RNA-seq data. Methods Publicly available scRNA-seq (GSE136088) and bulk RNA-seq (GSE153485) data from mice MI models were analyzed. Cell types were annotated, and differential expression analysis conducted. Bulk RNA-seq underwent quality control, principal component analysis, and differential expression analysis. Results In scRNA-seq data, the comparison between MI and sham groups unveiled a reduction in endothelial cell populations, but macrophages and monocytes increased. Within fibroblast subgroups, three distinct categories were discerned, with two exhibiting upregulation in MI. Notably, endothelial cells exhibited an elevated expression of genes associated with apoptosis and ferroptosis. In bulk RNA-seq analysis, distinct patterns emerged when comparing MI and sham groups. Specifically, six genes linked to endothelial ferroptosis exhibited heightened expression in MI group, thereby corroborating the scRNA-seq findings. Moreover, the examination of isolated cardiac macrophages from mice MI model revealed increased expression of Spp1, Col1a2, Col3a1, Ctsd, and Lgals3 compared to sham group, thus substantiating the dysregulation of macrophage apoptosis-related proteins following MI. Conclusion MI altered the transcriptomic landscapes of cardiac cells with increased expression of apoptotic genes. Moreover, the upregulation of macrophage apoptosis marker was confirmed within MI models. The presence of endothelial cell depletion and ferroptosis in MI has been demonstrated.

Left ventricular pseudoaneurysm is a serious and rare disorder that usually develops after acute myocardial infarction. It can lead to potentially lethal mechanical complications, such as acute left ventricular free wall rupture. This report presents the case of a 64-year-old man with a left ventricular pseudoaneurysm and myocardial rupture that was managed by left ventricular restoration with aneurysmectomy and coronary artery bypass with 2 grafts.

Nomagugu Ndlovu,&ast; Benedicta Ngwenchi Nkeh-Chungag&ast; Department of Biological and Environmental Sciences, Walter Sisulu University, Mthatha, South Africa&ast;These authors contributed equally to this workCorrespondence: Nomagugu Ndlovu, Email nondlovu@wsu.ac.zaAbstract: Indoor air pollution accounts for approximately 3.8 million inopportune deaths annually at global level. Due to spending more time indoors, children and older adults are especially susceptible to the health risks of indoor air pollution. This review seeks to summarise existing knowledge on the cardiovascular health effects of three common indoor air pollutants, namely carbon monoxide (CO), particulate matter (PM2.5 and PM10), and Nitrogen dioxide (NO2), focusing on older adults. We systematically reviewed the literature (PROSPERO CRD42024479220) on PubMed, Google Scholar, Scopus, Web of Science and Embase. The search yielded 20,914 records. Two independent reviewers screened the articles using titles, abstracts, and full-length articles written in English. Upon a detailed assessment of all the records, the review considered 38 full-length articles. Several studies reported mortality, myocardial infarction, stroke, increased hospitalisation and increased emergency room visits due to exposure to indoor air pollution. A few studies reported arrhythmias, hypertension and Ischaemic heart disease due to exposure to indoor air pollutants. The increased mortality, morbidity, hospitalization, and emergency rooms visits resulting from indoor air pollution associated CVDs makes indoor air pollution a health risk for older adults. There is, therefore, a need to synthesize information on studies relate d to how the selected indoor air pollutants affected the cardiovascular health of older adults.Keywords: particulate matter, PM2.5, PM10, nitrogen dioxide, myocardial infarction, stroke, hospitalisation, mortality, older adults

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

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

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

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

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

OBJECTIVES: To assess clinical and coronary angiographic characteristics, previous medical history, and clinical course, by age group, in older adults after myocardial infarction who underwent primary percutaneous coronary intervention (pPCI). METHODS: Single-center, cohort study that enrolled all patients with ST-segment elevation myocardial infarction who underwent pPCI at a specialized cardiology reference center in the South of Brazil. Older adults were defined as age ≥ 60 years, as set out in Brazilian legislation. Patients in the following age groups were compared: 60 to 64 years, 65 to 69 years, 70 to 74 years, 75 to 79 years, and ≥ 80 years. Patients' clinical course was assessed at initial hospital admissions and after 2 years of clinical follow-up. Data were analyzed using SPSS 19, and significance was established at p < 0.05. RESULTS: From December 2015 to December 2018, a total of 636 patients were enrolled consecutively. Angiographic success rates were around 90% in all age groups. There were no differences in medications used, except for glycoprotein IIb/IIIa inhibitors, which were more frequently used in patients of lower age groups. Older patients had more in-hospital acute renal failure and higher in-hospital mortality. Predictors of mortality were age over 75, chronic renal failure, need for ventilatory support, severe arrhythmia, and sepsis. CONCLUSIONS: pPCI in older adult patients is a saf e procedure with a high success rate.

In many patients, mainly in the age group of 60–75 years, with coronary heart disease, valvular diseases, cardiac conduction disorders and other accompanying age-associated pathology are detected. This article presents a clinical case of a patient who was hospitalized with a primary diagnosis of myocardial infarction complicated by complete atrioventricular block. During the examination, a bicuspid aortic valve with stenosis of the second degree, subocclusion of the right coronary artery (95 %) were additionally revealed. The patient underwent emergency stenting of the right coronary artery and was implanted a temporary pacemaker. Due to persisted block after 10 days permanent pacemaker was implanted, but during further observation and examination, ultrasound and tomographic signs of infective endocarditis of the aortic valve were detected with an increase in the degree of its stenosis up to the third degree, abscess of the aortic root and interventricular septum and formation of left ventricular to right atrial shunt (Gerbode defect). The patient underwent aortic valve replacement, Gerbode defect repair with xenopericardial flaps, and pacemaker replacement with epicardial electrode implantation with good clinical results. Step-by-step diagnostic, therapeutic and surgical tactics are given.

Erectile dysfunction after myocardial infarction can have a variety of aetiologies, associated with damage to the blood vessels and nerves responsible for normal penile erection, stress, fatigue, endocrine disruption, side effects of pharmacotherapy, and psychiatric disorders. The aim of this study is to provide knowledge and insight into the nursing care of a patient with erectile dysfunction after myocardial infarction. The study used a case study research method, including a description of the patient’s condition, aiming at its in-depth analysis and evaluation. The C-HOBIC care outcome indicators were used in the case description. ICNP® reference terminology was used for the nursing process. Nursing care of patients with erectile dysfunction after myocardial infarction incorporates a holistic approach that addresses both physical and psychosocial aspects.

Background: Limited evidence is available regarding the effect of reflexology on Acute Myocardial Infarction (AMI). The present study evaluated the effect of foot reflexology on fatigue, sleep quality, physiological indices, and electrocardiogram changes in AMI. Materials and Methods: This clinical trial was conducted on 80 subjects with AMI. They were divided into an intervention (received reflexology for 3 consecutive days) and a control (received the routine care) group. The Multidimensional Fatigue Inventory, the Pittsburgh Sleep Quality Index, a pain numeric analog scale, a daily physiological indices form, and daily electrocardiogram were used to collect data. The collected data were analyzed in SPSS software. The study was conducted based on CONSORT criteria. Results: After controlling the covariates, a significant difference was found between the intervention and control groups with regard to the mean scores of fatigue (F5,80 = 16.33; p < 0.001), sleep quality (F5,80 = 16.56; p < 0.001), and chest pain intensity (F5,80 = 6.86; p = 0.010); means of systolic blood pressure (F5,80 = 22.20; p < 0.001), heart rate (F5,80 = 5.86; p = 0.010), respiration (F5,80 = 9.37; p = 0.003), and temperature (F5,80= -4.23; p < 0.001); and incidence of ST-segment (χ21,80 = 5.00; p = 0.020) and T-wave changes (χ21,80 = 6.05, p = 0.010) on the fourth day of the intervention. Conclusions: Given the effectiveness of foot reflexology in different aspects of AMI patients, the implementation of this intervention is recommended for these patients in coronary care units.

Abstract Unlike adult mammals, the hearts of neonatal mice possess the ability to completely regenerate from myocardial infarction (MI). This observation has sparked vast interest in deciphering the potentially lifesaving and morbidity-reducing mechanisms involved in neonatal cardiac regeneration. In mice, the regenerative potential is lost within the first week of life and coincides with a reduction of Insulin-like growth factor 1 receptor (Igf1r) expression in the heart. Igf1r is a well-known regulator of cardiomyocyte maturation and proliferation in neonatal mice. To test the role of Igf1r as a pivotal factor in cardiac regeneration, we knocked down (KD) Igf1r specifically in cardiomyocytes using recombinant adeno-associated virus (rAAV) delivery and troponin T promotor driven shRNAmirs. Cardiomyocyte specific Igf1r KD versus control mice were subjected to experimental MI by permanent ligation of the left anterior descending artery (LAD). Cardiac functional and morphological data were analyzed over a 21-day period. Neonatal Igf1r KD mice showed reduced systolic cardiac function and increased fibrotic cardiac remodeling 21 days post injury. This cardiac phenotype was associated with reduced cardiomyocyte nuclei mitosis and decreased AKT and ERK phosphorylation in Igf1r KD, compared to control neonatal mouse hearts. Our in vivo murine data show that Igf1r KD shifts neonatal cardiac regeneration to a more adult-like scarring phenotype, identifying cardiomyocyte-specific Igf1r signaling as a crucial component of neonatal cardiac regeneration.

Several previous research studies have shown that air pollution has broad impacts on human health, particularly in the cardiovascular field. Exposure to air pollution entering the respiratory system can trigger inflammatory responses and increase the risk of cardiovascular diseases such as coronary artery disease. This systematic review aim to determine the relationship between air pollution and the occurrence of Coronary Artery Disease (CAD). Journal searches were conducted on five electronic databases, namely Pubmed, Science Direct, Europe PMC, Wiley Online Library, and Cochrane, following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) method. The search results get six original articles that meet the inclusion and exclusion criteria for analysis. Based on the results of the analysis shows that there is a significant relationship between air pollution in the form of gas components or particulate matter with the incidence of coronary artery disease. High levels of air pollution in an area can also increase the risk of CAD higher than areas with lower levels of air pollution.