Anthracycline therapy induces an early decline of cardiac contractility in low-risk patients with breast cancer.

AIMS: Cancer therapy-related cardiac dysfunction (CTRCD) is a dreaded complication of anthracycline therapy. CTRCD most frequently appears in patients with cardiovascular risk factors (CVR) or known cardiovascular disease. However, limited data exist on incidence and course of anthracycline-induced CTRCD in patients without preexisting risk factors. We therefore aimed to longitudinally investigate a cohort of young women on anthracycline treatment due to breast cancer without cardiovascular risk factors or known cardiovascular disease (NCT03940625). METHODS AND RESULTS: We enrolled 59 women with primary breast cancer and scheduled anthracycline-based therapy, but without CVR or preexisting cardiovascular disease. We conducted a longitudinal assessment before, immediately and 12 months after cancer therapy with general laboratory, electrocardiograms, echocardiography and cardiovascular magnetic resonance (CMR), including myocardial relaxometry with T1, T2 and extracellular volume mapping. Every single patient experienced a drop in CMR-measured left ventricular ejection fraction (LVEF) of 6 ± 3% immediately after cancer therapy. According to the novel definition 32 patients (54.2%) developed CTRCD after 12 months defined by reduction in LVEF, global longitudinal strain (GLS) and/or biomarkers elevation, two of them were symptomatic. Global myocardial T2 relaxation times as well as myocardial mass increased coincidently with a decline in wall-thickening. While T2 values and myocardial mass normalized after 12 months, LVEF and GLS remained impaired. CONCLUSION: In every single patient anthracyclines induce a decline of myocardial contractility, even among patients without pre-existing risk factors for CTRCD. Our data suggest to thoroughly evaluate whether this may lead to an increased risk of future cardiovascular events.

Roles of MDA-LDL/OX-LDL/LOX-1 and TNF-α/TLR4/NF-κB Signaling Pathways in Myocardial Damage by Implantations of Cardiac Pacemakers in Elderly Patients.

INTRODUCTION: Permanent pacemakers are an established treatment for sick sinus syndrome and high-grade atrioventricular block. Permanent cardiac pacemaker implantations may damage the myocardium. OBJECTIVE: This study evaluated markers of myocardial injury, oxidative stress and inflammation in elderly patients with permanent pacemaker implantations. METHODS: Various markers were measured at 1, 2, 3 and 4 months after permanent pacemaker implantations in elderly patients. RESULTS: The levels of high-sensitivity troponin T (hsTnT), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), malondialdehyde-modified low-density lipoprotein (MDA-LDL), oxidized low-density lipoprotein (OX-LDL), tumour necrosis factor-α (TNF-α), toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) were increased in 2-month group compared with control and 1- month groups (P<0.001), and were further increased at 4-month group compared with 2- and 3- month groups after pacemaker implantations (P<0.001). Patients with dual-chamber pacemakers had higher levels of hsTnT, LOX-1, MDA-LDL, OX-LDL, TNF-α, TLR4 and NF-κB than patients with single chamber pacemakers (P<0.001). Patients who underwent the pacemakers with the active fixation leads had raised levels of hsTnT, LOX-1, MDA-LDL, OX-LDL, TNF-α, TLR4 and NF-κB compared patients with pacemakers using the passive fixation leads (P<0.001). Myocardial blood flows in 3-month and 4-month groups were lower than 1-month and 2-month groups (P<0.001). CONCLUSION: Levels of hsTnT, LOX-1, MDA-LDL, OX-LDL, TNF-α, TLR4 and NF-κB were elevated in elderly patients with permanent pacemaker implantations and the activations of oxidative stress and pro-inflammatory signalling pathways may be associated with myocardial damages and ischemia after pacemaker implantations in elderly patients.

Influence of trimetazidine on myocardial injury in mice with diabetic cardiomyopathy.

INTRODUCTION: The prevalence of diabetes mellitus is increasing year by year globally, and diabetic cardiomyopathy (DCM), as the most common complication of type 2 diabetes mellitus, seriously affects the prognosis of patients. Trimetazidine (TMZ), as a drug affecting myocardial energy metabolism, mainly reduces the oxidation rate of ß-oxidation by inhibiting 3-ketoacyl-CoA thiolase (3-KAT), a key enzyme in ß-oxidation of free fatty acid (FFA), so that the energy metabolism substrate of cardiomyocytes preferentially selects glucose rather than fatty acids, increases the content of intracellular adenosine triphosphate (ATP), enhances the contractile function of cardiomyocytes, and improves the state of cellular ischemia and hypoxia. Previous studies have shown that TMZ is closely related to the activation and induction of apoptosis of the MAPK pathway and AMPK pathway, and plays a role in the treatment of diabetic cardiomyopathy, but the specific mechanism is still unclear. OBJECTIVE: This study aims to investigate the impact of TMZ on myocardial damage in mice exhibiting diabetic cardiomyopathy (DCM), and to furnish a laboratory foundation for the clinical treatment of diabetic cardiomyopathy. METHOD: Male db/db mice (6 weeks old, n = 21) and male wild-type (wt) (6 weeks old, n = 20) mice were selected for the study. The wt mice were randomly assigned to the wt group (n = 10) and wt + TMZ group (n = 10), while the remaining db/db mice were randomly allocated to the db/db group (n = 11) and db/db + TMZ group (n = 10). Following 8 weeks of feeding, the wt + TMZ group and db/db + TMZ group received TMZ via gavage, whereas the remaining groups were administered physiological saline. Periodic measurements of blood glucose, blood lipids, and myocardial enzymes were conducted in mice, with samples obtained after the 12th week for subsequent biochemical analysis, myocardial pathology assessment, immunohistochemistry, western blot analysis, and TUNEL staining (TdT-mediated dUTP Nick-End Labeling). RESULT: GLU, TC, TG, LDL-C, and CK-MB levels were significantly higher in db/db mice compared to wt mice (GLU: M ± SD wt 5.94 ± 0.37, db/db 17.63 ± 0.89, p < 0.05, ES = 0.991; TC: M ± SD wt 3.01 ± 0.32, db/db 6.97 ± 0.36, p < 0.05, ES = 0.972; TG: M ± SD wt 0.58 ± 0.2, db/db 1.75 ± 0.14, p < 0.05, ES = 0.920; LDL-C: M ± SD wt 1.59 ± 0.12, db/db 3.87 ± 0.14, p < 0.05, ES = 0.989; CK-MB: M ± SD wt 0.12 ± 0.01, db/db 0.31 ± 0.04, p < 0.05, ES = 0.928). HDL-C levels were significantly lower in db/db mice (M ± SD wt 1.89 ± 0.08, db/db 0.64 ± 0.09, p < 0.05, ES = 0.963). Histopathological analysis confirmed myocardial damage in db/db mice. Treatment with TMZ reduced GLU, TC, TG, LDL-C, and CK-MB levels (p < 0.05, ES > 0.9) and increased HDL-C levels compared to untreated db/db mice. Additionally, TMZ treatment significantly decreased myocardial cell apoptosis (p < 0.05, ES = 0.980). These results demonstrate the efficacy of TMZ in reversing myocardial injury in DCM mice. CONCLUSION: TMZ can mitigate myocardial damage in db/db mice by downregulating the expression of caspase-12, a protein associated with the endoplasmic reticulum stress (ERS) cell apoptosis pathway, consequently diminishing cell apoptosis. This underscores the protective efficacy of TMZ against myocardial damage in mice afflicted with DCM.

Protective effect and mechanism of Qingfei Paidu decoction on myocardial damage mediated by influenza viruses.

Introduction: Significant attention has been paid to myocardial damage mediated by the single-stranded RNA virus. Qingfei Paidu decoction (QFPDD) has been proved to protect the damage caused by the influenza virus A/PR/8/1934 (PR8), but its specific mechanism is unclear. Methods: Molecular biological methods, together with network pharmacology, were used to analyze the effects and underlying mechanism of QFPDD treatment on PR8-induced myocardial damage to obtain insights into the treatment of COVID-19-mediated myocardial damage. Results: Increased apoptosis and subcellular damage were observed in myocardial cells of mice infected by PR8. QFPDD treatment significantly inhibited the apoptosis and subcellular damage induced by the PR8 virus. The inflammatory factors IFN-ß, TNF-α, and IL-18 were statistically increased in the myocardia of the mice infected by PR8, and the increase in inflammatory factors was prevented by QFPDD treatment. Furthermore, the expression levels or phosphorylation of necroptosis-related proteins RIPK1, RIPK3, and MLKL were abnormally elevated in the group of infected mice, while QFPDD restored the levels or phosphorylation of these proteins. Our study demonstrated that HIF-1α is a key target of QFPDD in the treatment of influenza virus-mediated injury. The HIF-α level was significantly increased by PR8 infection. Both the knockdown of HIF-1α and treatment of the myocardial cell with QFPDD significantly reversed the increased inflammatory factors during infection. Overexpression of HIF-1α reversed the inhibition effects of QFPDD on cytokine expression. Meanwhile, seven compounds from QFPDD may target HIF-1α. Conclusion: QFPDD can ameliorate influenza virus-mediated myocardial damage by reducing the degree of cell necroptosis and apoptosis, inhibiting inflammatory response and the expression of HIF-1α. Thus, our results provide new insights into the treatment of respiratory virus-mediated myocardial damage.

Association of epicardial fat volume with subclinical myocardial damage in patients with type 2 diabetes mellitus.

Background: In type 2 diabetes mellitus (T2DM) patients, left ventricular systolic dyssynchrony (LVSD) with normal left ventricular ejection fraction (LVEF) and normal myocardial perfusion could referred to as subclinical myocardial damage, which is difficult to diagnose at an early stage. Epicardial adipose tissue, a distinctive heart-specific visceral fat, is closely related to various cardiovascular diseases. The objective of this study was to investigate the correlation between epicardial fat volume (EFV) and subclinical myocardial damage in T2DM patients. Methods: This retrospective cross-sectional study included 117 T2DM patients with normal myocardial perfusion by single photon emission computed tomography-computed tomography (SPECT-CT) and normal LVEF by echocardiography. The study was conducted from January 2018 to December 2022. Patient data were collected through electronic medical records including basic patient information, medical history, laboratory tests, and medication data. The EFV was quantified through a non-contrast CT scan. Quantitative indicators of LVSD including phase standard deviation (PSD) and phase histogram bandwidth (PBW) were obtained through phase analysis of the gated rest myocardial perfusion imaging (MPI). Additionally, 83 healthy individuals at the same time were selected to gain the reference threshold of LVSD indicators (13.1° for PSD and 37.6° for PBW). Univariate and multivariable logistic regression models were performed to analyze factors influencing LVSD. A generalized additive model (GAM) was applied to explore the relationship between EFV and LVSD. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of EFV for LVSD. Results: Among all patients, 32 (27.4%) patients had LVSD. Compared with the non-LVSD group, the body mass index (BMI) and EFV were higher in the LVSD group (25.83±2.66 vs. 23.94±3.13 kg/m2; 142.41±44.17 vs. 108.01±38.24 cm3, respectively, both P<0.05). Multivariate regression analysis revealed that EFV was independently associated with LVSD [odds ratio (OR) =1.19; 95% confidence interval (CI): 1.06-1.34; P=0.003]. Age, BMI, incidence of hypertension, and LVSD were increased with tertiles of EFV (all P<0.05). The GAM indicated a linear association between EFV and LVSD. The ROC curve analysis concluded that the area under the curve (AUC) of EFV for predicting subclinical myocardial damage in T2DM patients was 0.732 (95% CI: 0.633-0.831, P<0.001), with the optimal threshold of 122.26 cm3, sensitivity of 71.9%, and specificity of 69.4%. Conclusions: EFV is an independent risk factor for LVSD in T2DM patients with normal LVEF and normal MPI, which could potentially serve as a novel imaging marker and a potential therapeutic target for subclinical myocardial damage.

Association of myocardial injury with adverse long-term survival among cancer patients.

AIMS: Over time, cardiovascular disease (CVD) deaths increasingly exceed those from malignancy among cancer survivors. However, the association of myocardial injury with long-term survival (beyond three years) in cancer patients has not been previously described. METHODS: The National Health and Nutrition Examination Survey high-sensitivity cardiac troponin (hs-cTn) and morbidities databases (1999-2004) were linked with the latest mortality dataset isolating records were respondents reported cancer diagnosis by a healthcare professional. Myocardial injury was then determined by elevated hs-cTn. RESULTS: 16,225,560 weighted records (1,058 unweighted) were included in this observational study, with myocardial injury identified in 14·2%. Those with myocardial injury had progressively worse survival at 5 (51·6% vs. 89·5%), 10 (28·3% vs. 76·0%), and 15 years (12·6% vs. 61·4%) compared to those without myocardial injury. After adjusting for baseline characteristics, those with myocardial injury had an adjusted hazard ratio (aHR) of 2·10 (95% CI 2·09-2·10, p<0·001) for all-cause mortality, 2·23 (2·22-2·24, p<0·001) for cardiovascular mortality, and 1·59 (95% CI 1·59-1·60, p<0·001) for cancer mortality compared to those without myocardial injury. Among patients with no pre-existing CVD, the hs-cTn I Ortho assay was a strong independent predictor of all cause (aHR 6·29, 95% CI 6·25-6·33, p<0·001), CVD (aHR 11·38, 95% CI 11·23-11·54, p<0·001), and cancer (aHR 5·02, 95% CI 4·96-5·07, p<0·001) mortality. CONCLUSIONS: As a marker for myocardial injury, hs-cTn/s were independently associated with worse long-term survival among cancer patients with a stronger relationship with all-cause, cardiovascular, and cancer mortality using hs-cTn I ortho assay.

We conducted an observational analysis using the Unites States' National Health and Nutrition Examination Survey (NHANES) database to examine the association of myocardial injury, as defined by elevated cardiac biomarkers in the form of four different high sensitivity cardiac troponins, with long-term outcome among cancer survivors. Cancer survivors with myocardial injury had progressively worse survival at 5 (51·6% vs. 89·5%), 10 (28·3% vs. 76·0%), and 15 years (12·6% vs. 61·4%) compared to those without myocardial injury.After adjusting for population characteristics including cancer type, the risk of death from any cause among cancer survivors with myocardial injury were more than double that of those without myocardial injury (adjusted hazard ratio of 2·10 (95% CI 2·09­2·10, p<0·001).

The recent advance and prospect of natural source compounds for the treatment of heart failure.

Heart failure is a continuously developing syndrome of cardiac insufficiency caused by diseases, which becomes a major disease endangering human health as well as one of the main causes of death in patients with cardiovascular diseases. The occurrence of heart failure is related to hemodynamic abnormalities, neuroendocrine hormones, myocardial damage, myocardial remodeling etc, lead to the clinical manifestations including dyspnea, fatigue and fluid retention with complex pathophysiological mechanisms. Currently available drugs such as cardiac glycoside, diuretic, angiotensin-converting enzyme inhibitor, vasodilator and ß receptor blocker etc are widely used for the treatment of heart failure. In particular, natural products and related active ingredients have the characteristics of mild efficacy, low toxicity, multi-target comprehensive efficacy, and have obvious advantages in restoring cardiac function, reducing energy disorder and improving quality of life. In this review, we mainly focus on the recent advance including mechanisms and active ingredients of natural products for the treatment of heart failure, which will provide the inspiration for the development of more potent clinical drugs against heart failure.

Regulation of Sirtuins in Sepsis-Induced Myocardial Damage: The Underlying Mechanisms for Cardioprotection.

Sepsis is defined as "a life-threatening organ dysfunction caused by a dysregulated host response to infection". Although the treatment of sepsis has evolved rapidly in the last few years, the morbidity and mortality of sepsis in clinical treatment are still climbing. Sirtuins (SIRTs) are a highly conserved family of histone deacetylation involved in energy metabolism. There are many mechanisms of sepsis-induced myocardial damage, and more and more evidence show that SIRTs play a vital role in the occurrence and development of sepsis-induced myocardial damage, including the regulation of sepsis inflammation, oxidative stress and metabolic signals. This review describes our understanding of the molecular mechanisms and pathophysiology of sepsis-induced myocardial damage, with a focus on disrupted SIRTs regulation. In addition, this review also describes the research status of related therapeutic drugs, so as to provide reference for the treatment of sepsis.

A Case of Severe Rhabdomyolysis, Acute Myocardial Damage and Multi-Organ Dysfunction Syndrome in a Patient with Novel Coronavirus Pneumonia.

In recent years, healthcare systems worldwide have faced the challenge of the severe COVID-19 pandemic. However, cases of severe rhabdomyolysis, acute myocardial damage, and multiple organ dysfunction syndrome (MODS) caused by COVID-19 are currently rare. This report presents a case of severe rhabdomyolysis, acute myocardial damage, and MODS caused by COVID-19. The patient was treated at The University of Hong Kong-Shenzhen Hospital. The purpose of this report is to aid clinicians in quickly identifying and treating similar cases, ultimately improving patient outcomes.

Characteristics of deceased subjects transported to a postmortem imaging center due to unusual death related to epilepsy.

OBJECTIVE: Patients with epilepsy have high risk of experiencing uncommon causes of death. This study aimed to evaluate patients who underwent unusual deaths related to epilepsy and identify factors that may contribute to these deaths and may also include sudden unexpected death in epilepsy (SUDEP). METHODS: We analyzed 5291 cases in which a postmortem imaging (PMI) study was performed using plane CT, because of an unexplained death. A rapid troponin T assay was performed using peripheral blood samples. Clinical information including the cause of death suspected by the attending physician, body position, place of death, medical history, and antiseizure medications was evaluated. RESULTS: A total of 132 (2.6%) patients had an obvious history of epilepsy, while 5159 individuals had no history of epilepsy (97.4%). Cerebrovascular disease was the cause of death in 1.6% of patients in the group with epilepsy, and this was significantly lower than that in the non-epilepsy group. However, drowning was significantly higher (9.1% vs. 4.4%). Unspecified cause of death was significantly more frequent in the epilepsy group (78.0% vs. 57.8%). Furthermore, the proportion of patients who demonstrated elevation of troponin T levels without prior cardiac disease was significantly higher in the epilepsy group (37.9% vs. 31.1%). At discovery of death, prone position was dominant (30.3%), with deaths occurring most commonly in the bedroom (49.2%). No antiseizure medication had been prescribed in 12% of cases, while 29.5% of patients were taking multiple antiseizure medications. SIGNIFICANCE: The prevalence of epilepsy in individuals experiencing unusual death was higher than in the general population. Despite PMI studies, no definitive cause of death was identified in a significant proportion of cases. The high troponin T levels may be explained by long intervals between death and examination or by higher incidence of myocardial damage at the time of death. PLAIN LANGUAGE SUMMARY: This study investigated unusual deaths in epilepsy patients, analyzing 5291 postmortem imaging cases. The results showed that 132 cases (2.6%) had a clear history of epilepsy. In these cases, only 22% cases were explained after postmortem examination, which is less than in non-epilepsy group (42.2%). Cerebrovascular disease was less common in the epilepsy group, while drowning was more common. Elevated troponin T levels, which suggest possibility of myocardial damage or long intervals between death and examination, were also more frequent in the epilepsy group compared to non-epilepsy group.

S-100ß level is closely associated with myocardial work in patients with acute ischemic stroke.

BACKGROUND: The more severe the acute stroke is, the more serious myocardial damage is. This study aimed to determine the relationship between myocardial work and S100ß, a quantitative biomarker of active cerebral lesions, in patients with acute ischemic stroke (AIS). METHODS: A total of 63 patients with AIS were examined by myocardial work echocardiography, 4D echocardiography with the measurement of left ventricular (LV) myocardial work, volume and function within 24-48 h of symptom onset, respectively. Their plasma S100ß was measured from a peripheral blood sample within 2-6 h of symptom onset. RESULTS: Patients with elevated S-100ß level had significantly increased ratios of peak early diastolic transmitral filling velocity to peak early diastolic lateral mitral annulus tissue velocity(E/e') and global longitudinal strain (GLS), and significantly reduced global work index(GWI) and global constructive work (GCW) compared with those with normal S-100ß level (p < 0.05). S-100ß positively correlated with E/e'(r = 0.878, p < 0.0001) and GLS (r = 0.511, p = 0.002) but negatively correlated with GWI(r = -0.409, p = 0.034) and GCW(r = -0.353, p = 0.041). S-100ß showed an excellent ability to differentiate if a reduced GWI [cut-off value, 120.79 pg/mL; area under receiver operating characteristic curve (AUC), 1.000; sensitivity, 100%; specificity, 100%], GCW (cut-off value, 120.79 pg/mL;AUC,1.000; sensitivity,100%; specificity, 100%) and an increased E/e' (cut-off value, 91.1 pg/mL;AUC,0.913; sensitivity,80%; specificity, 100%) or not, but poor ability to differentiate if an increased GLS(cut-off value, 91.1 pg/mL; AUC,0.576; sensitivity,63.64%; specificity, 83.33%) or not. CONCLUSION: S-100ß level is closely associated with LV function. It is highly competent in determining an impaired myocardial work in patients with AIS.

Transcatheter aortic valve implantation in severe aortic stenosis does not necessarily reverse left ventricular myocardial damage: data of long-term follow-up.

AIMS: Aortic stenosis (AS) is causing myocardial damage and replacement is mainly indicated based on symptoms. Non-invasive estimation of myocardial work (MW) provides a less afterload-dependent too for assessing myocardial function. We sought to look at the impact of transcatheter aortic valve implantation (TAVI) on the myocardium at long-term follow-up and according to current indications. METHODS AND RESULTS: We conducted an observational, cross-sectional, single-centre study. Patients were selected based on the validated indication for a TAVI. Standardized echocardiographies were repeated. A total of 102 patients were included. The mean age was 85 years, 45% were female, 68% had high blood pressure, and 52% had a coronary disease. One-fifth was suffering from low-flow-low-gradient AS. A follow-up was performed at 22 ± 9.5 months after the TAVI. No TAVI dysfunction was observed. Left ventricular (LV) ejection fraction was stable (62 ± 8%), and global longitudinal strain had improved (-14.0 ± 3.7 vs. -16.0 ± 3.6%, P < 0.0001). No improvement of the MW parameters was noticed (LV global work index 2099 ± 692 vs. 2066 ± 706 mmHg%, P = 0.8, LV global constructive 2463 ± 736 vs. 2463 ± 676 mmHg%, P = 0.8). Global wasted work increased [214 (149; 357) vs. 247 (177; 394) mmHg%, P = 0.0008]. CONCLUSION: In a population of severe symptomatic AS patients who had undergone a TAVI, the non-invasive myocardial indices that assess the LV performance at long-term follow-up did not improve. These results are questioning the timing of the intervention and the need for more attention in the pharmacological management of these AS patients.

Associations of High-Sensitive Cardiac Troponin T in Healthy Newborns and Prolonged Second Stage of Labor, Neonatal and Maternal Factors: A Prospective Study.

INTRODUCTION: High-sensitivity cardiac troponin T (hs-cTnT) is not used routinely as a diagnostic biomarker in newborns. The high precision of hs-cTnT assays increases the ability to determine small differences in cTnT over time and to detect troponin T elevation; thus, we believe that hs-cTnT assays might improve clinical care. We explored the plausible association between hs-cTnT levels (ng/L) in healthy newborns and prolonged second stage of labor, neonatal, and maternal factors. METHODS: A prospective study was performed among healthy newborns in the Obstetrics and Gynecology Department at Hillel Yaffe Medical Center in Israel in January-June 2021. The sociodemographic characteristics of the participants, maternal age, gravidity, parity, Pitocin use, epidural analgesia, and neonatal anemia were obtained from the electronic medical records. Gestational age was determined by ultrasound biometric measurements. We classified second-stage labor as normal or prolonged using the WHO guidelines. Samples from umbilical cord blood were drawn using syringes rinsed with anticoagulant by a specialist in pediatrics. The remaining blood was used to determine hs-cTnT levels (ng/L), which was defined as a continuous quantitative variable with the median value and the 25th-75th percentiles. RESULTS: Overall, 184 cord blood samples were performed from healthy newborns (60.6% males) with a median hs-cTnT of 39.03 (25th-75th percentiles = 30.53-54.09) ng/L. A multivariable linear regression model showed no significant association between neonatal anemia and hs-cTnT levels (ng/L) (p = 0.8). Gestational age (B coefficient -4.24, p < 0.001) and gravidity (B coefficient -2.41, p = 0.03) were negatively associated with hs-cTnT levels (ng/L), while Pitocin use (B coefficient 6.91, p = 0.04) and prolonged second stage of labor (B coefficient 18.07, p = 0.02) were positively associated with hs-cTnT levels (ng/L). CONCLUSIONS: High hs-cTnT levels (ng/L) were documented in the cord blood of healthy newborns. Hs-cTnT levels were positively correlated with a prolonged second stage of labor and Pitocin use and negatively correlated with longer gestational age and higher gravidity. Hs-cTnT may signify labor-related fetal distress. A larger surveillance study is mandatory to establish this correlation and assess for possible prognostic significance of elevated hs-cTnT in this context.

Incidence of myocardial injury in patients submitted to carotid endarterectomy.

Myocardial injury following noncardiac surgery (MINS) is associated with higher mortality and major adverse cardiovascular event rates in the short- and long-term in patients undergoing carotid endarterectomy (CEA). However, its incidence is still unclear in this subset of patients. Therefore, this systematic review with meta-analysis aims to determine the incidence of MINS in patients undergoing CEA. Three electronic databases MEDLINE, Scopus, and Web of Science were used to search for studies assessing the occurrence of MINS in the postoperative setting of patients undergoing CEA. The incidence of MINS was pooled by random-effects meta-analysis, with sources of heterogeneity being explored by meta-regression and subgroup analysis (general anesthesia vs. regional anesthesia). Assessment of studies' quality was performed using National Heart, Lung, and Blood Institute Study Quality Assessment Tool, and Risk of Bias 2 tools. Twenty studies were included, with a total of 117,933 participants. Four of them were RCTs, while the remaining were cohort studies. All observational cohorts had an overall high risk of bias, except for Pereira Macedo et al. Three of them had repeated population, thus only data from the most recent one was considered. On the other hand, all RCT had an overall low risk of bias. In patients under regional anesthesia, the incidence of MINS in primary studies ranged between 2% and 15.3%, compared to 0-42.5% for general anesthesia. The meta-analytical incidence of MINS after CEA was of 6.3% [95% CI 2.0-10.6%], but severe heterogeneity was observed (I2=99.1%). MINS appears to be relatively common among patients undergoing CEA. The observed severe heterogeneity points to the need for further larger studies adopting consistent definitions of MINS and equivalent cut-off values.

Echinacoside Prevents Sepsis-Induced Myocardial Damage via Targeting SOD2.

Echinacoside (ECH) is a prominent naturally occurring bioactive compound with effects of alleviating myocardial damage. We aimed to explore the beneficial effects of ECH against sepsis-induced myocardial damage and elucidate the potential mechanism. Echocardiography and Masson staining demonstrated that ECH alleviates cardiac function and fibrosis in the cecal ligation and puncture (CLP) model. Transcriptome profiling and network pharmacology analysis showed that there are 51 overlapping targets between sepsis-induced myocardial damage and ECH. Subsequently, chemical carcinogenesis-reactive oxygen species (ROS) were enriched in multiple targets. Wherein, SOD2 may be the potential target of ECH on sepsis-induced myocardial damage. Polymerase chain reaction results showed that ECH administration could markedly increase the expression of SOD2 and reduce the release of ROS. Combined with injecting the inhibitor of SOD2, the beneficial effect of ECH on mortality, cardiac function, and fibrosis was eliminated, and release of ROS was increased after inhibiting SOD2. ECH significantly alleviated myocardial damage in septic mice, and the therapeutic mechanism of ECH is achieved by upregulating SOD2 which decreased the release of ROS.

Daño miocárdico en la COVID-19 / Myocardial Damage in COVID-19

Introducción: La enfermedad por coronavirus ha causado daño miocárdico, razón que ha impactado en las ciencias médicas por lo que ha sido motivo de investigación. Objetivo: Mostrar a través de resultados de recientes investigaciones, los mecanismos mediante los cuales el virus SARS-CoV-2 produce daño miocárdico en los pacientes afectados por la COVID-19, y su influencia en el pronóstico a corto y largo plazo. Métodos: Se realizó una búsqueda bibliográfica de la literatura médica actualizada sobre el tema publicada en idioma inglés y español, indexado en varias bases de datos en el período comprendido de mayo de 2019 a mayo de 2022. De un total de 198 artículos en la revisión, cumplieron con los criterios de selección 78 artículos. Se excluyeron los que no contenían información precisa en cuanto al daño miocárdico provocado por el SARS-CoV-2. Resultados: Se han descrito varios mecanismos que pueden ser los desencadenantes entre los que se destacan: daño directo por angiotensina II, lesión inducida por hipoxia, daño microvascular miocárdico y síndrome de respuesta inflamatoria sistémica. Conclusiones: Los diferentes mecanismos por los cuales el virus SARS-CoV-2 produce daño miocárdico, hacen que los pacientes con la COVID-19 tengan más probabilidades de sufrir una lesión miocárdica. Las manifestaciones clínicas en pacientes con la COVID-19 como miocarditis, insuficiencia cardíaca, arritmias cardíacas, síndrome coronario agudo y derrame pericárdico, son más comunes en pacientes con antecedentes de enfermedad cardiovascular que desfavorecen su pronóstico(AU)

Introduction: Coronavirus disease has caused myocardial damage. This reality has impacted medical sciences and it has been the subject of research. Objective: To show, through the results of recent research, the mechanisms by which the SARS-CoV-2 virus produces myocardial damage in patients affected by COVID-19, and its influence on short- and long-term prognosis. Methods: A bibliographic search was carried out of the updated medical literature on the topic published in English and Spanish, indexed in several databases from May 2019 to May 2022. One hundred ninety-eight articles were included in the review, only 78 met the selection criteria. Those that did not contain precise information regarding myocardial damage caused by SARS-CoV-2 were excluded. Results: Several mechanisms have been described as probable triggers, standing out direct damage by angiotensin II, hypoxia-induced injury, myocardial microvascular damage and systemic inflammatory response syndrome. Conclusions: The different mechanisms by which SARS-CoV-2 virus produces myocardial damage make COVID-19 patients more likely to suffer myocardial injury. Clinical manifestations in COVID-19 patients such as myocarditis, heart failure, cardiac arrhythmias, acute coronary syndrome and pericardial effusion are more common in patients with history of cardiovascular disease, which do not favors their prognosis(AU)

SNHG1/miR-21 axis mediates the cardioprotective role of aloin in sepsis through modulating cardiac cell viability and inflammatory responses.

BACKGROUND: Aloin has cardioprotective effects, however, its cardioprotective role in sepsis remains unclear. This study aimed to analyze whether aloin could prevent sepsis-related myocardial damage and explore the underlying mechanisms by examining the expression of long-noncoding RNA (lncRNA) SNHG1 and microRNA-21 (miR-21). METHODS: The interaction of SNHG1 with miR-21 was identified by dual-luciferase reporter assay. The levels of SNHG1 and miR-21 were measured by real-time quantitative PCR. The cardioprotective function of aloin was assessed in a sepsis animal model, which was induced by cecal ligation and puncture, and in a myocardial injury cell model in H9C2 cells stimulated by lipopolysaccharide. Myocardial injury biomarker levels and hemodynamic indicators in mice model were measured to evaluate cardiac function. The viability of H9C2 cells was assessed by cell counting kit-8 assay. Inflammatory cytokine levels were examined by an ELISA method. RESULTS: Decreased SNHG1 and increased miR-21 were found in sepsis patients with cardiac dysfunction, and they were negatively correlated. Aloin significantly attenuated myocardial damage and inflammatory responses of mice model, and increased the viability and suppressed inflammation in H9C2 cell model. In addition, SNHG1 expression was upregulated and miR-21 expression was downregulated by aloin in both mice and cell models. Moreover, in mice and cell models, SNHG1/miR-21 axis affected sepsis-related myocardial damage, and mediated the cardioprotective effects of aloin. CONCLUSION: Our findings indicated that aloin exerts protective effects in sepsis-related myocardial damage through regulating cardiac cell viability and inflammatory responses via regulating the SNHG1/miR-21 axis.

Activation of cannabinoid receptors 2 alleviates myocardial damage in cecal ligation and puncture-induced sepsis by inhibiting pyroptosis.

BACKGROUND: It has been reported that cannabinoid receptors 2 (CB2 receptors) play an important role in the pathophysiological process of sepsis, which may also be associated with the regulation of pyroptosis, an inflammatory programmed cell death. The present study aimed to investigate the protective effect of CB2 receptors on myocardial damage in a model of septic mice by inhibiting pyroptosis. METHODS: The C57BL/6 mice underwent cecal ligation and puncture (CLP) to induce sepsis. All mice were randomly divided into the sham, CLP, or CLP+HU308 group. Blood and heart tissue samples were collected 12 h after surgery. Hematoxylin and eosin staining was used for analyzing histopathological results. Creatine kinase isoenzymes (CK-MB) and IL-1ß were measured using ELISA, while lactate dehydrogenase (LDH) level was determined using photoelectric colorimetry. The expression levels of CB2 receptors and pyroptosis-associated proteins (NLRP3, caspase-1, and GSDMD) were measured using western blotting. The location and distribution of CB2 receptors and caspase-1 in myocardial tissues were assessed by immunofluorescence. TUNEL staining was used to quantify the number of dead cells in myocardial tissues. RESULTS: The CLP procedure increased CB2 receptor expression in mice. CB2 receptors were located in myocardial macrophages. Activating CB2 receptors decreased the levels of myocardial damage mediator LDH, CK-MB, and inflammatory cytokine IL-1ß. The results also showed that CLP increased the pyroptosis in myocardial tissues, while CB2 agonist HU308 inhibited pyroptosis by decreasing the level of NLRP3 and activating caspase-1 and GSDMD. CONCLUSIONS: CB2 receptor activation has a protective effect on the myocardium of mice with sepsis by inhibiting pyroptosis.

Study on the Common Molecular Mechanism of Metabolic Acidosis and Myocardial Damage Complicated by Neonatal Pneumonia.

Pneumonia is a common clinical disease in the neonatal period and poses a serious risk to infant health. Therefore, the understanding of molecular mechanisms is of great importance for the development of methods for the rapid and accurate identification, classification and staging, and even disease diagnosis and therapy of pneumonia. In this study, a nontargeted metabonomic method was developed and applied for the analysis of serum samples collected from 20 cases in the pneumonia control group (PN) and 20 and 10 cases of pneumonia patients with metabolic acidosis (MA) and myocardial damage (MD), respectively, with the help of ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). The results showed that compared with the pneumonia group, 23 and 21 differential metabolites were identified in pneumonia with two complications. They showed high sensitivity and specificity, with the area under the curve (ROC) of the receiver operating characteristic curve (ROC) larger than 0.7 for each differential molecule. There were 14 metabolites and three metabolic pathways of sphingolipid metabolism, porphyrin and chlorophyll metabolism, and glycerophospholipid metabolism existing in both groups of PN and MA, and PN and MD, all involving significant changes in pathways closely related to amino acid metabolism disorders, abnormal cell apoptosis, and inflammatory responses. These findings of molecular mechanisms should help a lot to fully understand and even treat the complications of pneumonia in infants.