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Copyright of Gaceta Médica de Caracas is the property of Academia Nacional de Medicina and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Farnesoid X receptor (FXR) plays critical regulatory roles in cardiovascular physiology/pathology. However, the role of FXR agonist obeticholic acid (OCA) in sepsis‐associated myocardial injury and underlying mechanisms remain unclear. C57BL/6J mice are treated with OCA before lipopolysaccharide (LPS) administration. The histopathology of the heart and assessment of FXR expression and mitochondria function are performed. To explore the underlying mechanisms, H9c2 cells, and primary cardiomyocytes are pre‐treated with OCA before LPS treatment, and extracellular signal‐regulated protein kinase (ERK) inhibitor PD98059 is used. LPS‐induced myocardial injury in mice is significantly improved by OCA pretreatment. Mechanistically, OCA pretreatment decreased reactive oxygen species (ROS) levels and blocked the loss of mitochondrial membrane potential (ΔΨm) in cardiomyocytes. The expression of glutathione peroxidase 1 (GPX1), superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), and nuclear factor erythroid 2‐related factor 2 (NRF‐2) increased in the case of OCA pretreatment. In addition, OCA improved mitochondria respiratory chain with increasing Complex I expression and decreasing cytochrome C (Cyt‐C) diffusion. Moreover, OCA pretreatment inhibited LPS‐induced mitochondria dysfunction via suppressing ERK1/2‐DRP signaling pathway. FXR agonist OCA inhibits LPS‐induced mitochondria dysfunction via suppressing ERK1/2‐DRP signaling pathway to protect mice against LPS‐induced myocardial injury. [ABSTRACT FROM AUTHOR]

This research is concentrated on investigating the role and mechanism of miR-652-3p in the protective effects of isoflurane (ISO) against myocardial ischemia–reperfusion (I/R) injury. H9c2 cells underwent pretreatment with varying concentrations of ISO, and subsequently, a hypoxia/reoxygenation (H/R) model was constructed. The levels of miR-652-3p, ISL LIM homeobox 1 (ISL1), and inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) were evaluated through reverse transcription polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay was employed to investigate concentrations of myocardial injury markers, such as creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI). Cell counting kit-8 was used to evaluate cell viability, while flow cytometry was utilized to measure apoptosis. Additionally, a dual luciferase reporter assay was conducted to validate the targeting relationship between ISL1 and miR-652-3p. Herein, we confirmed that the level of miR-652-3p was gradually increased with prolonged hypoxia; nevertheless, this increase was suppressed by ISO pretreatment (P < 0.05). Additionally, ISO pretreatment prevented the decrease in cell viability, increase in apoptosis, and overproduction of IL-6, TNF-α, CK-MB, and cTnI induced by H/R (P < 0.05). However, the inhibitory effects of ISO were counteracted by the increased levels of miR-652-3p (P < 0.05). ISL1 is a potential target of miR-652-3p. H/R induction suppressed ISL1 levels compared to the control, but ISO treatment increased its expression (P < 0.05). Overexpression of ISL1 inhibited the elimination of the protective effect of ISO on myocardial damage induced by the elevation of miR-652-3p (P < 0.05). The findings of this research confirm that miR-652-3p attenuated the protective effect of ISO on cardiomyocytes in myocardial ischemia by targeting ISL1. [ABSTRACT FROM AUTHOR]

To investigate the role of microRNA-195-3p (miR-195-3p) in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury. AC16 human cardiomyocyte cells were cultured and pretreated with different concentrations of isoflurane (ISO) (1%, 2%, and 3%), followed by 6 h each of hypoxia and reoxygenation to construct H/R cell models. The optimum ISO concentration was assessed based on the cell viability. miR-195-3p expression was regulated by in vitro cell transfection. Cell viability was determined by MTT assay, and apoptosis was evaluated by flow cytometry. The levels of myocardial injury and inflammation were determined by enzyme-linked immunosorbent assay. Compared with the control group, the cell viability of the H/R group had significantly decreased and that of ISO pretreatment had increased in a dose-dependent manner. Therefore, we selected a 2% ISO concentration for pretreatment. MiR-195-3p expression had significantly increased in the H/R group and decreased after 2% ISO pretreatment. Additionally, the number of apoptotic cells and the levels of lactate dehydrogenase, creatine kinase-myoglobin binding, cardiac troponin I, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α had increased significantly. ISO preconditioning inhibited H/R-induced AC16 cell damage, whereas miR-195-3p overexpression reversed the protective effects of ISO on cardiomyocytes. The expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was reduced in the H/R-induced AC16 cells, and PTEN is a downstream target gene of miR-195-3p. Preconditioning with 2% ISO plays a protective role in H/R-induced AC16 cell damage by inhibiting miR-195-3p expression. [ABSTRACT FROM AUTHOR]

Anthracyclines have significantly improved the survival of children with malignant tumors, but the associated cardiotoxicity, an effect now under the purview of pediatric cardio-oncology, due to its cumulative and irreversible effects on the heart, limits their clinical application. A systematic screening and risk stratification approach provides the opportunity for early identification and intervention to mitigate, reverse, or prevent myocardial injury, remodeling, and dysfunction associated with anthracyclines. This review summarizes the risk factors, surveillance indexes, and preventive strategies of anthracycline-related cardiotoxicity to improve the safety and efficacy of anthracyclines. [ABSTRACT FROM AUTHOR]

Aims Adequate animal models are necessary to understand human conditions, such as takotsubo syndrome (TS) characterized by the heart's transient regional wall motion abnormalities. This study aims to develop a reproducible, low-mortality TS model that closely mimics the human condition and addresses the limitations of existing models. Methods and results We conducted six experiments using 309 Sprague Dawley rats, each approximately 300 g and aged 7–8 weeks. Initially, we replicated an established model using intraperitoneal isoprenaline injections. Subsequent experiments varied the doses and infusion durations of intravenous isoprenaline and assessed the effects of sex, strain, and breeder on the development of reversible akinetic segments. High-resolution echocardiography monitored the regional wall motion over 30 days to correlate with histological changes. Increasing the isoprenaline dose and the infusion time significantly enhanced akinesia (P < 0.01), resulting in pronounced apical ballooning observed in three-dimensional imaging. Akinesia peaked at 6 h post-infusion, with recovery observed at 24 h; most rats recovered from akinetic segments within 48–72 h. Optimizing the mode of administration, dose, and duration achieved a TS-like phenotype in 90% of cases, with a 16.7% mortality rate. Histological examinations confirmed that myocardial injury occurred, independent of apical ballooning. Conclusion This study presents a refined TS model that reliably replicates the syndrome's key features, including morphological and electrocardiographic changes, demonstrating its transient nature with high fidelity and reduced mortality. The model's reproducibility, evidenced by consistent results across trials, suggests its potential for broader application pending further validation. [ABSTRACT FROM AUTHOR]

Background: Growth differentiation factor-15 (GDF-15) has been shown to be associated with adverse clinical outcomes in patients after an acute coronary syndrome when measured soon after an event. Although dynamic in the acute phase after myocardial injury, GDF-15 has been shown to remain stable during convalescence. In this study, we aimed to assess the value of GDF-15 as a long-term prognostic marker for clinical outcomes when measured in the convalescent phase following an acute coronary syndrome. Methods: GDF-15 concentrations were measured in 1945 patients who were recruited between 2002 and 2009 to the Coronary Disease Cohort Study. For this analysis, follow-up was curtailed at 10 years and association of GDF-15 with all-cause death, cardiovascular death, recurrent myocardial infarction, and heart failure hospitalizations were assessed with multivariate Cox proportional hazard regression analysis. Results: After 10 years of follow-up, there were 648 deaths (348 from cardiovascular causes), 500 admissions for myocardial infarction, and 436 for heart failure. Four-month convalescent GDF-15 demonstrated a robust independent association with all endpoints, which remained after adjustment for Global Registry of Acute Coronary Events score and other convalescent biomarkers. When compared to the lowest quartile of GDF-15 concentrations, those in the highest quartile had a 3-fold increased risk of all-cause death. Conclusions: Convalescent plasma GDF-15 is a strong and independent predictor of 10-year all-cause death, cardiovascular death, recurrent myocardial infarction, and heart failure admission following an acute coronary syndrome. [ABSTRACT FROM AUTHOR]

Background Cardiac blunt trauma clinically presents as a spectrum of injuries of varying severity. However, the diagnosis of complications of remote myocardial trauma is often challenging, especially if the patient forgets to mention a remote history of chest trauma. Case summary In this study, we present a patient who recently experienced traumatic myocardial dissection and interventricular septal rupture, alongside three patients exhibiting a mimic double-chambered left ventricle, indicative of prior remote myocardial trauma potentially associated with myocardial dissecting tear. Discussion Patients with recent severe myocardial injury are detectable through cardiac imaging. However, forgotten remote myocardial trauma can lead to adverse myocardial remodelling, heart failure, and arrhythmias. Long-term myocardial remodelling can obscure initial myocardial imaging characteristics, posing challenges in interpretation. Our case series suggests that remote myocardial trauma may be more prevalent than commonly thought of in clinical practice. [ABSTRACT FROM AUTHOR]

Background Coronavirus disease 2019 (COVID-19) is predominantly known to cause respiratory injury; however, the present case series highlights four instances in which the infection resulted in significant cardiac complications. Among such cases, some represent severe cardiogenic shock, which necessitates the immediate introduction of mechanical circulatory support (MCS) for salvage. Case summary This case series involved patients with COVID-19-associated myocardial injury leading to fulminant cardiogenic shock. These patients required immediate implementation of peripheral MCS, followed by an instant upgrade to a central MCS system due to anatomical limitations and severe biventricular dysfunction. Central MCS provided effective ventricular unloading, resulting in a significant and prompt improvement in ventricular function. The treatment timeline showed rapid deterioration followed by remarkable recovery within 2 weeks of MCS initiation, demonstrating the effectiveness of aggressive and tailored MCS strategies in managing severe COVID-19-related cardiac complications. Discussion This study provides significant insights into the cardiovascular implications of COVID-19, particularly in the context of severe myocardial injury that leads to cardiogenic shock. The report underscores the importance of early recognition and intervention in such cases, focusing on the use of MCS as a life-saving modality. The findings also revealed unique pathological features of COVID-19-associated myocardial injury, including macrophage-predominant infiltration and microthrombosis, which are distinct from the features of conventional myocarditis. These findings highlight the need for further research on the pathophysiology of COVID-19-related cardiac injuries and the development of targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy of indobuprofen combined with nicodil for the treatment of acute coronary syndromes (ACS) and the effects of percutaneous coronary intervention on patients Effects of myocardial injury markers, platelet function and inflammatory factors after intervention (PCI). Method A total of 150 patients with ACS admitted to the hospital from January 2021 to December 2022 were divided into groups according to different treatment methods. The control group (n = 75) was given nicodil combined with antiplatelet therapy, and the study group (n = 75) was given indobufen combined with nicodil combined with antiplatelet therapy. Both groups were treated for 2 weeks. The clinical efficacy of the two groups was compared, the changes of myocardial injury markers, platelet function and inflammatory factors before and after treatment were monitored, and the total incidence of adverse reactions was recorded. Results The total effective rate of the group treated with nicodil combined with indobufen was 98.67% higher than that of the control group treated with nicodil alone, 90.67% (χ2 = 4.754, P < 0.05). The levels of myocardial injury markers such as cTnI and CK-MB in the study group after treatment were lower than those in the control group (t = 15.492, 3.250, P < 0.05). The levels of platelet function indexes such as CD62p, CD63, GP'b/IIIa in the study group after treatment were lower than those in the control group (t = 2.034, 3.257, 2.221, P < 0.05). The levels of CRP, TNF- α, IL-6 and other inflammatory factors in the study group were lower than those in the control group after treatment (t = 21.862, 3.378, 2.131, P < 0.05). The total incidence of adverse reactions after treatment was 4.00% in the study group and 2.67% in the control group (P > 0.05). Conclusion The efficacy of indobufien combined with nicodil in the treatment of ACS is better than that of nicodil alone, and it can improve myocardial injury and platelet function after PCI, inhibit the release of inflammatory factors, and the incidence of adverse reactions is lower. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy is a primary local treatment for tumors, yet it may lead to complications such as radiation-induced heart disease (RIHD). Currently, there is no standardized approach for preventing RIHD. Dexmedetomidine (Dex) is reported to have cardio-protection effects, while its role in radiation-induced myocardial injury is unknown. In the current study, we aimed to evaluate the radioprotective effect of dexmedetomidine in X-ray radiation-treated mice. Methods: 18 male mice were randomized into 3 groups: control, 16 Gy, and 16 Gy + Dex. The 16 Gy group received a single dose of 16 Gy X-ray radiation. The 16 Gy + Dex group was pretreated with dexmedetomidine (30 µg/kg, intraperitoneal injection) 30 min before X-ray radiation. The control group was treated with saline and did not receive X-ray radiation. Myocardial tissues were collected 16 weeks after X-ray radiation. Hematoxylin-eosin staining was performed for histopathological examination. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining was performed to assess the state of apoptotic cells. Immunohistochemistry staining was performed to examine the expression of CD34 molecule and von Willebrand factor. Besides, western blot assay was employed for the detection of apoptosis-related proteins (BCL2 apoptosis regulator and BCL2-associated X) as well as autophagy-related proteins (microtubule-associated protein 1 light chain 3, beclin 1, and sequestosome 1). Results: The findings demonstrated that 16 Gy X-ray radiation resulted in significant changes in myocardial tissues, increased myocardial apoptosis, and activated autophagy. Pretreatment with dexmedetomidine significantly protects mice against 16 Gy X-ray radiation-induced myocardial injury by inhibiting apoptosis and autophagy. Conclusion: In summary, our study confirmed the radioprotective effect of dexmedetomidine in mitigating cardiomyocyte apoptosis and autophagy induced by 16 Gy X-ray radiation. [ABSTRACT FROM AUTHOR]

Background: COVID-19 is a new infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Since the outbreak in December 2019, it has caused an unprecedented world pandemic, leading to a global human health crisis. Although SARS CoV-2 mainly affects the lungs, causing interstitial pneumonia and severe acute respiratory distress syndrome, a number of patients often have extensive clinical manifestations, such as gastrointestinal symptoms, cardiovascular damage and renal dysfunction. Purpose: This review article discusses the pathogenic mechanisms of cardiovascular damage in COVID-19 patients and provides some useful suggestions for future clinical diagnosis, treatment and prevention. Methods: An English-language literature search was conducted in PubMed and Web of Science databases up to 12th April, 2024 for the terms "COVID-19", "SARS CoV-2", "cardiovascular damage", "myocardial injury", "myocarditis", "hypertension", "arrhythmia", "heart failure" and "coronary heart disease", especially update articles in 2023 and 2024. Salient medical literatures regarding the cardiovascular damage of COVID-19 were selected, extracted and synthesized. Results: The most common cardiovascular damage was myocarditis and pericarditis, hypertension, arrhythmia, myocardial injury and heart failure, coronary heart disease, stress cardiomyopathy, ischemic stroke, blood coagulation abnormalities, and dyslipidemia. Two important pathogenic mechanisms of the cardiovascular damage may be direct viral cytotoxicity as well as indirect hyperimmune responses of the body to SARS CoV-2 infection. Conclusions: Cardiovascular damage in COVID-19 patients is common and portends a worse prognosis. Although the underlying pathophysiological mechanisms of cardiovascular damage related to COVID-19 are not completely clear, two important pathogenic mechanisms of cardiovascular damage may be the direct damage of the SARSCoV-2 infection and the indirect hyperimmune responses. [ABSTRACT FROM AUTHOR]

Background: Perioperative myocardial injury/infarction (PMI) following noncardiac surgery is a frequent cardiac complication. This study aims to evaluate PMI risk and explore preoperative assessment tools of PMI in patients at increased cardiovascular (CV) risk who underwent noncardiac surgery under the surgical and medical co-management (SMC) model. Methods: A prospective cohort study that included consecutive patients at increased CV risk who underwent intermediate- or high-risk noncardiac surgery at the Second Medical Center, Chinese PLA General Hospital, between January 2017 and December 2022. All patients were treated with perioperative management by the SMC team. The SMC model was initiated when surgical intervention was indicated and throughout the entire perioperative period. The incidence, risk factors, and impact of PMI on 30-day mortality were analyzed. The ability of the Revised Cardiac Risk Index (RCRI), frailty, and their combination to predict PMI was evaluated. Results: 613 eligible patients (mean [standard deviation, SD] age 73.3[10.9] years, 94.6% male) were recruited consecutively. Under SMC, PMI occurred in 24/613 patients (3.9%). Patients with PMI had a higher rate of 30-day mortality than patients without PMI (29.2% vs. 0.7%, p = 0.00). The FRAIL Scale for frailty was independently associated with an increased risk for PMI (odds ratio = 5.91; 95% confidence interval [CI], 2.34–14.93; p = 0.00). The RCRI demonstrated adequate discriminatory capacity for predicting PMI (area under the curve [AUC], 0.78; 95% CI, 0.67–0.88). Combining frailty with the RCRI further increased the accuracy of predicting PMI (AUC, 0.87; 95% CI, 0.81–0.93). Conclusions: The incidence of PMI was relatively low in high CV risk patients undergoing intermediate- or high-risk noncardiac surgery under SMC. The RCRI adequately predicted PMI. Combining frailty with the RCRI further increased the accuracy of PMI predictions, achieving excellent discriminatory capacity. These findings may aid personalized evaluation and management of high-risk patients who undergo intermediate- or high-risk noncardiac surgery. [ABSTRACT FROM AUTHOR]

Gallium-68 fibroblast activation protein inhibitor [(68Ga)Ga-FAPI] is a new radiopharmaceutical positioning itself as the preferred agent in patients with malignant tumours, competing with 2-Deoxy-2-[18F]fluoro-d-glucose [2-(18F) FDG] using positron emission tomography (PET). While imaging oncology patients with [68Ga]Ga-FAPI PET, incidental uptake of [68Ga]Ga-FAPI has been detected in the myocardium. This review summarises original research studies associating the visualisation of FAPI-based tracers in the myocardium with underlying active cardiovascular disease. [ABSTRACT FROM AUTHOR]

In different areas of the heart, action potential waveforms differ due to differences in the expressions of sodium, calcium, and potassium channels. One of the characteristics of myocardial infarction (MI) is an imbalance in oxygen supply and demand, leading to ion imbalance. After MI, the regulation and expression levels of K+, Ca2+, and Na+ ion channels in cardiomyocytes are altered, which affects the regularity of cardiac rhythm and leads to myocardial injury. Myocardial fibroblasts are the main effector cells in the process of MI repair. The ion channels of myocardial fibroblasts play an important role in the process of MI. At the same time, a large number of ion channels are expressed in immune cells, which play an important role by regulating the in- and outflow of ions to complete intracellular signal transduction. Ion channels are widely distributed in a variety of cells and are attractive targets for drug development. This article reviews the changes in different ion channels after MI and the therapeutic drugs for these channels. We analyze the complex molecular mechanisms behind myocardial ion channel regulation and the challenges in ion channel drug therapy. [ABSTRACT FROM AUTHOR]

Background: Dipeptidyl peptidase 3 (DPP3) is a ubiquitous cytosolic enzyme released into the bloodstream after tissue injury, that can degrade angiotensin II. High concentrations of circulating DPP3 (cDPP3) have been associated with worse outcomes during sepsis. The aim of this study was to assess the effect of Procizumab (PCZ), a monoclonal antibody that neutralizes cDPP3, in an experimental model of septic shock. Methods: In this randomized, open-label, controlled study, 16 anesthetized and mechanically ventilated pigs with peritonitis were randomized to receive PCZ or standard treatment when the mean arterial pressure (MAP) dropped below 50 mmHg. Resuscitation with fluids, antimicrobial therapy, peritoneal lavage, and norepinephrine was initiated one hour later to maintain MAP between 65–75 mmHg for 12 h. Hemodynamic variables, tissue oxygenation indices, and measures of organ failure and myocardial injury were collected. Organ blood flow was assessed using isotopic assessment (99mtechnetium albumin). cDPP3 activity, equilibrium analysis of the renin–angiotensin system and circulating catecholamines were measured. Tissue mRNA expression of interleukin-6 and downregulation of adrenergic and angiotensin receptors were assessed on vascular and myocardial samples. Results: PCZ-treated animals had reduced cDPP3 levels and required less norepinephrine and fluid than septic control animals for similar organ perfusion and regional blood flow. PCZ-treated animals had less myocardial injury, and higher PaO2/FiO2 ratios. PCZ was associated with lower circulating catecholamine levels; higher circulating angiotensin II and higher angiotensin II receptor type 1 myocardial protein expression, and with lower myocardial and radial artery mRNA interleukin-6 expression. Conclusions: In an experimental model of septic shock, PCZ administration was associated with reduced fluid and catecholamine requirements, less myocardial injury and cardiovascular inflammation, along with preserved angiotensin II signaling. [ABSTRACT FROM AUTHOR]

Despite impressive improvements in the care of patients with ST-segment elevation myocardial infarction, mortality remains high. Reperfusion is necessary for myocardial salvage, but the abrupt return of flow sets off a cascade of injurious processes that can lead to further necrosis. This has been termed myocardial ischemia-reperfusion injury and is the subject of this review. The pathologic and molecular bases for myocardial ischemia-reperfusion injury are increasingly understood and include injury from reactive oxygen species, inflammation, calcium overload, endothelial dysfunction, and impaired microvascular flow. A variety of pharmacologic strategies have been developed that have worked well in preclinical models and some have shown promise in the clinical setting. In addition, there are newer mechanical approaches including mechanical unloading of the heart prior to reperfusion that are in current clinical trials. [Display omitted] • MIRI exacerbates myocardial necrosis in patients with STEMI, contributing to mortality. • MIRI is mediated by varying combinations of ROS, inflammation, endothelial dysfunction, impaired microvascular flow, and other factors. • A variety of pharmacologic and mechanical strategies that mitigate MIRI in preclinical models have shown promise in clinical trials. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether two-dimensional speckle-tracking echocardiography (2DSTE) can be considered a criterion for early left ventricular (LV) systolic impairment in patients with systemic lupus erythematosus (SLE) and to further explore the association with each other. Methods: We included 38 patients with SLE and assessed the degree of disease activity according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000 scoring criteria, together with 38 healthy controls who were matched by sex and age. Routine LV systolic function evaluation parameters were obtained by echocardiography as well as 2DSTE measurement of LV strain parameters to obtain global longitudinal strain (GLS) values, respectively. Results: (I) On routine LV function parameters such as ejection fractions (EF) and left ventricular end-diastolic internal diameter (LVIDd), the SLE group and the control group did not reflect differences. In contrast, on the LV strain parameter obtained from 2DSTE measurements, the GLS values in all cardiac planes were lower in the SLE group than in the control group and showed statistically significant differences. (II) Correlation analysis showed that there was a correlation between SLEDAI and GLS, especially a meaningful correlation with GLS Avg and GLS A4C, with correlation coefficients of 0.35 and 0.47, respectively. Conclusions: The use of 2DSTE can detect early impaired LV systolic function in SLE patients, and GLS is progressively gaining attention as an indicator of subclinical myocardial injury and LV function in SLE patients. The correlation that exists between GLS and SLEDAI might contribute to a better assessment of cardiac involvement in SLE patients. Key Points • Cardiac involvement has become one of the major factors in the poor prognosis of SLE patients, which directly affects the mortality of SLE patients. Traditional echocardiography is difficult to detect early left ventricular function impairment, thus affecting clinicians' judgment and diagnosis. • 2DSTE can recognize subclinical myocardial injury in SLE patients at an early stage, and its derived strain parameters may be used as an indicator to evaluate myocardial involvement and reflect disease activity in SLE patients [ABSTRACT FROM AUTHOR]

Aims: Mitochondrial homeostasis is essential for maintaining redox balance. Besides canonical autophagy, Rab9-dependent alternative autophagy is a crucial mechanism in metabolic cardiomyopathy. Here, we aim to investigate the role of alternative mitophagy and Beclin 1 haploinsufficiency (Beclin 1+/−) in high-fat diet (HFD)–induced metabolic cardiomyopathy. Results: Twenty-four-week HFD impaired glucose tolerance and cardiomyocyte contraction in wild-type mice, both of which were rescued in Beclin 1+/− mice. Beclin 1 haploinsufficiency had little effect on the conventional autophagy mediators (ATG5, LC3 II/LC3 I) but further upregulated Rab9 expression, a marker of alternative autophagy, in response to HFD challenge. Furthermore, either the inhibition of alternative autophagy or Beclin 1 haploinsufficiency abolished palmitic acid (PA)-induced cardiomyocyte contractile anomalies. In vitro, PA overactivated mitophagy, resulting in decreased mitochondrial content in H9C2 cells. These aberrations were alleviated in cells deficient in alternative autophagy but not in cells deficient in conventional autophagy. Mechanistically, HFD promoted reactive oxygen species (ROS) production, activated Rab9-dependent alternative mitophagy, and inhibited mitochondrial biosynthesis. Beclin 1+/− rescued HFD-induced ROS overflow, mitochondrial biogenesis impairment, and prevented Rab9 translocation from the cytoplasm to the mitochondria, thereby inhibiting Rab9-mediated mitophagy overactivation. Innovation: For the first time, this study suggests that prolonged alternative mitophagy exacerbates chronic HFD-induced cardiac dysfunction and supports the protective role of Beclin 1 haploinsufficiency in metabolic cardiomyopathy. This provides additional evidence for a target-based pharmacological intervention. Conclusion:Beclin 1 haploinsufficiency protects against HFD-induced cardiac dysfunction by inhibiting Rab9-dependent alternative mitophagy and ROS production, while promoting mitochondrial biogenesis. Modulating Beclin 1 expression holds promise in preventing chronic HFD-related cardiomyopathy. [ABSTRACT FROM AUTHOR]

Myocardial injury in open-heart surgery is related to several factors including ischemia–reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes. The aim of this study was to study the effect of L-carnitine on myocardial injury in children undergoing open-heart surgery. This clinical trial was performed on 60 children with congenital heart disease (CHD) who underwent open-heart surgery. They were randomized into two groups: L-carnitine group who received L-carnitine 50 mg\kg\day once daily for 1 month before cardiac surgery and control group who received placebo for 1 month before cardiac surgery. Left ventricular cardiac function was assessed by conventional echocardiography to measure left ventricular ejection fraction (LVEF) and two-dimensional speckle tracking echocardiography (2D-STE) to determine left ventricular global longitudinal strain (2D-LV GLS). Blood samples were obtained pre-operatively at baseline before the administration of L-carnitine or placebo and 12 h post-operatively to measure the level of malondialdehyde (MDA), superoxide dismutase (SOD), fas, caspase-3, creatinine kinase-MB (CK-MB), and troponin I. L-carnitine group had significantly lower post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I), but they had significantly higher SOD post-operative level compared to the control group. In addition, post-operative LVEF and 2D-LVGLS were significantly lower in the control group compared to L-carnitine group. Conclusion: L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery. Trial registration: The clinical trial was registered at www.pactr.org with registration number PACTR202010570607420 at 29/10/2020 before recruiting the patients. What is Known: • Myocardial injury in open-heart surgery is related to several factors including ischemia–reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes. • L-carnitine was reported to have myocardial protective effects in rheumatic valvular surgery and coronary artery bypass graft (CABG) in adults; however, there is no evidence on its effectiveness in children undergoing open-heart surgery. What is New: • L-carnitine significantly lowered the post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I) in the treatment group. • L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Feline infectious peritonitis (FIP) is a very common coronavirus (FCoV) infectious disease in the feline population. FIP infection is a cause of death in cats and is widespread in domestic cats. FIP can have an acute or chronic clinical form, also known as effusive or non-effusive FIP, respectively. The typical lesion found in the acute form is an effusion in the thoracic and/or abdominal cavities, while collection in the pericardial sac is rare. The chronic form is characterized by pyogranulomatous necrotizing lesions in organs such as the kidney, liver, intestine, lung, eyes, skin, and central nervous system. FIP does not represent a zoonotic risk. The reported case is an uncommon pyogranuloma found in the myocardium in a cat with clinical heart dysfunction. The most important histopathological finding was the myocarditis/myocardial necrosis associated with the presence of S gene-mutated FCoV (M1058L biotype). This is the first described case of myocarditis in an FCoV/FIP M1058L biotype-positive cat. An 8-month-old intact male domestic shorthair cat was referred to the Emergency Service of the Veterinary Teaching Hospital (VTH) of the Department of Veterinary Science of the University of Parma (Italy) from the Parma municipal multi-cat shelter, during the winter season (January 2023), for lethargy, anorexia, hypothermia, and hypoglycemia. At the VTH, upon cardiologic examination, an increase in heart rate, under normal blood pressure conditions, was detected. Signalment, clinical history, basal metabolic panel (BMP), ultrasound investigations, and cytological findings were all consistent with a diagnosis of feline infectious peritonitis (FIP). FIP was confirmed in the effusive abdominal fluid by a molecular genetic test (real-time PCR for feline coronavirus RNA). The molecular genetic investigation also detected an FCoV S gene single-nucleotide mutation: biotype M1058L. At necropsy, an effusive collection was recorded in the abdomen, thoracic cavity, and pericardium sac. White parenchymal nodules, of about 1 mm diameter, were found on the surface and deep in the lungs, liver, kidneys, and heart. Histopathology revealed the typical FIP pyogranulomatous vasculitis and IHC confirmed the presence of the FIP virus (FIPV) antigen. The most relevant histopathological finding was the myocarditis/myocardial necrosis associated with the presence of the S gene-mutated FCoV (M1058L biotype). This is the first case of myocarditis in a cat positive for the FCoV/FIP M1058L biotype. Further studies are necessary to support the mutated FCoV M1058L biotype, as an uncommon, but possible, causative pathogen of myocarditis in FCoV/FIP-positive cats. Studies including several FCoV/FIP M1058L-positive cases could allow us to make a correlation with heart gross pathology, histopathology, and immunolocalization of the FCoV/FIP M1058L biotype in the myocardium. The investigation will potentially allow us to determine the effective tropism of the FCoV/FIP M1058L biotype for myocardiocytes or whether myocardiocyte lesions are evident in the presence of concomitant causes related to the patient, its poor condition, or external environmental distress such as cold season, and whether the aforementioned concomitant events are correlated. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction and myocardial remodeling have been reported to be the main underlying molecular mechanisms of doxorubicin‐induced cardiotoxicity. SIRT6 is a nicotinamide adenine dinucleotide‐dependent enzyme that plays a vital role in cardiac protection against various stresses. Moreover, previous studies have demonstrated that FSTL1 could alleviate doxorubicin‐induced cardiotoxicity by inhibiting autophagy. The present study investigated the probable mechanisms of FSTL1 on doxorubicin‐induced cardiotoxicity in vivo and in vitro. We confirmed that FSTL1 exerted a pivotal protective role on cardiac tissue in vivo and on doxorubicin‐induced cell injury in vitro. Furthermore, FSTL1 can alleviate doxorubicin‐induced mitochondrial dysfunction by inhibiting autophagy and apoptosis. Further studies demonstrated that FSTL1 can activate SIRT6 signaling by restoring the SIRT6 protein expression in doxorubicin‐induced myocardial injury. SIRT6 activation elevated the protein expression of Nrf2 in doxorubicin‐induced H9C2 injury. Treatment with the Nrf2 inhibitor ML385 partially antagonized the cardioprotective role of SIRT6 on doxorubicin‐induced autophagy or apoptosis. These results suggested that the protective mechanism of FSTL1 on doxorubicin‐induced cardiotoxicity may be related with the inhibition of autophagy and apoptosis, partly through the activation of SIRT6/Nrf2. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) is one of the most prevalent cardiovascular diseases, accounting for a high incidence rate and high mortality worldwide. Hypoxia/reoxygenation (H/R)-induced myocardial cell injury is the main cause of AMI. Several studies have shown that circular RNA contributes significantly to the pathogenesis of AMI. Here, we established an AMI mouse model to investigate the effect of circDiaph3 in cardiac function and explore the functional role of circDiaph3 in H/R-induced cardiomyocyte injury and its molecular mechanism. Bioinformatics tool and RT-qPCR techniques were applied to detect circDiaph3 expression in human patient samples, heart tissues of AMI mice, and H/R-induced H9C2 cells. CCK-8 was used to examine cell viability, while annexin-V/PI staining was used to assess cell apoptosis. Myocardial reactive oxygen species (ROS) levels were detected by immunofluorescence. Western blot was used to detect the protein expression of anti-apoptotic Bcl-2 while pro-apoptotic Bax and cleaved-Caspase-3. Furthermore, ELISA was used to detect inflammatory cytokines production. While bioinformatics tool and RNA pull-down assay were used to verify the interaction between circDiaph3 and miR-338-3p. We found that circDiaph3 expression was high in AMI patients and mice, as well as in H/R-treated H9C2 cells. CircDiaph3 silencing ameliorated apoptosis and inflammatory response of cardiomyocytes in vivo. Moreover, the knockdown of cirDiaph3 mitigated H/R-induced apoptosis and the release of inflammatory mediators like IL-1β, IL-6, and TNF-α in H9C2 cells. Mechanistically, circDiaph3 induced cell apoptosis and inflammatory responses in H/R-treated H9C2 cells by sponging miR-338-3p. Overexpressing miR-338-3p in H/R-treated cells prominently reversed circDiaph3-induced effects. Notably, miR-338-3p inhibited SRSF1 expression in H/R-treated H9C2 cells. While overexpressing SRSF1 abrogated miR-338-3p-mediated alleviation of apoptosis and inflammation after H/R treatment. To summarize, circDiaph3 aggravates H/R-induced cardiomyocyte apoptosis and inflammation through the miR-338-3p/SRSF1 axis. These findings suggest that the circDiaph3/miR-338-3pp/SRSF1 axis could be a potential therapeutic target for treating H/R-induced myocardial injury. [ABSTRACT FROM AUTHOR]

Although kidney insufficiency has been shown to be associated with increased risk of myocardial injury, benefit of coronary angiography (CAG) and revascularization remains uncertain, with implications on management strategies and outcomes. We aimed to compare rates of CAG and revascularization and subsequent risk of cardiovascular and kidney outcomes in hospitalized patients with myocardial injury and kidney dysfunction. Retrospective cohort study encompassing hospitalized patients with myocardial injury i.e. elevated troponin I or T and an eGFR ≤60 ml/min/1.73 m2 identified between 2011 and 2021 in Danish national registers. 30-day odds for CAG were computed across granular eGFR-categories based on multiple logistic regression. Standardized one-year risks of cardiovascular and kidney outcomes including mortality were determined based on hazards obtained in multiple Cox regression. A total of 52,798 patients with myocardial injury were identified. CAG was performed in 14.3 % (n = 7549). 30-day odds ratios for CAG were 0.64 [0.60–0.68], 0.38 [0.34–0.42], 0.18 [0.14–0.22], and 0.35 [0.30–0.40] in patients with eGFR 31–45 ml/min/1.73 m2, eGFR 15–30 ml/min/1.73 m2 for eGFR<15 ml/min/1.73 m2 and chronic dialysis, respectively (eGFR 46-60 ml/min/1.73 m2 as reference). Median follow-up was 4.1 years. One-year mortality risk differences associated with CAG and revascularization (no CAG as reference) were −7.8 [−7.0; −8.7] and −9.1 [−8.4; −9.9] for eGFR 46-60 ml/min/1.73 m2; −7.0 [−5.7;-8–3] and −8.0 [−6.6; −9.5] for eGFR 31-45 ml/min/1.73 m2; −5.4 [−3.0; −7.2] and −5.2 [−2.2; −8.3] for eGFR 15-30 ml/min/1.73 m2; −8.8 [−3.1; −13.7] and −5.4 [3.1; −13.4] for eGFR<15 ml/min/1.73 m2; and −4.9 [−0.1; −9.7] and −4.2 [1.5; −9.2] for chronic dialysis, respectively. Probability of CAG following myocardial injury declined with progressive kidney dysfunction. Overall, CAG was associated with lower mortality irrespective of kidney function and subsequent revascularization. • Myocardial injury i.e. elevated cardiac troponins is common in hospitalized patients • Implications of elevated troponin remain uncertain in patients with kidney insufficiency beyond overt myocardial infarction • Probability of coronary angiography and revascularization declines with progressive kidney dysfunction • Revascularization benefit is curtailed with increasing kidney dysfunction [ABSTRACT FROM AUTHOR]

Objective: Sepsis-induced cardiomyopathy (SICM) is a life-threatening complication. Phospholipase D2 (PLD2) is crucial in mediating inflammatory reactions and is associated with the prognosis of patients with sepsis. Whether PLD2 is involved in the pathophysiology of SICM remains unknown. This study aimed to investigate the effect of PLD2 knockout on SICM and to explore potential mechanisms. Methods: The SICM model was established using cecal ligation and puncture in wild-type and PLD2-knockout mice and lipopolysaccharide (LPS)-induced H9C2 cardiomyocytes. Transfection with PLD2-shRNA lentivirus and a PLD2 overexpression plasmid were used to interfere with PLD2 expression in H9C2 cells. Cardiac pathological alterations, cardiac function, markers of myocardial injury, and inflammatory factors were used to evaluate the SICM model. The expression of pyroptosis-related proteins (NLRP3, cleaved caspase 1, and GSDMD-N) was assessed using western blotting, immunofluorescence, and immunohistochemistry. Results: SICM mice had myocardial tissue damage, increased inflammatory response, and impaired heart function, accompanied by elevated PLD2 expression. PLD2 deletion improved cardiac histological changes, mitigated cTNI production, and enhanced the survival of the SICM mice. Compared with controls, PLD2-knockdown H9C2 exhibits a decrease in inflammatory markers and lactate dehydrogenase production, and scanning electron microscopy results suggest that pyroptosis may be involved. The overexpression of PLD2 increased the expression of NLRP3 in cardiomyocytes. In addition, PLD2 deletion decreased the expression of pyroptosis-related proteins in SICM mice and LPS-induced H9C2 cells. Conclusion: PLD2 deletion is involved in SICM pathogenesis and is associated with the inhibition of the myocardial inflammatory response and pyroptosis through the NLRP3/caspase 1/GSDMD pathway. [ABSTRACT FROM AUTHOR]

To analyze the effect of tanshinone inhibiting oxidative stress and myocardial injury in patients with coronary heart disease through nuclear factor E2 related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway. A prospective study was conducted on 84 patients with unstable angina pectoris diagnosis in our hospital from June 2022 to June 2023. They were randomly divided into control group and observation group, with 42 patients in each group. The control group received conventional drugs and intervention, while the observation group received tanshinone IIA sulfonate sodium injection (40 mg/d) on the basis of control group for 2 weeks continuous treatment. Comparisons of peripheral blood Nrf2, ARE, and hypoxia inducible factor-1α (HIF-1α) and Caspase-1 proteins expression, oxidative stress indicators such as reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD), inflammatory mediators tumor necrosis factor (TNF)-α and interleukin (IL)-1β, myocardial injury indicators troponin I (cTnI) and creatine kinase isoenzyme (CK-MB) were made between two groups before and after treatment. There were no differences of above indicators between the two groups before treatment (P>0.05). After treatment, there were significant improvements compared to before treatment (P<0.05), and the expressions of Nrf2 and ARE proteins in observation group were significantly higher than those in control group, while HIF-1α and Caspase-1 proteins expression were significantly lower than control group, ROS level was less, MDA and SOD levels were higher, TNF-α and IL-1β levels were less, cTnI and CK-MB levels were lower, too (P<0.05). Tanshinone may inhibit oxidative stress, inflammatory response, cell apoptosis, and myocardial injury in patients with coronary heart disease by activating Nrf2/ARE signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) is a persistent metabolic condition resulting from insufficient insulin or insulin resistance, which gives rise to diverse complications endangering human well-being. Ramulus Mori (Sangzhi) alkaloids -(SZ-A) have various pharmacological effects, potentially benefiting clinical comprehensive kidney and cardiovascular protection. Nevertheless, the potential protective effect of SZ-A on myocardial injury in individuals with type 2 diabetes mellitus (T2DM) remains unexplored. Materials and Methods: Sprague-Dawley (SD) rats were divided into four groups, including control, model, metformin, and SZ-A. The establishment of the type 2 diabetes model was initiated by injecting streptozotocin (STZ) along with a diet of high glucose and fat. Following a 12-week period of treatment, measurements were taken for heart mass index (HMI), fasting blood glucose (FBG), and 2-h postprandial blood glucose (2hPG). Additionally, serum glycated hemoglobin (HbA1c), indicators of myocardial injury, and oxidative stress were assessed. The expressions of mammalian target of rapamycin (mTOR), p-mTOR, beclin-1, and LC3 in myocardial tissue were detected by Western blot. Results: The administration of SZ-A effectively reduced the levels of HMI, FBG, 2hPG, HbA1c, malondialdehyde (MDA), lactate dehydrogenase (LDH), and creatine kinase isoenzymes (CK-MB) in rats with type 2 diabetes while enhancing the activity of superoxide dismutase (SOD). Additionally, SZ-A could improve myocardial tissue arrangement structure and fibrosis degree. Additional analysis revealed that SZ-A suppressed the activation of p-mTOR while enhancing the levels of Beclin-1 and LC3, suggesting that the potential therapeutic impact of SZ-A on myocardial damage could be attributed to its ability to regulate autophagy, thereby mitigating oxidative stress. Conclusion: In summary, the results indicate that SZ-A might possess inhibitory properties against myocardial damage in rats with type 2 diabetes, presenting a potential therapeutic approach in the clinic. [ABSTRACT FROM AUTHOR]

Introduction: Myocardial infarction (MI) is a global burden that implies on quality of life. Platelet-rich plasma (PRP) is an autologous source of growth factors that is recently suggested due to its healing properties. Isoproterenol (ISO) is a β-agonist drug used as experimental model of myocardial injury through cardiac hyperactivity and production of reactive oxygen species. Aim of Work: To investigate the role of PRP in preservation of cardiac tissue and enhancing healing in isoproterenol (ISO) induced myocardial injury. Materials and Methods: 48 adult male albino rats were used as follows; Control group (N=18), Myocardial injury group (N=18) and Myocardial injury with PRP group (N=12). ISO was administered as a single subcutaneous dose (67 mg/kg) and PRP was injected intracardiac after 12 h from ISO injection. Hearts were harvested at 7 days and 21 days and left ventricular sections were stained for histological and immunohistochemical study. Results: Isoproterenol treated sections showed necrosis and apoptosis of myocardial fibers with loss of striations. Interstiuim showed mononuclear cellular infiltration and significant increase in collagen deposition. Moreover, blood vessels showed congestion and hemorrhage. Examination of PRP treated sections showed restoration of normal architecture of myocardial fibers. There was a statistically significant decrease in apoptosis and necrosis of myocardial cells. Also, interstitium showed an apparent decrease in mononuclear cellular infiltration and hemorrhage. These findings were observed after one week of PRP administration and became more evident after three weeks. Meanwhile, collagen deposition showed highly significant decrease in PRP treated group only after three weeks in comparison to ISO only treated group. Conclusion: PRP was found to decrease myocardial death and accelerate healing. PRP can be considered a simple, economically feasible and favorable strategy in management of myocardial injury. [ABSTRACT FROM AUTHOR]

The article focuses on the SPACE trial, which examined the impact of discontinuing renin-angiotensin system inhibitors (RASI) before elective non-cardiac surgery in older patients. It aimed to assess whether stopping RASI prior to surgery would reduce postoperative myocardial injury and other adverse events. It is reported that the results showed that discontinuing RASI did not decrease the incidence of myocardial injury and may have increased the occurrence of hypertensive adverse events.

Objective: To investigate the cardioprotective potential of betulin in isoproterenol (ISO)-induced myocardial injury in rats. Methods: Wistar rats were divided into five groups (n=10): normal, ISO, nebivolol 5 mg/kg, and betulin (20 & 40 mg/kg). Nebivolol and betulin were administered orally for 29 days. ISO (85 mg/kg) was administered subcutaneously on day 27 and day 28 to induce myocardial injury. On day 29, blood was collected for determination of cardiac markers, and hemodynamic parameters were investigated. The levels of oxidative stress markers and the gene expressions of apoptotic markers and inflammatory mediators were evaluated. Moreover, 2,3,5-triphenyltetrazolium chloride staining and histopathological analysis were also performed. Results: Betulin reduced the size of myocardial infarction, decreased elevated levels of cardiac enzymes, and maintained hemodynamic functions. It also inhibited ISO-induced upregulation of Bax, caspase-3, NF-κB, and IL-6, enhanced endogenous antioxidant enzymes, and reduced lipid peroxidation. Additionally, pretreatment with betulin alleviated myocardial ischemic damage, as reflected by reduced myonecrosis, edema, and inflammatory changes. Conclusions: Betulin exhibits strong cardioprotective activity against ISO-induced myocardial injury by anti-inflammatory, antiapoptotic, and antioxidant activities. [ABSTRACT FROM AUTHOR]

The infusion of glucose-insulin-potassium (GIK) has yielded conflicting results in terms of cardioprotective effects. We conducted a meta-analysis to examine the impact of perioperative GIK infusion in early outcome after cardiac surgery. Randomized controlled trials (RCTs) were eligible if they examined the efficacy of GIK infusion in adults undergoing cardiac surgery. The main study endpoint was postoperative myocardial infarction (MI) and secondary outcomes were hemodynamics, any complications and hospital resources utilization. Subgroup analyses explored the impact of the type of surgery, GIK composition and timing of administration. Odds ratio (OR) or mean difference (MD) with 95% confidence interval (CI) were calculated with a random-effects model. Fifty-three studies (n=6129) met the inclusion criteria. Perioperative GIK infusion was effective in reducing MI (k=32 OR 0.66[0.48, 0.89] P=0.0069), acute kidney injury (k=7 OR 0.57[0.4, 0.82] P=0.0023) and hospital length of stay (k=19 MD -0.89[-1.63, -0.16] days P=0.0175). Postoperatively, the GIK-treated group presented higher cardiac index (k=14 MD 0.43[0.29, 0.57] L/min P<0.0001) and lesser hyperglycemia (k=20 MD -30[-47, -13] mg/dL P=0.0005) than in the usual care group. The GIK-associated protection for MI was effective when insulin infusion rate exceeded 2 mUI/kg/min and after coronary artery bypass surgery. Certainty of evidence was low given imprecision of the effect estimate, heterogeneity in outcome definition and risk of bias. Perioperative GIK infusion is associated with improved early outcome and reduced hospital resource utilization after cardiac surgery. Supporting evidence is heterogenous and further research is needed to standardize the optimal timing and composition of GIK solutions. [ABSTRACT FROM AUTHOR]

Diagnosis of cardiac diseases and their therapeutic interventions mostly rely on combined clinical examination, radiography, electrocardiography, and echocardiography. However, wide variability among different dog breeds may also mislead the interpretation of ECG, echocardiography, and thoracic radiographs. Thus, the identification and monitoring of blood-based cardiac biomarkers along or in combination with other diagnostic tools could be a promising approach to diagnose cardiac diseases. The most extensively studied cardiac biomarkers in canines are cardiac troponin-I (cTnI) and B-type natriuretic peptide (BNP) concerned with myocardial injury. Recently galectin-3 and interleukin 1 receptor-like 1 protein (ST2) have been reported to be suitable cardiac biomarkers for human patients but, their application is limited in canines due to a lack of research. Genes specific for cytoskeletal protein synthesis in cardio-myocytes such as a-cardiac actin, LIM domain binding factor 3 (LDB3), and myosin heavy polypeptide 7 were reported to be associated with dilated cardiomyopathy (DCM) in dogs. DCM in dogs has been linked to metabolites such as 4-guanidinobutanoate, fructose, N-linolenoyltaurine, uracil, 2-methoxyhydroquinone, and 2-methoxyhydroquinone sulfate. Therefore, the metabolomic and genomic approaches to diagnosing cardiac diseases in dogs could be a promising approach in the future. [ABSTRACT FROM AUTHOR]

Licochalcone A (Lico A), a flavonoid found in licorice, possesses multiple pharmacological activities in modulating oxidative stress, glycemia, inflammation, and lipid metabolism. This study aimed to explore the potential mechanism of Lico A in mitigating ferroptosis associated with doxorubicin-induced cardiotoxicity (DIC). Initially, network pharmacology analysis was applied to identify the active components present in licorice and their targeted genes associated with DIC. Subsequently, to assess the role of Lico A in a DIC mouse model, electrocardiograms, myocardial injury markers, and myocardial histopathological changes were measured. Additionally, cell viability, reactive oxygen species (ROS), ferrous iron, glutathione/glutathione disulfide (GSH/GSSG), and malondialdehyde (MDA) were measured in the cell model as hallmarks of ferroptosis. Finally, the PI3K/AKT/MDM2/p53 signaling pathway and ferroptosis-related proteins were measured in vitro and in vivo. Bioinformatics results revealed that 8 major compounds of licorice, including Lico A, primarily regulated targets such as p53 and the PI3K/AKT signaling pathways in DIC. In the mouse model of DIC, Lico A significantly ameliorated serum biomarkers, histopathology, and electrocardiogram abnormalities. Pretreatment with Lico A enhanced the viability of H9C2 cells treated with doxorubicin. Furthermore, Lico A administration resulted in decreased levels of ROS, ferrous iron, and MDA and increased levels of GSH/GSSG. At the protein level, Lico A increased the phosphorylation of PI3K/AKT/MDM2, reduced p53 accumulation, and induced the upregulation of SLC7A11 and GPX4 expression. However, selective inhibition of PI3K/AKT and plasmid-based overexpression of p53 significantly abolished the anti-ferroptosis functions of Lico A. In conclusion, Lico A attenuates DIC by suppressing p53-mediated ferroptosis through activating PI3K/AKT/MDM2 signaling. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to assess the importance of T1-mapping sequences in the diagnosis of hypertrophic cardiomyopathy (HCM) in patients without foci of non-ischemic myocardial injury in classic cardiac magnetic resonance (CMR) sequences. Methods: Two groups were compared: 28 patients with HCM, without any foci of myocardial injury in the late gadolinium enhancement (LGE) sequence (HCM group), and 28 patients without cardiomyopathy (CON group). Classic CMR sequences and T1-mapping sequences were performed. The following parameters were assessed: T1 time of the whole left ventricular myocardium, T1 time of myocardium in the basal, middle and apical layers of the left ventricle, and T1 time in individual segments of the left ventricular myocardium. Myocardial extracellular volume (ECV) was assessed similarly. Results: ECV was significantly higher in the HCM group than in the CON group, for the whole left ventricular myocardium, for the basal and apical layers of the left ventricle, and for segments 1–3, 8, and 13–16 of the left ventricle. Regression analysis showed that a higher left-ventricular mass index (LVMI), a higher body mass index and older age are factors independently associated with a higher ECV of the whole myocardium but only in the group with LVMI ≥ 131.84 g/m2. Conclusion: In patients with HCM without foci of non-ischemic myocardial injury, higher ECV values of the left ventricular myocardium are observed. [ABSTRACT FROM AUTHOR]

Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy, characterized by an increased concentration of catecholamines, free radicals, and inflammatory cytokines, endothelial dysfunction, and increased apoptotic activity. High doses of isoprenaline are used in animal models to induce Takotsubo (TT)-like myocardial injury. The aim of the study was to investigate the antiapoptotic effects of liraglutide in experimental TTS and its role in the NF-κB pathway. Wistar rats were pretreated with liraglutide for 10 days, and on days 9 and 10, TT-like myocardial injury was induced with isoprenaline. After the sacrifice on day 11, hearts were isolated for histopathological and immunohistochemical analysis. Liraglutide reduced isoprenaline-induced cardiomyocyte apoptosis by decreasing cleaved caspase-3 (CC3), BCL-2-associated X protein (BAX), and NF-κB and increasing B-cell lymphoma/leukemia-2 (BCL-2). An increase in NF-κB in isoprenaline-treated rats was in positive correlation with proapoptotic markers (BAX and CC3) and in negative correlation with antiapoptotic marker BCL-2. Liraglutide increased BCL-2 and decreased NF-κB, BAX, and CC3, preserving the same correlations of NF-κB to apoptotic markers. It is concluded that liraglutide protects cardiomyocytes against isoprenaline-induced apoptosis in experimental TT-like myocardial injury through downregulation of the NF-κB pathway. [ABSTRACT FROM AUTHOR]

Introduction: Percutaneous Coronary Intervention (PCI) is a fundamental procedure for coronary artery disease management, yet the risk of adverse events such periprocedural myocardial injury (PMI) persists. This double-blind, randomized clinical trial aims to assess the efficacy of empagliflozin in preventing myocardial injury during PCI procedure. Methods: A total of 90 patients were randomly assigned to two groups A and B; Group A as the intervention group received empagliflozin 25 mg 24 hours before and empagliflozin 10 mg 1-2 hours before coronary intervention and group Bas the control group received placebo at similar intervals. The primary outcome involved comparing baseline, 8-hour, and 24-hour cTnI and baseline and 24-hour hs-CRP levels after PCI in both groups to measure the incidence of periprocedural myocardial injury (PMI) and anti-inflammatory effects of empagliflozin. Results: Baseline cTnI levels with P = 0.955, 8 hours after PCI with P = 0.469, and 24 hours after the intervention with P = 0.980 were not statistically different in the two groups. Baseline levels of hs-CRP in both intervention and control groups were not statistically significantly different (P = 0.982). Also, there was no statistically significant difference in hs-CRP levels 24 hours after PCI in two groups (P = 0.198). Finally, the results showed that MACEs did not occur in any of the groups. Conclusion: The results of this trial could not express the advantages of acute pretreatment with empagliflozin in preventing PCI-related myocardial injury. [ABSTRACT FROM AUTHOR]

Background and Objectives: Carbon monoxide (CO) intoxication is one of the most common causes of poisoning-related deaths and complications. Myocardial injury is an important complication of CO poisoning. In our study, we aimed to evaluate the relationship between the presence and prevalence of fragmented QRS (fQRS) and myocardial injury in patients with CO intoxication. Materials and Methods: We retrospectively evaluated patients who presented to the emergency department of our tertiary care center with CO intoxication between January 2020 and December 2023. In our study, we performed subgroup analyses according to the presence of myocardial injury and fQRS. We evaluated the parameters and risk factors associated with myocardial injury. Results: Myocardial injury was detected in 44 patients, and fQRS was detected in 38 patients. In the myocardial injury (+) group, the fQRS rate was 38.6%, and the median number of leads with fQRS was 3 (2–6) and was significantly higher than in the myocardial injury (−) group (p < 0.001). We found that carboxyhemoglobin had a significant positive correlation with troponin (p = 0.001) and pro-B-type natriuretic peptide (proBNP) (p = 0.009). As a result of multivariate analysis, we determined that age, creatinine, proBNP, fQRS, and ≥3 leads with fQRS are independent risk factors for myocardial injury. Conclusions: Myocardial injury in CO intoxication patients is associated with proBNP, the presence of fQRS, and the number of leads with fQRS. Age, creatinine level, proBNP, the presence of fQRS, and ≥3 leads with fQRS are independent risk factors for myocardial injury in patients with CO intoxication. [ABSTRACT FROM AUTHOR]

Background and Objectives: SARS-CoV-2 affects multiple organ systems, including the cardiovascular system, leading to immediate and long-term cardiovascular complications. Acute myocardial injury is one of the earliest and most common cardiac issues in the acute phase of COVID-19. This study aimed to evaluate the prognostic value of cardiac troponin I (cTnI) levels in predicting in-hospital mortality among hospitalised COVID-19 patients. Materials and Methods: A retrospective observational cohort study included 2019 adult patients hospitalised with a confirmed COVID-19 infection stratified by cTnI levels on admission into three groups: <19 ng/L (1416 patients), 19–100 ng/L (431 patients), and >100 ng/L (172 patients). Myocardial injury was defined as blood serum cTnI levels increased above the 99th percentile upper reference limit. Depersonalised datasets were extracted from digital health records. Statistical analysis included multivariable binary logistic and Cox proportional hazards regressions. Results: Overall, 29.87% of patients experienced acute myocardial injury, which development was associated with age, male sex, chronic heart failure, arterial hypertension, obesity, and chronic kidney disease. Among patients with cTnI levels of 19–100 ng/L, the odds ratio for requiring invasive mechanical ventilation was 3.18 (95% CI 2.11–4.79) and, for those with cTnI > 100 ng/L, 5.38 (95% CI 3.26–8.88). The hazard ratio for in-hospital mortality for patients with cTnI levels of 19–100 ng/L was 2.58 (95% CI 1.83–3.62) and, for those with cTnI > 100 ng/L, 2.97 (95% CI 2.01–4.39) compared to patients with normal cTnI levels. Conclusions: Increased cardiac troponin I, indicating myocardial injury, on admission is associated with a more adverse clinical disease course, including a higher likelihood of requiring invasive mechanical ventilation and increased risk of in-hospital mortality. This indicates cardiac troponin I to be a beneficial biomarker for clinicians trying to identify high-risk COVID-19 patients, choosing the optimal monitoring and treatment strategy for these patients. [ABSTRACT FROM AUTHOR]

Myocarditis (MC) is a myocardial inflammatory disease that threats human life. Pitavastatin (Pit) is a unique lipophilic statin with potent effects on lowering plasma total cholesterol and triacylglycerols. It has been reported to have pleiotropic effects, such as reducing inflammation and oxidative stress. However, the regulatory mechanism of Pit in MC remains a mystery. Two MC models were established in vitro (lipopolysaccharides-(LPS)-stimulated H9c2 cells) and in vivo (intraperitoneal injection of LPS in mice). The levels of microRNA-106b-5p (miR-106b-5p) and mitogenactivated protein kinase kinase kinase 2 (MAP3K2) were detected. ELISA was used to analyze in vivo cell inflammatory factors and myocardial injury markers, kits were used to detect the expression of antioxidant enzymes, cell counting kit- 8 (CCK-8) was used to detect cell proliferation, and flow cytometry was used to detect apoptosis. Hematoxylin and eosin (HE) staining was used to detect the pathological changes of myocardial tissue in mice, and TUNEL staining was used to detect in vivo tissue cell apoptosis. The regulatory mechanism of Pit on miR-106b-5p/MAP3K2 was verified by a series of functional rescue experiments. The results demonstrated that in LPS-induced H9c2 cells, antioxidant enzymes decreased and pro-inflammatory factors and cardiac injury markers increased (p<0.05). However, these phenomenons were attenuated by Pit pretreatment. LPS decreased miR-106b-5p and elevated MAP3K2 in H9c2 cells, while Pit could recover their expression patterns (p<0.05). MAP3K2 was confirmed as a target gene of miR-106b-5p. Upregulating miR-106b-5p or downregulating MAP3K2 could further promote the protective effect of Pit, and vice versa (p<0.05). In addition, in the LPS-induced MC mouse model, histological examination showed that Pit significantly improved the myocardial tissue damage in MC mice, while downregulating miR-106b-5p or upregulating MAP3K2 could suppress the ameliorative effect of Pit (p<0.05). In conclusion, our study demonstrated that Pit ameliorates myocardial injury by suppressing myocardial inflammation and oxidative stress by modulating the miR-106b-5p/MAP3K2 axis. [ABSTRACT FROM AUTHOR]

Background: Myocardial injury is common in severe fever with thrombocytopenia syndrome (SFTS) patients. Currently, research on the prognostic value of cardiac troponin I (cTnI) for predicting the mortality of SFTS patients, especially death within 7 days is limited. Methods: Between May 2011 and October 2022, clinical and laboratory data on admission of consecutive SFTS cases were collected from six medical centres in China. The clinical endpoint was in-hospital all-cause death within seven days. Risk factors of myocardial injury and death were analysed using multivariable regression models. Prognostic models were established using Cox regression and performance of indicators was evaluated in terms of calibration, discrimination. Results: A total of 1379 laboratory-confirmed patients were enrolled, in which 686 subjects were included for analysis. The median age was 66 years, with 48.1% of male. Eighty-seven patients died within seven days and 396 patients diagnosed with myocardial injury during hospitalization. Non-survivors had significant higher levels of cardiac indices than survivors, including cTnI, aspartic transaminase (AST) and lactate dehydrogenase (LDH). Elevated levels of cTnI (HR = 1.058, 95% CI:1.032– 1.085), AST (HR = 1.191, 95% CI:1.150– 1.234) and LDH (HR = 1.019, 95% CI:1.009– 1.029) predicted risk of early in-hospital mortality. cTnI model performed best, with area under curve of 0.850 (0.774– 0.926) and concordance index of 0.842, respectively. Statistical differences were found between high and low levels of cTnI for mortality (P< 0.001) using 0.35 ng/mL as the optimal cut-off. Conclusion: The risk of early in-hospital death can be predicted by cTnI. Clinical doctors should remind vigilant concerning the elevation of cardiac enzyme as soon as possible. [ABSTRACT FROM AUTHOR]

miR-135 is a highly conserved miRNA in mammals and includes miR-135a and miR-135b. Recent studies have shown that miR-135b is a key regulatory factor in cardio-cerebrovascular diseases. It is involved in regulating the pathological process of myocardial infarction, myocardial ischemia/reperfusion injury, cardiac hypertrophy, atrial fibrillation, diabetic cardiomyopathy, atherosclerosis, pulmonary hypertension, cerebral ischemia/reperfusion injury, Parkinson's disease, and Alzheimer's disease. Obviously, miR-135b is an emerging player in cardio-cerebrovascular diseases and is expected to be an important target for the treatment of cardio-cerebrovascular diseases. However, the crucial role of miR-135b in cardio-cerebrovascular diseases and its underlying mechanism of action has not been reviewed. Therefore, in this review, we aimed to comprehensively summarize the role of miR-135b and the signaling pathway mediated by miR-135b in cardio-cerebrovascular diseases. Drugs targeting miR-135b for the treatment of diseases and related patents, highlighting the importance of this target and its utility as a therapeutic target for cardio-cerebrovascular diseases, have been discussed.

Summary: Background: We aimed to study the clinical characteristics, myocardial injury, and longitudinal outcomes of COVID-19 vaccine-associated myocarditis (C-VAM). Methods: In this longitudinal retrospective observational cohort multicenter study across 38 hospitals in the United States, 333 patients with C-VAM were compared with 100 patients with multisystem inflammatory syndrome in children (MIS-C). We included patients ≤30 years of age with a clinical diagnosis of acute myocarditis after COVID-19 vaccination based on clinical presentation, abnormal biomarkers and/or cardiovascular imaging findings. Demographics, past medical history, hospital course, biochemistry results, cardiovascular imaging, and follow-up information from April 2021 to November 2022 were collected. The primary outcome was presence of myocardial injury as evidenced by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging. Findings: Patients with C-VAM were predominantly white (67%) adolescent males (91%, 15.7 ± 2.8 years). Their initial clinical course was more likely to be mild (80% vs. 23%, p 15 years, OR 2.74 [95% CI: 1.28, 5.83, p = 0.009]) and when C-VAM occurred after the first or second dose as compared to the third dose of mRNA vaccine. Mid-term clinical outcomes of C-VAM at a median follow-up of 178 days (IQR 114–285 days) were reassuring. No cardiac deaths or heart transplantations were reported until the time of submission of this report. LGE persisted in 60% of the patients at follow up. Interpretation: Myocardial injury at initial presentation and its persistence at follow up, despite a mild initial course and favorable mid-term clinical outcome, warrants continued clinical surveillance and long-term studies in affected patients with C-VAM. Funding: The U.S. Food and Drug Administration.

Abstract Background Manually derived electrocardiographic (ECG) parameters were not associated with mortality in mechanically ventilated COVID‐19 patients in earlier studies, while increased high‐sensitivity cardiac troponin‐T (hs‐cTnT) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) were. To provide evidence for vectorcardiography (VCG) measures as potential cardiac monitoring tool, we investigated VCG trajectories during critical illness. Methods All mechanically ventilated COVID‐19 patients were included in the Maastricht Intensive Care Covid Cohort between March 2020 and October 2021. Serum hs‐cTnT and NT‐proBNP concentrations were measured daily. Conversion of daily 12‐lead ECGs to VCGs by a MATLAB‐based script provided QRS area, T area, maximal QRS amplitude, and QRS duration. Linear mixed‐effect models investigated trajectories in serum and VCG markers over time between non‐survivors and survivors, adjusted for confounders. Results In 322 patients, 5461 hs‐cTnT, 5435 NT‐proBNP concentrations and 3280 ECGs and VCGs were analyzed. Non‐survivors had higher hs‐cTnT concentrations at intubation and both hs‐cTnT and NT‐proBNP significantly increased compared with survivors. In non‐survivors, the following VCG parameters decreased more when compared to survivors: QRS area (−0.27 (95% CI) (−0.37 to −0.16, p

Abstract Doxorubicin (DOX) is an effective anticancer agent, but its clinical utility is constrained by dose‐dependent cardiotoxicity, partly due to cardiomyocyte ferroptosis. However, the progress of developing cardioprotective medications to counteract ferroptosis has encountered obstacles. Protosappanin A (PrA), an anti‐inflammatory compound derived from hematoxylin, shows potential against DOX‐induced cardiomyopathy (DIC). Here, it is reported that PrA alleviates myocardial damage and dysfunction by reducing DOX‐induced ferroptosis and maintaining mitochondrial homeostasis. Subsequently, the molecular target of PrA through proteome microarray, molecular docking, and dynamics simulation is identified. Mechanistically, PrA physically binds with ferroptosis‐related proteins acyl‐CoA synthetase long‐chain family member 4 (ACSL4) and ferritin heavy chain 1 (FTH1), ultimately inhibiting ACSL4 phosphorylation and subsequent phospholipid peroxidation, while also preventing FTH1 autophagic degradation and subsequent release of ferrous ions (Fe2+) release. Given the critical role of ferroptosis in the pathogenesis of ischemia‐reperfusion (IR) injury, this further investigation posits that PrA can confer a protective effect against IR‐induced cardiac damage by inhibiting ferroptosis. Overall, a novel pharmacological inhibitor is unveiled that targets ferroptosis and uncover a dual‐regulated mechanism for cardiomyocyte ferroptosis in DIC, highlighting additional therapeutic options for chemodrug‐induced cardiotoxicity and ferroptosis‐triggered disorders.

Background Higher cardiac troponin is associated with worse outcomes in patients with acute heart failure. The significance of repeat measurements over hours remains unclear. We assessed whether a repeat measurement and the Δ between measurements of high‐sensitivity cardiac troponin I (hs‐cTnI) were associated with outcomes in hypervolemic patients with acute heart failure without acute coronary syndrome. Methods and Results We analyzed 582 individuals from AKINESIS (Acute Kidney Injury Neutrophil Gelatinase‐Associated Lipocalin Evaluation of Symptomatic Heart Failure Study) with hs‐cTnI measured ≤12 hours from admission and repeated ≤6 hours thereafter. Associations between hs‐cTnI levels and their Δ with short‐term (death, intensive care unit admission, receipt of inotropes, or positive pressure ventilation during hospitalization) and long‐term (death or heart failure readmission within 1 year) outcomes were assessed. The average age was 69±13 years, 62% were men, 65% were White, 46% had coronary artery disease, and 22% had chest pain. Median hs‐cTnI levels were 27 (interquartile range [IQR], 13–62) ng/L initially and 28 (IQR, 14–68) ng/L subsequently, with a Δ of 0 [IQR, −2 to 4] ng/L over 3.4±1 hours. Only the second measurement was associated with short‐term outcomes (odds ratio, 1.14 per 2‐fold higher [95% CI, 1.02–1.28]). Both individual measurements and the Δ were associated with long‐term outcomes (hazard ratios, 1.09, 1.12, and 1.16 for first, second, and Δ, respectively). Associated risk for the first and second measurements were not constant over the year but highest early after being measured and decreased over 1 year. Conclusions Repeat measurements of hs‐cTnI over hours can identify individuals with acute heart failure without acute coronary syndrome at risk for short‐ and long‐term outcomes.

ObjectiveTo investigate the incidence of myocardial injury in children with critically ill children without primary cardiac disease and the association between elevated cardiac troponin I (cTnl) and creatine kinase MB (CK-MB) concentrations and disease progression and prognosis to guide early treatment.MethodsThe serum cTnI and CK-MB concentrations of 292 children with critically ill children without primary cardiac disease in Yantai Yuhuangding Hospital between January 2021 and January 2024 were retrospectively analyzed within 24 h after entering the Pediatric Intensive Care Unit (PICU). The children were divided into normal and abnormal groups according to the myocardial marker results. The abnormal group was further divided into the cTnI-elevated, CK-MB-elevated, single-elevated (cTnI- or CK-MB-elevated) and double-elevated (cTnI- and CK-MB-elevated) groups. The differences in the clinical indicators and their relationships with prognosis for the groups were compared.ResultsThe incidence of myocardial injury among the critically ill children without primary cardiac disease was 55.1%. The incidence of myocardial injury in children with infectious diarrhea combined with moderate and severe dehydration reached 85.19%. The pediatric critical illness score; frequency of use of vasoactive drugs; hypotension, shock, heart failure, respiratory failure, and multiple organ dysfunction syndrome; and mortality indexes differed significantly for the normal and abnormal myocardial marker groups (P