[HTD4010 attenuates myocardial injury in mice with septic cardiomyopathy by promoting autophagy via the AMPK/mTOR signaling pathway].

OBJECTIVE: To investigate the protective effects of HTD4010 against lipopolysaccharide (LPS)-induced septic cardiomyopathy (SCM) in mice and explore the mechanisms mediating its effect. METHODS: Forty-five male ICR mice were randomized equally into control group, LPS (10 mg/kg) group, and LPS+HTD4010 group (in which 2.5 mg/kg HTD4010 was injected subcutaneously at 1 h and 6 h after LPS injection). Cardiac function of the mice was evaluated by ultrasound, and pathological changes in the myocardial tissues were observed with HE staining. The levels of IL-6 and TNF-α in serum and myocardial tissues were detected using ELISA, and apoptosis of the cardiomyocytes was detected with TUNEL staining. The expression levels of the key proteins associated with apoptosis, autophagy and the AMPK/mTOR pathway in the myocardial tissues were detected using Western blotting. The ultrastructural changes of cardiac myocardial mitochondria was observed with transmission electron microscopy. RESULTS: LPS exposure caused severe myocardial damage in mice, characterized by myocardial fiber rupture, structural disorder, inflammatory cell infiltration, and mitochondrial damage. The LPS-treated mice exhibited significantly decreased cardiac LVEF and FS values, elevated IL-6 and TNF-αlevels in serum and myocardial tissue, and an increased myocardial cell apoptosis rate with enhanced expressions of Bax, p-62 and p-mTOR and lowered expressions of Bcl-2, LC3 II/I, Beclin-1 and p-AMPK (P < 0.05 or 0.01). Treatment of the septic mice with HTD4010 significantly alleviated myocardial damage, increased LVEF and FS values, reduced IL-6 and TNF-α levels in serum and myocardial tissue, decreased cardiomyocyte apoptosis, lowered myocardial expressions of Bax, p-62 and p-mTOR, and increased Bcl-2, LC3 II/I, Beclin-1 and p-AMPK expressions (P < 0.05 or 0.01). CONCLUSION: HTD4010 can attenuate myocardial injury in SCM mice possibly by promoting autophagy via modulating the AMPK/mTOR signaling pathway.

The impact of preoperative serum lactate dehydrogenase on mortality and morbidity after noncardiac surgery.

Preoperative serum lactate dehydrogenase (LDH) has been reported to be associated with adverse outcomes following thoracic surgery. However, its association with outcomes in noncardiac surgery as a whole has not been investigated. We conducted a retrospective cohort study at West China Hospital, Sichuan University, from 2018 to 2020, including patients undergoing noncardiac surgery. Multivariable logistic regression and propensity score weighting were employed to assess the link between LDH levels and postoperative outcomes. Preoperative LDH was incorporated into four commonly used clinical models, and its discriminative ability, reclassification, and calibration were evaluated in comparison to models without LDH. Among 130,879 patients, higher preoperative LDH levels (cut-off: 220 U/L) were linked to increased in-hospital mortality (4.382% vs. 0.702%; OR 1.856, 95% CI 1.620-2.127, P < 0.001), myocardial injury after noncardiac surgery (MINS) (3.012% vs. 0.537%; OR 1.911, 95% CI 1.643-2.223, P < 0.001), and ICU admission (15.010% vs. 6.414%; OR 1.765, 95% CI 1.642-1.896, P < 0.001). The inverse probability of treatment-weighted estimation supported these results. Additionally, LDH contributed significantly to four surgical prognostic models, enhancing their predictive capability. Our study revealed a significant association between preoperative LDH and in-hospital mortality, MINS, and ICU admission following noncardiac surgery. Moreover, LDH provided supplementary predictive information, extending the utility of commonly used surgical prognostic scores.

Quantitative assessment of left ventricular myocardial work in patients with different types of atrial fibrillation by non-invasive pressure-strain loop technique.

OBJECTIVE: This study aimed to analyze myocardial work in patients with atrial fibrillation (AF) using a noninvasive pressure strain loop (PSL) technique to provide a basis for the quantitative assessment of left ventricular (LV) systolic function. METHODS: LV myocardial work of 107 AF patients (56 with paroxysmal atrial fibrillation and 51 with persistent atrial fibrillation) and 55 healthy individuals were assessed by the noninvasive PSL and then compared. RESULTS: Global longitudinal strain (GLS) in absolute values, global work index (GWI), global constructive work (GCW), and global work efficiency (GWE) were significantly lower in the AF group than control group, whereas peak strain dispersion (PSD) and global wasted work (GWW) were significantly higher (P < .05). Further subdivision according to the AF type revealed that, compared with the controls, GLS in absolute values and GWE decreased significantly; PSD and GWW increased significantly in the paroxysmal AF group (P < .05). Nevertheless, GWI and GCW were not significantly different between paroxysmal AF and control groups (P > .05). Compared to paroxysmal AF, persistent AF induced a further decrease in absolute GLS and GWE and a further increase in GWW (P < .05), but PSD did not increase further (P > .05). Multiple linear regression analysis showed that GWI and GCW were independently associated with systolic blood pressure. GWW was associated with types of AF and left atrial volume index (LAVI). GWE was correlated with age, types of AF, disease duration, and LAVI. Receiver operating characteristic curve analysis showed that the area under the curve predicting myocardial injury was higher for GWE and GWW than for GLS (area under the curve:  .880,  .846, and  .821, respectively). CONCLUSIONS: Non-invasive PSL can quantitatively assess LV systolic function in patients with different kinds of AF and detect early subclinical myocardial injury in patients with paroxysmal AF. GWE and GWW outperform GLS and LV ejection fraction when assessing myocardial injury. Systolic blood pressure, type of AF, LVAI, disease duration, and age may be associated with myocardial injury in patients with AF.

Management of contained penetrating cardiac injury in a patient with prior cardiac surgery.

Penetrating cardiac injuries usually require emergent surgical intervention. Our patient presented to the trauma centre with multiple stab wounds to the neck, chest, epigastric region and abdomen. She arrived haemodynamically stable, and her initial Focused Assessment with Sonography for Trauma exam was negative. Her chest X-ray did not show any evident pneumothorax or haemothorax. Due to her injury pattern, she was taken to the operating room for exploratory laparotomy and neck exploration. Postoperatively, she was taken for CT and found to have a contained cardiac rupture. The injury was contained within previous scar tissue from her prior cardiac surgery. Further evaluation revealed that the injury included a penetrating stab wound to the right ventricle and a traumatic ventricular septal defect (VSD). She subsequently underwent a redo sternotomy with the repair of the penetrating stab wound and the VSD. Cardiology, intensive care, trauma surgery and cardiothoracic surgery coordinated her care from diagnosis, management and recovery. This case highlights the challenges in the management of cardiac injuries and the benefits of a multidisciplinary approach to care for complex cardiac injuries.

mTor-inhibition within the first days after pediatric heart transplantation is a potentially safe option to prevent cardiac allograft vasculopathy.

BACKGROUND: Immunosuppression after heart transplantation (HTX) with mammalian target of rapamycin (mTOR) inhibitors serves as a prophylaxis against rejection and to treat coronary vascular injury. However, there is little data on the early, preventive use of everolimus after pediatric HTX. METHODS: Retrospective study of 61 pediatric HTX patients (48 cardiomyopathy and 13 congenital heart disease), 28 females, median age 10.1 (range 0.1-17.9) years transplanted between 2008 and 2020. We analyzed survival, rejection, renal function, occurrence of lymphoproliferative disorder, and allograft vasculopathy together with adverse effects of early everolimus therapy combined with low-dose calcineurin inhibitors. RESULTS: Everolimus therapy was started at a median 3.9 (1-14) days after HTX. Median follow-up was 4.3 (range 0.5-11.8) years, cumulative 184 patient years. The estimated 1- and 5-year survival probability was 89% (CI 82%:98%) and 87% (CI 78%:97%). Four patients developed rejection (6.6%) (maximum 2R ISHLT criteria). No patient suffered from chronic renal failure. Three patients (4.9%) developed post-transplant lymphoproliferative disorder. Five patients suffered relevant wound-healing disorders after transplantation, four of them carrying relevant risk factors before HTX (mechanical circulatory support (n = 3), delayed chest closure after HTX (n = 3)). No recipient developed cardiac allograft vasculopathy. CONCLUSION: Initiating everolimus within the first 14 days after HTX seems to be well tolerated, enabling a low incidence of rejection, post-transplant lymphoproliferative disorders, renal failure, and reveals no evidence of cardiac allograft vasculopathy as well as good overall survival in pediatric heart transplant recipients.

[Methyltransferase WTAP aggravates hypoxia/reoxygenation-induced myocardial cell injury by regulating the expression of activator of transcription 4].

OBJECTIVE: To investigate the regulatory role of Wilms tumor 1-associating protein (WTAP) in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and its molecular mechanism. METHODS: (1) Experiment I: H9C2 cardiomyocytes were divided into blank control group and H/R model group. H/R was used to induce myocardial ischemia/reperfusion (I/R) injury model in H9C2 cells. The blank control group was not treated. N6-methyladenosine (m6A) RNA methylation assay kit was used to detect the level of m6A. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to detect the mRNA and protein expression levels of methyltransferases [WTAP, methyltransferase-like proteins (METTL3, METTL14)], respectively. (2) Experiment II: H9C2 cardiomyocytes were divided into blank control group, H/R+sh-NC group, and H/R+sh-WTAP group. sh-WTAP was transfected to knock down the expression of WTAP in H/R+sh-WTAP group, and the model establishment method in the other groups was the same as experiment I. At 48 hours after transfection, the apoptosis rate of cells was detected by flow cytometry. The protein expressions of WTAP, activated caspase-3, activated poly (ADP-ribose) polymerase (PARP), activating transcription factor 4 (ATF4), proline-rich receptor-like protein kinase (PERK), phosphorylated PERK (p-PERK) and CCAAT/enhancer-binding protein homologous protein (CHOP) were detected by Western blotting. The positive expression of ATF4 was observed by immunofluorescence staining. (3) Experiment III: H9C2 cardiomyocytes were divided into blank control group, H/R+sh-NC group, H/R+sh-WTAP group and H/R+sh-WTAP+ATF4 group. The overexpression plasmid ATF4 was transfected into H9C2 cardiomyocytes, and the modeling method of the other groups were modeled the same as experiment II. The apoptosis rate was detected by flow cytometry. Western blotting was used to detect the protein expressions of ATF4, CHOP, activated caspase-3 and activated PARP. RESULTS: (1) Experiment I: the methylation level of m6A in the H/R group was significantly higher than that in the blank control group. RT-qPCR results showed that the gene expressions of METTL3, METTL14 and WTAP in the H/R model group were significantly higher than those in the blank control group, and WTAP was the most significantly up-regulated. Western blotting results showed the same trend. These results suggested that the expression level of methyltransferase WTAP is significantly up-regulated in H/R-induced cardiomyocytes. (2) Experiment II: the apoptosis level in H/R+sh-WTAP group was significantly lower than that in H/R+sh-NC group [(14.16±1.58)% vs. (24.51±2.38)%, P < 0.05]. Western blotting results showed that the protein expressions of WTAP, activated caspase-3, activated PARP, p-PERK, ATF4 and CHOP in the H/R+sh-WTAP group were significantly lower than those in the H/R+sh-NC group. Fluorescence microscopy results showed that the ATF4 positive signal in the H/R+sh-WTAP group was significantly weaker than that in the H/R+sh-NC group [(19.36±1.81)% vs. (32.83±2.69)%, P < 0.01]. The above results suggested that knockdown of WTAP could inhibit H/R-induced cardiomyocyte apoptosis and endoplasmic reticulum stress. (3) Experiment III: the apoptosis level of H/R+sh-WTAP+ATF4 group was significantly higher than that of H/R+sh-WTAP group [(26.61±2.76)% vs. (17.14±0.87)%, P < 0.05]. Western blotting results showed that the protein expressions of ATF4, CHOP, activated caspase-3 and activated PARP in the H/R+sh-WTAP+ATF4 group were significantly higher than those in the H/R+sh-WTAP group. These results suggested that overexpression of ATF4 reversed the inhibitory effect of sh-WTAP on endoplasmic reticulum stress and apoptosis in H/R-induced cardiomyocytes. CONCLUSIONS: Methyltransferase WTAP could regulate ATF4 expression, mediate cell apoptosis and endoplasmic reticulum stress, and promote H/R-induced myocardial cell injury.

Arglabin: A mediator of inflammasome modulated and independent myocardial injury (PARA-AMI study).

BACKGROUND: Arglabin is a plant alkaloid (sesquiterpene lactone) that is used as an anticancer drug. It has potential anti-diabetic and anti-atherogenic effects. PURPOSE: Arglabin has drawn particular attention because of its therapeutic effects as an anti-inflammatory agent in multiple diseases. Since arglabin inhibits Epidermal Growth Factor Receptor (EGFR) tyrosine kinase, concerns for cardiotoxic effects are valid. The present study was designed to investigate the protective effects of arglabin on the myocardium. STUDY DESIGN: This study was designed to evaluate the effect of arglabin on the myocardium in an experimental model of myocardial necrosis in rats. Different doses of arglabin (2.5, 5, and 10 µg/kg) were investigated as pre-treatment for 21 days in the isoproterenol (ISO) model of myocardial necrosis groups and per se groups. METHODS: On the 22nd day, hemodynamic, histopathological, electron microscopy, oxidative stress markers, inflammatory mediators, apoptotic markers, inflammasome mediators, and Western blot analysis were performed to evaluate the effects of arglabin. RESULTS: Arglabin pre-treatment showed improvement in hemodynamic parameters and histopathological findings at low doses in isoproterenol-induced myocardial necrosis model of rats. Arglabin administration altered myocardial structure and modulated myocardial function via activation of NFκB/MAPK pathway that led to myocardial injury with an increase in dose. CONCLUSION: Arglabin imparted partial cardio-protection via an inflammasome-dependent pathway and mediated injury through the inflammasome-independent pathway.

One-year outcomes of pulmonary vein isolation with a novel cryoballoon: Primary results of the FROZEN AF trial.

INTRODUCTION: Cryoablation therapy for pulmonary vein isolation (PVI) to treat paroxysmal atrial fibrillation (PAF) is well established. A novel 28 mm cryoballoon system designed to operate under low pressure to safely reach a lower nadir temperature and maintain constant balloon size during cooling has not been prospectively studied in a large patient population for safety and efficacy. The FROZEN AF (NCT04133168) trial was an international multicenter, open-label, prospective, single-arm study on the safety and performance of a novel cryoballoon system for treatment of PAF. METHODS AND RESULTS: The study enrolled patients at 44 sites in 10 countries across North America, Europe, and Asia. Subjects were indicated for PVI treatment of PAF and had failed or were intolerant of one or more antiarrhythmic drugs. Procedural outcomes were defined based on the 2017 HRS consensus statement. Follow-up was performed at 7 days, 3, 6, and 12 months. Data are reported as mean ± SD or median (IQR). PVI was performed with a 28 mm cryoballoon in 325 drug refractory PAF patients. Complete PVI was achieved in 95.7% of patients. In cryoablation lesions longer than 60 s, 60.1% of PV isolations required only a single cryoballoon application. Procedure related complications included: phrenic nerve palsy [temporary 4 (1.2%), persistent 0 (0.0%)], cardiac tamponade/perforation 2 (0.6%), and air embolism 1 (0.3%). Freedom from documented atrial arrhythmia recurrence at 12 months was 79.9% (AF 82.7%, AFL 96.5%, AT 98.1%), antiarrhythmic drugs (AAD) were continued or re-initiated in 26.8% of patients after the 3-month blanking period. Additionally, an extension arm enrolled 50 pts for treatment with 28/31 mm variable size cryoballoon. A single temporary PNP occurred in this group, which resolved before discharge. Freedom from documented recurrence at 12 months in these pts was 82.0%. CONCLUSIONS: This novel cryoballoon may facilitate PVI to treat PAF, providing more options to address the variety of anatomies present in patients with PAF. This cryoballoon system proved to be safe and effective for treatment of patients with drug refractory or drug intolerant PAF.

Irisin protects against cardiac injury by inhibiting NLRP3 inflammasome-mediated pyroptosis during remodeling after infarction.

This study aimed to explore the cardioprotective mechanism of irisin in the context of cardiac injury. Utilizing a myocardial infarction (MI) mouse model, we investigated the therapeutic potential of recombinant human irisin (rhIrisin) administered for 28 days post-infarction. The efficacy of irisin treatment was evaluated through echocardiographic assessment of cardiac function and serum analysis of myocardial injury markers. Our research provided novel insights into the impacts of irisin on the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation and pyroptosis, assessed both in vivo in MI mice and in vitro in hypoxia/reoxygenation-treated H9C2 cells. Remarkably, irisin treatment significantly reduced levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and troponin I, indicating reduced myocardial injury. Echocardiography highlighted substantial improvements in left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and dimensions (LVIDd and LVIDs) in irisin-treated mice, underscoring enhanced cardiac function. Moreover, irisin was shown to significantly suppress the mRNA and protein expressions of key components involved in NLRP3 inflammasome pathway (NLRP3, ASC, caspase-1 (p20), and interleukin-18 (IL-18)) both in MI-induced mice and hypoxia/reoxygenation-treated cells. This study firstly reveals that the cardioprotective effect of irisin is mediated through the attenuation of NLRP3 inflammasome activation and pyroptosis, positioning irisin as a promising therapeutic agent for cardiac injury.

Ticagrelor regulates the differentiation of MDSCs after acute myocardial infarction to reduce cardiac injury.

Myeloid-derived suppressor cells (MDSCs) are important participants after acute myocardial infarction (AMI), but the role of their different subtypes in AMI remains controversial. The anti-inflammatory effect of ticagrelor in AMI has been discovered. However, the detailed anti-inflammatory mechanism has not been fully demonstrated. In this study, we aimed to determine whether ticagrelor can regulate the differentiation of MDSCs into anti-inflammatory subgroups to exert anti-inflammatory effects after AMI. In vitro experiments revealed no difference in the mRNA and protein expression of P2Y12 receptors on MDSCs and macrophages. Ticagrelor promotes the differentiation of in vitro cultured MDSCs to monocytic-MDSCs (M-MDSCs). A mouse AMI model was established to investigate the anti-inflammatory effects of ticagrelor in vivo after AMI by interfering with the differentiation of MDSCs. On the first day after AMI, spleen-derived polymorphonuclear-MDSCs (PMN-MDSCs) were predominant in the circulation and infarcted heart. Ticagrelor increased the percentage of M-MDSCs in the circulation and infarcted heart of AMI mice in a dose-dependent manner, attenuated cardiac inflammation and increased cardiac contractile function. M-MDSC injection significantly decreased cardiac inflammation levels and improved cardiac function in splenectomized AMI mice compared with PMN-MDSC injection. These data point to a novel anti-inflammatory role for ticagrelor after AMI by interfering with the differentiation of MDSCs.

Extracellular vesicle mediated targeting delivery of growth differentiation factor-15 improves myocardial repair by reprogramming macrophages post myocardial injury.

OBJECTIVE: Extracellular vesicles (EVs) have garnered considerable attention among researchers as candidates for natural drug delivery systems. This study aimed to investigate whether extracellular vesicle mediated targeting delivery of growth differentiation factor-15 (GDF15) improves myocardial repair by reprogramming macrophages post myocardial injury. METHODS: EVs were isolated from macrophages transfected with GDF15 (EXO-GDF15) and control macrophages (EXO-NC). In vitro and vivo experiments, we compared their reprogram ability of macrophages and regeneration activity. Furthermore, proteomic analysis were employed to determine the specific mechanism by which GDF15 repairs the myocardium. RESULTS: Compared with EXO-NC, EXO-GDF15 significantly regulated macrophage phenotypic shift, inhibited cardiomyocyte apoptosis, and enhanced endothelial cell angiogenesis. Moreover, EXO-GDF15 also significantly regulated macrophage heterogeneity and inflammatory cytokines, reduced fibrotic area, and enhanced cardiac function in infarcted rats. Proteomic analysis revealed a decrease in fatty acid-binding protein 4 (FABP4) protein expression following treatment with EXO-GDF15. Mechanistically, the reprogramming of macrophages by EXO-GDF15 is accomplished through the activation of Smad2/3 phosphorylation, which subsequently inhibits the production of FABP4. CONCLUSIONS: Extracellular vesicle mediated targeting delivery of growth differentiation factor-15 improves myocardial repair by reprogramming macrophages post myocardial injury via down-regulating the expression of FABP4. EXO-GDF15 may serve as a promising approach of immunotherapy.

The DNA-dependent protein kinase catalytic subunit exacerbates endotoxemia-induced myocardial microvascular injury by disrupting the MOTS-c/JNK pathway and inducing profilin-mediated lamellipodia degradation.

Rationale: The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) promotes pathological mitochondrial fission during septic acute kidney injury. The mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) is a mitochondria-derived peptide that exhibits anti-inflammatory properties during cardiovascular illnesses. We explored whether endotoxemia-induced myocardial microvascular injury involved DNA-PKcs and MOTS-c dysregulation. Methods: To induce endotoxemia in vivo, endothelial cell-specific DNA-PKcs-knockout mice were injected intraperitoneally with a single dose of lipopolysaccharide (10 mg/kg) and evaluated after 72 h. Results: Lipopolysaccharide exposure increased DNA-PKcs activity in cardiac microvascular endothelial cells, while pharmacological inhibition or endothelial cell-specific genetic ablation of DNA-PKcs reduced lipopolysaccharide-induced myocardial microvascular dysfunction. Proteomic analyses showed that endothelial DNA-PKcs ablation primarily altered mitochondrial protein expression. Verification assays confirmed that DNA-PKcs drastically repressed MOTS-c transcription by inducing mtDNA breaks via pathological mitochondrial fission. Inhibiting MOTS-c neutralized the endothelial protective effects of DNA-PKcs ablation, whereas MOTS-c supplementation enhanced endothelial barrier function and myocardial microvascular homeostasis under lipopolysaccharide stress. In molecular studies, MOTS-c downregulation disinhibited c-Jun N-terminal kinase (JNK), allowing JNK to phosphorylate profilin-S173. Inhibiting JNK or transfecting cells with a profilin phosphorylation-defective mutant improved endothelial barrier function by preventing F-actin depolymerization and lamellipodial degradation following lipopolysaccharide treatment. Conclusions: DNA-PKcs inactivation during endotoxemia could be a worthwhile therapeutic strategy to restore MOTS-c expression, prevent JNK-induced profilin phosphorylation, improve F-actin polymerization, and enhance lamellipodial integrity, ultimately ameliorating endothelial barrier function and reducing myocardial microvascular injury.

18ß-Glycyrrhetinic acid exerts cardioprotective effects against BPA-induced cardiotoxicity through antiapoptotic and antioxidant mechanisms.

Bisphenol A (BPA) is a synthetic environmental pollutant widely used in industry, as well as is an endocrine disrupting chemicals and has a toxic effects on heart tissue. The aim of this study is to reveal the cardioprotective effects of 18ß-glycyrretinic acid (GA) against BPA-induced cardiotoxicity in rats. In this study, 40 male rats were used and five different groups (each group includes eight rats) were formed. The rats were applied BPA (250 mg/kg b.w.) alone or with GA (50 and 100 mg/kg b.w.) for 14 days. Rats were killed on Day 15 and heart tissues were taken for analysis. GA treatment decreased serum lactate dehydrogenase and creatine kinase MB levels, reducing BPA-induced heart damage. GA treatment showed ameliorative effects against lipid peroxidation and oxidative stress caused by BPA by increasing the antioxidant enzyme activities (glutathione peroxidase, superoxide dismutase, and catalase) and GSH level of the heart tissue and decreasing the MDA level. In addition, GA showed antiapoptotic effect by increasing Bcl-2, procaspase-3, and -9 protein expression levels and decreasing Bax, cytochrome c, and P53 protein levels in heart tissue. As a result, it was found that GA has cardioprotective effects on heart tissue by exhibiting antioxidant and antiapoptotic effects against heart damage caused by BPA, an environmental pollutant. Thus, it was supported that GA could be a potential cardioprotective agent.

Management of penetrating cardiac injury and tricuspid regurgitation with extracorporeal-membrane oxygenation (ECMO): a case report.

BACKGROUND: Gunshot wounds (GSW) to the heart are lethal, and most patients die before they arrive to the hospital. Survival decreases with number of cardiac chambers involved. We report a case of a 17-year-old male who survived a GSW injury involving two cardiac chambers with acute severe tricuspid regurgitation (TR) who subsequently developed cardiogenic shock requiring extracorporeal membrane oxygenation (ECMO) support. CASE PRESENTATION: A 17-year-old male sustained a single gunshot wound to the left chest, resulting in pericardial tamponade and right hemothorax. Emergency sternotomy revealed injury to the right ventricle and inferior cavoatrial junction with the adjacent pericardium contributing to a right hemothorax. The cardiac injuries were repaired primarily. Tricuspid regurgitation was confirmed immediately postoperatively. Five days after presentation, the patient developed cardiogenic shock secondary to TR requiring emergent stabilization with ECMO. He subsequently underwent successful tricuspid valve replacement. CONCLUSIONS: This is the first report to our knowledge of successful ECMO support of severe TR due to gunshot injury to the heart.

Copeptin for the differentiation of type 1 versus type 2 myocardial infarction or myocardial injury.

BACKGROUND: The rapid and reliable differentiation of myocardial infarction (MI) due to atherothrombosis (T1MI) from MI due to supply-demand mismatch (T2MI) or acute myocardial injury is of major clinical relevance due to very different treatments, but still a major unmet clinical need. This study aimed to investigate whether copeptin, a stress hormone produced in the hypothalamus, helps to differentiate between T1MI versus T2MI or injury. METHODS: In a retrospective analysis, 1271 unselected consecutive patients presenting with symptoms suggestive of MI to the emergency department were evaluated. Patients diagnosed with ST-elevation MI were excluded. All patients with elevated cardiac troponin I (cTnI) concentration possibly indicating MI were classified into T1MI, T2MI, or acute myocardial injury using detailed clinical assessment and coronary imaging. Copeptin plasma concentration was measured in a blinded fashion. A multicenter diagnostic study with central adjudication of the final diagnosis served as external validation cohort (n = 1390). RESULTS: Among 1161 patients, 154 patients had increased cTnI concentration. Of these, 78 patients (51%) were classified as T1MI and 76 (49%) as T2MI or myocardial injury. Patients with T2MI or myocardial injury had significantly higher copeptin plasma concentration between patients versus T1MI (21,4 pmol/l versus 8,1 pmol/l, p = 0,001). A multivariable regression analysis revealed that higher concentrations of copeptin and C-reactive protein, higher heart rate at presentation and lower frequency of smoking remained significantly associated with T2MI and myocardial injury. Findings were largely confirmed in the external validation cohort. CONCLUSION: In patients without ST-segment elevation, copeptin concentration was higher in T2MI and myocardial Injury versus T1MI and may help in their differential diagnosis.

Development and validation of a prognostic model based on clinical laboratory biomarkers to predict admission to ICU in Omicron variant-infected hospitalized patients complicated with myocardial injury.

Aims: The aim of this study was to develop and validate a prognostic model based on clinical laboratory biomarkers for the early identification of high-risk patients who require intensive care unit (ICU) admission among those hospitalized with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and complicated with myocardial injury (MI). Methods: This single-center study enrolled 263 hospitalized patients with confirmed Omicron variant infection and concurrent MI. The patients were randomly divided into training and validation cohorts. Relevant variables were collected upon admission, and the least absolute shrinkage and selection operator (LASSO) was used to select candidate variables for constructing a Cox regression prognostic model. The model's performance was evaluated in both training and validating cohorts based on discrimination, calibration, and net benefit. Results: Of the 263 eligible patients, 210 were non-ICU patients and 53 were ICU patients. The prognostic model was built using four selected predictors: white blood cell (WBC) count, procalcitonin (PCT) level, C-reactive protein (CRP) level, and blood urea nitrogen (BUN) level. The model showed good discriminative ability in both the training cohort (concordance index: 0.802, 95% CI: 0.716-0.888) and the validation cohort (concordance index: 0.799, 95% CI: 0.681-0.917). For calibration, the predicted probabilities and observed proportions were highly consistent, indicating the model's reliability in predicting outcomes. In the 21-day decision curve analysis, the model had a positive net benefit for threshold probability ranges of 0.2 to 0.8 in the training cohort and nearly 0.2 to 1 in the validation cohort. Conclusion: In this study, we developed a clinically practical model with high discrimination, calibration, and net benefit. It may help to early identify severe and critical cases among Omicron variant-infected hospitalized patients with MI.

Serum metabolism characteristics of patients with myocardial injury after noncardiac surgery explored by the untargeted metabolomics approach.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is one of the most common complications associated with postoperative adverse cardiovascular outcomes and mortality. However, MINS often fails to be timely diagnosed due to the absence of clinical symptoms and limited diagnostic methods. The metabolomic analysis might be an efficient way to discover new biomarkers of MINS. Characterizing the metabolomic features of MINS patients may provide new insight into the diagnosis of MINS. METHODS: In this study, serum samples from 20 matched patients with or without MINS (n = 10 per group) were subjected to untargeted metabolomics analysis to investigate comprehensive metabolic information. Differential metabolites were identified, and the enriched metabolic pathway was determined based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. RESULTS: A comprehensive analysis revealed 124 distinct metabolites, predominantly encompassing lipids, amino acids and other compounds. The observed modifications in metabolic pathways in patients with or without MINS showed significant clustering in cholesterol metabolism, aldosterone synthesis and secretion, primary bile acid biosynthesis, as well as cysteine and methionine metabolism. Four specific metabolites (taurocholic acid, L-pyroglutamic acid, taurochenodeoxycholic acid, and pyridoxamine) exhibited promising potential as biomarkers for prognosticating MINS. CONCLUSIONS: This study contributes valuable insights into the metabolomic features of MINS and the discovery of potential biomarkers which may help the early diagnosis of MINS. The identified metabolites and altered pathways offer valuable insights into the molecular underpinnings of MINS, paving the way for improved diagnostic approaches and potential intervention strategies.

No cupid, just an arrow: a penetrating injury into the interventricular septum.

BACKGROUND: Penetrating cardiac injuries are rare but often fatal, with 16-55% mortality. We report a patient who suffered a non-fatal occupational cardiac injury. CASE PRESENTATION: A 47-year-old man was operating an ironworker machine. A thin 3-cm metal fragment catapulted from the machine piercing the chest wall and the right ventricular outflow tract (RVOT), burrowing into the interventricular septum (IVS). The patient remained hemodynamically stable and walked to the nearest hospital. ECG-gated computed tomography revealed the exact location of the fragment within the IVS, allowing for detailed preoperative planning. The fragment was removed through a sternotomy and an incision through the RVOT. The postoperative course was uneventful. CONCLUSIONS: This case underscores the value of detailed preoperative imaging and the wide spectrum of clinical scenarios of penetrating cardiac injuries.