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The objective of the study was to assess the therapeutic efficacy of targeting remote zone cardiomyocytes with cardiosphere-derived cell (CDC) extracellular vesicles (EVs) delivered via intramyocardial and intravenous routes following acute myocardial infarction (MI). Cardiomyocyte (CM) cell death plays a significant role in left ventricular (LV) remodeling and cardiac dysfunction following MI. While EVs secreted by CDCs have shown efficacy in promoting cardiac repair in preclinical models of MI, their translational potential is limited by their biodistribution and requirement for intramyocardial delivery. We hypothesized that engineering the surface of EVs to target cardiomyocytes would enhance their therapeutic efficacy following systemic delivery in a model of acute MI. CDC-derived EVs were engineered to express a CM-specific binding peptide (CMP) on their surface and characterized for size, morphology, and protein expression. Mice with acute MI underwent both intramyocardial and intravenous delivery of EVs, CMP-EVs and placebo in a double-blind study. LVEF was assessed by echo at 2- and 28-days post-MI and tissue samples processed for assessment of EV biodistribution and histological endpoints. CMP-EVs demonstrated superior cardiac targeting and retention when compared with unmodified EVs 24 h post-MI. Mice treated with IV delivered CMP-EVs demonstrated a significant improvement in LVEF and a significant reduction in remote zone cardiomyocyte apoptosis when compared with IV delivered non-targeted EVs at 28-day post-MI. Systemic administration of CMP-EVs improved cardiac function and reduced remote zone cardiomyocyte apoptosis compared with IV-administered unmodified EVs, demonstrating a strategy to optimize therapeutic EV delivery post-MI., (© 2024 Federation of American Societies for Experimental Biology.)

Aims: The incidence of heart failure hospitalization is higher in women than in men after myocardial infarction (MI). Sex-related differences in left ventricular (LV) remodelling may contribute to the differences in post-MI outcomes. The aim of this study was to assess sex differences in echocardiographic parameters post-MI, and whether the relationship between echocardiographic parameters and clinical outcomes differs by sex., Methods and Results: In the PARADISE-MI trial, patients were randomized to sacubitril/valsartan or ramipril within 0.5 to 7 days of high-risk MI. In the pre-specified echocardiographic substudy, 544 patients underwent echocardiography at the time of randomization and after 8 months. We compared key echocardiographic parameters in men and women and their association with primary composite outcome (cardiovascular death or incident heart failure). At baseline, women had higher LV ejection fraction (LVEF), lower LV end-diastolic volume (LVEDV) index, LV end-systolic volume (LVESV) index, and LV mass index. After adjusting for baseline clinical differences, changes in these echocardiographic parameters from baseline to 8 months were not significantly different in women versus men. Lower LVEF, higher LVEDV, LVESV, left atrial volume index, and average E/e' were associated with a higher risk of the primary composite outcome. Sex did not modify the relationship between echocardiographic parameters and clinical outcome., Conclusions: Despite baseline differences in measures of cardiac function between men and women following acute high-risk MI, there were no significant sex-related changes in chamber size or LV function. Sex did not modify the association between echocardiographic parameters and clinical outcome., (© 2024 European Society of Cardiology.)

Background: BMP9 (bone morphogenetic protein 9) is a member of the TGF-β (transforming growth factor β) family of cytokines with pleiotropic effects on glucose metabolism, fibrosis, and lymphatic development. However, the role of BMP9 in myocardial infarction (MI) remains elusive., Methods: The expressional profiles of BMP9 in cardiac tissues and plasma samples of subjects with MI were determined by immunoassay or immunoblot. The role of BMP9 in MI was determined by evaluating the impact of BMP9 deficiency and replenishment with adeno-associated virus-mediated BMP9 expression or recombinant human BMP9 protein in mice., Results: We show that circulating BMP9 and its cardiac levels are markedly increased in humans and mice with MI and are negatively associated with cardiac function. It is important to note that BMP9 deficiency exacerbates left ventricular dysfunction, increases infarct size, and augments cardiac fibrosis in mice with MI. In contrast, replenishment of BMP9 significantly attenuates these adverse effects. We further demonstrate that BMP9 improves lymphatic drainage function, thereby leading to a decrease of cardiac edema. In addition, BMP9 increases the expression of mitochondrial DECR1 (2,4-dienoyl-CoA reductase 1), a rate-limiting enzyme involved in β-oxidation, which, in turn, promotes cardiac mitochondrial bioenergetics and mitigates MI-induced cardiomyocyte injury. Moreover, DECR1 deficiency exacerbates MI-induced cardiac damage in mice, whereas this adverse effect is restored by the treatment of adeno-associated virus-mediated DECR1. Consistently, DECR1 deletion abrogates the beneficial effect of BMP9 against MI-induced cardiomyopathy and cardiac damage in mice., Conclusions: These results suggest that BMP9 protects against MI by fine-tuning the multiorgan cross-talk among the liver, lymph, and the heart.

Objective: To evaluate the efficacy and safety of discriminative application of Chinese patent medicines in female patients after percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS). Methods: The study population was from the Chinese Patent Medicine (CPM) trial. CPM trial was a multicenter prospective cohort study, which enrolled patients from 40 centers in mainland China between February 2012 and December 2015, with the discriminative use of Chinese patent medicines as the exposure factor. Female patients with ACS after PCI who completed 36-month follow-up were included in this analysis, and were divided into a conventional treatment group (using conventional western medicine recommended by the guidelines) and a group with the discriminative use of proprietary Chinese medicines (on the basis of conventional western medicine treatment, discriminative use of Qishen Yiqi dropping pills for Qi deficiency and blood stasis syndrome, Guanxin Danshen dropping pills for blood stasis syndrome, and Danlou tablets for phlegm and blood stasis syndrome combined with the conventional western medicine). The primary endpoint event was a composite endpoint event including cardiovascular death, nonfatal myocardial infarction, and emergency revascularization surgery. Secondary endpoint events were composite endpoint events including readmission for ACS, heart failure, stroke, and other thrombotic events. Adverse events were collected. Cox proportional risk model was used to assess the effect of discriminatory application of Chinese patent medicine on endpoint events, and sensitivity analysis was performed by comparing the results with propensity score matching analysis. Results: A total of 748 female ACS post-PCI patients were included in the analysis, aged (63.2±8.3) years. There were 370 patients in the group of discriminative application of Chinese patent medicines and 378 patients in the conventional treatment group. There were 37 cases (10.0%) and 58 cases (15.3%) of primary endpoint events in the discriminatory application of Chinese patent medicines group and the conventional treatment group, respectively. Cox analysis showed that the risk of primary endpoint in the discriminatory application of Chinese patent medicines group was lower than that in the conventional treatment group after adjusting for confounding factors (adjusted HR =0.62, 95% CI 0.40-0.96, P =0.031). There were 38 (10.3%) and 57 (15.1%) cases of secondary endpoint events in the two groups, respectively. Cox regression analysis showed that the risk of secondary endpoint events in the discriminatory application of Chinese patent medicine group was lower than that in the conventional treatment group after adjusting for confounders (adjusted HR =0.56, 95% CI 0.37-0.87, P =0.001). The results of propensity score matching analysis also showed that Chinese patent medicines based on discriminatory application could reduce the risk of primary endpoint ( HR= 0.62,95% CI 0.40-0.97 ,P =0.033) and second endpoint ( HR =0.56, 95% CI 0.37-0.87, P =0.009) significantly. There was no significant difference in adverse events between the two groups (12.4% (46/370) vs. 10.3% (39/378), P =0.362). Conclusion: On the basis of conventional western medicine treatment, discriminatory application of Chinese patent medicines can reduce the risk of endpoints in female patients after PCI due to ACS without significant adverse effects.

Background: Lower air temperature and cold spells have been associated with an increased risk of various diseases. However, the short-term effect of lower air temperature and cold spells on myocardial infarction (MI) remains incompletely understood., Objectives: The purpose of this study was to investigate the short-term effects of lower air temperature and cold spells on the risk of hospitalization for MI in Sweden., Methods: This population-based nationwide study included 120,380 MI cases admitted to hospitals in Sweden during the cold season (October to March) from 2005 to 2019. Daily mean air temperature (1 km 2 resolution) was estimated using machine learning, and percentiles of daily temperatures experienced by individuals in the same municipality were used as individual exposure indicators to account for potential geographic adaptation. Cold spells were defined as periods of at least 2 consecutive days with a daily mean temperature below the 10th percentile of the temperature distribution for each municipality. A time-stratified case-crossover design incorporating conditional logistic regression models with distributed lag nonlinear models using lag 0 to 1 (immediate) and 2 to 6 days (delayed) was used to evaluate the short-term effects of lower air temperature and cold spells on total MI, non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI)., Results: A decrease of 1-U in percentile temperature at a lag of 2 to 6 days was significantly associated with increased risks of total MI, NSTEMI, and STEMI, with ORs of 1.099 (95% CI: 1.057-1.142), 1.110 (95% CI: 1.060-1.164), and 1.076 (95% CI: 1.004-1.153), respectively. Additionally, cold spells at a lag of 2 to 6 days were significantly associated with increased risks for total MI, NSTEMI, and STEMI, with ORs of 1.077 (95% CI: 1.037-1.120), 1.069 (95% CI: 1.020-1.119), and 1.095 (95% CI: 1.023-1.172), respectively. Conversely, lower air temperature and cold spells at a lag of 0 to 1 days were associated with decreased risks for MI., Conclusions: This nationwide case-crossover study reveals that short-term exposures to lower air temperature and cold spells are associated with an increased risk of hospitalization for MI at lag 2 to 6 days., Competing Interests: Funding Support and Author Disclosures This study has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 820655 (EXHAUSTION). This work was supported by a scholarship under the State Scholarship Fund by the China Scholarship Council (File No. 201906010316). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

HIF-1α (hypoxia induced factor-1α), a vital protective signal against hypoxia, has a short lifetime after myocardial infarction (MI). Increasing HIF-1α stability by inhibiting its hydroxylation with prolyl hydroxylases inhibitors such as DPCA (1,4-dihydrophenonthrolin-4-one-3-carboxylic acid) presents positive results. However, the optimal inhibitor administration profile for MI treatment is still unexplored. Here, injectable, thermosensitive hydrogels with programmable DPCA release are designed and synthesized. Hydrogel degradation and slow DPCA release are coupled to form a feedback loop by attaching pendant DPCA to polymer backbone, which serve as additional crosslinking points through π-π and hydrophobic interactions. Pendant carboxyl groups are added to the copolymer to accelerate DPCA release. Burst release in the acute phase for myocardial protection and extended near zero-order release across the inflammatory and fibrotic phases with different rates are achieved. All DPCA-releasing hydrogels upregulate HIF-1α, decrease apoptosis, promote angiogenesis, and stimulate cardiomyocyte proliferation, leading to preserved cardiac function and ventricular geometry. Faster hydrogel degradation induced by faster DPCA release results in a HIF-1α expression eight times of healthy control and better therapeutic effect in MI treatment. This research demonstrates the value of precise regulation of HIF-1α expression in treating MI and other relevant diseases and provides an implantable device-based modulation strategy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

This study explores the relationship between influenza infection, both clinically diagnosed in primary care and laboratory confirmed in hospital, and atherothrombotic events (acute myocardial infarction and ischemic stroke) in Spain. A population-based self-controlled case series design was used with individual-level data from electronic registries (n = 2 230 015). The risk of atherothrombotic events in subjects ≥50 years old increased more than 2-fold during the 14 days after the mildest influenza cases in patients with fewer risk factors and more than 4-fold after severe cases in the most vulnerable patients, remaining in them more than 2-fold for 2 months. The transient increase of the association, its gradient after influenza infection, and the demonstration by 4 different sensitivity analyses provide further evidence supporting causality. This work reinforces the official recommendations for influenza prevention in at-risk groups and should also increase the awareness of even milder influenza infection and its possible complications in the general population., Competing Interests: Potential conflicts of interest. C. M. Q., M. L. L., J. D. D., and A. O. S. have attended several congresses whose registration, travel, and accommodation costs have been covered by GlaxoSmithKline, Merck Sharp and Dohme, and Sanofi. J. D. D. has been principal investigator in clinical trials sponsored by Sanofi, Merck Sharp and Dohme, GlaxoSmithKline, and Pfizer. J. D. D. and A. O. S. have acted as advisors for GlaxoSmithKline and Sanofi. A. U. declares no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

After myocardial infarction (MI), patients with type 2 diabetes have an increased rate of adverse outcomes, compared to patients without. Diabetes confers a 1.5-2-fold increase in early mortality and, importantly, this discrepancy has been consistent over recent decades, despite advances in treatment and overall survival. Certain assumptions have emerged to explain this increased risk, such as differences in infarct size or coronary artery disease severity. Here, we re-evaluate that evidence and show how contemporary analyses using state-of-the-art characterization tools suggest that the received wisdom tells an incomplete story. Simultaneously, epidemiological and mechanistic biological data suggest additional factors relating to processes of diabetes-related inflammation might play a prominent role. Inflammatory processes after MI mediate injury and repair and are thus a potential therapeutic target. Recent studies have shown how diabetes affects immune cell numbers and drives changes in the bone marrow, leading to pro-inflammatory gene expression and functional suppression of healing and repair. Here, we review and re-evaluate the evidence around adverse prognosis in patients with diabetes after MI, with emphasis on how targeting processes of inflammation presents unexplored, yet valuable opportunities to improve cardiovascular outcomes in this vulnerable patient group., Competing Interests: Conflict of interest: RPC has received payment for consultancy from NovoNordisk, Nodthera, and Velakor., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

This article focuses on screening the major secreted proteins by the ischemia-challenged cardiac stromal fibroblasts (CF), the assessment of their expression status and functional role in the post-ischemic left ventricle (LV) and in the ischemia-challenged CF culture and to phenotype CF at single cell resolution based on the positivity of the identified mediators. The expression level of CRSP2, HSP27, IL-8, Cofilin-1, and HSP90 in the LV tissues following coronary artery bypass graft (CABG) and myocardial infarction (MI) and CF cells followed the screening profile derived from the MS/MS findings. The histology data unveiled ECM disorganization, inflammation and fibrosis reflecting the ischemic pathology. CRSP2, HSP27, and HSP90 were significantly upregulated in the LV-CABG tissues with a concomitant reduction ion LV-MI whereas Cofilin-1, IL8, Nrf2, and Troponin I were downregulated in LV-CABG and increased in LV-MI. Similar trends were exhibited by ischemic CF. Single cell transcriptomics revealed multiple sub-phenotypes of CF based on their respective upregulation of CRSP2, HSP27, IL-8, Cofilin-1, HSP90, Troponin I and Nrf2 unveiling pathological and pro-healing phenotypes. Further investigations regarding the underlying signaling mechanisms and validation of sub-populations would offer novel translational avenues for the management of cardiac diseases., (© 2024. The Author(s).)

Background and Aims: Prophylactic implantable cardioverter-defibrillators (ICDs) are not recommended until left ventricular ejection fraction (LVEF) has been reassessed 40 to 90 days after an acute myocardial infarction. In the current therapeutic era, the prognosis of sustained ventricular arrhythmias (VAs) occurring during this early post-infarction phase (i.e. within 3 months of hospital discharge) has not yet been specifically evaluated in post-myocardial infarction patients with impaired LVEF. Such was the aim of this retrospective study., Methods: Data analysis was based on a nationwide registry of 1032 consecutive patients with LVEF ≤ 35% after acute myocardial infarction who were implanted with an ICD after being prescribed a wearable cardioverter-defibrillator (WCD) for a period of 3 months upon discharge from hospital after the index infarction., Results: ICDs were implanted either because a sustained VA occurred while on WCD (VA+/WCD, n = 72) or because LVEF remained ≤35% at the end of the early post-infarction phase (VA-/WCD, n = 960). The median follow-up was 30.9 months. Sustained VAs occurred within 1 year after ICD implantation in 22.2% and 3.5% of VA+/WCD and VA-/WCD patients, respectively (P < .0001). The adjusted multivariable analysis showed that sustained VAs while on WCD independently predicted recurrence of sustained VAs at 1 year (adjusted hazard ratio [HR] 6.91; 95% confidence interval [CI] 3.73-12.81; P < .0001) and at the end of follow-up (adjusted HR 3.86; 95% CI 2.37-6.30; P < .0001) as well as 1-year mortality (adjusted HR 2.86; 95% CI 1.28-6.39; P = .012)., Conclusions: In patients with LVEF ≤ 35%, sustained VA during the early post-infarction phase is predictive of recurrent sustained VAs and 1-year mortality., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aim: The 2023 ESC guidelines for acute coronary syndrome note that contemporary data are heterogenous regarding beta-blockers (BB) use post-myocardial infarction (MI) in patients without reduced ejection fraction (EF) or heart failure (HF). We aimed to address the heterogeneity in contemporary data around BB post-MI in this population., Methods: We searched 6 databases from Jan 1, 2000 to Sep 1, 2024 to identify contemporary studies enrolling MI patients without reduced EF (≤40%) or history of HF receiving BB at index MI, and comparing outcomes between BB users and non-users. The primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiac and cerebrovascular events (MACCE) and cardiovascular (CV) mortality. Random-effects meta-analysis was conducted using the restricted maximum likelihood method., Results: There were 24 studies including 290,349 patients enrolled in the contemporary era. Overall, BB use was associated with a significant 11% reduction in all-cause mortality (HR, 0.89; 95% CI, 0.81 to 0.97; I2 = 40%; Figure 1), however with moderate-to-high statistical heterogeneity. Prespecified subgroup analyses demonstrate comparable all-cause mortality (HR, 0.99; 95% CI, 0.94 to 1.06; I2 = 0%), CV mortality (HR, 0.99; 95% CI, 0.85 to 1.15; I2 = 0%), and MACCE (HR, 1.24; 95% CI, 1.01 to 1.52; I2 = 0%) in patients with a 1-year event-free period, defined as no death, recurrent MI, or HF while on BB following index MI. In patients with no event-free period, meta-regression revealed that BB mortality benefits were modified by the study inclusion period (P = 0.01), reflecting a temporal trend of decreasing BB mortality benefits over time. Based on the temporal trend, in patients with preserved EF post-2010, BB exhibited no reduction in all-cause mortality (HR, 0.97; 95% CI, 0.90 to 1.04; I2 = 0%), but a non-significant trend towards increased CV mortality (HR, 1.29; 95% CI, 0.96 to 1.72; I2 = 0%) and a significant increase in MACCE (HR, 1.24; 95% CI, 1.01 to 1.52; I2 = 0%)., Conclusion: In the contemporary reperfusion era, BB may not confer additional mortality benefits beyond a 1-year event-free period post-MI in patients without reduced EF. Moreover, post-MI BB use was associated with detrimental effects in patients with preserved EF., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The use of proteomics in human studies investigating stroke and myocardial infarction (MI) has been increasing, prompting a review of the literature. This revealed proteinaceous biomarkers of stroke from thrombi, brain tissue, cells, and particles, some of which cross the blood-brain barrier (BBB). Several proteins were also implicated in coronary artery disease (CAD), which often underlies MI, cholesterol transportation, and inflammation. Furthermore, the platelet proteome revealed itself as a potential therapeutic target, along with differentially expressed proteins associated with MI progression. Moreover, proteomic data enhanced the performance of conventional risk scores and causal protein discovery has improved interventions and drug development for patients with MI and other conditions. These findings suggest that proteomics holds much promise for future stroke and MI research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Cardiovascular (CV) pathologies remain a leading cause of death worldwide, often associated with common comorbidities such as overweight, obesity, type 2 diabetes or hypertension. An innovative mouse model of metabolic syndrome induced by postnatal overfeeding (PNOF) through litter size reduction after birth was developed experimentally. This study aimed to evaluate the impact of PNOF on cardiac remodelling and the development of heart failure following myocardial infarction., Methods: C57BL/6 male mice were raised in litter adjusted to 9 or 3 pups for normally-fed (NF) control and PNOF group respectively. After weaning, all mice had free access to standard diet and water. At 4 months, mice were subjected to myocardial infarction (MI). Echocardiographic follows-up were performed up to 6-months post-surgery and biomolecular analyses were carried-out after heart collection., Findings: At 4 months, PNOF mice exhibited a significant increase in body weight, along with a basal reduction in left ventricular ejection fraction (LVEF) and an increase in left ventricular end-systolic area (LVESA), compared to NF mice. Following MI, PNOF mice demonstrated a significant decrease in stroke volume and an increased heart rate compared to their respective initial values, as well as a notable reduction in cardiac output 4-months after MI. After 6-months, left ventricle and lung masses, fibrosis staining, and mRNA expression were all similar in the NF-MI and PNOF-MI groups., Interpretation: After MI, PNOF mice display signs of cardiac function worsening as evidenced by a decrease in cardiac output, which could indicate an early sign of heart failure decompensation., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: Our prior research determined that USP7 exacerbates myocardial injury. Additionally, existing studies indicate a strong connection between USP7 and ferroptosis. However, the influence of USP7 on ferroptosis-mediated myocardial infarction (MI) remains unclear. Given these findings, we are particularly interested in USP7's regulatory role in ferroptosis-mediated MI and its underlying mechanisms., Methods: In this study, we established MI models and lentivirus-transfected groups to inhibit USP7 expression both in vivo and in vitro. Cardiac function was detected with Echocardiography. TTC and HE staining were employed to assess myocardial alterations. The expression of ferroptosis markers (PTGS2, ACSL4, GPX4) were analyzed by RT-qPCR and Western blotting. Flow cytometry and ELISA were used for measuring Fe 2+ , lipid ROS, GSH, and GSSG levels. TEM and Prussian blue staining were used to observe mitochondrial alterations and iron deposition. RT-qPCR, Western blotting, and immunofluorescence were conducted to analyze Keap1, Nrf2, and nuclear Nrf2 expression in vitro and in vivo., Results: In the MI model group, USP7 expression significantly increased, worsening ferroptosis-mediated MI. Conversely, in the USP7-inhibited group, activation of the Keap1-Nrf2 signaling pathway improved ferroptosis-mediated MI outcomes. In vitro, the MI model exhibited a marked decline in cardiomyocyte viability and notable mitochondrial damage. However, these issues improved in the USP7-inhibited groups. In vivo, USP7 intensified MI and iron deposition within the MI model group, with decreased values of LVEF, LVFS, SV, LVAWd, and LVPWs, all of which showed improvement in the USP7-inhibited group, except for LVPWd and LVPWs, which showed no significant variation. Importantly, both the in vitro and in vivo experiments revealed analogous results: a reduction in Keap1 expression and an increase in both Nrf2 and nuclear Nrf2 post USP7 inhibition. Additionally, GPX4 expression decreased while PTGS2 and ACSL4 expressions increased. Notably, concentrations of Fe 2+ , lipid ROS, GSH, and GSSG significantly decreased., Conclusion: In vitro and in vivo studies have found that inhibition of USP7 attenuates iron deposition and suppresses oxidative stress, resulting in amelioration of ferroptosis-induced MI., Competing Interests: Declaration of competing interest The authors have declared that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study focuses on key genes (Caspase-3, JAK2, BCL2L1 and MAPK8) and their modulation in response to hypoxia-induced stress using Methyl Glycoside (MG), a small molecule spectroscopically screened from Aganosma dichotoma. Hypoxia/reoxygenation (H/R) induced H9C2 cells, pre- treated with MG, were subjected to cell viability assay, free radical scavenging activities (catalase, GST, GSH-Px, SOD), caspase activity, mitochondrial membrane potential, and gene expression profiling through standard assays and molecular techniques. Results indicated that MG treatment, has potential protective effects against H/R induced stress in H9C2 cell lines. Cell viability assays showed that MG maintained cellular viability with significant protection (P < 0.05) observed from 10 µM. Free radical scavenging assays revealed that MG, enhanced detoxification mechanisms and exhibited potential antioxidant effect in a significantly (P < 0.05) in a dose dependant manner. MG pre-treatment in H9C2 cells protected cellular damage from caspase activity, cells exhibited high mitochondrial membrane potential, and gene expression profiles, including upregulation of anti-apoptotic BCL2L1 and modulation of stress-responsive genes like CASP3, JAK2 and MAPK8. Hence, MG exhibited concentration-dependent protective effects on viability, oxidative stress, and apoptosis-related pathways, laying the foundation for further exploration and translational applications in cardiovascular interventions., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: High-sensitivity cardiac troponins (Hs-cTns) are reliable indicators of myocardial injury, but their relationship with cardiovascular outcomes remains less understood. This study explores the association between adverse cardiac events and Hs-cTnT levels exceeding 14 ng/L in patients with stable CAD., Methods: Thirteen pertinent studies were identified using specific keywords from a pool of 208 articles retrieved from PubMed, Scopus, and Google Scholar, spanning 2013 to 2023. The primary outcomes included all-cause mortality (ACM), myocardial infarction (MI), cardiovascular death (CVD), rehospitalization due to decompensated heart failure (RDHF), need for revascularization, and stroke. Comprehensive meta-analysis (CMA) was employed to analyze the data for odds ratios (OR) and 95% confidence intervals (CI). Heterogeneity was assessed using I 2 statistics, and both qualitative assessment (Newcastle-Ottawa Scale) and quantitative analysis (Egger's and Beggs test, funnel plots) were conducted., Results: The analysis included 29,115 participants (74.72% male) with a mean age of 68.34 years. It revealed a significantly elevated risk of ACM among stable CAD patients with Hs-cTnT levels >14 ng/L compared to those with levels <14 ng/L (11.2% vs. 3.3%; OR = 5.46; 95% CI = 1.53-19.54; p  = 0.009). Similarly, higher risks were observed for MI (10.9% vs 3.6%; OR = 3.12; 95% CI = 0.98-9.95, p  = 0.053), CVD (8.1% vs. 2.1%; OR = 3.37; 95% CI = 1.74-6.50; p  < 0.0001), and RDHF (6.62% vs. 0.92%; OR = 9.46; 95% CI = 4.65-19.24; p  < 0.0001). Notably, major adverse cardiovascular events (MACE) exhibited a stronger association with Hs-cTnT levels (18.2% vs 7.81%; OR = 1.89; 95% CI = 0.80-4.43; I 2  = 97%; p  = 0.14) compared to Hs-cTnI levels (20.1% vs 21.1%; OR = 1.30; 95% CI = 1.03-1.64; I 2 <0.0001%; p  = 0.03)., Conclusion: Elevated levels of Hs-cTnT (>14 ng/L) are significantly associated with increased risks of RDHF and ACM in patients with stable CAD. Further large-scale prospective studies are warranted to refine risk assessment strategies and mitigate cardiovascular mortality in this population.

Myocardial infarction (MI) is a serious cardiovascular disease with high morbidity and mortality rates, posing a significant threat to patient's health and quality of life. Following a MI, the damaged myocardial tissue is typically not fully repaired, leading to permanent impairment of myocardial function. While traditional treatments can alleviate symptoms and reduce pain, their ability to repair damaged heart muscle tissue is limited. Functionalized hydrogels, a broad category of materials with diverse functionalities, can enhance the properties of hydrogels to cater to the needs of tissue engineering, drug delivery, medical dressings, and other applications. Recently, functionalized hydrogels have emerged as a promising new therapeutic approach for the treatment of MI. Functionalized hydrogels possess outstanding biocompatibility, customizable mechanical properties, and drug-release capabilities. These properties enable them to offer scaffold support, drug release, and tissue regeneration promotion, making them a promising approach for treating MI. This paper aims to evaluate the advancements and delivery methods of functionalized hydrogels for treating MI, while also discussing their potential and the challenges they may pose for future clinical use.

Whether a physiology-guided complete revascularization of non-culprit lesions is superior to culprit lesion-only percutaneous coronary intervention (PCI) in patients with myocardial infarction (MI) and multivessel disease (MVD) remains debated. Online databases were searched for randomized controlled trials (RCTs) comparing physiology-guided complete revascularization and culprit lesion-only PCI in MI patients. The outcomes of interest were all-cause death, cardiovascular (CV) death, repeat revascularization, MI, stent thrombosis and contrast associated nephropathy/acute kidney injury (AKI). Pooled odds ratios (OR) along with 95% confidence intervals (CI) were calculated. A total of 4,849 patients (n = 2,288 physiology-guided complete revascularization, n = 2,561 culprit lesion-only PCI) were included. Mean age was 66 years and 76% were men. At mean follow-up of 2.5 years, physiology-guided complete revascularization was associated with significant reductions in CV death (OR 0.72, 95% CI 0.54-0.97, p = 0.03) and repeat revascularizations (0.50, 95% CI 0.38-0.66, p < 0.00001) as compared to culprit lesion-only PCI. There were no differences between the two approaches in all-cause death (0.91, 95% CI 0.69-1.19, p = 0.50), MI (0.85, 95% CI 0.59-1.21, p = 0.36), stent thrombosis (1.24, 95% CI 0.58-2.69, p = 0.58) and contrast associated nephropathy/AKI (1.07, 95% CI 0.88-1.31, p = 0.50). In conclusion, among patients with MI and MVD, physiology-guided complete revascularization was associated with significant reductions in CV death and revascularizations when compared to culprit lesion-only PCI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Persistent post-COVID conditions (PCCs) have become inevitable challenges for individuals who have survived COVID. The National Research Plan on Long COVID-19 underscores the priority of addressing post-COVID conditions (PCCs) within specific subgroups of the United States (US) population. This study aimed to investigate the prevalence and factors associated with PCCs among stroke survivors in the US., Method: In this retrospective cross-sectional study, we utilized the Behavioral Risk Factor Surveillance System (BRFSS) 2022 dataset. First, we identified respondents with a positive history of both COVID-19 and stroke. Subsequently, we categorized these respondents based on whether they experienced PCCs and conducted a comparative analysis of their characteristics. Additionally, our study included a comparison of our findings with those among individuals who have survived myocardial infarction (MI) and cancer., Results: A total of 3999 stroke, 5406 MI, and 10551 cancer survivors were included. The estimated prevalence of PCCs among stroke survivors was 30.6%, compared to 22.4%, 29.2%, and 24.6% among non-stroke (p<0.001), MI, and cancer survivors, respectively. Fatigue, dyspnea, and taste/smell loss were the most common primary symptoms. In multivariate regression analysis, female sex (adjusted odds ratio (aOR):1.62, 95%CI:[1.17-2.24]), stroke-belt residence (aOR:1.67, 95%CI: [1.13-2.46]), pulmonary disease (aOR:2.12, 95%CI:[1.53-2.92]), and depression (aOR:1.55, 95%CI: [1.1-2.2]) were independent factors associated with higher odds of PCCs among stroke survivors. Additionally, age above 64 years was associated with lower odds of PCCs (aOR:0.6, 95%CI: [0.41-0.86])., Conclusion: Our study highlights a considerable prevalence of PCCs among stroke survivors, particularly among younger women and individuals with other chronic conditions., Competing Interests: Declaration of competing interest none, (Copyright © 2024. Published by Elsevier Inc.)

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

Background: Empagliflozin administered after acute myocardial infarction proofed to improve cardiometabolic parameters and biomarkers, but the impact on cardiac function is still largely unknown. The aim of this post-hoc echocardiographic sub-analysis of the EMMY trial was to provide in-depth echocardiographic analysis on the effects of empagliflozin versus placebo on standard and novel echocardiographic structural and functional parameters after acute myocardial infarction., Methods: In this post-hoc analysis of the EMMY trial a subset of 313 patients (157 empagliflozin vs. 156 placebo) was enrolled for post-processing analysis of echocardiographic structural and functional parameters. On top of two-dimensional and Doppler parameters, myocardial deformation analyses were performed to assess ventricular and atrial strain values., Results: Left ventricular volumes showed significant differences in favor of empagliflozin over the course of the trial (change in left ventricular end-diastolic volume median [interquartile range] 8 [-3;19]% versus 13 [0;29]%, p = 0.048; left ventricular end-systolic volume -3 [-15;12]% versus 4 [-12;18]%, p = 0.044). This effect persisted after adjusting for baseline values, age, and sex. Left ventricular systolic and diastolic function overall improved over the course of the trial and parameters for diastolic function showed a distinct trend between groups but did not meet statistical significance in this cohort., Conclusion: In this post-hoc analysis among patients with acute myocardial infarction, treatment with empagliflozin resulted in a significant beneficial effect on left ventricular end-diastolic and end-systolic volume, without significantly improving left ventricular or right ventricular functional parameters compared to placebo after 26 weeks., Gov Registration: NCT03087773., (© 2024. The Author(s).)

Intravenously administered perfluorocarbon nanoemulsion (PFC) are taken up by phagocytic immune cells which enables the non-invasive visualization of inflammatory hot spots by combined 1H/19F magnetic resonance imaging (MRI). However, little is known about the influence of inflammatory stimuli on cellular uptake and biodistribution of PFCs. Here, we systematically investigated the impact of inflammation induced by subcutaneous implantation of Matrigel/lipopolysaccharide (Matrigel/LPS) or myocardial infarction (MI; 50 minutes ischemia reperfusion) on PFC-uptake and biodistribution in C57BL/6J mice. We detected strong 19F signals in Matrigel/LPS plugs and infarcted hearts, which were completely absent in controls. Cellular uptake of PFCs was increased in neutrophils isolated from the blood and Matrigel/LPS plugs, whereas uptake by monocytes was only slightly elevated. In contrast, MI caused only a moderate early increase of PFC-uptake in monocytes and neutrophils. Interestingly, the inflammatory model did also affect the biodistribution of the PFCs. The blood half-life of PFCs was slightly increased after Matrigel/LPS implantation, whereas it was reduced after MI. Compared to controls, the 19F signal of the liver was significantly stronger in Matrigel/LPS, but not in MI animals. Interestingly, stimulation of primary immune cells and RAW264.7 macrophages with LPS had no effect on PFC-uptake, whereas CRP-incubation elevated internalization of PFCs at least in RAW264.7 cells. In conclusion, we show that the cellular PFC-uptake can differ between individual inflammatory conditions. This is an important aspect that has to be considered for the proper interpretation of 1H/19F MRI data obtained from inflammatory hot spots., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)

Cardiomyocyte proliferation is a challenging metric to assess. Current methodologies have limitations in detecting the generation of new cardiomyocytes and technical challenges that reduce widespread applicability. Here, we describe an improved cell suspension and imaging-based methodology that can be broadly employed to assess cardiomyocyte cell division in standard laboratories across a multitude of model organisms and experimental conditions. We highlight additional metrics that can be gathered from the same cell preparations to enable additional relevant analyses to be performed. We incorporate additional antibody stains to address potential technical concerns of miscounting. Finally, we employ this methodology with a dual-thymidine analog-labeling approach to a post-infarction murine model, which allowed us to robustly identify unique cycling events, such as cardiomyocytes undergoing multiple rounds of cell division., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Acute Coronary Syndrome (ACS) is characterized by the suspicion or confirmation of acute ischemia or acute myocardial infarction (MI). The presence of ST segment elevation (STE) consists in the main criterion for indication of immediate reperfusion therapy due to acute coronary occlusion, although significant part of the acute coronary occlusion cases do not fit the ST-segment elevation myocardial infarction (STEMI) criteria. A case report of a 50 year-old male presenting typical anginal pain, whose electrocardiogram (EKG) presented Aslanger's pattern. The patient had severe lesion of the left anterior descending artery (ADA) and chronic occlusion of the right coronary artery on cardiac catheterization, with important collateral flow from branches of the left coronary artery to the right coronary artery. The dichotomy between STEMI and Non-ST segment elevation myocardial infarction (NSTEMI) must be contested, owing to the evidence that one third of the NSTEMI patients presents a total coronary occlusion. There are other electrocardiographic patterns which must be considered to diagnose ACS. Our case report outlines a different clinical presentation of Aslanger pattern, that shows a ADA acute occlusion, instead of the lesion being in the right coronary system. There is evidence that, in addition to the STEMI vs NSTEMI criteria, the Aslanger pattern and other electrocardiographic patterns characterize occlusive ACS. Recognizing those patterns in clinical practice is essential to improve the diagnosis and early treatment of patients with ACS., Competing Interests: Declaration of competing interest Authors state no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Contemporary cardiac injury models in zebrafish larvae include cryoinjury, laser ablation, pharmacological treatment and cardiac dysfunction mutations. Although effective in damaging cardiomyocytes, these models lack the important element of myocardial hypoxia, which induces critical molecular cascades within cardiac muscle. We have developed a novel, tractable, high throughput in vivo model of hypoxia-induced cardiac damage that can subsequently be used in screening cardioactive drugs and testing recovery therapies. Our potentially more realistic model for studying cardiac arrest and recovery involves larval zebrafish (Danio rerio) acutely exposed to severe hypoxia (PO2=5-7 mmHg). Such exposure induces loss of mobility quickly followed by cardiac arrest occurring within 120 min in 5 days post fertilization (dpf) and within 40 min at 10 dpf. Approximately 90% of 5 dpf larvae survive acute hypoxic exposure, but survival fell to 30% by 10 dpf. Upon return to air-saturated water, only a subset of larvae resumed heartbeat, occurring within 4 min (5 dpf) and 6-8 min (8-10 dpf). Heart rate, stroke volume and cardiac output in control larvae before hypoxic exposure were 188±5 bpm, 0.20±0.001 nL and 35.5±2.2 nL/min (n=35), respectively. After briefly falling to zero upon severe hypoxic exposure, heart rate returned to control values by 24 h of recovery. However, reflecting the severe cardiac damage induced by the hypoxic episode, stroke volume and cardiac output remained depressed by ∼50% from control values at 24 h of recovery, and full restoration of cardiac function ultimately required 72 h post-cardiac arrest. Immunohistological staining showed co-localization of Troponin C (identifying cardiomyocytes) and Capase-3 (identifying cellular apoptosis). As an alternative to models employing mechanical or pharmacological damage to the developing myocardium, the highly reproducible cardiac effects of acute hypoxia-induced cardiac arrest in the larval zebrafish represent an alternative, potentially more realistic model that mimics the cellular and molecular consequences of an infarction for studying cardiac tissue hypoxia injury and recovery of function., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Ethnopharmacological Relevance: Yiqitongmai decoction (YQTMD), a classic TCM, has been widely used in clinical treatment for MI. However, it is still difficult to clarify the potential active compounds and pharmacological mechanisms of it in treating MI., Aim of the Study: To explore the active ingredients, pharmacological effects, potential targets and mechanisms of YQTMD against MI., Materials and Methods: Serum pharmacochemistry by UPLC-MS/MS was applied to analyze the phytochemical components in serum from YQTMD. These components were then used to predict the potential targets using network pharmacology approach and molecular dynamics simulations, and then the protective effect of them on H9c2 cells following hypoxic conditions was assessed. Afterwards, the pharmacological effects of YQTMD on MI in mice were tested by determining electrocardiogram (ECG), echocardiography, cardiac biomarkers, oxidative stress, inflammation and pathophysiological changes. The protein levels involving STAT3 signal were detected using Western blot and immunofluorescence assays. Furthermore, STAT3 inhibitor Sttatic was employed to further elucidate the underlying mechanisms., Results: Totally, 26 compounds derived from YQTMD were identified in mice serum, and 201 genes associated with the compounds were collected. The compounds including safflomin A, ferulic acid, gypenoside XVII, ginsenoside Rg1 and glycyrrhizic acid were identified as the critical compounds of YQTMD to regulate STAT3 pathway. In vitro, compounds combination significantly enhanced the viability of H9c2 cells and reduced ROS level compared to model cells. The in vivo results showed that YQTMD effectively reduced myocardial injury, as evidenced by the decreased serum cardiac injury markers, reduction in the size of myocardial infarct, restoration of abnormal alterations in ECG and decrease in cardiomyocyte apoptosis. Additionally, YQTMD attenuated MI-induced cardiac dysfunction, alleviated pathological changes, reduced MDA levels, and enhanced SOD and GSH levels compared with model mice. Significantly, the levels of IL-6, IL-1β, and TNF-α were observed to decrease in the YQTMD group. The expression levels of key proteins (p-STAT3, HIF-1α, NOX2, TLR5 and Caspase3) in STAT3 pathway were also regulated by YQTMD. However, the cardioprotective effects of YQTMD on MI were attenuated by STAT3 inhibitor Sttatic., Conclusions: This study investigated the active ingredients and potential mechanisms of YQTMD for MI treatment based on serum pharmacochemistry and network pharmacology approaches, revealing that YQTMD exerts its therapeutic effects on MI by alleviating oxidative stress, inflammation and apoptosis through adjusting STAT3 signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The prognostic efficacy of a coronary computed tomography angiography (CCTA)-derived myocardial radiomics model in patients with chronic myocardial infarction (MI) is unclear., Methods: In this retrospective study, a cohort of 236 patients with chronic MI who underwent both CCTA and cardiac magnetic resonance (CMR) examinations within 30 days were enrolled and randomly divided into training and testing datasets at a ratio of 7:3. The clinical endpoints were major adverse cardiovascular events (MACE), defined as all-cause death, myocardial reinfarction and heart failure hospitalization. The entire three-dimensional left ventricular myocardium on CCTA images was segmented as the volume of interest for the extraction of radiomics features. Five models, namely the clinical model, CMR model, clinical+CMR model, CCTA-radiomics model, and clinical+CCTA-radiomics model, were constructed using multivariate Cox regression. The prognostic performances of these models were evaluated through receiver operating characteristic curve analysis and the index of concordance (C-index)., Results: Fifty-one (20.16%) patients experienced MACE during a median follow-up of 1439.5 days. The predictive performance of the CCTA-radiomics model surpassed that of the clinical model, CMR model, and clinical+CMR model in both the training (area under the curve (AUC) of 0.904 vs. 0.691, 0.764, 0.785; C-index of 0.88 vs. 0.71, 0.75, 0.76, all p values <0.001) and testing (AUC of 0.893 vs. 0.704, 0.851, 0.888; C-index of 0.86 vs. 0.73, 0.85, 0.85, all p values <0.05) datasets., Conclusions: The CCTA-based myocardial radiomics model is a valuable tool for predicting adverse outcomes in chronic MI, providing incremental value to conventional clinical and CMR parameters., Competing Interests: Declaration of competing interest All authors disclosed no relevant conflicts., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The 2023 American Heart Association (AHA)/American College of Cardiology (ACC) Multisociety Guideline for the Management of Patients with Chronic Coronary Disease presents important updates to the care of patients with chronic coronary disease (1). The recommendations of these guidelines inform the care for patients with (1) asymptomatic coronary artery disease, (2) stable angina or equivalent symptoms (e.g., dyspnea upon exertion), (3) symptomatic nonobstructive coronary disease including coronary microvascular dysfunction and vasospasm, and (4) left ventricular (LV) systolic dysfunction with known coronary artery disease. In this review, we aim to demonstrate key recommendations in the 2023 guideline using the following four hypothetical cases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Aims: We aimed to investigate the association of electrocardiogram (ECG) findings with outcomes in patients with chronic coronary syndrome., Methods: This secondary analysis of the ISCHEMIA and ISCHEMIA-CKD trials divided patients with chronic coronary syndrome into two groups, those with a normal ECG tracing and abnormal ECG tracing. Repolarization abnormalities included ST-segment depression ≥0.5mm and T-wave inversion ≥1mm; conduction abnormalities included left and right bundle branch block (LBBB and RBBB). The primary endpoint was cardiovascular death. Outcomes were assessed using a covariate-adjusted Cox-regression model., Results: Of 5876 patients, 2901 (49.4%) had a normal and 2975 (50.6%) an abnormal ECG tracing. An abnormal ECG tracing at baseline, compared with normal ECG, was associated with an increased risk of cardiovascular death (257 of 2975 [8.6%] vs 97 of 2901 [3.3%], adjusted hazard ratio [aHR] 2.01, 95%CI 1.58-2.55) over a median follow-up period of 3.1 years [IQR 2.1-4.2]. This finding was consistent across subgroups except for patients with black skin color and current smokers, in whom an abnormal ECG was not significantly associated with increased risk of cardiovascular death. Individual ECG abnormalities (ST-segment depression [aHR 2.0, 95%CI 1.52-2.63], T-wave inversion [aHR 1.89, 95%CI 1.40-2.54], LBBB [aHR 1.74, 95%CI 1.05-2.90], and RBBB [aHR 1.52, 95%CI 1.04-2.22],) were independently associated with an increased risk of cardiovascular death., Conclusion: In patients with chronic coronary syndrome, an abnormal ECG tracing was associated with an increased risk of cardiovascular death. Our findings underscore the importance of the ECG in cardiovascular risk stratification and prognostication., Trial Registration: NCT01471522, BioLINCC ID 14539., Competing Interests: Declaration of competing interest No author reports conflict of interests relevant to this work., (Copyright © 2024. Published by Elsevier Inc.)

Background: The Manhattan Lupus Surveillance Program (MLSP), a population-based retrospective registry of patients with systemic lupus erythematosus (SLE), was used to investigate the prevalence of cardiovascular disease events (CVE) and compare rates among sex, age and race/ethnicity to population-based controls., Methods: Patients with prevalent SLE in 2007 aged ≥ 20 years in the MLSP were included. CVE required documentation of a myocardial infarction or cerebrovascular accident. We calculated crude risk ratios and adjusted risk ratios (ARR) controlling for sex, age group, race and ethnicity, and years since diagnosis. Data from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) and the 2013-2014 NYC Health and Nutrition Examination Survey (NYC HANES) were used to calculate expected CVE prevalence by multiplying NHANES and NYC HANES estimates by strata-specific counts of patients with SLE. Crude prevalence ratios (PRs) using national and NYC estimates and age standardized prevalence ratios (ASPRs) using national estimates were calculated., Results: CVE occurred in 13.9% of 1,285 MLSP patients with SLE, and risk was increased among men (ARR:1.7, 95%CI:1.2-2.5) and older adults (age > 60 ARR:2.5, 95%CI:1.7-3.8). Compared with non-Hispanic Asian patients, CVE risk was elevated among Hispanic/Latino (ARR:3.1, 95%CI:1.4-7.0) and non-Hispanic Black (ARR:3.5, 95%CI1.6-7.9) patients as well as those identified as non-Hispanic and in another or multiple racial groups (ARR:4.2, 95%CI:1.1-15.8). Overall, CVE prevalence was higher among patients with SLE than nationally (ASPR:3.1, 95%CI:3.0-3.1) but did not differ by sex. Compared with national race and ethnicity-stratified estimates, CVE among patients with SLE was highest among Hispanics/Latinos (ASPR:4.3, 95%CI:4.2-4.4). CVE was also elevated among SLE registry patients compared with all NYC residents. Comparisons with age-stratified national estimates revealed PRs of 6.4 (95%CI:6.2-6.5) among patients aged 20-49 years and 2.2 (95%CI:2.1-2.2) among those ≥ 50 years. Male (11.3, 95%CI:10.5-12.1), Hispanic/Latino (10.9, 95%CI:10.5-11.4) and non-Hispanic Black (6.2, 95%CI:6.0-6.4) SLE patients aged 20-49 had the highest CVE prevalence ratios., Conclusions: These population-based estimates of CVE in a diverse registry of patients with SLE revealed increased rates among younger male, Hispanic/Latino and non-Hispanic Black patients. These findings reinforce the need to appropriately screen for CVD among all SLE patients but particularly among these high-risk patients., (© 2024. The Author(s).)

Patients with heart failure (HF) are often accompanied by skeletal muscle abnormalities, which can lead to exercise intolerance and compromise daily activities. Irisin, an exercise training (ET) -induced myokine, regulates energy metabolism and skeletal muscle homeostasis. However, the precise role of Irisin in the benefits of ET on inhibiting skeletal muscle atrophy, particularly on endoplasmic reticulum (ER) stress, autophagy, and myogenesis following myocardial infarction (MI) remains unclear. In this study, we investigated the expression of Irisin protein in wild-type mice with MI, and assessed its role in the beneficial effects of ET using an Fndc5 knockout mice. Our findings revealed that MI reduced muscle fiber cross-sectional area (CSA), while downregulating the expression of Irisin, PGC-1α and SOD1. Concurrently, MI elevated the levels of ER stress and apoptosis, and inhibited autophagy in skeletal muscle. Conversely, ET mitigated ER stress and apoptosis in the skeletal muscle of infarcted mice. Notably, Fndc5 knockout worsened MI-induced ER stress and apoptosis, suppressed autophagy and myogenesis, and abrogated the beneficial effects of ET. In conclusion, our findings highlight the role of Irisin in the ET-mediated alleviation of skeletal muscle abnormalities. This study provides valuable insights into MI-induced muscle abnormalities and enhances our understanding of exercise rehabilitation mechanisms in clinical MI patients., (© 2024. The Author(s) under exclusive licence to University of Navarra.)

Background: In acute heart failure (HF), reduced cardiac output, vasoconstriction and congestion may damage the intestinal mucosa and disrupt its barrier function. This could facilitate the leakage of bacterial products into circulation and contribute to inflammation and adverse cardiac remodelling. We aimed to investigate gut leakage markers and their associations with inflammation, infarct size and cardiac function., Methods: We examined 61 ST-elevation myocardial infarction (STEMI) patients who developed acute HF within 48 hours of successful percutaneous coronary intervention (PCI). Serial blood samples were taken to measure lipopolysaccharide (LPS), LPS-binding protein (LBP), soluble cluster of differentiation 14 (sCD14) and intestinal fatty acid binding protein (I-FABP). Cumulative areas under the curve (AUCs) from baseline to day 5 were calculated. Serial echocardiography was performed to assess left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and wall motion score index (WMSI). Single-photon emission CT (SPECT) was performed at 6 weeks to determine infarct size and LVEF., Results: I-FABP AUC correlated positively with infarct size (r s =0.45, p=0.002), GLS (r s =0.32, p=0.035) and WMSI (r s =0.45, p=0.002) and negatively with LVEF measured by SPECT (r s =-0.40, p=0.007) and echocardiography (r s =-0.33, p=0.021) at 6 weeks. LPS AUC , LBP AUC and sCD14 AUC did not correlate to any cardiac function marker or infarct size. Patients, who at 6 weeks had above median GLS and WMSI, and below-median LVEF measured by SPECT, were more likely to have above median I-FABP AUC during admission (adjusted OR (aOR) 5.22, 95% CI 1.21 to 22.44; aOR 5.05, 95% CI 1.25 to 20.43; aOR 5.67, 95% CI 1.42 to 22.59, respectively). The same was observed for patients in the lowest quartile of LVEF measured by echocardiography (aOR 9.99, 95% CI 1.79 to 55.83) and three upper quartiles of infarct size (aOR 20.34, 95% CI 1.56 to 264.65)., Conclusions: In primary PCI-treated STEMI patients with acute HF, I-FABP, a marker of intestinal epithelial damage, was associated with larger infarct size and worse cardiac function after 6 weeks., Competing Interests: Competing interests: The Department of Cardiology, Oslo University Hospital Ullevaal received an unrestricted educational grant from the manufacturer of levosimendan, Orion Pharma in 2005. Orion Pharma did not, however, provide study medication or participate in the design, monitoring or analyses of the present study. The authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Elevated susceptibility to acute myocardial infarction and various cardiovascular diseases has been observed in individuals infected with the human immunodeficiency virus compared with the uninfected population, as demonstrated in numerous studies. The precise mechanism by which human immunodeficiency virus infection heightens the risk of acute myocardial infarction remains elusive. The manifestation of acute coronary syndrome in young patients with human immunodeficiency virus may deviate from the typical, displaying distinct pathophysiological and clinical characteristics. The occurrence of myocardial infarction with non-obstructive coronary arteries in young patients with human immunodeficiency virus poses diagnostic and treatment challenges., Case Presentation: We present the case of a 46-year-old African woman with no traditional atherosclerotic risk factors. She was diagnosed with human immunodeficiency virus-1 infection 2 years prior to her current admission for chest pain. Her troponin levels were elevated, suggestive of acute coronary syndrome. Although coronary angiography ruled out coronary artery stenosis, it revealed mild myocardial bridging in the left anterior descending artery. Cardiac magnetic resonance imaging confirmed myocardial infarction, indicating a myocardial infarction with non-obstructive coronary arteries with an apical thrombus in the left ventricle. Following medical treatment, the patient experienced resolution of chest pain and improvement in ST-segment elevation., Conclusions: In young female patients without traditional risk factors, human immunodeficiency virus infection is a possible etiological factor for myocardial infarction with non-obstructive coronary arteries. The likely pathophysiological pathway is superficial endothelial cell denudation as a result of chronic inflammation and immune activation., (© 2024. The Author(s).)

Interleukin-6 (IL-6) plays a crucial role in the pathogenesis of cardiovascular disease (CVD), and IL-6 receptor (IL-6R) blockade has emerged as a promising therapeutic option. However, their specific therapeutic effects in different types of CVDs remain unclear. This study aimed to assess the efficacy of IL-6R blockade in the management of various CVDs, including hypertension (HTN), coronary heart disease (CHD), myocardial infarction (MI), atrial fibrillation (AF), and heart failure (HF). The Mendelian randomization (MR) approach was utilized to investigate the therapeutic impact of IL-6R blockade on HTN, CHD, MI, AF, and HF based on the genome-wide association study (GWAS) summary statistics. MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were used for sensitivity analysis to verify the reliability of the MR results. The Bonferroni method was used to correct for bias caused by multiple comparisons. Inverse variance weighted (IVW) results demonstrated that IL-6R blockade significantly influenced CHD (odds ratio (OR) = 0.757, 95% confidence interval (CI): 0.690 - 0.832, P = 5.804 × 10 -9 ) and MI (OR = 0.840, 95% CI: 0.744 - 0.949, P = 0.005). However, IL-6R blockade had no significant effect on HTN (OR = 1.015, 95% CI: 0.950 - 1.084, P = 0.663), AF (OR = 0.905, 95% CI: 0.800 - 1.025, P = 0.116) and HF (OR = 1.012, 95% CI: 0.921 - 1.113, P = 0.805). Genetically predicted IL-6R blockade was associated with a protective effect on CHD and MI, but not HTN, AF and HF. This study's findings offer valuable insights for tailoring IL-6R blockade treatment for different types of CVD, and serve as a reference for future research., (© 2024. The Author(s).)

Competing Interests: T.A. McKinsey is a cofounder of Myracle Therapeutics, is on the scientific advisory boards of Eikonizo Therapeutics and Revier Therapeutics, received funding from Italfarmaco for an unrelated project, and has a subcontract from Eikonizo Therapeutics for an Small Business Innovation Research grant from the National Institutes of Health (HL154959). The other authors report no conflicts.

Aims: Previous studies on disparities in healthcare and outcomes have shown conflicting results. The aim of this study was to assess differences in baseline characteristics, management, and outcomes in myocardial infarction (MI) patients, by country of birth., Methods and Results: In total, 194 259 MI patients (64% male, 15% foreign-born) from the nationwide SWEDEHEART (The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry were included and compared by geographic region of birth. The primary outcome was 1-year major adverse cardiovascular events (MACEs) including all-cause death, MI, and stroke. Secondary outcomes were long-term MACE (up to 12 years), the individual components of MACE, 30-day mortality, management, and risk factors. Logistic regression, Cox proportional hazard models, and propensity score match (PSM), accounting for baseline differences, were used. Foreign-born patients were younger, often male, and had a higher cardiovascular (CV) risk factor burden, including smoking, diabetes, and hypertension. In PSM analyses, Asia-born patients had higher likelihood of revascularization [odds ratio 1.16, 95% confidence interval (CI) 1.04-1.30], statins and beta-blocker prescription at discharge, and a 34% lower risk of 30-day mortality. Furthermore, no statistically significant differences were found in primary outcomes except for Asia-born patients having lower risk of 1-year MACE [hazard ratio (HR) 0.85, 95% CI 0.73-0.98], driven by lower mortality (HR 0.72, 95% CI 0.57-0.91). The results persisted over the long-term follow-up., Conclusion: This study shows that in a system with universal healthcare coverage in which acute and secondary preventive treatments do not differ by country of birth, foreign-born patients, despite higher CV risk factor burden, will do at least as well as native-born patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Apelin is an endogenous prepropeptide that regulates cardiac homeostasis and various physiological processes. Intravenous injection has been shown to improve cardiac contractility in patients with heart failure. However, its short half-life prevents studying its impact on left ventricular remodeling in the long term. Here, we aim to study whether microparticle-mediated slow release of apelin improves heart function and left ventricular remodeling in mice with myocardial infarction (MI)., Methods: A cardiac patch was fabricated by embedding apelin-containing microparticles in a fibrin gel scaffold. MI was induced via permanent ligation of the left anterior descending coronary artery in adult C57BL/6J mice followed by epicardial patch placement immediately after (acute MI) or 28 days (chronic MI) post-MI. Four groups were included in this study, namely sham, MI, MI plus empty microparticle-embedded patch treatment, and MI plus apelin-containing microparticle-embedded patch treatment. Cardiac function was assessed by transthoracic echocardiography. Cardiomyocyte morphology, apoptosis, and cardiac fibrosis were evaluated by histology. Cardioprotective pathways were determined by RNA sequencing, quantitative polymerase chain reaction, and Western blot., Results: The level of endogenous apelin was largely reduced in the first 7 days after MI induction and it was normalized by day 28. Apelin-13 encapsulated in poly(lactic-co-glycolic acid) microparticles displayed a sustained release pattern for up to 28 days. Treatment with apelin-containing microparticle-embedded patch inhibited cardiac hypertrophy and reduced scar size in both acute and chronic MI models, which is associated with improved cardiac function. Data from cellular and molecular analyses showed that apelin inhibits the activation and proliferation of cardiac fibroblasts by preventing transforming growth factor-β-mediated activation of Smad2/3 (supporessor of mothers against decapentaplegic 2/3) and downstream profibrotic gene expression., Conclusions: Poly(lactic-co-glycolic acid) microparticles prolonged the apelin release time in the mouse hearts. Epicardial delivery of the apelin-containing microparticle-embedded patch protects mice from both acute and chronic MI-induced cardiac dysfunction, inhibits cardiac fibrosis, and improves left ventricular remodeling., Competing Interests: None.

Background: Sudden and unexpected deaths are increasing drastically. The main cause of sudden death is cardiovascular disease, out of which coronary artery disease predominates forming 80% of the cases. Most of the time, detecting early changes in myocardial infarction during the autopsy is challenging since gross infarct changes do not appear until after 24 to 48 hours of myocardial ischemia injury. So, the aim of this study was to compare two test to detect early changes of Myocardial Infarction one by using Triphenyl Tetrazolium Chloride (TTC) staining of the myocardial tissue, during autopsy and other by histopathological examination., Methods: The sample size of 60 hearts taken from all the sudden deaths cases brought to Mortuary with suspected cause of death due to cardiac origin. The heart was obtained from the deceased by standard post-mortem technique. Serial full-thickness transverse sections of the heart were taken at 2 cm intervals from the apex to the atrioventricular groove. All the serial slices of heart are taken for histochemical staining and TTC staining., Results: In histopathological examination 34 hearts were diagnosed with myocardial infarction and 26 hearts reported non myocardial infarction. With TTC 40 hearts remained unstained suggestive of myocardial infarction and 20 hearts were stained suggestive of non-infarcted hearts. TTC staining in our study shows an accuracy of 88.33%., Conclusion: The result of this study shows that the Triphenyl Tetrazolium Chloride test, a histochemical staining technique of heart, is reliable approach for forensic pathologists to diagnose early myocardial infarction during the post-mortem examination., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Krishna B V et al.)

microRNAs (miRNAs) are small regulatory RNAs implicated in various cardiac disorders. In this review, the role of miRNAs is discussed in relation to acute myocardial infarction and chronic heart failure. In both settings, miRNAs are altered, contributing to injury and adverse remodeling. Notably, miRNA profiles differ between acute ischemic injury and progressive heart failure. Owing to miRNA variabilities between disease stages and delivery difficulties, translation of animal studies to the clinic remains challenging. The identification of distinct miRNA signatures could lead to the development of miRNA therapies tailored to different disease stages. Here, we summarize the current understanding of miRNAs in acute and chronic cardiac diseases, identify knowledge gaps and discuss progress in developing miRNA-based treatment strategies., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Myocardial infarction (MI) is a critical emergency condition that affects all aspects of health. Patients with MI need specialized care in the Coronary care unit (CCU). The main goal of care is to ensure their comfort, which can be significantly affected by their illness and hospitalization. This study aims to explore MI patients' perceptions of support network challenges to ensure comfort in the CCU., Methods: A qualitative approach was adopted, and semi-structured interviews and notes were used for collecting data between 2020 and mid-2021. The participants were 27 MI patients in our country who had been hospitalized in the CCU of the University Heart Hospital. They were selected using purposive sampling. The data were analyzed using conventional content analysis by Graneheim and Lundman., Findings: The results of this research were revealed in the form of a "support network" theme comprising five categories: "Physical support", "Mental occupations", "Presence of peers", "relatives support "and "Spiritual strategies"., Conclusion: The study results showed that MI patients, in critical condition, receiving care, and hospitalized in the CCU require continuity in their support network to ensure comfort. The inconsistency between the components of each dimension leads to the challenge of ensuring comfort., (© 2024. The Author(s).)

Background: Myocardial fibrosis, a hallmark of heart disease, is closely associated with macrophages, yet the genetic pathophysiology remains incompletely understood. In this study, we utilized integrated single-cell transcriptomics and bulk RNA-seq analysis to investigate the relationship between macrophages and myocardial fibrosis across omics integration., Methods: We examined and curated existing single-cell data from dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), myocardial infarction (MI), and heart failure (HF), and analyzed the integrated data using cell communication, transcription factor identification, high dimensional weighted gene co-expression network analysis (hdWGCNA), and functional enrichment to elucidate the drivers of macrophage polarization and the macrophage-to-myofibroblast transition (MMT). Additionally, we assessed the accuracy of single-cell data from the perspective of driving factors, cell typing, anti-fibrosis performance of left ventricular assist device (LVAD). Candidate drugs were screened using L1000FWD., Results: All four heart diseases exhibit myocardial fibrosis, with only MI showing an increase in macrophage proportions. Macrophages participate in myocardial fibrosis through various fibrogenic molecules, especially evident in DCM and MI. Abnormal RNA metabolism and dysregulated transcription are significant drivers of macrophage-mediated fibrosis. Furthermore, profibrotic macrophages exhibit M1 polarization and increased MMT. In HF patients, those responding to LVAD therapy showed a significant decrease in driver gene expression, M1 polarization, and MMT. Drug repurposing identified cinobufagin as a potential therapeutic agent., Conclusion: Using integrated single-cell transcriptomics, we identified the drivers of macrophage-mediated myocardial fibrosis in four heart diseases and confirmed the therapeutic effect of LVAD on improving HF with single-cell accuracy, providing novel insights into the diagnosis and treatment of myocardial fibrosis., (© 2024. The Author(s).)