Prognostic Value of Segmental Strain After ST-Elevation Myocardial Infarction: Insights From the EARLY Assessment of MYOcardial Tissue Characteristics by Cardiac Magnetic Resonance (EARLY-MYO-CMR) Study.

BACKGROUND: The prognostic value of left ventricular segmental strain (SS) in ST-elevation myocardial infarction (STEMI) remains unclear. HYPOTHESIS: To assess the prognostic value and application of SS. STUDY TYPE: Retrospective analysis of a prospective registry. POPULATION: Five hundred and forty-four patients after STEMI (500 in Cohort 1, 44 in Cohort 2). FIELD STRENGTH/SEQUENCE: 3 T, balanced steady-state free precession, gradient echo, and gradient echo contrast-enhanced images. ASSESSMENT: Participants underwent cardiac MR during the acute phase after STEMI. Infarct-related artery (IRA) strain was determined based on SS obtained from cine images. The primary endpoint was the composite of major adverse cardiovascular events (MACEs) after 8 years of follow-up. In Cohort 2, SS stability was assessed by MR twice within 8 days. Contrast and non-contrast risk models based on SS were established, leading to the development of an algorithm. STATISTICAL TEST: Student's t-test, Mann-Whitney U-test, Cox and logistic regression, Kaplan-Meier analysis, net reclassification index (NRI). P < 0.05 was considered significant. RESULTS: During a median follow-up of 5.2 years, 83 patients from Cohort 1 experienced a MACE. Among SS, IRA peak circumferential strain (IRA-CS) was an independent factor for MACEs (adjusted hazard ratio 1.099), providing incremental prognostic value (NRI 0.180, P = 0.10). Patients with worse IRA-CS (>-8.64%) demonstrated a heightened susceptibility to MACE. Additionally, IRA-CS was significantly associated with microvascular obstruction (MVO) (adjusted odds ratio 1.084) and infarct size (r = 0.395). IRA-CS showed comparable prognostic effectiveness to global peak circumferential strain (NRI 0.100, P = 0.39), also counterbalancing contrast and non-contrast risk models (NRI 0.205, P = 0.05). In Cohort 2, IRA-CS demonstrated stability between two time points (P = 0.10). Based on risk models incorporating IRA-CS, algorithm "HJKL" was preliminarily proposed for stratification. DATA CONCLUSIONS: IRA-CS is an important prognostic factor, and an algorithm based on it is proposed for stratification. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

The interaction between hyperuricemia and low-density lipoprotein cholesterol increases the risk of 1-year post-discharge all-cause mortality in ST-segment elevation myocardial infarction patients.

BACKGROUND AND AIMS: Hyperuricemia is a known risk factor for cardiovascular diseases, but little is known on whether the association between hyperuricemia and poor outcomes in ST-segment elevation myocardial infarction (STEMI) is modified by low-density lipoprotein cholesterol (LDL-c). This study aimed to investigate the effect of the interaction between hyperuricemia and LDL-c on the risk of 1-year post-discharge all-cause mortality in STEMI patients. METHODS AND RESULTS: A total of 1396 STEMI patients were included. Cox proportional hazards models were used to determine the association between hyperuricemia and 1-year all-cause mortality in the overall population and subgroups stratified based on LDL-c levels (<3.0 mmol/L or ≥3.0 mmol/L). Multivariate analysis indicated that hyperuricemia was associated with 1-year mortality (HR: 2.66; 95% CI: 1.30-5.47; p = 0.008). However, the prognostic effect of hyperuricemia was only observed in patients with LDL-c level ≥3.0 mmol/L (HR: 12.90; 95% CI: 2.98-55.77; p < 0.001), but not in those with LDL-c level <3.0 mmol/L (HR: 0.91, 95% CI: 0.30-2.79, p = 0.875). The interaction between hyperuricemia and LDL-c levels had a significant effect on 1-year mortality. CONCLUSION: Hyperuricemia was associated with increased 1-year post-discharge mortality in patients with LDL-c level≥ 3.0 mmol/L, but not in those with LDL-c level< 3.0 mmol/L.

Sclareol attenuates angiotensin II-induced cardiac remodeling and inflammation via inhibiting MAPK signaling.

Chronic inflammation plays an important role in hypertensive heart failure. Suppressing angiotensin II (Ang II)-induced cardiac inflammation may contribute to the treatment of hypertension-associated heart failure. Sclareol, a natural product initially isolated from the leaves and flowers of Salvia sclarea, possesses antiinflammatory and immune-regulation activity in various systems. However, its effect on Ang II-induced cardiac remodeling remains unknown. In this study, we have explored the potential effects of sclareol on Ang II-induced heart failure. In vivo experiments were conducted in mice with Ang II-pump infusion for 28 days. Sclareol administration at 5 mg·kg-1 ·d-1 significantly reduced the expression of myocardial injury markers. Sclareol also exerts protective effects against Ang II-induced cardiac dysfunction in mice which is associated with alleviated cardiac inflammation and fibrosis. Transcriptome analysis revealed that inhibition of the Ang II-activated mitogen-activated protein kinase (MAPK) pathway contributed to the protective effect of sclareol. Sclareol inhibits Ang II-activated MAPKs pathway to reduce inflammatory response in mouse hearts and cultured cardiomyocytes. Blockage of MAPKs in cardiomyocytes abolished the antiinflammatory effects of sclareol. In conclusion, we show that sclareol protects hearts against Ang II-induced injuries through inhibiting MAPK-mediated inflammation, indicating the potential use of sclareol in the prevention of hypertensive heart failure.

Celastrol Attenuates Angiotensin II-Induced Cardiac Remodeling by Targeting STAT3.

RATIONALE: Excessive Ang II (angiotensin II) levels lead to a profibrotic and hypertrophic milieu that produces deleterious remodeling and dysfunction in hypertension-associated heart failure. Agents that disrupt Ang II-induced cardiac dysfunction may have clinical utility in the treatment of hypertension-associated heart failure. OBJECTIVE: We have examined the potential effect of celastrol-a bioactive compound derived from the Celastraceae family-on Ang II-induced cardiac dysfunction. METHODS AND RESULTS: In rat primary cardiomyocytes and H9C2 (rat cardiomyocyte-like H9C2) cells, celastrol attenuates Ang II-induced cellular hypertrophy and fibrotic responses. Proteome microarrays, surface plasmon resonance, competitive binding assays, and molecular simulation were used to identify the molecular target of celastrol. Our data showed that celastrol directly binds to and inhibits STAT (signal transducer and activator of transcription)-3 phosphorylation and nuclear translocation. Functional tests demonstrated that the protection of celastrol is afforded through targeting STAT3. Overexpression of STAT3 dampens the effect of celastrol by partially rescuing STAT3 activity. Finally, we investigated the in vivo effect of celastrol treatment in mice challenged with Ang II and in the transverse aortic constriction model. We show that celastrol administration protected heart function in Ang II-challenged and transverse aortic constriction-challenged mice by inhibiting cardiac fibrosis and hypertrophy. CONCLUSIONS: Our studies show that celastrol inhibits Ang II-induced cardiac dysfunction by inhibiting STAT3 activity.

Trimetazidine affects pyroptosis by targeting GSDMD in myocardial ischemia/reperfusion injury.

OBJECTIVE: Trimetazidine (TMZ) exerts a strong inhibitory effect on ischemia/reperfusion (I/R) injury. Inflammation plays a key role in I/R injury. We hypothesized that TMZ may protect cardiomyocytes from I/R injury by inhibiting inflammation. METHODS: The left anterior descending coronary artery was ligated for 30 min followed by 6 h of reperfusion to establish a model of I/R injury. H9c2 cardiomyocytes were subjected to 2 h of hypoxia and 3 h of normoxic conditions to establish a model of hypoxia/reoxygenation (H/R) injury. We monitored the change in pyroptosis by performing Western blot analysis, microscopy and ELISA. RESULTS: I/R and H/R treatment stimulated gasdermin D-N domain (GSDMD-N) expression in cardiomyocytes (sham onefold vs. I/R 2.5-fold; control onefold vs. H/R 2.0-fold). Moreover, TMZ increased the viability of H9c2 cardiomyocytes subjected to H/R treatment (H/R 65.0% vs. H/R + TMZ 85.3%) and reduced the infarct size in vivo (I/R 47.0% vs. I/R + TMZ 28.3%). H/R and I/R treatment increased the levels of TLR4, MyD88, phospho-NF-κB p65 and the NLRP3 inflammasome; however, TMZ reduced the expression of these proteins. Additionally, TMZ inhibited noncanonical inflammasome signaling induced by I/R injury. CONCLUSIONS: In summary, TMZ alleviated pyroptosis induced by myocardial I/R injury through the TLR4/MyD88/NF-κB/NLRP3 inflammasome pathway. Therefore, TMZ represents an alternative treatment for myocardial I/R injury.

Direct cardio-protection of Dapagliflozin against obesity-related cardiomyopathy via NHE1/MAPK signaling.

Obesity is an important independent risk factor for cardiovascular diseases, remaining an important health concern worldwide. Evidence shows that saturated fatty acid-induced inflammation in cardiomyocytes contributes to obesity-related cardiomyopathy. Dapagliflozin (Dapa), a selective SGLT2 inhibitor, exerts a favorable preventive activity in heart failure. In this study, we investigated the protective effect of Dapa against cardiomyopathy caused by high fat diet-induced obesity in vitro and in vivo. Cultured rat cardiomyocyte H9c2 cells were pretreated with Dapa (1, 2.5 µM) for 1.5 h, followed by treatment with palmitic acid (PA, 200 µM) for 24 h. We showed that Dapa pretreatment concentration-dependently attenuated PA-induced cell hypertrophy, fibrosis and apoptosis. Transcriptome analysis revealed that inhibition of PA-activated MAPK/AP-1 pathway contributed to the protective effect of Dapa in H9c2 cells, and this was confirmed by anti-p-cJUN fluorescence staining assay. Using surface plasmon resonance analysis we found the direct binding of Dapa with NHE1. Gain and loss of function experiments further demonstrated the role of NHE1 in the protection of Dapa. In vivo experiments were conducted in mice fed a high fat diet for 5 months. The mice were administered Dapa (1 mg·kg-1·d-1, i.g.) in the last 2 months. Dapa administration significantly reduced the body weight and improved the serum lipid profiles. Dapa administration also alleviated HFD-induced cardiac dysfunction and cardiac aberrant remodeling via inhibiting MAPK/AP-1 pathway and ameliorating cardiac inflammation. In conclusion, Dapa exerts a direct protective effect against saturated fatty acid-induced cardiomyocyte injury in addition to the lowering effect on serum lipids. The protective effect results from negative regulating MAPK/AP-1 pathway in a NHE1-dependent way. The current study highlights the potential of clinical use of Dapa in the prevention of obesity-related cardiac dysfunction.

Long-term Prognostic Value of Cardiac MRI Left Atrial Strain in ST-Segment Elevation Myocardial Infarction.

Background Left atrial (LA) dysfunction is associated with morbidity and mortality. To the knowledge of the authors, the relationship of LA strain to long-term prognosis in participants with ST-segment elevation myocardial infarction (STEMI) is unknown. Purpose To evaluate LA strain as a long-term outcome predictor in STEMI in a prospective, multicenter cardiac MRI cohort. Materials and Methods Participants with STEMI who underwent primary percutaneous coronary intervention and cardiac MRI from 10 sites (EARLY-MYO-CMR registry, clinical trial number NCT03768453) were included. The parent study took place between August 2013 and December 2018. LA longitudinal strain and strain rate parameters were derived from cine cardiac MRI by using an in-house semiautomated method. Major adverse cardiac events (MACEs) were defined as cardiovascular death, myocardial reinfarction, hospitalization for heart failure, and stroke. The association between LA performance and MACE was evaluated by using time-dependent receiver operating characteristic analysis, Kaplan-Meier analysis, and multivariable Cox regression analysis. Results A total of 321 participants (median age, 59 years; age range, 27-75 years; 90% men) were included in this study. During median follow-up of 3.7 years, MACE occurred in 76 participants (23.7%). Participants with impaired reservoir (≤22%) and conduit strain (≤10%) had a higher risk of MACE than those with reservoir strain greater than 22% and conduit strain greater than 10% (P < .001). Reservoir strain (hazard ratio, 0.84; 95% confidence interval: 0.77, 0.91; P < .001) and conduit strain (hazard ratio, 0.81; 95% confidence interval: 0.73, 0.89; P < .001) were independent predictors for MACE after adjustment for known risk factors. Finally, LA reservoir and conduit strains provided incremental prognostic value over traditional outcome predictors (Uno C statistic comparing models, 0.75 vs 0.68; P = .04). Conclusion Assessment of left atrial strain, as a measure of left atrial function, provided incremental prognostic information to established predictors in ST-segment elevation myocardial infarction. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kawel-Boehm and Bremerich in this issue.

Clinical features and prognosis of acute myocardial infarction caused by non-tumor origin coronary artery embolism.

BACKGROUND: Several studies have indicated that acute myocardial infarction (AMI) secondary to coronary artery embolism (CE) has a poor prognosis. However, in the latter studies, CE of tumor origin accounts for a considerable proportion of cases and the clinical features and contribution to overall prognosis of non-tumor CE are unknown and therefore the subject of this study. METHODS: We retrospectively studied 2006 consecutive patients with AMI at our medical center from January 2014 to October 2018. Non-tumor CE was diagnosed based on angiographic, biochemical, and imaging criteria. Patients were divided into two groups: patients without CE (control) and patients with non-tumor CE. RESULTS: Atrial fibrillation was the most frequent etiology (n = 32, 69.6%) in the non-tumor CE group (n = 46). Compared with the control group, the non-tumor CE group had (all p < 0.05): higher incidence of atrial fibrillation; larger left atrial diameter, left ventricular end-diastolic diameter and left ventricular end-systolic diameter; lower left ventricular ejection fraction, ST-segment-elevation myocardial infarction incidence and low density lipoprotein cholesterol level; lower incidence of multivessel coronary stenosis, level of culprit lesion stenosis and proportion of angioplasty; higher ratio of manual thrombectomy and antithrombotic drugs alone therapy; lower thrombolysis in myocardial infarction (TIMI) grade and higher corrected TIMI frame counts (CTFC) after reperfusion; and statistically similar overall survival at median 864 (interquartile range, 413-1272) days. CONCLUSIONS: The overall incidence of non-tumor CE was 2.3%, with atrial fibrillation as its most common etiology. Midterm overall survival was similar between AMI patients secondary to non-tumor CE and those without CE.

Pacing parameters and success rates of permanent His-bundle pacing in patients with narrow QRS: a single-centre experience.

AIMS: High and unstable capture thresholds affect the success rate of permanent His-bundle pacing (HBP). We aimed to introduce the modified techniques during different periods and the corresponding success rate of HBP implantation. METHODS AND RESULTS: Patients from a single centre who had intrinsic QRS < 120 ms and HBP attempts were included in the study. The success rate and pacing parameters were described for three periods based on procedural modifications, i.e. Stage 1 using the conventional HBP procedure (August 2012 to May 2013), Stage 2 with addition of the dual-lead method (June 2013 to October 2014), and Stage 3 with the further addition of stability assessment during fixation (November 2014 to October 2016). The patients with successful permanent HBP were followed. A total of 310 patients were included with the average age of 70.3 ± 10.7 years. The success rate of acute HBP was 84.85%, 98.3%, and 99.20% during Stages 1-3, respectively (P < 0.001). The permanent HBP implantation rates increased from 77.3% during Stage 1 to 85.7% during Stage 2 and 89.6% during Stage 3 (P = 0.07). The acute His-bundle capture threshold reduced from 1.30 ± 0.7 V/0.5 ms during Stage 1 to 1.11 ± 0.6 V/0.5 ms during Stage 2 and further to 0.85 ± 0.51 V/0.5 ms during Stage 3 (P < 0.001). At the 12-month follow-up, the mean change in the HBP threshold decreased from 0.60 ± 0.59 V/0.5 ms during Stage 1 to 0.33 ± 0.39 V/0.5 ms during Stage 3 (P = 0.002). CONCLUSION: The HBP implantation success rate, pacing threshold, and its stability during follow-up were improved by using the dual-lead method and stability assessment techniques.

Inhibition of LncRNA-HRIM Increases Cell Viability by Regulating Autophagy Levels During Hypoxia/Reoxygenation in Myocytes.

Backgrund/Aims: Ischemia reperfusion (I/R) promotes the severity of cardiomyocyte injury. Long noncoding RNAs (LncRNAs) are key regulators in cardiovascular diseases. However, the association between LncRNAs and myocardial I/R injury has not been thoroughly characterized to date. We attempted to clarify the potential biological role of a LncRNA (E230034O05Rik), which we named hypoxia/reoxygenation (H/R) injury-related factor in myocytes (HRIM), by investigating the differential expression of LncRNAs between groups of myocytes exposed to either a normal level of oxygen or to H/R. METHODS: Microarray analysis was used to determine analyze the global differential expression of LncRNAs in H9c2 myocytes exposed either to a normal level of oxygen or to H/R. Target LncRNA levels were further verified in vitro and ex vivo by real-time polymerase chain reaction (qPCR). Cell viability was analyzed using the Cell Counting Kit-8 assay. Autophagy levels were confirmed by Western blotting, transmission electron microscopy, and autophagic double-labeled (mRFP-GFP-LC3) adenovirus analyses. RESULTS: Gene expression profiling revealed that 797 LncRNAs and 1898 mRNAs were differentially expressed in the H/R group compared with the normal oxygen group. Among these LncRNAs and mRNAs, 6 upregulated LncRNAs and 2 downregulated LncRNAs in the H/R group were selected and further validated by qPCR in vitro and ex vivo. Additionally, LncRNA-HRIM was inhibited by specific siRNAs in H9c2 myocytes exposed to H/R. The inhibition of LncRNA-HRIM by siRNA prevented cell death by suppressing excessive autophagic activity in myocytes, This finding suggests a detrimental role of LncRNA-HRIM in the regulation of I/R injury. CONCLUSIONS: LncRNAs are involved in H/R injury of H9c2 myocytes. Inhibition of LncRNA-HRIM increased cell viability by reducing autophagy in myocytes during H/R.

Spontaneous dissection in the left main coronary artery.

We present two cases of spontaneous left main stem coronary artery dissection. One was underdiagnosed with suboptimal percutaneous coronary artery intervention followed by acute vessel occlusion again during the hospitalization. The other one was identified and confirmed by intravascular ultrasound, followed by conservative medical treatment, with completed healing of SCAD during two-month follow up.

MicroRNA-21 protects against cardiac hypoxia/reoxygenation injury by inhibiting excessive autophagy in H9c2 cells via the Akt/mTOR pathway.

MicroRNAs and autophagy play critical roles in cardiac hypoxia/reoxygenation (H/R)-induced injury. Here, we investigated the function of miR-21 in regulating autophagy and identified the potential molecular mechanisms involved. To determine the role of miR-21 in regulating autophagy, H9c2 cells were divided into the following six groups: control group, H/R group, (miR-21+ H/R) group, (miR-21-negative control + H/R) group, (BEZ235+ H/R) group and (miR-21+ BEZ235+ H/R) group. The cells underwent hypoxia for 1 hr and reoxygenation for 3 hrs. Cell count kit-8 was used to evaluate cell function and apoptosis was analysed by Western blotting. Western blotting and transmission electron microscopy were used to investigate autophagy. We found that miR-21 expression was down-regulated, and autophagy was remarkably increased in H9c2 cells during H/R injury. Overexpression of miR-21 with a miR-21 precursor significantly inhibited autophagic activity and decreased apoptosis, accompanied by the activation of the AKT/mTOR pathway. In addition, treatment with BEZ235, a novel dual Akt/mTOR inhibitor, resulted in a significant increase in autophagy and apoptosis. However, we found that miR-21-mediated inhibition of apoptosis and autophagy was partly independent of Akt/mTOR activation, as demonstrated in cells treated with both miR-21 and BEZ235. We showed that miR-21 could inhibit H/R-induced autophagy and apoptosis, which may be at least partially mediated by the Akt/mTOR signalling pathway.

Influence of Body Mass Index on the Activated Clotting Time Under Weight-Based Heparin Dose.

BACKGROUND: Activated clotting time (ACT) has been successfully applied during percutaneous coronary intervention (PCI) to monitor the extent of thrombin inhibition and anti-coagulation from unfractionated heparin (UFH) aiming to reduce the incidence of thrombotic adverse events and hemorrhagic complications. And this investigation was to explore the influence of body mass index (BMI) on ACT in patients received weight-based dose of UFH during PCI treatment. METHODS: 78 male patients undergoing coronary angiography or PCI treatment with a mean age of 63.86 ± 6.89 years were enrolled in this study. The patients were statistically divided into four quartiles according to their BMI. The ACT values were recorded as ACT0 , ACT5 , ACT10 , ACT30 and ACT60 , respectively. Taking the preoperative ACT0 as reference, and the differences of the other ACT values with ACT0 was indicated as ΔACTs. ACT values peaked at 5 min in 33.33% of the patients, 10 min in 51.33% of the patients and 30 min in 15.34% of the patients, respectively. RESULTS: In addition, significant differences were found in overall maximum post-UFH ACT values among all BMI quartiles. UFH doses per blood volume were significantly different among the BMI quartiles, showing a positive association with BMI quartiles; further evidence revealed that the areas under the ΔACT-time curves increased gradually from quartile I to quartile IV. The proportions of ACT60 > 250 s and ACT60 > 300 s were found to be positively correlated with the increased BMI at 60 min after heparin loading. CONCLUSIONS: The results of our study have shown that a standardized dosing nomogram that uses the actual body weight to calculate the heparin doses may result in UFH overdose for patients with higher BMI compared to patients with lower BMI.

Overexpression of microRNA-133a inhibits ischemia-reperfusion-induced cardiomyocyte apoptosis by targeting DAPK2.

To examine microRNA-133a (miR-133a) endogenous expression in cardiomyocytes after ischemia-reperfusion (I/R) injury and study the effects of miR-133a overexpression on I/R injury-induced cardiomyocyte apoptosis. Dual-Luciferase Reporter Assay detected dynamic expression of miR-133a. In an in vitro hypoxia-reoxygenation (HR) injury model and an in vivo rat model of I/R injury, rat cardiomyocytes were transfected with miR-133a mimic to test the effects of miR-133a overexpression on apoptosis. MiR-133a and Death Associated Protein Kinase 2 (DAPK2) mRNA expression was measured using real-time-PCR, and DAPK2 protein expression was detected by western blotting. Annexin V-fluorescein isothiocyanate/propidium iodide (PI) double-staining measured the apoptosis rate in H9C2 cells and transferase dUTP nick end labeling assay quantified the cardiomyocyte apoptosis rate in tissues obtained from in vivo the rat model. DAPK2 is a target of miR-133a. Both in vitro and in vivo results confirmed that after expression of miR-133a mimics, miR-133a levels increased, which was accompanied by decrease in DAPK2 mRNA and protein expression. In H9C2 cells, HR injury caused a sharp decrease in miR-133a expression and a significant upregualtion of DAPK2 mRNA and protein levels. However, exogenous miR-133a expression led to a significant reduction in DAPK2 mRNA and protein levels despite HR injury. Similar results were obtained from in vivo I/R injury model. After HR injury or I/R injury the apoptosis rate of myocardial cells was highly elevated and decreased significantly only after transfection of miR-133a into cardiomyocytes. MiR-133a overexpression may inhibit I/R injury-mediated cardiomyocyte apoptosis by targeting DAPK2, leading to reduced DAPK2 protein, thus miR-133a may potentially have a high therapeutic value in I/R injury.

ST-segment elevation after direct current shock mimicking acute myocardial infarction: a case report and review of the literature.

External direct current (DC) shocks are and have long been commonly used for electrical cardioversion/defibrillation of atrial or ventricular arrhythmias. ST-segment elevation after cardio version with DC is an easily ignored phenomenon, occurring acutely and resolving during the first few minutes postshock. Here, we describe electrocardiographic findings of widespread ST-segment elevation lasting at least 1 hour after DC cardioversion for ventricular defibrillation due to Brugada syndrome and mimicking acute myocardial infarction (AMI). This case of ST-segment elevation without a dynamic and evolving AMI underscores the need to consider other causes of ST-segment elevation.

Cardiomyocyte-expressed farnesoid-X-receptor is a novel apoptosis mediator and contributes to myocardial ischaemia/reperfusion injury.

AIMS: Emerging evidence indicates that nuclear receptors play a critical regulatory role in cardiovascular physiology/pathology. Recently, farnesoid-X-receptor (FXR), a member of the metabolic nuclear receptor superfamily, has been demonstrated to be expressed in vascular cells, with important roles in vascular physiology/pathology. However, the potential cardiac function of FXR remains unclear. We investigated the cardiac expression and biological function of FXR. METHODS AND RESULTS: Farnesoid-X-receptor was detected in both isolated neonatal rat cardiac myocytes and fibroblasts. Natural and synthetic FXR agonists upregulated cardiac FXR expression, stimulated myocyte apoptosis, and reduced myocyte viability dose- and time-dependently. Mechanistic studies demonstrated that FXR agonists disrupted mitochondria, characterized by mitochondrial permeability transition pores activation, mitochondrial potential dissipation, cytochrome c release, and both caspase-9 and -3 activation. Such mitochondrial apoptotic responses were abolished by siRNA-mediated silencing of endogenous FXR or pharmacological inhibition of mitochondrial death signalling. Furthermore, low levels of FXR were detected in the adult mouse heart, with significant (∼2.0-fold) upregulation after myocardial ischaemia/reperfusion (MI/R). Pharmacological inhibition or genetic ablation of FXR significantly reduced myocardial apoptosis by 29.0-53.4%, decreased infarct size by 23.4-49.7%, and improved cardiac function in ischaemic/reperfused myocardium. CONCLUSION: These results demonstrate that nuclear receptor FXR acts as a novel functional receptor in cardiac tissue, regulates apoptosis in cardiomyocytes, and contributes to MI/R injury.

Analyzing predictors of in-hospital mortality in patients with acute ST-segment elevation myocardial infarction using an evolved machine learning approach.

Acute ST-segment elevation myocardial infarction (STEMI) is a severe cardiac ailment characterized by the sudden complete blockage of a portion of the coronary artery, leading to the interruption of blood supply to the myocardium. This study examines the medical records of 3205 STEMI patients admitted to the coronary care unit of the First Affiliated Hospital of Wenzhou Medical University from January 2014 to December 2021. In this research, a novel predictive framework for STEMI is proposed, incorporating evolutionary computational methods and machine learning techniques. A variant algorithm, AGCOSCA, is introduced by integrating crossover operation and observation bee strategy into the original Sine Cosine Algorithm (SCA). The effectiveness of AGCOSCA is initially validated using IEEE CEC 2017 benchmark functions, demonstrating its ability to mitigate the deficiency in local mining after SCA random perturbation. Building upon this foundation, the AGCOSCA approach has been paired with Support Vector Machine (SVM) to forge the predictive framework referred to as AGCOSCA-SVM. Specifically, AGCOSCA is employed to refine the selection of predictors from a substantial feature set before SVM is utilized to forecast the occurrence of STEMI. In our analysis, we observed that SVM excels at managing nonlinear data relationships, a strength that becomes particularly prominent in smaller datasets of STEMI patients. To assess the effectiveness of AGCOSCA-SVM, diagnostic experiments were conducted based on the STEMI sample data. Results indicate that AGCOSCA-SVM outperforms traditional machine learning methods, achieving superior Accuracy, Sensitivity, and Specificity values of 97.83 %, 93.75 %, and 96.67 %, respectively. The selected features, such as acute kidney injury (AKI) stage, fibrinogen, mean platelet volume (MPV), free triiodothyronine (FT3), diuretics, and Killip class during hospitalization, are identified as crucial for predicting STEMI. In conclusion, AGCOSCA-SVM emerges as a promising model framework for supporting the diagnostic process of STEMI, showcasing potential applications in clinical settings.

Admission proteinuria predicts the incidence of acute kidney injury among patients with acute ST-segment elevation myocardial infarction: a retrospective cohort study.

BACKGROUND: Proteinuria indicates renal dysfunction and is associated with the development of acute kidney injury (AKI) in several conditions, but the association between proteinuria and AKI in patients with ST-segment elevation myocardial infarction (STEMI) remains unclear. This research aims to investigate the predictive value of proteinuria for the development of AKI in STEMI patients. METHODS: A total of 2735 STEMI patients were enrolled. The present study's endpoint was AKI incidence during hospitalization. AKI is defined according to the Kidney Disease: Improving Global Outcomes criteria. We defined proteinuria, measured with a dipstick, as mild (1+) or heavy (2+ to 4+). Multivariate logistic regression and subgroup analyses were used to testify to the association between proteinuria and AKI. RESULTS: Overall, proteinuria was observed in 634 (23.2%) patients. Multivariate logistic regression analyses revealed that proteinuria [odds ratio (OR), 1.58; 95% confidence interval (CI), 1.25-2.00; P  < 0.001] was the independent predictive factor for AKI. Severe proteinuria was associated with a higher adjusted risk for AKI compared with the nonproteinuria group (mild proteinuria: OR, 1.35; 95% CI, 1.04-1.75; P  = 0.025; severe proteinuria: OR, 2.50; 95% CI, 1.70-3.68; P  < 0.001). The association was highly consistent across all studied subgroups. (all P for interaction >0.05). CONCLUSION: Admission proteinuria measured using a urine dipstick is an independent risk factor for the development of AKI in STEMI patients.