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Cardiovascular disease such as myocardial infarction is one of the chief reasons for death universally. An extensive variety of natural and synthetic biodegradable polymers have been studied lately for cardiac tissue engineering applications. Cardiac tissue regeneration is a substitute approach for in situ cellular cardiomyoplasties, which is considered to renovate infarcted myocardium utilizing cells, scaffold, and growth factors. Polymer-based scaffolds including graphene and carbon nanotubes can be employed for heart tissue engineering. In this review, we consider the literature in terms of cardiac tissue engineering and discuss the most recent developments in terms of scaffold-based polymers for cardiac tissue regeneration. [ABSTRACT FROM AUTHOR]

The effectiveness of complete revascularization is well established in patients with ST-segment elevation myocardial infarction (STEMI), but it is less investigated in those with non–ST-segment elevation myocardial infarction (NSTEMI). This study aimed to assess whether complete revascularization, compared with culprit-only revascularization, was associated with consistent outcomes in older patients with STEMI and NSTEMI. In the FIRE (Functional Assessment in Elderly MI Patients with Multivessel Disease) trial, 1,445 older patients with myocardial infarction (MI) were randomized to culprit-only or physiology-guided complete revascularization, stratified by STEMI (n = 256 culprit-only vs n = 253 complete) and NSTEMI (n = 469 culprit-only vs n = 467 complete). The primary outcome comprised a composite of death, MI, stroke, or revascularization at 1 year. The key secondary outcome included a composite of cardiovascular death or MI at 1 year. In the overall study population, physiology-guided complete revascularization reduced both primary and key secondary outcomes. The primary outcome occurred in 54 (21.1%) STEMI patients randomized to culprit-only vs 41 (16.2%) STEMI patients of the complete group (HR: 0.75; 95% CI: 0.50-1.13) and in 98 (20.9%) NSTEMI patients randomized to culprit-only vs 72 (15.4%) NSTEMI patients of the complete group (HR: 0.71; 95% CI: 0.53-0.97), with negative interaction testing (P for interaction, 0.846). Similarly, no signal of heterogeneity with respect to the initial clinical presentation was observed for the key secondary endpoint (P for interaction, 0.654). Physiology-guided complete revascularization, compared with culprit-only revascularization, provided consistent benefit across the whole spectrum of patients with MI. (FIRE [Functional Assessment in Elderly MI Patients With Multivessel Disease]; NCT03772743) [ABSTRACT FROM AUTHOR]

Introduction: There are sex differences in the extent, severity, and outcomes of coronary artery disease. We aimed to assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men. Methods: In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men. Results: Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27–434] versus 205 [51–571] Agatston units; p = 0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p = 0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p = 0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n = 80) and 48.3% (n = 73); p = 0.42), or CMA values > 1.56 (21.8% (n = 33) and 21.8% (n = 33); p = 1.00). Over a median follow-up of 4.5 [4.0–6.0] years, myocardial infarction occurred in 6.6% of women (n = 10) and 7.8% of men (n = 66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p = 0.04) and men (HR: 5.29; 95% CI:2.28–12.28; p < 0.001). Conclusion: Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex. [ABSTRACT FROM AUTHOR]

The mitochondrial permeability transition (MPT) pore regulates necrotic cell death following diverse cardiac insults. While the componentry of the pore itself remains controversial, Cyclophilin D (CypD) has been well-established as a positive regulator of pore opening. We have previously identified Complement 1q-binding protein (C1qbp) as a novel CypD-interacting molecule and a negative regulator of MPT-dependent cell death in vitro. However, its effects on the MPT pore and sensitivity to cell death in the heart remain untested. We therefore hypothesized that C1qbp would inhibit MPT in cardiac mitochondria and protect cardiac myocytes against cell death in vivo. To investigate the effects of C1qbp in the myocardium we generated gain- and loss-of-function mice. Transgenic C1qbp overexpression resulted in decreased complex protein expression and reduced mitochondrial respiration and ATP production but MPT was unaffected. In contrast, while C1qbp +/− mice did not exhibit any changes in mitochondrial protein expression, respiration, or ATP, the MPT pore was markedly sensitized to Ca2+ in these animals. Neither overexpression nor depletion of C1qbp significantly affected baseline heart morphology or function at 3 months of age. When subjected to myocardial infarction, C1qbp transgenic mice exhibited similar infarct sizes and cardiac remodeling to non-transgenic mice, consistent with the lack of an effect on MPT. In contrast, cardiac scar formation and dysfunction were significantly increased in the C1qbp +/− mice compared to C1qbp +/+ controls. Our results suggest that C1qbp is required for normal regulation of the MPT pore and mitochondrial function, and influences cardiac remodeling following MI, the latter more likely being independent of C1qbp effects on the MPT pore. [Display omitted] • Examined the ability of C1qbp to regulate the MPT pore and cardiac injury in mice • C1qbp transgenesis reduced mitochondrial function but did not affect MPT or cardiac damage and dysfunction following MI • C1qbp haploinsufficiency did not affect function but sensitized the MPT pore to Ca2+ and exacerbated MI-induced pathology • Endogenous C1qbp acts a brake on the MPT pore and the progression of cardiac remodeling and dysfunction following MI [ABSTRACT FROM AUTHOR]

Although some studies have suggested that macrophages may secrete structural collagens, and convert to fibroblast-like cells, macrophage to fibroblast transdifferentiation in infarcted and remodeling hearts remains controversial. Our study uses linage tracing approaches and single cell transcriptomics to examine whether macrophages undergo fibroblast conversion, and to characterize the extracellular matrix expression profile of myeloid cells in myocardial infarction. To examine whether infarct macrophages undergo fibroblast conversion, we identified macrophage-derived progeny using the inducible CX3CR1CreER mice crossed with the PDGFRαEGFP reporter line for reliable fibroblast identification. The abundant fibroblasts that infiltrated the infarcted myocardium after 7 and 28 days of coronary occlusion were not derived from CX3CR1+ macrophages. Infarct macrophages retained myeloid cell characteristics and did not undergo conversion to myofibroblasts, endothelial or vascular mural cells. Single cell RNA-seq of CSF1R+ myeloid cells harvested from control and infarcted hearts showed no significant expression of fibroblast identity genes by myeloid cell clusters. Moreover, infarct macrophages did not express significant levels of genes encoding structural collagens. However, infarct macrophage and monocyte clusters were the predominant source of the fibrogenic growth factors Tgfb1 and Pdgfb, and of the matricellular proteins Spp1 /Osteopontin, Thbs1 /Thrombospondin-1, Emilin2 , and Fn1 /fibronectin, while expressing significant amounts of several other matrix genes, including Vcan /versican, Ecm1 and Sparc. ScRNA-seq data suggested similar patterns of matrix gene expression in human myocardial infarction. In conclusion, infarct macrophages do not undergo fibroblast or myofibroblast conversion and do not exhibit upregulation of structural collagens but may contribute to fibrotic remodeling by producing several fibrogenic matricellular proteins. Infarct fibroblasts and myofibroblasts are not derived from macrophages. Infarct macrophages do not produce significant amounts of structural matrix proteins but contribute to fibroblast activation through secretion of matricellular proteins, such as EMILIN2, Thrombospondin-1, Osteopontin, but also fibronectin, versican, ECM1 and SPARC. Created with Biorender.com. [Display omitted] • Infarct macrophages do not express fibroblast identity genes. • Lineage tracing shows no significant macrophage to fibroblast conversion. • Infarct macrophages do not express structural collagens. • Human and mouse infarct macrophages express Spp1 , Emilin2, and Thbs1. • Infarct macrophages are a major source of Mmp8, Mmp9, Mmp12, Mmp13, Tgfb1 , and Pdgfb. [ABSTRACT FROM AUTHOR]

Background: Providing secondary prevention through structured and comprehensive cardiac rehabilitation programmes to patients after a myocardial infarction (MI) reduces mortality and morbidity and improves health-related quality of life. Cardiac rehabilitation has the highest recommendation in current guidelines. While treatment target attainment rates at Swedish cardiac rehabilitation centres is among the highest in Europe, there are considerable differences in service delivery and variations in patient-level outcomes between centres. In this trial, we aim to study whether centre-level guideline adherence and patient-level outcomes across Swedish cardiac rehabilitation centres can be improved through a) regular audit and feedback of cardiac rehabilitation structure and processes through a national quality registry and b) supporting cardiac rehabilitation centres in implementing guidelines on secondary prevention. Furthermore, we aim to evaluate the implementation process and costs. Methods: The study is an open-label cluster-randomized effectiveness-implementation hybrid trial including all 78 cardiac rehabilitation centres (attending to approximately 10 000 MI patients/year) that report to the SWEDEHEART registry. The centres will be randomized 1:1:1 to three clusters: 1) reporting cardiac rehabilitation structure and process variables to SWEDEHEART every six months (audit intervention) and being offered implementation support to implement guidelines on secondary prevention (implementation support intervention); 2) audit intervention only; or 3) no intervention offered. Baseline cardiac rehabilitation structure and process variables will be collected. The primary outcome is an adherence score measuring centre-level adherence to secondary prevention guidelines. Secondary outcomes include patient-level secondary prevention risk factor goal attainment at one-year after MI and major adverse coronary outcomes for up to five-years post-MI. Implementation outcomes include barriers and facilitators to guideline adherence evaluated using semi-structured focus-group interviews and relevant questionnaires, as well as costs and cost-effectiveness assessed by a comparative health economic evaluation. Discussion: Optimizing cardiac rehabilitation centres' delivery of services to meet standards set in guidelines may lead to improvement in cardiovascular risk factors, including lifestyle factors, and ultimately a decrease in morbidity and mortality after MI. Trial registration: ClinicalTrials.gov. Identifier: NCT05889416. Registered 2023-03-23. [ABSTRACT FROM AUTHOR]

The article discusses the importance of pediatric organ donation, highlighting the impact children and adolescents have on saving lives through organ transplantation. A retrospective study conducted in a Portuguese hospital from 2006 to 2021 found that 62 pediatric patients were eligible for organ donation, resulting in 252 solid organs being collected and benefiting 202 recipients. Kidneys were the most frequently donated organs, with a median of four organs donated per child. The study emphasizes the need for further research to better understand the contribution of pediatric organ donation to both adults and children awaiting transplants. [Extracted from the article]

For aromatase inhibitor treatment (AIT) in breast cancer, there is an unresolved concern about ischaemic cardiotoxicity. We investigated the association between AIT and ischaemic cardiotoxicity in a prospective cohort of female patients with early breast cancer who received contemporary treatment in Denmark. In this prospective cohort study in Denmark, we identified postmenopausal patients of any age diagnosed with breast cancer as recorded in the nationwide Danish Breast Cancer Cooperative Group (DBCG) clinical database between Jan 1, 2009, and Dec 31, 2020, and linked them to other nationwide registries. Exclusion criteria included having a history of other primary cancer, less than 2 years of residency in Denmark, and no inclusion in a treatment protocol according to the DBCG database, including for metastatic or locally advanced breast cancer. Information on demography, hospital diagnoses, filled prescriptions, laboratory testing, and socioeconomic status were recorded. We stratified the patient cohort according to history (yes vs no) of selected cardiovascular disease defined as ischaemic heart disease, ischaemic stroke, and heart failure, and defined the primary outcome as two-point major adverse cardiovascular events (MACE; acute myocardial infarction or ischaemic stroke). We estimated cause-specific hazard ratios (HRs) according to allocation to AIT versus not in an intention-to-treat analysis using a Cox proportional hazards regression model with age as the underlying time scale, adjusting for demographic characteristics, tumour characteristics, and other anti-cancer treatments. 43 440 postmenopausal patients diagnosed with breast cancer were identified, of whom 32 635 were followed up and included in analyses. Of 29 118 postmenopausal patients with no history of selected cardiovascular disease, we observed 510 two-point MACEs among 22 135 patients allocated to AIT (incidence rate 4·3/1000 person-years of follow-up) and 170 two-point MACEs among 6983 patients not allocated to AIT (4·1/1000 person-years). The adjusted HR was 0·91 (95% CI 0·73–1·14) for patients allocated to AIT versus patients not allocated to AIT. Among 3517 patients with a history of selected cardiovascular disease, we observed 158 two-point MACEs among 2661 patients allocated to AIT (incidence rate 12·4/1000 person-years) and 50 two-point MACEs (12·1/1000 person-years) among 856 patients not allocated to AIT (adjusted HR 0·81 [95% CI 0·58–1·15]). Our findings do not support a clinically relevant ischaemic cardiotoxic potential of AIT in patients with early breast cancer and do not support avoiding AIT prescription in patients with early breast cancer. Bispebjerg and Frederiksberg Hospital, Kræftens Bekæmpelse, Fonden til Lægevidenskabens Fremme, Aase og Ejnar Danielsens Fond, Helsefonden, and Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis' Legat. [ABSTRACT FROM AUTHOR]

[Display omitted] • This study is the first attempt to clarify the role of circRNA in surgical ventricular reconstruction (SVR). • We identified a novel circRNA, named circMap4k2, is preferentially expressed in myocardial tissue and significantly up-regulated in response to SVR. • We confirmed that circMap4k2 promotes cardiomyocyte proliferation, and also enhances cardiac regeneration in the plication zone of SVR and thus attenuate residual cardiac remodelling. • CircMap4k2 prompts cardiac regeneration through miR-106a-3p/Azin1 pathway. • This work would provide opportunity to search new therapeutic approach for advanced heart failure. Surgical ventricular reconstruction (SVR) is an alternative therapeutic approach in patients with refractory heart failure (HF), but residual remodeling after SVR limits the improvement of HF. Recently, we reported that SVR may act as an environmental cue to reactivate endogenous proliferation of cardiomyocytes; however, it is unclear whether enhancing endogenous cardiomyocyte regeneration further improves HF after SVR. We aimed to explore whether circular RNAs (circRNAs) would involved in SVR and their mechanisms. Male C57BL/6 mice were subjected to myocardial infarction (MI) or sham surgery. Four weeks later, MI mice with a large ventricular aneurysm underwent SVR or a second open-chest operation only. Echocardiography and histological analysis were used to evaluate heart function, cardiac remodeling, and myocardial regeneration. Sequencing of circular RNAs, RNA immunoprecipitation, RNA pulldown, and luciferase reporter assay were used to explore the underlying mechanisms. SVR markedly attenuated cardiac remodeling and induced cardiomyocyte regeneration, as evidenced by positive staining of Ki-67, phospho-histone H3 (pH3), and Aurora B in the plication zone, but significant residual remodeling still existed in comparison with the sham group. Sequencing results showed that SVR altered the expression profile of cardiac circRNAs, and circMap4k2 was identified as the most upregulated one. After characterizing circMap4k2, we noted that overexpression of circMap4k2 significantly promoted proliferation of cardiomyocytes in cultured neonatal rat cardiomyocytes and silencing of circMap4k2 significantly inhibited it; similar results were obtained in SVR-treated MI mice but not in MI mice without SVR treatment. Residual cardiac remodeling after SVR was further attenuated by circMap4k2 overexpression. CircMap4k2 bound with miR-106a-3p and inhibited cardiomyocyte proliferation by targeting a downstream effector of the antizyme inhibitor 1 (Azin1) gene. CircMap4k2 acts as an environmental cue and targets the miR-106a-3p/Azin1 pathway to increase cardiac regeneration in the plication zone and attenuate residual remodeling after SVR. [ABSTRACT FROM AUTHOR]

Whether angiotensin II receptor blockers (ARBs) can be an alternative to angiotensin-converting enzyme inhibitors (ACEIs) in patients without heart failure (HF) after acute myocardial infarction (MI) remains controversial. The aim of this study was to compare clinical outcomes between initial ARB and ACEI therapy in patients with MI without HF. Between 2010 and 2016, a total of 31,013 patients who underwent coronary revascularization for MI with prescription of ARBs or ACEIs at hospital discharge were enrolled from the Korean nationwide medical insurance data. Patients who had HF at index MI were excluded. The primary outcome was all-cause death. The secondary outcomes included recurrent MI, hospitalization for new heart HF, stroke, and a composite of each outcome. Of 31,013 patients, ARBs were prescribed in 12,685 (40.9%) and ACEIs in 18,328 (59.1%). Patients receiving ARBs had a lower discontinuation rate compared with those receiving ACEIs (28.2% vs 43.5%, adjusted hazard ratio [HR] 0.34; 95% confidence interval [CI] 0.31-0.37; P <.01). During a median follow-up of 2.2 years, 2480 patients died. The incidence rate of all-cause death in patients receiving ARBs and those receiving ACEIs was 27.7 and 22.9 per 1000 person-years, respectively (adjusted HR 1.04; 95% CI 0.95-1.13; P =.40). There were no significant differences in the secondary outcomes between patients receiving ARBs and those receiving ACEIs, except stroke (19.2 vs 13.6 per 1000 person-years; adjusted HR 1.17; 95% CI 1.04-1.32; P =.01). In a subgroup analysis, a higher mortality was observed with ARBs compared with ACEIs in patients with diabetes. In this nationwide cohort, there was no significant difference in the incidence of all-cause death between ARBs and ACEIs as discharge medications in patients with myocardial infarction without heart failure. Angiotensin II receptor blockers would be an alternative to ACEIs for those intolerant to ACEI therapy. ▪ACEIs = angiotensin-converting enzyme inhibitors; ARBs = angiotensin II receptor blockers; CI = confidence interval; HF = heart failure; HR = hazard ratio; MI = myocardial infarction. [ABSTRACT FROM AUTHOR]

Myocardial infarction resulting from coronary artery atherosclerosis is the leading cause of heart failure, which represents a significant global health burden. The limitations of conventional pharmacologic thrombolysis and flow reperfusion procedures highlight the urgent need for new therapeutic strategies to effectively treat myocardial infarction. In this study, we present a novel biomimetic approach that integrates polyphenols and metal nanoenzymes, inspired by the structure of pomegranates. We developed tannic acid-coated Mn-Co 3 O 4 (MCT) nanoparticles in combination with an injectable collagen hydrogel for the effective treatment of myocardial infarction. The hydrogel enhanced the infarct microenvironment, while the slow-released MCT targets mitochondria to inhibit the post-infarction surge of reactive oxygen species, providing anti-apoptotic and anti-inflammatory effects. RNA sequencing revealed the potential of hydrogels to serve as an interventional mechanism during the post-infarction inflammatory phase. Notably, we found that the hydrogel, when combined with the nanopomegranate-based therapy, significantly improves adverse ventricular remodeling and restores cardiac function in early infarction management. The MCT hydrogel leverages the unique benefits of both MCT nanopomegranates and collagen, demonstrating a synergistic effect. This approach provides a promising example of the potential cooperation between nanomimetic structures and natural biomaterials in therapeutic applications. [Display omitted] • Developed novel pomegranate-inspired MCT nanoparticles combined with collagen hydrogel for MI therapy. • Efficacious in attenuating the inflammatory response, safeguarding cardiomyocytes and preserving their contractile function. • The MCT hydrogel can effectively alleviate the post-infarction inflammatory response and improve the long-term prognosis in MI rats. • Biomimetic MCT hydrogels offer a potential therapy for myocardial infarction. [ABSTRACT FROM AUTHOR]

A phase 3b, open-label, multicenter, expanded-access study (NCT04123548) evaluated safety and clinical outcomes of StrataGraft treatment in adults with deep partial-thickness thermal burns with intact dermal elements. Adult patients with 3 % to < 50 % total body surface area burns were treated with a single application of ≤ 1:1 meshed StrataGraft and followed for 24 weeks. Primary endpoint was count and percentage of patients with treatment-emergent adverse events (TEAEs). Secondary endpoints included confirmed wound closure (WC) at Week 12, durable WC at Week 24, time to WC, scar evaluation, and wound infection-related events. Fifty-two patients with 96 treatment sites were enrolled. Pruritus was the most common TEAE (22 patients [42.3 %]). Twenty serious TEAEs occurred in 10 patients (19.2 %); none were related to StrataGraft. There were 4 (7.7 %) deaths (aspiration, myocardial infarction, self-injury, Gram-negative rod sepsis); none were related to StrataGraft. Confirmed WC was achieved by Week 12 in 33 patients (63.5 %; 95 % CI: 50.4–76.5 %) and 69 treatment sites (71.9 %; 95 % CI: 62.9–80.9 %). Durable WC was achieved by Week 24 in 29 patients (55.8 %; 95 % CI: 42.3–69.3 %) and 58 treatment sites (60.4 %; 95 % CI: 50.6–70.2 %). StrataGraft demonstrated clinical benefit. Safety data were consistent with previously reported findings. • The safety of StrataGraft remained consistent with the prescribing information. • StrataGraft showed clinical benefit in adults with deep partial-thickness burns. • Use of StrataGraft in adults with deep partial-thickness burns spared donor sites. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI), referred to as a heart attack, is a life-threatening condition that happens due to blood clots, typically, blood flow to a portion of the heart muscle is blocked. The cardiac muscle may become permanently damaged if there is insufficient oxygen and blood flow to the affected area. It's crucial to treat MI as soon as possible because even a small delay might have serious effects. The primary diagnostic tool to track and identify the signs of MI is the electrocardiogram (ECG). The complexity of MI signals combined with noise makes it difficult for clinicians to make a precise and prompt diagnosis. It might be laborious and time-consuming to manually analyse an enormous quantity of ECG data. Therefore, techniques for autonomously diagnosing from the ECG data are required. There have been numerous research on the topic of MI espial, but the majority of the algorithms are cognitively intensive when working with empirical data. The current study suggests a unique method for the efficient and reliable identification of MI. We employed circulant singular spectrum analysis (CSSA) for baseline wander removal, a 4-stage Savitzky–Golay (SG) filter to expunge powerline interference from the ECG signal and segmented in the preprocessing stage. Thus segmented ECG has been decomposed using CSSA, entropy based features are extracted. The best features are selected by using binary Harris hawk optimization (BHHO) and to machine learning (ML) classifiers like Naive Bayes, Decision tree, K-nearest neighbor (KNN), Support vector machine (SVM), and Ensemble subspace KNN. Our suggested method has been examined from both class as well as subject oriented perspectives. While the subject-oriented technique uses data from one patient for testing while using data from the other subjects for training, the class-wise strategy divides data as test data as well as training data regardless of subjects. We succeeded in achieving accuracy ( A c % ) of 99.8, sensitivity ( S e % ) of 99, and 100 specificity (Sp%) under the class-oriented approach. Similarly, for the subject wise strategy we achieved a mean A c % , Se%, and Sp% of 85.2, 83.1, and 84.5, respectively. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies showed that long-term use of proton pump inhibitors (PPIs) was associated with cardiovascular events. However, the impact of short-term PPI exposure on intensive care unit (ICU) patients with myocardial infarction (MI) remains largely unknown. This study aims to determine the precise correlation between short-term PPI usage during hospitalization and prognostic outcomes of ICU-admitted MI patients using Medical Information Mart for Intensive Care IV database (MIMIC-IV). Methods: Propensity score matching (PSM) was applied to adjust confounding factors. The primary study outcome was rehospitalization with mortality and length of stay as secondary outcomes. Binary logistic, multivariable Cox, and linear regression analyses were employed to estimate the impact of short-term PPI exposure on ICU-admitted MI patients. Results: A total of 7249 patients were included, involving 3628 PPI users and 3621 non-PPI users. After PSM, 2687 pairs of patients were matched. The results demonstrated a significant association between PPI exposure and increased risk of rehospitalization for MI in both univariate and multivariate [odds ratio (OR) = 1.157, 95% confidence interval (CI) 1.020–1.313] analyses through logistic regression after PSM. Furthermore, this risk was also observed in patients using PPIs > 7 days, despite decreased risk of all-cause mortality among these patients. It was also found that pantoprazole increased the risk of rehospitalization, whereas omeprazole did not. Conclusion: Short-term PPI usage during hospitalization was still associated with higher risk of rehospitalization for MI in ICU-admitted MI patients. Furthermore, omeprazole might be superior to pantoprazole regarding the risk of rehospitalization in ICU-admitted MI patients. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the relationship between the stress‐hyperglycaemia ratio (SHR) and the clinical prognosis of patients with moderate‐to‐severe coronary artery calcification (MSCAC). Methods: We consecutively enrolled 3841 patients with angiography‐detected MSCAC. The individuals were categorized into three groups based on SHR tertiles: T1 (SHR ≤ 0.77), T2 (0.77 < SHR ≤ 0.89) and T3 (SHR > 0.89). The SHR value was calculated using the formula SHR = [admission glucose (mmol/L)]/[1.59 × HbA1c (%) − 2.59]. The primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCEs), including all‐cause death, non‐fatal myocardial infarction and non‐fatal stroke. Results: During a median follow‐up of 3.11 years, 241 MACCEs were recorded. Kaplan–Meier survival analysis showed that the SHR T3 group had the highest incidence of MACCEs (P <.001). Moreover, findings from the restricted cubic spline analysis showed a significant and positive association between the SHR and MACCEs. This correlation remained consistent even after considering other variables that could potentially impact the results (Pnon‐linear =.794). When comparing SHR T1 with SHR T3, it was found that SHR T3 was significantly associated with an increased risk of the primary outcome (adjusted hazard ratio = 1.50; 95% confidence interval: 1.10‐2.03). Conclusions: Patients with MSCAC showed a positive correlation between the SHR and MACCE rate over a 3‐year follow‐up period. The study showed that an SHR value of 0.83 is the key threshold, indicating a poor prognosis. Future large‐scale multicentre investigations should be conducted to determine the predictive value of the SHR in patients with MSCAC. [ABSTRACT FROM AUTHOR]

Aim: To assess the disease burden of familial partial lipodystrophy (FPLD) caused by LMNA (FPLD2) and PPARG (FPLD3) variants to augment the knowledge of these rare disorders characterized by selective fat loss and metabolic complications. Materials and Methods: An observational longitudinal study, including 157 patients (FPLD2: 139 patients, mean age 46 ± 17 years, 70% women; FPLD3: 18 patients, mean age: 44 ± 17 years, 78% women) from 66 independent families in two countries (83 from Turkey and 74 from Spain), was conducted. Results: Patients were diagnosed at a mean age of 39 ± 19 years, 20 ± 16 years after the first clinical signs appeared. Men reported symptoms later than women. Symptom onset was earlier in FPLD2. Fat loss was less prominent in FPLD3. In total, 92 subjects (59%) had diabetes (age at diagnosis: 34 ± 1 years). Retinopathy was more commonly detected in FPLD3 (P <.05). Severe hypertriglyceridaemia was more frequent among patients with FPLD3 (44% vs. 17%, P =.01). Hepatic steatosis was detected in 100 subjects (66%) (age at diagnosis: 36 ± 2 years). Coronary artery disease developed in 26 patients (17%) and 17 (11%) suffered from a myocardial infarction. Turkish patients had a lower body mass index, a higher prevalence of hepatic steatosis, greater triglyceride levels and a tendency towards a higher prevalence of coronary artery disease. A total of 17 patients died, with a mean time to death of 75 ± 3 years, which was shorter in the Turkish cohort (68 ± 2 vs. 83 ± 4 years, P =.01). Cardiovascular events were a major cause of death. Conclusions: Our analysis highlights severe organ complications in patients with FPLD, showing differences between genotypes and Mediterranean countries. FPLD3 presents a milder phenotype than FPLD2, but with comparable or even greater severity of metabolic disturbances. [ABSTRACT FROM AUTHOR]

Background and Purpose: Remote ischaemic preconditioning (rIPC) for cardioprotection is severely impaired in diabetes, and therapeutic options to restore it are lacking. The vascular endothelium plays a key role in rIPC. Given that the activity of endothelial nitric oxide synthase (eNOS) is inhibited by proline‐rich tyrosine kinase 2 (Pyk2), we hypothesized that pharmacological Pyk2 inhibition could restore eNOS activity and thus restore remote cardioprotection in diabetes. Experimental Approach: New Zealand obese (NZO) mice that demonstrated key features of diabetes were studied. The consequence of Pyk2 inhibition on endothelial function, rIPC and infarct size after myocardial infarction were evaluated. The impact of plasma from mice and humans with or without diabetes was assessed in isolated buffer perfused murine hearts and aortic rings. Key Results: Plasma from nondiabetic mice and humans, both subjected to rIPC, caused remote tissue protection. Similar to diabetic humans, NZO mice demonstrated endothelial dysfunction. NZO mice had reduced circulating nitrite levels, elevated arterial blood pressure and a larger infarct size after ischaemia and reperfusion than BL6 mice. Pyk2 increased the phosphorylation of eNOS at its inhibitory site (Tyr656), limiting its activity in diabetes. The cardioprotective effects of rIPC were abolished in diabetic NZO mice. Pharmacological Pyk2 inhibition restored endothelial function and rescued cardioprotective effects of rIPC. Conclusion and Implications: Endothelial function and remote tissue protection are impaired in diabetes. Pyk2 is a novel target for treating endothelial dysfunction and restoring cardioprotection through rIPC in diabetes. [ABSTRACT FROM AUTHOR]

The present study investigated the characteristics of rare but often fatal cases of acute coronary syndrome and aortic dissection and the factors affecting mortality. HEART score, aortic dissection detection risk score, and Global Registry of Acute Coronary Event (GRACE) Score were calculated by evaluating biochemical tests and symptoms/signs of the 20 patients who were admitted to our clinic with a preliminary diagnosis of acute myocardial infarction and subsequently diagnosed with aortic dissection. The assumption of normal distribution was checked with the Shapiro–Wilk test, and independent group comparisons were made with the t test or the Mann–Whitney U test. Relationships between qualitative variables were analyzed with chi-square tests. Relationships between quantitative variables were analyzed with Pearson or Spearman correlation coefficients. Patients with conditions like hypertension and diabetes are at higher risk for aortic dissection. We recommend the use of the GRACE Score with the risk parameters we have determined for the prediction of operative mortality. We suggest that the axillary region and antegrade cerebral perfusion may be preferred as the cannulation area in dissection repair. We emphasize preliminary risk assessment according to the aortic dissection detection risk score and remind physicians that ECG ST-T and troponin changes may be misleading. [ABSTRACT FROM AUTHOR]

Herpes zoster increases stroke and myocardial infarction risk. The objective of this study is to evaluate the impact of live attenuated zoster vaccination on stroke and myocardial infarction risk in patients at risk of zoster, including those with hypertension, diabetes mellites, obesity, hypercholesterolemia, chronic kidney disease, chronic obstructive pulmonary disease, emphysema, asthma, and chronic liver disease. This is a retrospective cohort study utilizing continuous de-identified claims data from the IBM MarketScan Commercial Claims and Encounters Database (collected from 2005–2018) containing data for 200 million commercially insured Americans. Participants included 27,093 adults vaccinated against zoster with at least 5 years of continuous enrollment, age and sex-matched 1:5 with unvaccinated controls. OR, risk difference, and the number needed to treat evaluated the effect of vaccination on stroke and myocardial infarction while controlling for relevant comorbidities. Over the period of 5 years, proportions of myocardial infarction (1.29% vs 1.82%; p< 0.05) and stroke (1.61% vs 2.20%; p< 0.05) were lower in vaccinated versus unvaccinated individuals, respectively, controlling for age and sex, with the greatest benefit for people with diabetes (stroke OR=0.64, 95% CI=0.58, 0.71; myocardial infarction OR=0.63, 95% CI=0.57, 0.71). Although hypertension and chronic obstructive pulmonary disease had the highest odds of stroke and myocardial infarction, vaccination still provided significant risk-reduction (hypertension: stroke 0.75 [0.68, 0.83], myocardial infarction 0.73 [0.65, 0.81]; chronic obstructive pulmonary disease: stroke 0.75 [0.68, 0.83], myocardial infarction 0.74 [0.66, 0.83]). Live attenuated zoster vaccination is associated with lower risk of stroke and myocardial infarction in adults with at-risk comorbidities, controlling for age and sex. Vaccination may provide cardiovascular benefits beyond zoster prevention. [ABSTRACT FROM AUTHOR]

• Fibroblast-specific ablation of CCN1 neither impacts cardiac function nor myocardial collagen levels; however, it disrupts collagen fibril organization and increases matrix compliance. • Fibroblast-specific Ccn1 ablated mice display an increased incidence of mortality and cardiac rupture after myocardial infarction. • Post-myocardial infarct scars in fibroblast-specific Ccn1 ablated mice exhibit increased ECM complexity and diminished collagen alignment. • Alterations in ECM structure in fibroblast-specific Ccn1 ablated mice are associated with reductions in fibroblast-matrix interactions. • Findings suggest that CCN1 plays a critical role in acute scar formation by directing the alignment of fibrillar collagen within the developing scar, thereby shaping the structural attributes that underlie its structural integrity. Members of the cellular communication network family (CCN) of matricellular proteins, like CCN1, have long been implicated in the regulation of cellular processes underlying wound healing, tissue fibrogenesis, and collagen dynamics. While many studies suggest antifibrotic actions for CCN1 in the adult heart through the promotion of myofibroblast senescence, they largely relied on exogenous supplementation strategies in in vivo models of cardiac injury where its expression is already induced—which may confound interpretation of its function in this process. The objective of this study was to interrogate the role of the endogenous protein on fibroblast function, collagen structural dynamics, and its associated impact on cardiac fibrosis after myocardial infarction (MI). Here, we employed CCN1 loss-of-function methodologies, including both in vitro siRNA-mediated depletion and in vivo fibroblast-specific knockout mice to assess the role of the endogenous protein on cardiac fibroblast fibrotic signaling, and its involvement in acute scar formation after MI. In vitro depletion of CCN1 reduced cardiac fibroblast senescence and proliferation. Although depletion of CCN1 decreased the expression of collagen processing and stabilization enzymes (i.e. , P4HA1, PLOD1, and PLOD2), it did not inhibit myofibroblast induction or type I collagen synthesis. Alone, fibroblast-specific removal of CCN1 did not negatively impact ventricular performance or myocardial collagen content but did contribute to disorganization of collagen fibrils and increased matrix compliance. Similarly, Ccn1 ablated animals subjected to MI showed no discernible alterations in cardiac structure or function one week after permanent coronary artery ligation, but exhibited marked increases in incidence of mortality and cardiac rupture. Consistent with our findings that CCN1 depletion does not assuage myofibroblast conversion or type I collagen synthesis in vitro, Ccn1 knockout animals revealed no measurable differences in collagen scar width or mass compared to controls; however, detailed structural analyses via SHG and TEM of scar regions revealed marked alterations in their scar collagen topography—exhibiting changes in numerous macro- and micro-level collagen architectural attributes. Specifically, Ccn1 knockout mice displayed heightened ECM structural complexity in post-MI scar regions, including diminished local alignment and heightened tortuosity of collagen fibers, as well as reduced organizational coherency, packing, and size of collagen fibrils. Associated with these changes in ECM topography with the loss of CCN1 were reductions in fibroblast-matrix interactions, as evidenced by reduced fibroblast nuclear and cellular deformation in vivo and reduced focal-adhesion formation in vitro ; findings that ultimately suggest CCN1's ability to influence fibroblast-led collagen alignment may in part be credited to its capacity to augment fibroblast-matrix interactions. These findings underscore the pivotal role of endogenous CCN1 in the scar formation process occurring after MI, directing the appropriate arrangement of the extracellular matrix's collagenous components in the maturing scar—shaping the mechanical properties that support its structural stability. While this suggests an adaptive role for CCN1 in regulating collagen structural attributes crucial for supporting scar integrity post MI, the long-term protracted expression of CCN1 holds maladaptive implications, potentially diminishing collagen structural complexity and compliance in non-infarct regions. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

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 < 0.0001) after MI. In subgroup analyses, type 2 diabetes was associated with a poorer prognosis across the spectrum of MI patients. The excess mortality risk was attenuated by increasing age but was similar in both sexes. Male sex, age, cardiovascular and noncardiovascular co-morbidities, lack of revascularization, a longer duration of diabetes, and baseline insulin therapy were associated with increased mortality in patients with type 2 diabetes. The one-year prognosis of patients with type 2 diabetes improved during the study period, but the mortality gap compared to patients without diabetes was not altered. Conclusions: Type 2 diabetes had a negative impact on both short- and long-term outcome after MI, but effect sizes were relatively small. Patients with longer duration of diabetes or need for insulin therapy are still at particular risk. [ABSTRACT FROM AUTHOR]

Background: Postinfarct ventricular septal defect (PIVSD) is a serious complication of acute myocardial infarction (AMI). Transcatheter closure is a potential alternative to surgical closure for PIVSD patients. Objective: This meta‐analysis compares the clinical outcomes of transcatheter closure versus surgical closure for PIVSD. Methods: A systemic search of PubMed and Embase until January 2023 identified studies comparing transcatheter versus surgical PIVSD closure. Primary outcomes included short‐term mortality. Short‐term mortality referred to the number of in‐hospital or 30‐day deaths. Secondary outcomes comprised residual shunt/reintervention incidence, difference in time from AMI or PIVSD diagnosis to intervention, the presence of cardiogenic shock, incidence of perioperative mechanical support, PIVSD size difference, and overall mortality at follow‐up. Results: Seven studies comprising 603 patients were included. Short‐term mortality (OR, 1.30; 95% CI [0.90, 1.89]; p = 0.17; I2 = 3.0%) did not significantly differ between the two groups. The incidence of residual shunt/reintervention (OR, 3.56; CI, 1.33–9.59; p = 0.01; I2 = 63.0%) and PIVSD size (mean difference, −3.94 mm; CI [−6.90, −0.99]; p = 0.09; I2 = 83.0%) were significantly different; however, the other secondary outcomes were not significantly different. Conclusion: Transcatheter and surgical closure demonstrate similar short‐term mortality. Despite a higher incidence of residual shunt or reintervention in transcatheter closure, it may be a viable option in patients with small size of PIVSD. [ABSTRACT FROM AUTHOR]

Background: Utilizing the two available prediction models, i.e., the dual antiplatelet therapy (DAPT) score and predicting bleeding complication in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE‐DAPT) score, we aimed to determine the appropriateness of the DAPT in patients with acute myocardial infarction (AMI) in patients undergoing percutaneous coronary intervention (PCI). Methods: We retrospectively enrolled 235 patients of AMI and for all the patients and thorough information regarding history, risk factors, and medications were collected. Both DAPT and PRECISE‐DAPT scores were calculated. The patients were divided by their recommended cutoffs and the appropriateness of the duration of the recommended DAPT was measured based on the observed scores. Bleeding academic research consortium (BARC) classification was used to define the bleeding events. In the patients with DAPT score ≥ 2 and PRESICE‐DAPT < 25, the prolonged use of DAPT was recommended. Results: Overall, 235 patients, predominantly male (78.7%), with baseline characteristics exhibiting high rate of smoking (31.1%), diabetes (35.3%), and hypertension (32.8%) were found. The widely prescribed DAPT combination was aspirin with clopidogrel (72.3% at discharge and 46% on current use). Among all the enrolled patients, 163 patients were on DAPT while 71 were on single antiplatelet therapy (SAPT). A significant association between DAPT and PRECISE‐DAPT scores was noted in terms of SAPT and DAPT. The appropriateness of DAPT was checked based on the scores, where 81% of the patients with DAPT ≥ 2 and 77.24% with PRECISE‐DAPT score < 25 were appropriately prescribed with DAPT. The primary reason for drug interruptions was self‐advised. The incidence of bleeding events was observed to be 7.23%, among which 5.1% had Type 1 bleeding according to BARC. Conclusion: Both DAPT and PRECISE‐DAPT scores could be used to determine the appropriateness of the recommendations of DAPT in patients with AMI or undergoing PCI. [ABSTRACT FROM AUTHOR]

Background Aim Methods Results Conclusions Relevance to Clinical Practice After acute myocardial infarction, the prevalence of anxiety and depression is quite high in patients because of severe chest pain, distance from relatives, unfamiliar environment and orientation problems.To assess the effect of listening to the voice recordings of relatives of patients with acute myocardial infarction who were treated in the coronary intensive care unit (ICU) on chest pain, anxiety and depression parameters of the patients.In the study, which was conducted as a randomized controlled trial, voice recordings of the family members of the patients were created and played to the patients through a music pillow. The study was carried out with 60 patients, 30 experimental and 30 control groups. Three tests were applied to the patients 15 min before, and 15 and 30 min after the application. The data of the study were collected using the Patient Introduction Form, Hospital Anxiety Depression Scale, Visual Analogue Scale and Patient Follow‐up Form.It was found that there was a significant decrease in the anxiety level of the patients in the intervention group after listening to the audio recording (p < .001, 95% CI: −3.796; −0.070). However, there was no significant difference between the pain and depression scores of the control and intervention groups (p > .05).In the ICUs of patients with acute myocardial infarction, it may be recommended to play audio recordings of their relatives to reduce the severity of anxiety.In the intensive care setting, the use of voice recordings of relatives can be used as an effective, non‐pharmacological intervention to reduce anxiety in patients with acute myocardial infarction. This approach may potentially improve overall recovery by reducing patient anxiety in the intensive care setting. [ABSTRACT FROM AUTHOR]

In the elderly population, coronary heart disease (CHD) often coexists with hypertension. However, excessive blood pressure reduction can paradoxically increase the incidence of adverse events. Understanding the molecular mechanisms underlying hypertension and CHD in aged populations is crucial for developing targeted therapies and improving clinical outcomes. In this study, we constructed myocardial infarction (MI) and transverse aortic constriction (TAC) modelsY in aged mice to simulate the disease states of CHD and hypertension, respectively. Using integrated proteomic and phosphoproteomic analyses, we investigated the molecular signatures associated with MI and TAC in these models. Our aim was to identify key molecules involved in these conditions and to understand their unique and shared characteristics. Through our comprehensive proteomic and phosphoproteomic analysis, we identified a total of 1583 proteins and 232 phosphorylated proteins. We observed significant upregulation of heart disease markers such as Myh7, Xirp2, and Acta1, indicating the successful establishment of the MI and TAC models. The overlapped differentially expressed proteins (DEPs) and differentially phosphorylated proteins (DPPs) in MI and TAC were involved in heart failure‐related processes including cardiac muscle contraction and hypertrophic cardiomyopathy, further supporting the validity of the models. Among the DEPs, Ppme1 was upregulated in the TAC model but downregulated in the MI model, while Sec31a and Gm56451 displayed the opposite expression patterns. Among the DPPs, Ablim1 and Atp2a2 were found to be significantly upregulated in the TAC model, whereas their expression was markedly reduced in the MI model. In addition, five other DPPs, including REV_Q3TAY5, Cbx3, PITPNB, Eif4b, and A0A1Y7VP73, were elevated in the MI model but decreased in the TAC model. In conclusion, these findings suggest that MI and TAC not only share certain molecular features but also retain their unique characteristics, providing potential biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) is a growing concern among people with spinal cord injury (SCI). This meta-analysis aims to explore the risk of overall CVD and specific types of cardiovascular events among SCI patients. Methods: This meta-analysis is registered on PROSPERO (CRD CRD42024537888). The data sources comprised PubMed, Embase, the Cochrane Library, and reference lists of the included studies. The literature collection span is from database establishment until April 17, 2024. This meta-analysis encompassed observational studies investigating the association between SCI and the risk of overall types of CVD or specific CVD types. Risk of bias was evaluated utilizing the Newcastle-Ottawa Quality Assessment Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) Scale. Odds ratios (ORs) with 95% confidence intervals (CIs) were aggregated using a random-effects model. Results: Our initial search generated 5357 relevant records form these international databases. This meta-analysis encompassed 9 observational studies involving 2,282,691 individuals, comprising 193,045 patients with SCI and 2,209,646 controls. We observed a 1.56-fold [OR = 1.56, 95% CI (1.43, 1.70), I2 = 91.3%, P < 0.001] rise in the risk of overall types of CVD among SCI patients, with a 1.82-fold increase in males and a 1.76-fold increase in females. SCI patients without comorbidities exhibited a 2.10-fold elevated risk of overall CVD types, while those with comorbidities had a 1.48-fold increased risk. Concerning specific CVD types, SCI patients showed a 1.58-fold [OR = 1.57, 95% CI (1.22, 2.03), I2 = 92.4%] higher risk of myocardial infarction, a 1.52-fold [OR = 1.52, 95% CI (1.07, 2.16), I2 = 88.7%] increase in atrial fibrillation, a 1.64-fold [OR = 1.64, 95% CI (1.22, 2.20), I2 = 95.5%] elevation in heart failure risk, and 2.38-fold [OR = 2.38, 95% CI (1.29, 4.40), I2 = 92.5%] increments in stroke risk. But there was no statistically significant difference in the risk of hypertension [OR = 1.54, 95% CI (0.98, 2.42), I2 = 96.6%]. Conclusions: The risk of overall CVD in SCI patients surpassed that of the non-SCI control group, with elevated risks of specific cardiovascular events like myocardial infarction, atrial fibrillation, heart failure, and stroke. Clinicians should prioritize awareness of CVD risks in SCI patients. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion The relationship between systemic lupus erythematosus (SLE) and low‐grade metabolic inflammation (MI) with the microbiota is crucial for understanding the pathogenesis of these diseases and developing effective therapeutic interventions. In this context, it has been observed that the gut microbiota plays a key role in the immune regulation and inflammation contributing to the exacerbation through inflammatory mediators. This research aimed to describe similarities/differences in anthropometric, biochemical, inflammatory, and hepatic markers as well as to examine the putative role of gut microbiota concerning two inflammatory conditions: SLE and MI.Data were obtained from a cohort comprising adults with SLE and MI. Faecal samples were determined by 16S technique. Statistical analyses compared anthropometric and clinical variables, and LEfSe and MetagenomeSeq were used for metagenomic data. An interaction analysis was fitted to investigate associations of microbiota with fatty liver index (FLI) depending on the inflammatory condition.Participants with low‐grade MI showed worse values in anthropometry and biochemicals compared with patients with SLE. The liver profile of patients with MI was unhealthier, while no relevant differences were found in most of the inflammatory markers between groups. LEfSe analysis revealed an overrepresentation of Bifidobacteriaceae family in SLE group. An interactive association between gut Bifidobacterium abundance and type of disease was identified for FLI values, suggesting an effect modification of the gut microbiota concerning liver markers depending on the inflammatory condition.This study found phenotypical and microbial similarities and disparities between these two inflammatory conditions, evidenced in clinical and hepatic markers, and showed the interactive interplay between gut Bifidobacterium and liver health (measured by FLI) that occur in a different manner depending on the type of inflammatory disease. These results underscore the importance of personalized approaches and individual microbiota in the screening of different inflammatory situations, considering unique hepatic and microbiota profiles. [ABSTRACT FROM AUTHOR]

Aim Materials and methods Results Conclusions Intraindividual body weight variability (BWV), that is, the degree of weight fluctuations over time, is associated with an increased risk of cardiovascular diseases (CVDs) in multiple settings. The impact of BWV on cardiovascular risk in type 1 diabetes (T1D) remains unclear, despite the issues relative to weight management in individuals with this condition.Using data from the Swedish National Diabetes Register, we identified individuals with T1D and without CVD at baseline with at least three measurements of body weight taken over three consecutive years. We estimated BWV as quartiles of the standard deviation of weight measures and explored its longitudinal association with the incidence of CVD during a 12.7 ± 4.6 year follow‐up through adjusted Cox regression models. The primary endpoint was the composite of nonfatal myocardial infarction, nonfatal stroke and all‐cause mortality. We modelled the function of risk in relation to the magnitude of BWV, testing also whether weight trends, that is, increasing, stable or decreasing, age, sex and glycaemic control modified the association between BWV and the outcome.Among the 36 333 individuals with T1D in the register, we identified 19 373 individuals with at least three measures of body weight and without CVD at baseline. Participants with the highest BWV had a 42% increased risk of reaching the primary endpoint compared to those with the lowest BWV (hazard ratio [HR] = 1.42, 95% confidence interval [CI]: 1.24–1.62). In addition, high BWV was significantly associated with a 51% increased risk of all‐cause mortality (HR = 1.51, 95% CI: 1.28–1.78), a 37% increased risk of peripheral artery disease (HR = 1.37, 95% CI: 1.06–1.77) and a 55% increased risk of hospitalization for heart failure (HR = 1.55, 95% CI: 1.20–2.01). BWV showed a quasi‐linear association with the primary endpoint. No interaction was observed when comparing subgroups for weight trends, sex or degree of glycaemic control. In the subgroup of elderly individuals, the association of BWV with the primary endpoint was no longer significant.High BWV is associated with an increased risk of CVD and all‐cause mortality in individuals with T1D, independently of canonical risk factors. Weight trends, sex and glycaemic control do not modify such association while older age attenuates it. [ABSTRACT FROM AUTHOR]

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a protein crucial for cellular stress response and survival, particularly in the nervous and cardiovascular systems. Unlike traditional neurotrophic factors, MANF primarily regulates endoplasmic reticulum (ER) stress and protects cells by reducing ER stress-induced apoptosis. MANF operates both inside and outside cells, influencing key pathways like JAK/STAT and NF-κB to enhance cell survival during stress. Beyond its neuroprotective role, MANF is also vital in cardiovascular protection, mitigating damage by reducing inflammation and maintaining cellular function. Elevated MANF levels have been observed in patients experiencing myocardial infarction and murine models of ischemia–reperfusion (I/R) injury, highlighting its importance in these conditions. Overexpression of MANF in cardiomyocytes reduces ER-stress-induced cell death, while its depletion worsens this effect. Treatment with recombinant MANF (rMANF) has been shown to improve cardiac function in mice with I/R injury by decreasing infarct size and inflammation. Research also indicates that alterations in the α1-helix region of MANF can impact its structure, expression, secretion, and overall function. Given its protective effects and involvement in critical signaling pathways, MANF is being explored as a potential therapeutic target for ER stress-related diseases, including neurodegenerative disorders and cardiovascular conditions like myocardial I/R injury. [ABSTRACT FROM AUTHOR]

Background: The Pooled Cohort Equations (PCEs) do not accurately estimate atherosclerotic cardiovascular disease (ASCVD) risk in certain populations. The 2018 AHA/ACC cholesterol guideline identified risk-enhancing factors as a supplement to PCEs-based risk assessment. However, the role of each risk-enhancing factor in ASCVD risk assessment has not been well quantified. Further, social determinants of health (SDOH) are not included in the PCEs nor considered as risk-enhancing factors in the US cholesterol guideline. We sought to evaluate ASCVD risk associated with each risk-enhancing factor and commonly collected SDOH including education, income, and employment status, and to assess if adding risk-enhancing factors and SDOH to the PCEs improve ASCVD risk prediction. Methods: We included individuals aged 40 to 75 years, without ASCVD or diabetes at baseline, and with low-density lipoprotein cholesterol 70–189 mg/dL from two contemporary prospective cohort studies (MESA and REGARDS) and from Kaiser Permanente Southern California (KPSC). The primary endpoint was incident ASCVD defined as nonfatal myocardial infarction, fatal coronary heart disease, or fatal or nonfatal stroke over a 10-year period (median follow-up 10 years). We used Cox proportional hazards models to estimate associations between risk-enhancing factors and SDOH with ASCVD. We also assessed changes in model performance after adding risk-enhancing factors and SDOH to the PCEs. Results: We included 13,863 adults (mean age 60.7 years) from the prospective cohorts and 307,931 adults (mean age 54.8 years) from KPSC. Risk-enhancing factors including hypercholesterolemia, hypertriglyceridemia, metabolic syndrome, and chronic kidney disease were associated with a higher ASCVD risk, independent of 10-year risk estimated by the PCEs. Low education, low income, and unemployment were also associated with higher ASCVD risk. While adding individual risk-enhancing factors or SDOH to the PCEs had limited impact on model performance, adding multiple risk-enhancing factors and SDOH simultaneously led to modest improvements in discrimination (C-index increased by up to 0.07), calibration (integrated Brier score reduced by up to 2.3%), and net reclassification improvement up to 41.4%. Conclusions: These findings suggest including SDOH and risk-enhancing factors may improve ASCVD risk assessment. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Previous studies have demonstrated that people with HIV have an increased atherosclerotic plaque vulnerability, making them more susceptible to severe cardiovascular complications. This study aimed to examine the clinical characteristics of people with HIV in comparison to people without HIV admitted to Veterans Health Administration (VHA) with their first major acute cardiovascular events (MACE) and compare their total mortality.We used national VHA data to extract data of those admitted to VHA hospitals with MACE defined as acute myocardial infarction (AMI), acute cerebrovascular accident (CVA) or cardiac arrest during the fiscal years 2003–2021. The hazard ratio (HR) of mortality for people with HIV versus people without HIV was estimated using Cox proportional hazard regression analysis.Out of 280 311 veterans, 2510 people with HIV and 277 801 people without HIV had their first MACE during the study period. People with HIV were younger, more likely to be African American, had a lower prevalence of diabetes mellitus and hypertension, similar total cholesterol levels and a lower mean 10‐year cardiovascular risk score (25.4 in people with HIV vs. 28.7 in people without HIV). Among MACE components, people with HIV had a higher proportion of CVA (27% vs. 21.3%, p < 0.001) and cardiac arrest (13.0% vs. 8.4%, p < 0.001) but a lower incidence of AMI (62.4% vs. 72.5%, p < 0.001) than people without HIV. Additionally, people with HIV had a higher risk of total mortality (adjusted HR: 2.05, 95% confidence interval: 1.90–2.22) compared with people without HIV.People with HIV experience MACE at younger ages despite lower cardiovascular risks and similar baseline cholesterol and blood pressure levels. People with HIV had higher mortality and a higher risk of having ventricular fibrillation arrest and stroke as their first MACE. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Methods Results Conclusions Estimating patient risk before heart surgery (HS) is crucial. Perioperative inflammation is associated with several complications and mortality. This study investigated blood cell count inflammatory indices (BCCII) to predict risks, including neutrophil‐to‐lymphocyte ratio (NLR), derivate NLR (DNLR), neutrophil‐to‐platelet‐lymphocyte ratio (NLPR), lymphocyte‐to‐monocyte ratio, platelet‐to‐lymphocyte ratio (PLR), Systemic Inflammatory Index (SII), Systemic Inflammatory Reaction Index (SIRI), and Aggregate Index of Systemic Inflammation (AISI).Data from a cohort of patients undergoing on‐pump HS at a single center in Brazil were retrospectively analyzed. Data were obtained from medical records and a laboratory analyzer, and SPSS version 20.0 was used for index calculations and statistical analyses.In total, 444 surgeries were performed, and 40 in‐hospital deaths occurred. Except for PLR, all other indexes were independent predictors of death after multivariate adjustment (all p < 0.05). Discrimination performance was absent for PLR and AISI, and NLR, NLPR, and DNLR demonstrated the best area under the receiver operating characteristic curve (AUC > 0.7; all p < 0.0001). For survivors (n = 404), all indexes exhibited a correlation with the length of hospital stay (all p < 0.03), and NLR, NLPR, and DNLR were predictors (p < 0.026) of poor operative outcomes (acute myocardial infarction, cerebrovascular attack, cardiac arrest, low cardiac output, prolonged mechanical ventilation, renal failure, and sepsis).All BCCII scores were associated with length of hospital stay. Apart from PLR, all indexes were independent predictors of in‐hospital mortality. Accuracy was highest for NLR, NLPR, and DNLR; for survivors, these three factors were good predictors of poor operative outcomes. [ABSTRACT FROM AUTHOR]

Introduction Objectives Methods Results Conclusion There is a paucity of data evaluating early initiation of sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) in patients with diabetes following acute coronary syndrome (ACS) and coronary artery bypass graft surgery (CABG).To describe the efficacy and safety of SGLT2i initiated early after CABG in patients with type 2 diabetes who experienced ACS.This is a retrospective cohort study of patients with type 2 diabetes (T2DM) who experienced ACS and subsequent CABG with follow up at 3 and 12 months. Patients who filled a SGLT2i prescription within 14 days of discharge were allocated to the SGLT2i group and those who did not were included in the no SGLT2i group. The primary efficacy end point was first occurrence of a 4‐point Major Adverse Cardiovascular Event (MACE), and the primary safety end point was a composite of hypoglycemia, hypotension, diabetic ketoacidosis, acute kidney injury, and urinary tract infection. Secondary end points included a comparative analysis of the primary outcome, 30‐day readmission rates, and subgroup analyses of key populations.A total of 1629 patients were included: 226 received a SGLT2i within 14 days of discharge and 1403 did not. At 12 months, 8.9% and 15.3% of patients experienced MACE in the SGLT2i and no SGLT2i groups, respectively (adjusted Hazard Ratio [aHR] 0.65, 95% confidence interval [CI] 0.41–1.04). The primary safety outcome occurred in 12.0% of the SGLT2i group and 19.1% of the no SGLT2i group at 12 months (aHR 0.68, 95% CI 0.45–1.01).Early initiation of SGLT2i use was not associated with a reduction in MACE in patients with T2DM who experienced ACS and underwent subsequent CABG surgery. However, no apparent safety concerns were identified. Adequately powered trials are required to confirm this finding. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We developed a comprehensive kidney protection strategy (KPS), which comprises left ventricular end-diastolic pressure-guided saline hydration, ultralow contrast coronary angiography, and a staged coronary revascularization procedure under suitable conditions. This study aimed to investigate KPS's effect on the risk of developing contrast-associated acute kidney injury (CA-AKI) among persons with moderate-to-advanced kidney insufficiency (KI). Seventy patients who had undergone cardiac catheterization with an estimated glomerular filtration rate (eGFR) of 15–45 mL/min/1.73 m2 were investigated retrospectively. Among these, 19 patients who had received KPS and 51 who had undergone cardiac catheterization with usual care (UC) were enrolled. CA-AKI was defined as a 0.3-mg/dL increase in serum creatinine levels or dialysis initiation within 72 h after contrast exposure. The inverse probability of treatment weighting (IPTW)-adjusted cohort was analyzed according to the Mehran 2 risk categories. Patients' mean age was 73.3 ± 9.6 years; mean eGFR was 29.8 ± 8.5 mL/min/1.73 m2; and median of Mehran 2 risk score, 8. Most patients presented with acute myocardial infarction (AMI) or heart failure, and one-fifth of the administered cardiac catheterizations were emergency procedures. After the IPTW adjustment, the KPS group showed a significantly lower CA-AKI risk than the UC group (4% vs. 20.4%; odds ratio 0.19, 95% confidence interval 0.05–0.66). This effect was consistent across various subgroups according to different variables, including old age, AMI, advanced KI, high-risk category, left ventricular systolic dysfunction, and multivessel disease. Conclusively, KPS may reduce the CA-AKI risk in high-risk patients with moderate-to-advanced KI who have undergone cardiac catheterization. [ABSTRACT FROM AUTHOR]

AbstractPurpose Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide. Ischemic heart diseases, particularly acute myocardial infarction (MI), represent the most common cause of death. MI is influenced by multiple factors, including the release of inflammatory mediators. A significant percentage of individuals with CVD experience psychological effects, such as anxiety and depression, which are linked to an increased risk of coronary heart disease. Certain anti-anxiety medications have demonstrated immunomodulatory and anti-inflammatory effects. Tofisopam, a 2,3-benzodiazepine with anxiolytic properties, has been shown to exert in vitro anti-inflammatory and immunomodulatory effects. The present study investigates the potential of tofisopam as a protective adjuvant against isoprenaline-induced MI in rats and explores the possible underlying mechanisms. Methods: The study included four groups: a control group, a group pretreated with tofisopam, an isoprenaline toxic group, and an isoprenaline toxic group pretreated with tofisopam. Results: The findings demonstrated that isoprenaline significantly increased cardiac enzyme levels, as well as elevated oxidative and inflammatory stress parameters, along with evident apoptosis in cardiac cells. In contrast, the tofisopam-pretreated group showed a significant reversal of the cardiac damage induced by isoprenaline. Conclusions: Tofisopam protects against isoprenaline-induced MI through its antioxidant, anti-inflammatory, and anti-apoptotic properties. [ABSTRACT FROM AUTHOR]

Aims/Introduction Materials and Methods Results Conclusion We investigated the association between impaired fasting glucose (IFG) and cardiometabolic multimorbidity (CMM) in the Chinese population.We included 119,368 participants, free of diabetes mellitus and cardiovascular disease, who participated in the health examination (2006, 2008, 2010) of the Kailuan Study. According to World Health Organization diagnostic criteria, participants were divided into normal fasting blood glucose (FBG) (<6.1 mmol/L) and IFG (FBG 6.1–6.9 mmol/L) groups. CMM was defined as having two or more cardiometabolic diseases, including myocardial infarction, stroke and diabetes mellitus. We used Cox proportional hazards models to evaluate associations between IFG and CMM.During a median follow‐up period of 13.94 years, 2,432 CMM incident events occurred. After adjusting potential confounders, the hazard ratio (HR) and 95% confidence interval (CI) for CMM in the IFG group was 2.83 (95% CI 2.58–3.10) versus the normal FBG group. The HR of IFG for diabetes mellitus was 3.43 (95% CI 3.30–3.55), which was >1.25 (95% CI 1.13–1.37) for myocardial infarction, 1.16 (95% CI 1.07–1.25) for ischemic stroke and 1.06 (95% CI 0.88–1.27) for hemorrhagic stroke. Compared with normal FBG, HRs for risk of IFG for CMM were 2.73 (95% CI 2.48–3.02) in men and 3.86 (95% CI 2.92–5.09) in women.IFG was a risk factor for CMM. The effect of IFG on diabetes mellitus was stronger than that on other cardiometabolic diseases. The effects of IFG for CMM differed by sex. [ABSTRACT FROM AUTHOR]

Background: Patients with low-to-normal body mass index (BMI; < 25.0 kg/m2) were underrepresented in major randomized controlled trials on sodium-glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes. The present study aims to investigate the effectiveness of SGLT2 inhibitors for cardiovascular outcomes among patients with type 2 diabetes and low-to-normal BMI, using finer stratification than previous trials. Methods: This cohort study with a target trial emulation framework was conducted using insurance claims and health screening records of more than 30 million working-age citizens in Japan acquired from April 1, 2015 to March 31, 2022. 139,783 new users of SGLT2 inhibitors matched to 139,783 users of dipeptidyl protease (DPP) 4 inhibitors with stratification by BMI category (< 20.0, 20.0–22.4, 22.5–24.9, 25.0–29.9, 30.0–34.9, and 35.0 ≤ kg/m2). The primary outcome was a composite of all-cause death, myocardial infarction, stroke, or heart failure. Secondary outcomes were the components of the primary outcome. Cox proportional hazard models were used to compare SGLT2 inhibitors with DPP4 inhibitors in the whole population and subgroups defined by the BMI category. Results: Among participants, 17.3% (n = 48,377) were female and 31.0% (n = 86,536) had low-to-normal BMI (< 20.0 kg/m2, 1.9% [n = 5,350]; 20.0–22.4 kg/m2, 8.5% [n = 23,818]; and 22.5–24.9 kg/m2, 20.5% [n = 57,368]). Over a median follow-up of 24 months, the primary outcome occurred in 2.9% (n = 8,165) of participants. SGLT2 inhibitors were associated with a decreased incidence of the primary outcome in the whole population (HR [95%CI] = 0.92 [0.89 to 0.96]), but not in patients with low-to-normal BMI (< 20.0 kg/m2, HR [95%CI] = 1.08 [0.80 to 1.46]; 20.0–22.4 kg/m2, HR [95%CI] = 1.04 [0.90 to 1.20]; and 22.5–24.9 kg/m2, HR [95%CI] = 0.92 [0.84 to 1.01]). Conclusions: The protective effect of SGLT2 inhibitors on cardiovascular events among patients with type 2 diabetes appeared to decrease with lower BMI and was not significant among patients with low-to-normal BMI (< 25.0 kg/m2). These findings suggest the importance of considering BMI when initiating SGLT2 inhibitors. [ABSTRACT FROM AUTHOR]

Background: Premature myocardial infarction (PMI) is one of the most pressing global issues in modern cardiology. Recently, the incidence of PMI has gradually increased. Researches found that genetics is a major contributor in its development. SIRT1, an extremely conserved class III NAD-dependent deacetylase, has been linked to numerous cardiovascular disorders and engaged in a number of cellular functions. This work investigated the association between SIRT1 SNP rs7069102 in Egyptian patients ≤ 40 years old with premature ST-elevation Myocardial infarction (STEMI). Methods: This cross sectional, single-center study included patients younger than 40 with STEMI (PMI group, n = 140) and a control group (n = 140) of healthy subjects of comparable age. In addition to clinical examination and standard tests, all participants underwent echocardiography, coronary angiography, SIRT1 (rs7069102) genotyping, and nitric oxide assay. Results: The risk for PMI was increased in CG or CC genotype carriers of SIRT1 gene rs7069102 (OR: 3.93, 95% Cl: 2.25–6.86), as did carriers of the C allele (OR: 2.26, 95% Cl: 1.65–3.86). In the PMI group, endothelial nitric oxide synthase (eNOS) was significantly decreased; whereas, neuronal nitric oxide synthase (nNOS) was significantly increased. Conclusions: SIRT1 single-nucleotide polymorphism (rs7069102) may confer an increased risk for PMI in young Egyptian patients with affecting endothelial nitric oxide synthase protein expressions. Traditional cardiovascular risk factors are prevalent in patients with PMI, with dietary behaviors, obesity, diabetes and dyslipidemia serving as independent risk factors for PMI. Clinical trial registration number: NCT05160844. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated geographical disparities regarding the quality of care for acute myocardial infarction (AMI). The aim of this study was two-fold: first, to calculate the proportion of patients with AMI who received primary percutaneous coronary interventions (pPCIs) by secondary medical areas (SMAs), which provide general inpatient care, as a quality indicator (QI) of the process of AMI practice. Second, to identify patterns in their trajectories and to investigate the factors related to regional differences in their trajectories. Methods: We included patients hospitalized with AMI between April 2014 and March 2020 from the national health insurance claims database in Japan and calculated the proportion of pPCIs across 335 SMAs and fiscal years. Using these proportions, we conducted group-based trajectory modeling to identify groups that shared similar trajectories of the proportions. In addition, we investigated area-level factors that were associated with the different trajectories. Results: The median (interquartile range) proportions of pPCIs by SMAs were 63.5% (52.9% to 70.5%) in FY 2014 and 69.6% (63.3% to 74.2%) in FY 2020. Four groups, named low to low (LL; n = 48), low to middle (LM; n = 16), middle to middle (MM; n = 68), and high to high (HH; n = 208), were identified from our trajectory analysis. The HH and MM groups had higher population densities and higher numbers of physicians and cardiologists per capita than the LL and LM groups. The LL and LM groups had similar numbers of physicians per capita, but the number of cardiologists per capita in the LM group increased over the years of the study compared with the LL group. Conclusion: The trajectory of the proportion of pPCIs for AMI patients identified groups of SMAs. Among the four groups, the LM group showed an increasing trend in the proportions of pPCIs, whereas the three other groups showed relatively stable trends. [ABSTRACT FROM AUTHOR]

Cardiovascular disease has reached a mortality rate of 470,000 patients each year. Myocardial infarction accounts for 49.2% of these deaths, and the cTnI protein is a crucial target in diagnosing myocardial infarction. A peptide-based bioreceptor design using a computational approach is a good candidate to be developed for a rapid, effective, and selective detection method for cTnI although it is still lacking in study. Hence, to address the scientific gap, we develop a new candidate peptide for the cTnI biosensor by bioinformatics method and present new computational approaches. The sequential point mutations were made to the selected peptide to increase its stability and affinity for cTnI. Next, molecular docking was performed to select the mutated peptide, and one of the best results was subjected to the molecular dynamics simulation. Finally, the results showed that the best peptide showed the lowest affinity and good stability among other mutated peptide designs for interacting with the cTnI protein. In addition, the peptide has been tested to have a higher specificity towards cTnI than its major isomer, sTnI, through molecular docking and molecular dynamics simulation. Therefore, the peptide is considered a good potential bioreceptor for diagnosing myocardial infarction diseases. [ABSTRACT FROM AUTHOR]

The association between self-rated health (SRH) and the development of atrial fibrillation (AF) in the general population remains underexplored. We reviewed the data of 9,895 participants in the Ansung–Ansan cohort study, a community-based Korean study. SRH was categorised as 'poor', 'fair', or 'good'. A newly developed AF was identified through biennial electrocardiography examinations and/or a self-reported history of physician-determined diagnoses. Over a median follow-up of 11 years, 149 patients (1.5%) developed AF. Compared with the 'good' group, the 'poor' group exhibited a higher risk of incident AF (adjusted hazard ratio, 1.85; 95% confidence interval, 1.19–2.87). Old age, female sex, lower educational level, smoking, cardiovascular diseases (hypertension, diabetes mellitus, and coronary artery disease), and inflammation were associated with 'poor' SRH. Along with SRH, age, male sex, urban residence, hypertension, and myocardial infarction were also associated with a higher risk of incidental AF. The combined model, which included conventional risk factors and SRH, demonstrated a marginally improved performance in predicting incident AF (concordance index: 0.704 vs. 0.714, P = 0.058). Poor SRH is independently associated with the development of AF in Korean adults. However, it plays a limited role in AF surveillance when combined with conventional AF risk factors. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions To explore the association of hyperhomocysteinaemia (HHcy) and diabetes synergies with cardiovascular events in the adult population of northern China.Data were collected from the Asymptomatic Polyvascular Abnomalities Community study for 2010 to 2019. Serum homocysteine (Hcy) levels were determined by enzyme‐linked immunosorbent assay. The participants were categorized into four groups based on their Hcy levels and diabetes status: non‐diabetes/non‐HHcy, non‐diabetes/HHcy, diabetes/non‐HHcy and diabetes/HHcy. The composite endpoint consisted of the occurrence of first‐ever stroke, myocardial infraction (MI) or all‐cause mortality. Cox regression analyses were performed to evaluate the associations of diabetes and HHcy with cardiovascular disease (CVD) events.In total, 5278 participants were eligible (average age 55.1 years, 60% male). Over a follow‐up of 9.1 years, 618 events were identified, 202 stroke, 52 MI and 406 all‐cause deaths. Compared with the non‐diabetes/non‐HHcy group, hazard ratios with 95% confidence intervals in the diabetes/HHcy group for stroke, MI, major adverse cardiovascular event (MACE), all‐cause death and composite endpoint were 1.85 (1.12‐3.04), 1.33 (0.42‐4.23), 1.78 (1.13‐2.80), 2.24 (1.56‐3.23) and 1.97 (1.47‐2.65), respectively. Significant interactions between HHcy and diabetes status were found for stroke, MI and MACE (P for interaction = .002, .027 and .044, respectively). In addition, the association of diabetes/HHcy with stroke was modified by age (< 60 and ≥ 60 years; P for interaction = .016).The findings highlight the synergistic impact of diabetes and HHcy on CVD. Joint assessments of diabetes and Hcy levels should be emphasized for risk stratification and primary prevention of CVD. [ABSTRACT FROM AUTHOR]

Migratory cells exist in the heart, such as immune cells, fibroblasts, endothelial cells, etc. During myocardium injury, such as ischemia–reperfusion (MIRI), cells migrate to the site of injury to perform repair functions. However, excessive aggregation of these cells may exacerbate damage to the structure and function of the heart, such as acute myocarditis and myocardial fibrosis. Myocardial injury releases exosomes, which are a type of vesicle with signal transduction function and the miRNA carried by exosomes can control cell migration function. Therefore, regulating this migratory cell population through cardiac-derived exosomal miRNA is crucial for protecting and maintaining cardiac function. Through whole transcriptome RNA sequencing, exosomal miRNA sequencing and single-cell dataset analysis, we (1) determined the potential molecular regulatory role of the lncRNA‒miRNA‒mRNA axis in MIRI, (2) screened four important exosomal miRNAs that could be released by cardiac tissue, and (3) screened seven genes related to cell locomotion that are regulated by four miRNAs, among which Tradd and Ephb6 may be specific for promoting migration of different cells of myocardial tissue in myocardial infarct. We generated a core miRNA‒mRNA network based on the functions of the target genes, which may be not only a target for cardiac repair but also a potential diagnostic marker for interactions between the heart and other tissues or organs. In conclusion, we elucidated the potential mechanism of MIRI in cardiac remodeling from the perspective of cell migration, and inhibition of cellular overmigration based on this network may provide new therapeutic targets for MIRI and to prevent MIRI from developing into other diseases. [ABSTRACT FROM AUTHOR]

Emergency computed tomography (CT) often does not allow for comprehensive coronary artery assessment. However, CT may reveal pathological myocardial hypoperfusion suggestive of acute myocardial infarction (AMI), especially in patients presenting with a different diagnostic hypothesis. CT hypoperfusion is known to be associated with myocardial infarction, however the diagnostic value of CT hypoperfusion for the detection of AMI is still not well evaluated. This was a single-centre retrospective study including patients who underwent invasive coronary angiography (ICA) due to suspected AMI based on incidental perfusion defects upon emergency CT imaging between 2018 and 2023. A total of 22 patients (mean age 66.3 ± 10.8 years, 11 female) were included in this analysis. The diagnosis of AMI was established in all cases leading to ICA. Culprit coronary artery lesions with an indication of percutaneous coronary intervention were detected in all patients who underwent ICA. Spearmann correlation for hypoperfused segments on CT imaging and the corresponding vascular territory upon ICA was significantly substantial (ρ = 0.73, p = < 0.001). The higher the number of affected myocardial segments, the faster ICA was initiated. Mean time between the suspicion of AMI on CT imaging and ICA was 196 (29–4044) minutes. Myocardial hypoperfusion on emergency CT imaging should be considered as AMI until proven otherwise, independent of the clinical scenario leading to performance of CT imaging and whether imaging was performed for the exclusion of non-cardiac pathologies. Early initiation of further diagnostic workup may potentially avoid delays to invasive treatment and reduce the CT-to-catheter-time. Our study explicitly underlines that myocardial hypoperfusion upon contrast enhanced CT imaging needs to be considered as sign of acute myocardial infarction and indicates targeted clinical workup to rule out this diagnosis and to shorten the timeframe from imaging diagnosis to interventional treatment. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]