Early inhibition of the ATM/p53 pathway reduces the susceptibility to atrial fibrillation and atrial remodeling following acute myocardial infarction.

Atrial fibrillation (AF) emerges as a critical complication following acute myocardial infarction (AMI) and is associated with a significant increased risk of heart failure, stroke and mortality. Ataxia telangiectasia mutated (ATM), a key player in DNA damage repair (DDR), has been implicated in multiple cardiovascular conditions, however, its involvement in the development of AF following AMI remains unexplored. This study seeks to clarify the contribution of the ATM/p53 pathway in the onset of AF post-AMI and to investigate the underlying mechanisms. The rat model of AMI was established by ligating left anterior descending coronary artery in the presence or absence of Ku55933 (an ATM kinase inhibitor, 5 mg/kg/d) treatment. Rats receiving Ku55933 were further divided into the early administration group (administered on days 1, 2, 4, and 7 post-AMI) and the late administration group (administered on days 8, 9, 11 and 14 post-AMI). RNA-sequencing was performed 14 days post-operation. In vitro, H2O2-challenged HL-1 atrial muscle cells were utilized to evaluate the potential effects of different ATM inhibition schemes, including earlier, middle, and late periods of intervention. Fourteen days post-AMI injury, the animals exhibited significantly increased AF inducibility, exacerbated atrial electrical/structural remodeling, reduced ventricular function and exacerbated atrial DNA damage, as evidenced by enhanced ATM/p53 signaling as well as γH2AX level. These effects were partially consistent with the enrichment results of bioinformatics analysis. Notably, the deleterious effects were ameliorated by early, but not late, administration of Ku55933. Mechanistically, inhibition of ATM signaling successfully suppressed atrial NLRP3 inflammasome-mediated pyroptotic pathway. Additionally, the results were validated in the in vitro experiments demonstrating that early inhibition of Ku55933 not only attenuated cellular ATM/p53 signaling, but also mitigated inflammatory response by reducing NLRP3 activation. Collectively, hyperactivation of ATM/p53 contributed to the pathogenesis of AF following AMI. Early intervention with ATM inhibitors substantially mitigated AF susceptibility and atrial electrical/structural remodeling, highlighting a novel therapeutic avenue against cardiac arrhythmia following AMI.

Association between Hematocrit and Acute Kidney Injury in Patients with Acute Myocardial Infarction.

Backgrounds: Hematocrit is found an independent risk factor for acute kidney injury (AKI) in certain patients, but this effect in patients with acute myocardial infarction (AMI) is unclear. We aim to identify the relationship between hematocrit and AKI in patients with AMI. Methods: The patient data for the discovery and validation cohorts were extracted from the electronic Intensive Care Unit database and the Medical Information Mart for Intensive Care III database, respectively, to identify the relationship between hematocrit and AKI. With normal hematocrit as the reference, patients were divided into five groups based on the initial hematocrit value. The primary outcome was AKI during hospitalization. A multivariable logistic regression and a marginal effect analysis were used to evaluate the relationship between hematocrit and AKI. Results: In this study, a total of 9692 patients diagnosed with AMI were included, with 7712 patients in the discovery cohort and 1980 patients in the validation cohort. In the discovery cohort, hematocrit in 30-33%, 27-30% or < 27% were independent risk factors for AKI in the multivariate logistic analysis, with odds ratio (OR) of 1.774 (95% confidence interval [CI]: 1.203-2.617, p = 0.004), 1.834 (95% CI: 1.136-2.961, p = 0.013) and 2.577 (95% CI: 1.510-4.397, p < 0.001), respectively. Additionally, in the validation cohort, low hematocrit levels independently contributed to an increased risk of AKI among patients with AMI. During the analysis of marginal effects, a significant negative linear relationship between hematocrit levels and AKI was observed. Conclusions: Decreased hematocrit was an independent risk factor for AKI in patients with AMI. The relationship between hematocrit and AKI was negative linear.

Association between Blood Urea Nitrogen Level and In-Hospital Mortality in Patients with Acute Myocardial Infarction and Subsequent Gastrointestinal Bleeding.

Background: Limited studies have explored the association between blood urea nitrogen (BUN) levels and in-hospital mortality in patients with acute myocardial infarction (AMI) and subsequent gastrointestinal bleeding (GIB). Our objective was to explore this correlation. Methods: 276 individuals with AMI and subsequent GIB were retrospectively included between January 2012 and April 2023. The predictive value of BUN for in-hospital mortality was assessed through receiver operating characteristic (ROC) curve. Logistic regression models were constructed to assess the relationship between BUN and in-hospital mortality. Propensity score weighting (PSW), sensitivity and subgroup analyses were used to further explore the association. Results: Fifty-three (19.2%) patients died in the hospital. BUN levels were higher in non-survivors compared with the survivors [(11.17 ± 6.17) vs (8.09 ± 4.24), p = 0.001]. The ROC curve suggested that the optimal cut-off for BUN levels to predict in-hospital mortality was 8.45 mmol/L (AUC [area under the ROC curve] 0.678, 95% confidence interval [CI] 0.595-0.761, p < 0.001). Multivariable logistic regression showed that elevated BUN levels ( ≥ 8.45 mmol/L) were positively association with in-hospital mortality (odds ratio [OR] 4.01, 95% CI 1.55-10.42, p = 0.004). After PSW, sensitivity and subgroup analyses, the association remained significant. Conclusions: Elevated BUN levels were associated with in-hospital mortality in patients with AMI and subsequent GIB.

Ferroptosis and Lipid Metabolism in Acute Myocardial Infarction.

Acute myocardial infarction (AMI) is triggered by the blockage of coronary arteries, leading to restricted blood flow to the myocardium, which results in damage and cell death. While the traditional understanding of cell death primarily revolves around apoptosis, a new player in the game has emerged: ferroptosis. This novel form of cell death relies on iron and is propelled by reactive oxygen species (ROS). Lipid metabolism, an indispensable physiological process, plays a vital role in preserving cellular homeostasis. However, when this metabolic pathway is disrupted, the accumulation of excess waste increases, specifically lipid peroxides, which are strongly linked to the occurrence and progression of AMI. As a result, comprehending this complex interaction between ferroptosis and lipid metabolism could pave the way for new therapeutic approaches in tackling AMI.

A Prediction Nomogram for No-Reflow in Acute Myocardial Infarction Patients after Primary Percutaneous Coronary Intervention.

Background: The coronary no-reflow (NR) phenomenon is an independent predictor of major adverse cardiac events (MACEs). This study aimed to establish a clinical and comprehensive nomogram for predicting NR in acute myocardial infarction (AMI) patients after primary percutaneous coronary intervention (pPCI). Methods: The multivariable logistic regression analysis was performed to determine the NR-related factors. A nomogram was established via several clinical and biochemical factors, and the performance was evaluated via discrimination, calibration, and clinical factors. Results: The study consisted of 3041 AMI patients after pPCI, including 2129 patients in the training set (70%) and 912 patients in the validation set (30%). The NR event was 238 in the training set and 87 in the validation set. The level of N-terminal prohormone B-type natriuretic peptide (NT-proBNP), basophil count (BASO), neutrophil count (NEUBC), D-dimer, hemoglobin (Hb), and red blood cell distribution width (RDW.CV) in NR patients showed statistically significant differences. In the training set, the C-index was 0.712, 95% CI 0.677 to 0.748. In the validation set, the C-index was 0.663, 95% CI 0.604 to 0.722. Conclusions: A nomogram that may predict NR in AMI patients undergoing pPCI was established and validated. We hope this nomogram can be used for NR risk assessment and clinical decision-making and significantly prevent potentially impaired reperfusion associated with NR.

S-Nitroso Human Serum Albumin Enhances Left Ventricle Hemodynamic Performance and Reduces Myocardial Damage after Local Ischemia-Reperfusion Injury.

Endothelial nitric oxide (NO) production is crucial in maintaining vascular homeostasis. However, in the context of ischemia-reperfusion (I/R) injury, uncoupled endothelial nitric oxide synthase (eNOS) can exacerbate reactive oxygen species (ROS) generation. Supplementation with S-nitroso human serum albumin (S-NO-HSA) offers a potential solution by mitigating eNOS uncoupling, thereby enhancing NO bioavailability. In a study conducted at the University of Verona, male rats underwent thoracotomy followed by 30 min left anterior descendant coronary (LAD) occlusion and subsequent reperfusion. Hemodynamic parameters were meticulously assessed using a conductance catheter inserted via the carotid artery. The rats were stratified into two main groups based on reperfusion duration and the timing of drug infusion, with the effects of S-NO-HSA evaluated after 2 or 24 h. Remarkably, intravenous administration of S-NO-HSA, initiated before or during ischemia, exhibited notable benefits. It significantly improved left ventricular function, safeguarded energetic substrates such as phosphocreatine and ATP, and sustained glutathione levels akin to basal conditions, indicative of diminished oxidative stress. The data from this study strongly suggest a protective role for S-NO-HSA in mitigating I/R injury induced by LAD artery occlusion, a phenomenon observed at both 2 and 24 h post-reperfusion. These findings underscore the promising therapeutic potential of NO supplementation in alleviating myocardial damage subsequent to ischemic insult.

Unveiling the Potential of Migrasomes: A Machine-Learning-Driven Signature for Diagnosing Acute Myocardial Infarction.

BACKGROUND: Recent studies have demonstrated that the migrasome, a newly functional extracellular vesicle, is potentially significant in the occurrence, progression, and diagnosis of cardiovascular diseases. Nonetheless, its diagnostic significance and biological mechanism in acute myocardial infarction (AMI) have yet to be fully explored. METHODS: To remedy this gap, we employed an integrative machine learning (ML) framework composed of 113 ML combinations within five independent AMI cohorts to establish a predictive migrasome-related signature (MS). To further elucidate the biological mechanism underlying MS, we implemented single-cell RNA sequencing (scRNA-seq) of cardiac Cd45+ cells from AMI-induced mice. Ultimately, we conducted mendelian randomization (MR) and molecular docking to unveil the therapeutic effectiveness of MS. RESULTS: MS demonstrated robust predictive performance and superior generalization, driven by the optimal combination of Stepglm and Lasso, on the expression of nine migrasome genes (BMP1, ITGB1, NDST1, TSPAN1, TSPAN18, TSPAN2, TSPAN4, TSPAN7, TSPAN9, and WNT8A). Notably, ITGB1 was found to be predominantly expressed in cardiac macrophages in AMI-induced mice, mechanically regulating macrophage transformation between anti-inflammatory and pro-inflammatory. Furthermore, we showed a positive causality between genetic predisposition towards ITGB1 expression and AMI risk, positioning it as a causative gene. Finally, we showed that ginsenoside Rh1, which interacts closely with ITGB1, could represent a novel therapeutic approach for repressing ITGB1. CONCLUSIONS: Our MS has implications in forecasting and curving AMI to inform future diagnostic and therapeutic strategies for AMI.

The Role of Hyperuricemia in Cardiac Diseases: Evidence, Controversies, and Therapeutic Strategies.

Hyperuricemia (HUA) may lead to myocardial cell damage, thereby promoting the occurrence and adverse outcomes of heart diseases. In this review, we discuss the latest clinical research progress, and explore the impact of HUA on myocardial damage-related diseases such as myocardial infarction, arrhythmias, and heart failure. We also combined recent findings from basic research to analyze potential mechanisms linking HUA with myocardial injury. In different pathological models (such as direct action of high uric acid on myocardial cells or combined with myocardial ischemia-reperfusion model), HUA may cause damage by activating the NOD-like receptor protein 3 inflammasome-induced inflammatory response, interfering with cardiac cell energy metabolism, affecting antioxidant defense systems, and stimulating reactive oxygen species production to enhance the oxidative stress response, ultimately resulting in decreased cardiac function. Additionally, we discuss the impact of lowering uric acid intervention therapy and potential safety issues that may arise. However, as the mechanism underlying HUA-induced myocardial injury is poorly defined, further research is warranted to aid in the development novel therapeutic strategies for HUA-related cardiovascular diseases.

Postmortem Immunohistochemical Findings in Early Acute Myocardial Infarction: A Systematic Review.

The diagnosis of early acute myocardial infarction is of particular importance in forensic practice considering the frequency of sudden cardiac death and the difficulty of positively identifying it through classical histological methods if survival is less than 6 h. This article aims to analyze potential immunohistochemical markers that could be useful in diagnosing acute myocardial infarction within the first 6 h of its onset. We conducted an extensive evaluation of the literature according to the PRISMA guidelines for reporting systematic literature reviews. We searched the Web of Science and PubMed databases from their inception to 2023 using the following keywords: "myocardial infarction" and "immunohistochemistry". Fifteen studies met the inclusion criteria. Immunohistochemical markers as complement factors and CD59, myoglobin, fibrinogen, desmin, tumor necrosis factor alpha (TNF-α), P-38, JNK (Jun N Terminal Kinase), transforming growth factor ß1 (TGF-ß1), cardiac troponins, fibronectin, H-FABP (heart fatty acid binding protein), dityrosine, fibronectin, CD15, IL-1ß, IL-6, IL-15, IL-8, MCP-1, ICAM-1, CD18, and tryptase can be used to identify the first six hours of acute myocardial infarction. These markers are mostly studied in experimental animal models. It is necessary to conduct extensive studies on human myocardial tissue fragments, which will involve the analysis of several immunohistochemical markers and careful analysis of the available data on perimortem events, resuscitation, and postmortem intervals in the context of a uniform laboratory methodology.

A Machine Learning Model for Predicting In-Hospital Mortality in Chinese Patients With ST-Segment Elevation Myocardial Infarction: Findings From the China Myocardial Infarction Registry.

BACKGROUND: Machine learning (ML) risk prediction models, although much more accurate than traditional statistical methods, are inconvenient to use in clinical practice due to their nontransparency and requirement of a large number of input variables. OBJECTIVE: We aimed to develop a precise, explainable, and flexible ML model to predict the risk of in-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: This study recruited 18,744 patients enrolled in the 2013 China Acute Myocardial Infarction (CAMI) registry and 12,018 patients from the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE)-Retrospective Acute Myocardial Infarction Study. The Extreme Gradient Boosting (XGBoost) model was derived from 9616 patients in the CAMI registry (2014, 89 variables) with 5-fold cross-validation and validated on both the 9125 patients in the CAMI registry (89 variables) and the independent China PEACE cohort (10 variables). The Shapley Additive Explanations (SHAP) approach was employed to interpret the complex relationships embedded in the proposed model. RESULTS: In the XGBoost model for predicting all-cause in-hospital mortality, the variables with the top 8 most important scores were age, left ventricular ejection fraction, Killip class, heart rate, creatinine, blood glucose, white blood cell count, and use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs). The area under the curve (AUC) on the CAMI validation set was 0.896 (95% CI 0.884-0.909), significantly higher than the previous models. The AUC for the Global Registry of Acute Coronary Events (GRACE) model was 0.809 (95% CI 0.790-0.828), and for the TIMI model, it was 0.782 (95% CI 0.763-0.800). Despite the China PEACE validation set only having 10 available variables, the AUC reached 0.840 (0.829-0.852), showing a substantial improvement to the GRACE (0.762, 95% CI 0.748-0.776) and TIMI (0.789, 95% CI 0.776-0.803) scores. Several novel and nonlinear relationships were discovered between patients' characteristics and in-hospital mortality, including a U-shape pattern of high-density lipoprotein cholesterol (HDL-C). CONCLUSIONS: The proposed ML risk prediction model was highly accurate in predicting in-hospital mortality. Its flexible and explainable characteristics make the model convenient to use in clinical practice and could help guide patient management. TRIAL REGISTRATION: ClinicalTrials.gov NCT01874691; https://clinicaltrials.gov/study/NCT01874691.

Albumin corrected anion gap for predicting in-hospital death among patients with acute myocardial infarction: A retrospective cohort study.

OBJECTIVE: To explore the relationship between Anion Gap (AG), Albumin Corrected AG (ACAG), and in-hospital mortality of Acute Myocardial Infarction (AMI) patients and develop a prediction model for predicting the mortality in AMI patients. METHODS: This was a retrospective cohort study based on the Medical Information Mart for Intensive Care (MIMIC)-Ⅲ, MIMIC-IV, and eICU Collaborative Study Database (eICU). A total of 9767 AMI patients who were admitted to the intensive care unit were included. The authors employed univariate and multivariable cox proportional hazards analyses to investigate the association between AG, ACAG, and in-hospital mortality; p < 0.05 was considered statistically significant. A nomogram incorporating ACAG and clinical indicators was developed and validated for predicting mortality among AMI patients. RESULTS: Both ACAG and AG exhibited a significant association with an elevated risk of in-hospital mortality in AMI patients. The C-index of ACAG (C-index = 0.606) was significantly higher than AG (C-index = 0.589). A nomogram (ACAG combined model) was developed to predict the in-hospital mortality for AMI patients. The nomogram demonstrated a good predictive performance by Area Under the Curve (AUC) of 0.763 in the training set, 0.744 and 0.681 in the external validation cohort. The C-index of the nomogram was 0.759 in the training set, 0.756 and 0.762 in the validation cohorts. Additionally, the C-index of the nomogram was obviously higher than the ACAG and age shock index in three databases. CONCLUSION: ACAG was related to in-hospital mortality among AMI patients. The authors developed a nomogram incorporating ACAG and clinical indicators, demonstrating good performance for predicting in-hospital mortality of AMI patients.

Evaluating Long-Term Outcomes in STEMI Patients with New Left Bundle Branch Block: The Impact of Modifiable Risk Factors.

Background/Objectives: Coronary artery disease, a leading global cause of death, highlights the essential need for early detection and management of modifiable cardiovascular risk factors to prevent further coronary events. Methods: This study, conducted at a major tertiary academic PCI-capable hospital in Romania from 1 January 2011 to 31 December 2013, prospectively analyzed 387 myocardial infarction with ST-segment elevation (STEMI) patients to assess the long-term management of modifiable risk factors. This study particularly focused on patients with new-onset left bundle branch block (LBBB) and compared them with a matched control group without LBBB. Results: During median follow-up periods of 9.6 years for LBBB patients and 9.2 years for those without LBBB, it was found that smoking, obesity, and dyslipidemia were prevalent in 73.80%, 71.42%, and 71.42% of the LBBB group, respectively, at baseline. Significant reductions in smoking were observed in both groups, with the LBBB group's smoking rates decreasing significantly to 61.90% (p = 0.034). Patients with LBBB more frequently achieved low-density lipoprotein cholesterol (LDLc) target levels during the follow-up period (from 71.42% to 59.52%; p = 0.026) compared to the control group (from 66.67% to 71.42%; p = 0.046). Prescription rates for dual antiplatelet therapy (DAPT), angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs), beta-blockers, and statins were initially high but then decreased by the follow-up. Statin use was reduced from 97.62% to 69.04% (p = 0.036) in the LBBB group and from 100% to 61.90% (p = 0.028) in the non-LBBB group. This study also highlighted moderate correlations between obesity (r = 0.627, p = 0.040) and subsequent coronary reperfusion in the LBBB group, while dyslipidemia and smoking showed very strong positive correlations across both groups (dyslipidemia: r = 0.903, p = 0.019 for LBBB; r = 0.503, p = 0.048 for non-LBBB; smoking: r = 0.888, p = 0.035 for LBBB; r = 0.517, p = 0.010 for non-LBBB). Conclusions: These findings underscore the crucial need for targeted management of modifiable risk factors, particularly focusing on dyslipidemia and smoking cessation, to improve subsequent coronary reperfusion outcomes post-STEMI, especially in patients with complicating factors like LBBB.

Morphological Changes of Peri-Coronary Adipose Tissue Together with Elevated NLR in Acute Myocardial Infarction Patients in-Hospital.

Background: Inflammation triggers atherosclerotic plaque rupture, leading to acute myocardial infarction (AMI). Following AMI, peri-coronary adipose tissue (PCAT) undergoes a transition from lipid-rich to hydrophilic characteristics due to vascular inflammation. This study investigates PCAT changes and neutrophil-to-lymphocyte ratio levels during AMI. Patients and Methods: 60 AMI patients undergoing coronary computed tomography angiography and angiography (Jan 2020-Jun 2022) were studied 60 age, gender, BMI-matched stable angina, and 60 non-coronary artery disease patients were included. Siemens VB20.0 measured PCAT-volume and fat attenuation index (FAI). Neutrophil-to-lymphocyte ratio levels were calculated by peripheral blood tests. Results: The PCAT volume and PCAT-FAI gradually increased across the control, stable angina, and AMI groups, with a corresponding gradual rise in NLR. NLR exhibited weak positive correlation with PCAT-FAI (r=0.35) and PCAT-volume (r=0.24). Multivariable logistic regression identified increased PCAT-volume, PCAT-FAI and neutrophil-to-lymphocyte ratio as possible independent AMI risk factors. No significant PCAT-volume difference was observed between infarct-related artery (IRA) and non-IRA for all three coronary arteries. Only PCAT-FAI around IRA-LAD was higher than non-IRA-LAD (-74.84±6.93 HU vs -79.04±8.68 HU). PCAT-FAI around culprit vessels in AMI was higher than corresponding lesion related vessel in SA. PCAT-volume around narrowed non-IRA in AMI was higher than that of corresponding LRV in SA. PCAT-FAI of narrowed non-IRA-LADs and non-IRA-LCXs in AMI were elevated compared to LADs (-78.46±8.56HU vs -83.13±8.34 HU) and LCXs (-73.83±10.63 HU vs -81.38±7.88 HU) of lesion related vessel in stable angina. Conclusion: We found an association between AMI and inflammation in the coronary perivascular adipose tissue and systemic inflammatory response.

In-hospital outcomes in COVID-19 patients with non-alcoholic fatty liver disease by severity of obesity: Insights from national inpatient sample 2020.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) increases the risk of cardiovascular diseases independently of other risk factors. However, data on its effect on cardiovascular outcomes in coronavirus disease 2019 (COVID-19) hospitalizations with varied obesity levels is scarce. Clinical management and patient care depend on understanding COVID-19 admission results in NAFLD patients with varying obesity levels. AIM: To study the in-hospital outcomes in COVID-19 patients with NAFLD by severity of obesity. METHODS: COVID-19 hospitalizations with NAFLD were identified using International Classification of Disease -10 CM codes in the 2020 National Inpatient Sample database. Overweight and Obesity Classes I, II, and III (body mass index 30-40) were compared. Major adverse cardiac and cerebrovascular events (MACCE) (all-cause mortality, acute myocardial infarction, cardiac arrest, and stroke) were compared between groups. Multivariable regression analyses adjusted for sociodemographic, hospitalization features, and comorbidities. RESULTS: Our analysis comprised 13260 hospitalizations, 7.3% of which were overweight, 24.3% Class I, 24.1% Class II, and 44.3% Class III. Class III obesity includes younger patients, blacks, females, diabetics, and hypertensive patients. On multivariable logistic analysis, Class III obese patients had higher risks of MACCE, inpatient mortality, and respiratory failure than Class I obese patients. Class II obesity showed increased risks of MACCE, inpatient mortality, and respiratory failure than Class I, but not significantly. All obesity classes had non-significant risks of MACCE, inpatient mortality, and respiratory failure compared to the overweight group. CONCLUSION: Class III obese NAFLD COVID-19 patients had a greater risk of adverse outcomes than class I. Using the overweight group as the reference, unfavorable outcomes were not significantly different. Morbid obesity had a greater risk of MACCE regardless of the referent group (overweight or Class I obese) compared to overweight NAFLD patients admitted with COVID-19.

Electroacupuncture for slow flow/no-reflow phenomenon in patients with acute myocardial infarction undergoing percutaneous coronary intervention: protocol for a pilot randomized controlled trial.

Background: Slow flow/no-reflow (SF-NR) during percutaneous coronary intervention (PCI) is associated with poor prognosis of patients with acute myocardial infarction (AMI). Currently, effective treatment is not available for SF-NR. Electroacupuncture (EA) has shown significant efficacy as an adjuvant therapy for many cardiovascular diseases by improving microcirculation and reducing ischemia-reperfusion injury. However, its effects on SF-NR in the AMI patients during PCI are not clear. This pilot trial aims to determine the efficacy of intraoperative EA in alleviating SF-NR in AMI patients undergoing PCI. Methods: This prospective, single-center, randomized controlled, pilot trial will recruit 60 AMI patients scheduled for PCI at the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, China. The patients will be randomized in a 1:1 ratio into the EA or the control groups. Patients in the control group will undergo standard PCI. Patients in the EA group will undergo intraoperative electroacupuncture while undergoing standard PCI. Incidence of SF-NR is the primary outcome for this study. This study will also assess secondary outcomes including cardiac biomarkers, inflammatory biomarkers, pain and anxiety scores, electrocardiography parameters, traditional Chinese medicine (TCM) symptom score, and major adverse cardiovascular and cerebrovascular events (MACCE). All the included patients will undergo laboratory tests including routine blood tests, levels of electrolytes, as well as liver and renal function tests. Patients will be followed up for 1 month after the procedure. Discussion: This pilot trial will provide evidence for the potential benefits of intraoperative EA in improving microvascular perfusion and preventing or alleviating SF-NR during PCI in patients with AMI. If proven effective, intraoperative EA will provide a new and effective strategy against SF-NR and provide evidence for subsequent multicenter trials. Clinical Trial Registration: ClinicalTrials.gov, identifier (ChiCTR2300072265). Registered on 8 June 2023.

Inhibition of proline-rich tyrosine kinase 2 restores cardioprotection by remote ischaemic preconditioning in type 2 diabetes.

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

The effect of Empagliflozin on echocardiographic parameters in diabetic patients after acute myocardial infarction: A systematic review and meta-analysis with trial sequential analysis.

Patients with diabetes mellitus (DM) are at higher risk of cardiovascular events, particularly acute myocardial infarction (MI). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) can improve cardiac outcomes among heart failure individuals, however, the effects on acute myocardial infarction remain unclear. This meta-analysis investigates the impact of empagliflozin in diabetic patients following acute myocardial infarction. We comprehensively searched PubMed, Scopus, Cochrane, and Web of Science through August 10th, 2023. We included studies comparing empagliflozin versus placebo in diabetes patients with acute myocardial infarction. We used Revman to report the data as mean difference (MD) and 95% confidence interval (CI), and our effect size with a random effects model. Additionally, we performed Trial Sequential Analysis (TSA) to test the robustness of the results. The study protocol was published on PROSPERO with ID: CRD42023447733. Five studies with a total of 751 patients were included in our analysis. Empagliflozin was effective to improve LVEF% (MD: 1.80, 95% CI [0.50, 3.10], p = 0.007), left ventricular end-diastolic volume (LVEDV) (MD: -9.93, 95% CI [-16.07, -3.80], p = 0.002), and left ventricular end-systolic volume (LVESV) (MD: -7.91, 95% CI [-11.93, -3.88], p = 0.0001). However, there was no difference between empagliflozin and placebo groups in terms of NT-pro BNP (MD: - 136.59, 95% CI [-293.43, 20.25], p = 0.09), and HbA1c (MD: -0.72, 95% CI [-1.73, 0.29], p = 0.16). Additionally, empagliflozin did not prevent hospitalization due to heart failure (RR: 0.59, 95% CI [0.16, 2.24], p = 0.44, I-squared = 0%), and mortality (RR: 1.34, 95% CI [0.15,11.90], p = 0.79, I-squared = 25%). Empagliflozin initiation in diabetic patients following acute MI may improve echocardiographic parameters. However, empagliflozin might not be effective in heart failure prevention and optimal glycemic control in this patient population. Further large-scale trials are warranted to ascertain our findings.

Effect of Intramyocardial Administration of Baculovirus Encoding the Transcription Factor Tbx20 in Sheep With Experimental Acute Myocardial Infarction.

BACKGROUND: Gene therapy has been proposed as a strategy to induce cardiac regeneration following acute myocardial infarction (AMI). Given that Tbx20, a transcription factor of the T-box subfamily, stimulates cell proliferation and angiogenesis, we designed a baculovirus overexpressing Tbx20 (Bv-Tbx20) and evaluated its effects in cultured cardiomyocytes and in an ovine model of AMI. METHODS AND RESULTS: Cell proliferation and angiogenesis were measured in cardiomyocytes transduced with Bv-Tbx20 or Bv-Null (control). Subsequently, in sheep with AMI, Bv-Tbx20 or Bv-Null was injected in the infarct border. Cardiomyocyte cell cycle activity, angioarteriogenesis, left ventricular function, and infarct size were assessed. Cardiomyocytes transduced with BvTbx20 increased cell proliferation, cell cycle regulatory and angiogenic gene expression, and tubulogenesis. At 7 days posttreatment, sheep treated with Bv-Tbx20 showed increased Tbx20, promitotic and angiogenic gene expression, decreased levels of P21, increased Ki67- (17.09±5.73 versus 7.77±7.24 cardiomyocytes/mm2, P<0.05) and PHH3 (phospho-histone H3)-labeled cardiomyocytes (10.10±3.51 versus 5.23±2.87 cardiomyocytes/mm2, P<0.05), and increased capillary (2302.68±353.58 versus 1694.52±211.36 capillaries/mm2, P<0.001) and arteriolar (146.95±53.14 versus 84.06±16.84 arterioles/mm2, P<0.05) densities. At 30 days, Bv-Tbx20 decreased infarct size (9.89±1.92% versus 12.62±1.33%, P<0.05) and slightly improved left ventricular function. Baculoviral gene transfer-mediated Tbx20 overexpression exerted angiogenic and cardiomyogenic effects in vitro. CONCLUSIONS: In sheep with AMI, Bv-Tbx20 induced angioarteriogenesis, cardiomyocyte cell cycle activity, infarct size limitation, and a slight recovery of left ventricular function, suggesting that Bv-Tbx20 gene therapy may contribute to cardiac regeneration following AMI.

Prognostic value of cardiopulmonary exercise test in patients with acute myocardial infarction after percutaneous coronary intervention.

To determine the independent risk factors of cardiopulmonary exercise test (CPET) parameters related to adverse prognostic events within 5 years in patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), and establish a prediction model for the occurrence of adverse events within 5 years to provide a reference for cardiac rehabilitation training. From August 2015 to December 2021, patients who underwent PCI for AMI and completed CPET within 1-2 weeks after surgery before discharge from the Department of Cardiovascular Medicine of Zhengzhou Central Hospital Affiliated to Zhengzhou University, Henan Provincial Hospital of Traditional Chinese Medicine, and Anyang District Hospital were selected as participants. Univariate and multivariate analyses were used to screen for independent risk factors associated with 5-year adverse events. Feature importance was interpreted using SHapley Additive exPlanations (SHAP), and a logistic regression model was established for prediction. A receiver operating characteristic (ROC) curve was constructed to evaluate the performance of the prediction model. Calibration was assessed by the Hosmer-Lemeshow test and the calibration curve. In total, 375 patients met the inclusion criteria. Based on whether adverse events occurred during the 5-year follow-up period, the patients were divided into two groups: the event group (n = 53) and the non-event group (n = 322). Peak oxygen uptake (peakVO2), carbon dioxide ventilation equivalent slope (VE/VCO2slop), and peak end-tidal carbon dioxide partial pressure (PETCO2) were three independent risk factors for re-acute myocardial infarction (re-AMI), heart failure (HF), and even death after PCI for AMI (P < 0.05). The SHAP plots demonstrated that the significant contributors to model performance were related to peakVO2, VE/VCO2slop, and PETCO2. The risk of adverse events was significantly reduced when the peakVO2 was ≥ 20 mL/kg/min and the VE/VCO2slop was < 33. The ROC curves of the three models were drawn, including the no-event and event groups, re-AMI group, and HF group, which performed well, with AUC of 0.894, 0.760, and 0.883, respectively. The Hosmer-Lemeshow test showed that the three models were a good fit (P > 0.05). The calibration curve of the three models was close to the ideal diagonal lines. CPET parameters can predict the prognosis of adverse events within 5 years after PCI in patients with AMI and provide a theoretical basis for cardiac rehabilitation training.

A randomized controlled trial of ivabradine in patients with acute myocardial infarction related cardiogenic shock.

Objective: . Acute myocardial infarction-related cardiogenic shock (AMI-CS) is often accompanied by tachycardia, which, in turn, increases myocardial oxygen consumption and hinders the use of ventricular assist devices, such as intra-aortic balloon pump. Evidence suggests that ivabradine may reduce heart rate (HR) without affecting other hemodynamic parameters. The aim of the present study was to determine the effect of ivabradine on reducing HR and changes in other hemodynamic parameters such as cardiac index (CI), in patients with AMI-CS and tachycardia. Materials and methods: . A single-center, open label, randomized clinical trial included patients diagnosed with AMI-CS and tachycardia with >100 beats per minute (BPM). Heart rate, cardiac index, and other hemodynamic parameters measured by pulmonary flotation catheter were compared at 0, 6, 12, 24, and 48 hours after randomization. Results: . A total of 12 patients were randomized; 6 received standard therapy, and 6 received ivabradine in addition to standard therapy. Baseline clinical characteristics were similar at randomization. A statistically significant lower heart rate was found at 12 hours (p=0.003) and 48 hours (p=0.029) after randomization, with differences of -23.3 (-8.2 to -38.4) BPM and -12.6 (-0.5 to -25.9) BPM, respectively. No differences in cardiac index, or any other evaluated hemodynamic parameters, length of hospital stay, nor mortality rate were noted between both groups. Conclusions: . The use of ivabradine in patients with AMI-CS was associated with a significant reduction in heart rate at 12 and 48 h, without affecting other hemodynamic parameters.

Objetivo: . El choque cardiogénico relacionado con el infarto agudo de miocardio (AMI-CS, por sus siglas en inglés) suele ir acompañado de taquicardia, lo que, a su vez, aumenta el consumo de oxígeno miocárdico y dificulta el uso de dispositivos de asistencia ventricular, como la bomba de balón intraaórtico. La evidencia sugiere que la ivabradina puede reducir la frecuencia cardíaca (FC) sin afectar otros parámetros hemodinámicos. El objetivo del presente estudio fue determinar el efecto de la ivabradina en la reducción de la FC y los cambios en otros parámetros hemodinámicos como el índice cardíaco (CI) en pacientes con AMI-CS y taquicardia. Materiales y métodos: Se incluyeron pacientes diagnosticados con AMI-CS y taquicardia con >100 latidos por minuto (LPM) en un ensayo clínico aleatorizado de un solo centro. La frecuencia cardíaca, el índice cardíaco y otros parámetros hemodinámicos medidos mediante catéter de flotación pulmonar se compararon a las 0, 6, 12, 24 y 48 h después de la aleatorización. Resultados: Se aleatorizaron un total de 12 pacientes; 6 recibieron terapia estándar y 6 recibieron ivabradina además de la terapia estándar. Las características clínicas basales fueron similares en la aleatorización. Se encontró una frecuencia cardíaca significativamente más baja a las 12 h (p=0,003) y a las 48 h (p=0,029) después de la aleatorización, con diferencias de -23,3 (-8,2 a -38,4) LPM y -12,6 (-0,5 a -25,9) LPM, respectivamente. No se observaron diferencias en el índice cardíaco, en ningún otro parámetro hemodinámico evaluado; tampoco en la duración de la estancia hospitalaria, ni en la tasa de mortalidad entre ambos grupos. Conclusiones: El uso de ivabradina en pacientes con AMI-CS se asoció con una reducción significativa en la frecuencia cardíaca a las 12 y 48 h, sin afectar otros parámetros hemodinámicos.