BACKGROUND:Our objective was to compare the efficacy and safety of a drug-eluting stent featuring an abluminal bioabsorbable sirolimus-containing polymer coating (BP-SES) with an everolimus-eluting stent with a durable polymer (DP-EES) in patients undergoing percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs). METHODS:TARGET CTO is a multicenter, open-label, noninferiority trial that randomized patients to either BP-SES or DP-EES in a 1:1 fashion following successful CTO re-canalization. The primary endpoint that was powered for noninferiority assessment is in-stent late lumen loss (LLL) at 12 months. RESULTS:A total of 206 subjects underwent randomization, with 103 assigned to the BP-SES group and 103 to the DP-EES group. Baseline clinical and angiographic characteristics were comparable. The primary endpoint demonstrated noninferiority for the BP-SES group compared to the DP-EES group (0.21 ± 0.43 mm vs 0.21 ± 0.33 mm; P = .934, 2-sided; difference 0.01mm [BP-SES minus DP-EES]; 95% CI: -0.13 to 0.12 mm; p noninferiority < .001,1-sided). No significant differences were observed in secondary angiographic or clinical endpoints. The rates of 12-month in-stent and in-segment binary restenosis in the BP-SES group and the DP-EES group were similar (6.8% vs 7.5%, P = .86; and 8.1% vs 8.8%; P = .89, respectively). Although there was a trend favoring the BP-SES group, the difference between the BP-SES group and DP-EES group at 12 months in target lesion failure (2.1% vs 8.0%, P = .054) and target lesion revascularization (2.1% vs 7.1%, P = .089) did not reach statistical significance. No definite or probable stent thromboses were reported in either group. CONCLUSIONS:Compared to DP-EES, PCI of CTOs with BP-SES showed similar results in terms of late loss and binary restenosis at the 12-month follow-up. CLINICAL TRIAL:ClinictalTrial.gov, number NCT03040934.

This article describes a 44-year-old female with Fabry disease presenting with a 7-year history of chest discomfort, extremity pain, and hypohidrosis. ECG revealed sinus bradycardia (52 bpm), a short PR interval (100 ms) with a delta wave, and a QRS complex (126 ms) showing a complete right bundle branch block. T-wave inversion and ST-segment depression were observed in leads I, AVL, II, aVF, and V2-V6. Genetic testing confirmed Fabry disease (GLA: c.700_702del). Short PR interval with left ventricular hypertrophy (LVH) poses a diagnostic challenge, requiring advanced imaging and genetic testing to differentiate Fabry disease from other cardiomyopathies.

Doxorubicin (DOX) is an anthracycline class of chemotherapy drug, the application of which is limited due to its cardiotoxic effects. Recombinant Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), is a serine protease pivotal in lipid metabolism and has a profound correlation with the onset of cardiovascular diseases. This study uncovers a connection between PCSK9 and DOX-induced cardiotoxicity (DIC). This research found that injection of DOX in mice caused cardiac toxicity. DOX treatment up-regulated the expression of PCSK9 protein in myocardial tissue. Evolocumab (PCSK9 inhibitors) improved cardiac function, myocardial injury, and fibrosis in DOX-treated mice, indicating a protective effect against DIC. The mechanism involved modulation of cardiomyocyte apoptosis and regulation of apoptosis-related proteins, including Bax/Bcl-2 ratio and Cleaved Caspase-3/Pro Caspase-3 ratio. DOX exhibited concentration- and time-dependent cytotoxic effects on H9C2 cardiomyocytes, promoting apoptosis. PCSK9 nuclear aggregation occurred in H9C2 cardiomyocytes after DOX treatment, and PCSK9 interacted with the Importin subunit beta-1 (KPNB1) protein. Interference with PCSK9 up-regulated KPNB1 expression, affecting apoptosis-related proteins and improving DOX-induced H9C2 cardiomyocyte apoptosis. In short, the elucidation of this mechanism is helpful involve that PCSK9 inhibitor may be a potential drug for improving DIC.

A patient with episodic chest pain, diaphoresis, amaurosis, and dizziness, along with a history of hypertension, presented with electrocardiographic findings of ST elevation in aVR, diffuse T-wave inversion, and QTc prolongation. Initial diagnosis of NSTEMI was reconsidered after coronary angiography excluded significant stenosis, revealing myocardial bridging. Echocardiography and cardiac MRI showed preserved function without ischemia. Markedly elevated plasma renin and urinary normetanephrine, along with a retroperitoneal mass, suggested paraganglioma. Laparoscopic resection confirmed a 4.0 × 3.5 cm paraganglioma. This case highlights the importance of recognizing atypical ECG patterns that may mimic ischemia in catecholamine-secreting tumors to guide timely diagnosis and intervention.

The incidence and mortality rates of acute pulmonary embolism (APE) are high in clinical emergencies, making early diagnosis and risk stratification crucial. Electrocardiogram (ECG) plays a significant role in guiding the diagnosis and differential diagnosis of pulmonary embolism. Acute pulmonary embolism can present with various ECG manifestations. The presence of pulmonary hypertension and increased right ventricular load in pulmonary embolism can lead to T wave inversion in the right cardiac lead. Additionally, some patients may exhibit a prolonged QT interval, which is associated with the pathophysiological processes resulting from both pulmonary hypertension and myocardial ischemia.

This article describes the case of a 40-year-old individual who presented with fulminant myocarditis. Initial ECG displayed sinus tachycardia with a heart rate of 117 bpm, QS complexes in leads V1-V3, ST-segment depression in leads II, III, aVF, V5-V6, and ST-segment elevation >0.2 mV in leads V1 through V3. The initial clinical assessment suggested an acute anteroseptal myocardial infarction. However, subsequent diagnostic evaluation through coronary angiography disclosed that the coronary arteries were normal. Therefore, clinicians should carefully consider the differential diagnosis between these conditions, as their management strategies differ markedly. Two hours after admission, the patient unexpectedly developed syncope. The ECG findings were consistent with the typical characteristics of bidirectional ventricular tachycardia. Our report described the appearance and morphology as well as mechanism of bidirectional ventricular tachycardia in detail. Additionally, we delineate differential diagnoses for disease that can cause bidirectional ventricular tachycardia, such as aconite poisoning, digoxin overdose, immune checkpoint inhibitor (ICI), myocardial ischemia, and hereditary channelopathies, such as catecholaminergic polymorphic ventricular tachycardia (CPVT) and Andersen-Tawil syndrome. Therefore, clinicians should recognize this ECG finding immediately and initiate appropriate treatment promptly as these measures may be vital in saving the patient's life.

Background:Coronary atherosclerosis diseases (CADs) are associated with chronic inflammation. Neutrophil extracellular traps (NETs) are a type of novel proinflammatory cytokines whose levels are dramatically elevated in acute coronary syndrome. We conducted this study to further evaluate the association between circulating NET-associated markers and CAD in Chinese adults.Methods:A total of 174 patients with CAD and 55 healthy controls were screened using percutaneous coronary intervention or coronary computed tomography angiography. Blood lipid levels, blood glucose levels, and blood cell counts were determined using commercial kits. Serum levels of myeloperoxidase (MPO) and neutrophil elastase (NE) were measured using ELISA. Double-stranded DNA (dsDNA) in serum was quantified using the Quant-iT PicoGreen assay. We also compared the circulating NET levels with various parameters in the study subjects.Results:The levels of serum NET markers, dsDNA, MPO, and NE, were significantly elevated in patients with CAD, particularly in the severe group, consistent with the increase in neutrophil counts. The levels of NET markers correlated with the risk factors of AS, increasing with the number of risk factors. NET markers were identified as independent risk factors for severe coronary stenosis and also as predictors of severe CAD.Conclusion:NETs may be related to AS and serve as indicators or predictors of stenosis in patients with severe CAD.

Background.Coronary atherosclerosis diseases (CADs) are associated with chronic inflammation.Neutrophil extracellular traps (NETs) are a type of novel proinflammatory cytokines whose levels are dramatically elevated in acute coronary syndrome.We conducted this study to further evaluate the association between circulating NET-associated markers and CAD in Chinese adults.Methods.A total of 174 patients with CAD and 55 healthy controls were screened using percutaneous coronary intervention or coronary computed tomography angiography.Blood lipid levels, blood glucose levels, and blood cell counts were determined using commercial kits.Serum levels of myeloperoxidase (MPO) and neutrophil elastase (NE) were measured using ELISA.Double-stranded DNA (dsDNA) in serum was quantified using the Quant-iT PicoGreen assay.We also compared the circulating NET levels with various parameters in the study subjects.Results.The levels of serum NET markers, dsDNA, MPO, and NE, were significantly elevated in patients with CAD, particularly in the severe group, consistent with the increase in neutrophil counts.The levels of NET markers correlated with the risk factors of AS, increasing with the number of risk factors.NET markers were identified as independent risk factors for severe coronary stenosis and also as predictors of severe CAD. Conclusion.NETs may be related to AS and serve as indicators or predictors of stenosis in patients with severe CAD.

Background:Treatment of chronic total occlusions (CTOs) is referred to as the last frontier of percutaneous coronary interventions and is currently performed in 10% to 20% of procedures. Improved outcomes with newer generation drug-eluting stents require further research. Methods:The TARGET CTO trial (NCT03040934) is a prospective, multicenter, randomized, noninferiority trial that plans to randomize 196 subjects (1:1) to either a newer-generation sirolimus target-eluting stent or an everolimus-eluting stent. Patients are candidates if they present with at least 1 CTO lesion in a native coronary artery with a diameter of ≥2.50 mm to ≤4.00 mm and a length of <100 mm. In addition, 44 subjects will participate in an optical coherence tomography (OCT) substudy. Clinical follow-up is planned up to 5 years after stent implantation. Angiographic follow-up is planned at 12 months, whereas OCT will be obtained after the procedure, at 3 and 12 months. The primary end point is in-stent late lumen loss by quantitative coronary angiography at 12 months. The key secondary end point is neointimal thickness by OCT at 3 months. Imaging end points are assessed by an independent core lab. Clinical end points are adjudicated by an independent clinical events committee. Conclusion:The TARGET CTO trial compares a sirolimus target-eluting stent with an everolimus-eluting stent for management of CTOs according to contemporary interventional practices. The primary angiographic end points will be reported at 12 months and clinical follow-up will continue for up to 5 years.

[This retracts the article DOI: 10.3892/etm.2016.3236.].

Even though patients with pulmonary embolism usually present with respiratory distress and tachycardia, the patient presented with syncope only. Typical ECG changes associated with PE include right axis deviation, right bundle-branch block, S1Q3T3 pattern, arrhythmia, nonspecific ST-segment changes, QR pattern in lead V1, Brugada ECG pattern, and T-wave inversions in the precordial leads. However, his electrocardiogram showed QT-interval prolongation and simultaneous T-wave inversions in the inferior and anterior leads. This ECG pattern is crucial for diagnosing PE. The patient underwent computed tomography-pulmonary angiography, which revealed pulmonary embolism. At the same time, these ECG changes should be differentiated from those of long QT syndrome, myocardial ischemia, Takotsubo cardiomyopathy, post-pacing T-wave memory, hypertrophic cardiomyopathy, and subarachnoid hemorrhage.

Ivabradine (Iva), a heart rate reducing agent that specifically inhibits the pacemaker I(f) ionic current, has been demonstrated to be cardioprotective in many cardiovascular diseases. Autophagy is an evolutionarily conserved metabolic process that regulates cardiac homeostasis. This study is aimed to explore whether autophagy is functionally involved in the cardioprotective effect of Iva in a rat model of myocardial infarction (MI). We observed that Iva treatment (po, 10 mg/kg/day) showed significant recovery on the hemodynamics parameters in MI rats, including left ventricular systolic pressure, left ventricular end diastolic pressure, and maximal ascending/descending rate of left ventricular pressure. Also, Iva treatment dramatically decreased infarct size, inhibited myocardial apoptosis, and reduced the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in MI rats. Moreover, Iva treatment enhanced autophagy and inhibited PI3K/AKT/mTOR/p70S6K pathway in MI rats. Simultaneously, we observed that autophagy enhancer rapamycin (ip, 10 mg/kg/day) showed similar cardioprotective effects with Iva. Furthermore, we observed that addition of autophagy inhibitor 3-methyladenine (ip, 10 mg/kg/day) counteracted the therapeutic effect of Iva, addressing that Iva attenuated post-MI cardiac injury by enhancing autophagy. In summary, these findings demonstrated that Iva attenuated MI in rats by enhancing autophagy, and PI3K/AKT/mTOR/p70S6K pathway might be involved in the process. Autophagy activation by Iva may be a potential therapeutic strategy for the treatment of MI.

Oxidized low-density lipoprotein (ox-LDL)-induced endothelial dysfunction plays an important role in the initiation and development of cardiovascular diseases, especially atherosclerosis (AS). Protease-activated receptor 2 (PAR-2) is a receptor for inflammatory proteases. However, the biological function of PAR-2 in endothelial cells and the pathophysiological process of AS are still unknown. In the current study, we found that treatment with ox-LDL increased the gene and protein expressions of PAR-2 in EA.hy926 endothelial cells. Interestingly, we found that antagonism of PAR-2 with its specific antagonist AZ3451 could ameliorate ox-LDL-induced lactate dehydrogenase (LDH) release. Treatment with AZ3451 considerably improved the mitochondrial function by restoring the mitochondrial membrane potential and increasing the levels of intracellular adenosine triphosphate (ATP). Also, we found that AZ3451 attenuated ox-LDL-induced expression and production of pro-inflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8). Treatment with AZ3451 also mitigated the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Notably, our results demonstrated that the presence of AZ3451 alleviated ox-LDL-induced expression of the endothelial cell adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1). Mechanistically, we found that AZ3451 attenuated ox-LDL-induced activation of nuclear factor-κB (NF-κB) by reducing the levels of intracellular NF-κB p65 and the luciferase activity of NF-κB promoter. Based on these findings, we conclude that PAR-2 might become a novel therapeutic target for the treatment of AS.

BACKGROUND:Expression of cholecystokinin is found in myocardial tissues as a gastrointestinal hormone and may be involved in cardiovascular regulation. However, it is unclear whether there is an increase in cholecystokinin expression in myocardial hypertrophy progression induced by abdominal aortic constriction. The study is aimed at exploring the relationship between cholecystokinin expression and myocardial hypertrophy.METHODS:We randomly divided the 70 Sprague-Dawley rats into two groups: the sham operation group and the abdominal aortic constriction group. The hearts of rats were measured by echocardiography, and myocardial tissues and blood were collected at 4 weeks, 8 weeks, and 12 weeks after surgery. Morphological changes were assessed by microscopy. The cholecystokinin expression was evaluated by immunochemistry, Western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay.RESULTS:The relative protein levels of cholecystokinin were significantly increased in the abdominal aortic constriction groups compared with the corresponding sham operation groups at 8 weeks and 12 weeks. The cholecystokinin mRNA in the abdominal aortic constriction groups was significantly higher than the time-matched sham operation groups. Changes in the left ventricular wall thickness were positively correlated with the relative protein levels of cholecystokinin and the mRNA of cholecystokinin.CONCLUSIONS:The development of myocardial hypertrophy can affect the cholecystokinin expression of myocardial tissues.

Circular RNAs (circRNAs) are widely expressed in mammals and act as regulatory targets in the atherogenesis. The objective of this study was to research the biological role and molecular mechanism of circ_0093887 in oxidized low-density lipoprotein (ox-LDL)-induced atherosclerosis (AS) of human aortic endothelial cells (HAECs). Cell viability detection was performed by CCK-8 assay. Inflammatory molecules were examined using ELISA. Flow cytometry was used to measure cell-cycle progression and cell apoptotic rate. Caspase 3 activity was determined using caspase 3 activity assay. The expression levels of circ_0093887, miR-876-3p, CCND2 and SUCNR1 were assayed by quantitative real-time polymerase chain reaction (qRT-PCR). Dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays were used for the target analysis. EdU assay, wound healing assay/transwell assay and tube formation assay were, respectively, used to assess the effects of circ_0093887/miR-876-3p axis on cell proliferation, migration and tube formation. Oxidized low-density lipoprotein inhibited cell viability and cell-cycle progression but induced the inflammatory response and cell apoptosis. Circ_0093887 was downregulated and miR-876-3p was upregulated in AS patients and ox-LDL-treated HAECs. Functionally, the overexpression of circ_0093887 abrogated the cell injury of HAEC exposed to ox-LDL. For the functional mechanism, we found that circ_0093887 was a sponge for miR-876-3p and miR-876 targeted CCND2 or SUCNR1. The reverted experiment indicated that the function of circ_0093887 was achieved by sponging miR-876-3p. Meanwhile, miR-876-3p inhibitor relieved the inhibitory regulation of circ_0093887 knockdown in cell proliferation, migration and tube formation. Downregulation of miR-876-3p also alleviated the ox-LDL-induced cell injury by upregulating the expression of CCND2 or SUCNR1. Furthermore, circ_0093887 was validated to regulate the levels of CCND2 and SUCNR1 via the sponge effect on miR-876-3p. The protective effects of circ_0093887 on HAECs from ox-LDL were also ​alleviated by repressing the CCND2 and SUCNR1 levels. These findings suggested that circ_0093887 protected HAEC against the ox-LDL-induced inflammatory and apoptotic damages by targeting the miR-876-3p/CCND2 or miR-876/SUCNRA axis. Circ_0093887 could act as a potential therapeutic biomarker for AS patients.

One-to-one atrioventricular conduction (AVC) during atrial flutter (AFL) is one of the most life-threatening arrhythmias and hemodynamically perilous. We present the diagnostic and analytical strategy for a patient who developed a paroxysm of AFL with 1:1 AVC. We did Brugada’s stepwise approach and the ventricular tachycardia (VT) score for the diagnosis. Meanwhile, we did RS/QRS ratio in lead V6. Through observations of the dynamic changes during and after amiodarone treatment, we made the diagnosis. Firstly, we calculated the VT score, and the result showed score 1. Secondly, we made Brugada’s stepwise approach to exclude VT. Meanwhile, we did RS/QRS ratio in lead V6, and the result showed the rate of 0.369 (<0.41, cut off 0.41). The result also suggested that the wide QRS AV tachycardia was not VT. Finally, amiodarone was administered under the guidance of a cardiovascular physician. Through observations of the dynamic changes during and after amiodarone treatment, the electrocardiogram (ECG) showed AFL with 2:1 AVC. The AFL rate was the same as the rate of rapid arrhythmia attack. Retrospectively, the rapid arrhythmia ECG was diagnosed as AFL with 1:1 rapid wide QRS AVC. AFL with 1:1 AVC is an uncommon but challenging arrhythmia. Brugada’s stepwise approach and the VT score can assist clinical physicians in making the diagnosis. In our study, we also verify that the RS/QRS ratio in lead V6 is beneficial to differentiate supraventricular tachycardia (SVT) with a right bundle branch block (RBBB) pattern from VT. Through observation of the changes of ECG before and after amiodarone, we can make the diagnosis. One should be conscious of the different presentations of AFL with 1:1 wide QRS AVC to avoid misdiagnosis and mismanagement.

Background: Zeaxanthin is a newly discovered natural product in β-carotenoid family with multiple bioactivities. Recently, it has been shown that zeaxanthin may have cardioprotective effects in several studies, but its mechanisms have not been fully investigated. Herein, we explored the role and mechanism of zeaxanthin in myocardial injury. Methods and Results: In this study, three different models were used to investigate the mechanism by which zeaxanthin alleviates myocardial injury. H9C2 Cardiomyocyte injury models were induced by H 2 O 2 . TUNEL assay, Flow cytometry, and Western blot analysis showed that treatment with zeaxanthin significantly decreased cardiomyocyte apoptosis and apoptosis-related protein expression. And reactive oxygen species (ROS) measurement analysis and Western blot analysis showed that treatment with zeaxanthin also could reduce the production of ROS and affect the expression of p38-Mitogen activated protein kinase/nuclear factor-κ gene bindin (p38MAPK/NF-κB) signaling pathway. Transforming Growth Factor-β1 (TGF-β1) was used to establish the fibrosis model in cardiac fibroblasts (CFs). QRT-PCR and Western blot analysis showed that treatment with zeaxanthin significantly decreased the expression of fibrosis markers in CFs. Myocardial injury animal models were induced by high-fat diet (HFD). Our results demonstrated that zeaxanthin improved fibrosis damage and cardiomyocyte apoptosis in HFD mice. Furthermore, Western blot analysis showed that TGF-β/Drosophila mothers against decapentaplegic2/3 (TGF-β/Smad2/3) signaling pathway related protein p-Smad2/3, Smad2/3, and TGF-β1 were significantly downregulated by zeaxanthin treatment. Conclusions: Zeaxanthin may alleviate HFD and H 2 O 2 -induced heart injury by regulating TGF-β/Smad2/3 and p38MAPK/NF-κB signaling pathways, which is of immense clinical significance in the treatment of cardiovascular disease.

BACKGROUND AND AIMS: The G-protein-coupled receptor 43 (GPR43) is a post- transcriptional regulator involved in cholesterol metabolism. Our previous studies demonstrated that intracellular cholesterol accumulation contributed to podocyte injury in diabetic nephropathy (DN). This study aimed to investigate possible roles of GPR43 activation in lipid nephrotoxicity in DN and to explore its potential mechanisms. METHOD: The experiments were conducted by using diabetic GPR43 knockout mice and cell culture model of podocytes. Renal pathological changes were checked by periodic acid schiff staining, immunohistochemical staining and transmission electron microscopy (TEM). The lipid deposition and free cholesterol contents in kidney tissues were detected by Oil Red O staining, BODIPY staining, and cholesterol quantitative assay. The protein expressions of GPR43, LC3II, p62 and related molecules of LDLR pathway in kidney tissues and podocytes were detected by real-time PCR, immunofluorescent staining, and Western blotting. RESULTS: There were decreased plasma level of LDL-cholesterol and cholesterol accumulation in kidney tissues of diabetic GPR43 knockout mice. In vitro study demonstrated that acetate, a stimulator of GPR43, increased LDLR-mediated cholesterol uptake in podocytes, accompanied with reduced cholesterol autophagic degeneration, characterized by inhibited LC3 maturation, p62 degradation, and autophagosome formation. These may evoke synergistic effects attributing to cellular cholesterol accumulation in podocytes. While genetic knockdown or pharmacological inhibition of GPR43 inhibited this effect in podocytes. Furthermore, the activation of GPR43 led to the activation of ERK1/2/EGR1 pathway in podocytes, whereas blocking ERK1/2 activity or reducing EGR1 expression reversed cholesterol influx and the inhibition of autophagy mediated by GPR43 activation in podocytes. Meanwhile, deletion of the GPR43 improved autophagy and inhibited the ERK1/2-EGR1 pathway of podocyte in diabetic mice in vivo . CONCLUSION: Activation of the GPR43 mediated lipid nephrotoxicity contributes to podocyte injury in DN, which was mainly through the activation of ERK/EGR1 pathways. These findings suggested that the GPR43 receptor could be a potential therapeutic target for the prevention of DN progression. protein/creatinine spot) endpoint 50% in disease (ESKD) or regression adjusted for potential confounders or modifiers including eGFR calculated using the CKD-EPI equation and Mixed models were adjusted to study longitudinal