Multimodal data-driven prognostic model for predicting new-onset ST-elevation myocardial infarction following emergency percutaneous coronary intervention.

OBJECTIVES: We developed a nomogram model derived from inflammatory indices, clinical data, and imaging data to predict in-hospital major adverse cardiac and cerebrovascular events (MACCEs) following emergency percutaneous coronary intervention (PCI) in patients with new-onset ST-elevation myocardial infarction (STEMI). METHODS: Patients with new-onset STEMI admitted between June 2020 and November 2022 were retrospectively reviewed. Data pertaining to coronary angiograms, clinical data, biochemical indices, and in-hospital clinical outcomes were derived from electronic medical records. Lasso regression model was employed to screen risk factors and construct a prediction model. RESULTS: Overall, 547 patients with new-onset STEMI who underwent PCI were included and assigned to the training cohort (n = 384) and independent verification cohort (n = 163). Six clinical features (age, diabetes mellitus, current smoking, hyperuricemia, neutrophil-to-lymphocyte ratio, and Gensini score) were selected by LASSO regression to construct a nomogram to predict the risk of in-hospital MACCEs. The area-under-the-curve (AUC) values for in-hospital MACCEs risk in the training and independent verification cohorts were 0.921 (95% CI 0.881-0.961) and 0.898 (95% CI 0.821-0.976), respectively. It was adequately calibrated in both training cohort and independent verification cohorts, and predictions were correlated with actual outcomes. Decision curve analysis demonstrated that the nomogram was capable of predicting in-hospital MACCEs with good clinical benefit. CONCLUSIONS: Our prediction nomogram based on multi-modal data (inflammatory indices, clinical and imaging data) reliably predicted in-hospital MACCEs in new-onset STEMI patients with emergency PCI. This prediction nomogram can enable individualized treatment strategies.

Serum total bilirubin and long-term prognosis of patients with new-onset non-ST elevation myocardial infarction: a cohort study.

BACKGROUND: The potential prognostic role of total bilirubin (TBIL) in patients with new-onset non-ST elevation myocardial infarction (NSTEMI) is not fully understood. This study aims to evaluate the potential predictive value of TBIL for long-term prognosis in patients with new-onset NSTEMI. METHODS: Patients with new-onset NSTEMI that underwent emergency coronary angiography in our department from June 2015 to March 2020 were included. Baseline TBIL was measured at admission. SYNTAX scores were used to indicate the severity of coronary lesions. The association between TBIL and SYNTAX scores was analyzed using multivariate logistic regression. The patients were followed for the incidence of major adverse cardiac and cerebrovascular events (MACCEs). The association between TBIL and MACCEs was analyzed using Kaplan-Meier survival methods. RESULTS: In total 327 patients were included in this study. Patients were divided according to tertiles of TBIL (first tertile < 10.23 µmol/L, n = 109; second tertile 10.23-14.30 µmol/L, n = 109; and third tertile ≥ 14.30 µmol/L, n = 109). TBIL was independently associated with the severity of coronary lesions in patients with NSTEMI, with an adjusted odds ratio (OR) and 95% confidence interval (CI) for the third tertile and the second tertile compared with the first tertile of TBIL of 2.259 (1.197-4.263) and 2.167 (1.157-4.059), respectively (both p < 0.05). After a mean follow-up of 30.33 months, MACCE had occurred in 57 patients. TBIL was independently associated with the increased risk of MACCEs, with an adjusted hazard ratio (HR) and 95% CI for the third tertile and the second tertile compared with the first tertile of TBIL of 2.737 (1.161-6.450) and 3.272 (1.408-7.607), respectively (both p < 0.05). CONCLUSIONS: Higher myocardial infarction admission TBIL might independently predict poor prognosis in patients with NSTEMI.

Association between adiponectin-to-leptin ratio and heart rate variability in new-onset paroxysmal atrial fibrillation: A retrospective cohort study.

BACKGROUND: The adiponectin-to-leptin (A/L) ratio has been identified as a potential surrogate biomarker for metabolic disorders. However, it remains unknown whether the serum A/L ratio is associated with heart rate variability in paroxysmal atrial fibrillation (AF). METHODS: For this retrospective study, we included consecutive patients who underwent 24-h long-range electrocardiogram examination in our center for paroxysmal AF. The results of echocardiography, heart rate variability tests, and blood tests were also retrieved. Multivariate line regression analysis was performed to evaluate identify factors independently associated with heart rate variability. RESULTS: Among the 85 included patients with paroxysmal AF, the median A/L ratio was 1.71. Univariate analysis indicated that patients with a low A/L ratio (<1.71, n = 42) had a lower high-frequency (HF) power and a higher hs-CRP level, low-frequency (LF) power, and LF/HF ratio than those with a high A/L ratio (≥1.71, n = 43). Multivariate linear regression analysis showed that the serum leptin concentration was independently and positively associated with LF (ß = 0.175, p = .028), while the serum adiponectin concentration was independently and positively associated with HF (ß = 0.321, p = .001). Moreover, the A/L ratio was independently and negatively associated with the LF/HF ratio (ß = -0.276, p = .007). CONCLUSIONS: The A/L ratio was independently and negatively associated with the LF/HF ratio in patients with new-onset paroxysmal AF.

miR-381-3p inhibits high glucose-induced vascular smooth muscle cell proliferation and migration by targeting HMGB1.

BACKGROUND: Hyperglycemia increases the risk of many cardiovascular diseases (CVD), and the dysregulation of proliferation and migration in vascular smooth muscle cells (VSMCs) also participates in the pathogenesis of CVD. miR-381-3p is known to suppress the proliferation and migration of multiple human cell types. Nevertheless, the function of miR-381-3p in VSMCs remains largely indistinct. METHODS: A quantitative real-time polymerase chain reaction (qRT-PCR) was employed to investigate miR-381-3p expression in high-glucose-induced VSMCs. Inflammatory cytokines tumor necrosis factor-α, interleukin-1ß and interleukin-6, as well as oxidative stress markers SOD and MDA, were determined by an enzyme-linked immunosorbent assay. Reactive oxygen species generation was examined using a 2,7'-dichlorofluorescein kit. The proliferation, migration and apoptosis of VSMCs were monitored by 3-(4,5-dimethylthiazl2-yl)-2,5-diphenyltetazolium bromide (MTT), transwell and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays. The TargetScan database (http://www.targetscan.org) was employed to seek the potential target gene of miR-381-3p. Interaction between miR-381-3p and HMGB1 was determined by a qRT-PCR, western blotting and a luciferase reporter assay. RESULTS: miR-381-3p expression was significantly reduced in a VSMCs dysfunction model induced by high-glucose in a dose- and time-dependent manner. Transfection of miR-381-3p mimics suppressed the inflammation, oxidative stress, proliferation and migration of VSMCs, whereas apoptosis of VSMCs was promoted, and the transfection of miR-381-3p inhibitors had the opposite effect. Mechanistically, HMGB1, an important factor in inflammation response, was confirmed as a target gene of miR-381-3p. CONCLUSIONS: miR-381-3p targets HMGB1 to suppress the inflammation, oxidative stress, proliferation and migration of high-glucose-induced VSMCs by targeting HMGB1.

Zero-fluoroscopy approach for ablation of supraventricular tachycardia using the Ensite NavX system: a multicenter experience.

BACKGROUND: Three-dimensional electroanatomic mapping systems have demonstrated a significant reduction in radiation exposure during radiofrequency catheter ablation procedures. We aimed to investigate the safety, feasibility and efficacy of a completely zero-fluoroscopy approach for catheter ablation of supraventricular tachycardia using the Ensite NavX navigation system compared with a conventional fluoroscopy approach. METHODS: A multicenter prospective non-randomized registry study was performed in seven centers from January 2013 to February 2018. Consecutive patients referred for catheter ablation of supraventricular tachycardia were assigned either to a completely zero-fluoroscopic approach (ZF) or conventional fluoroscopy approach (CF) according to the operator's preference. Patients with atrial tachycardia were excluded. RESULTS: Totally, 1020 patients were enrolled in ZF group; 2040 patients ablated by CF approach were selected for controls. There was no significant difference between the zero-fluoroscopy group and conventional fluoroscopy group as to procedure time (60.3 ± 20.3 vs. 59.7 ± 22.6 min, P = 0.90), immediate success rate of procedure (98.8% vs. 99.2%, P = 0.22), arrhythmia recurrence (0.4% vs. 0.5%, P = 0.85), total success rate of procedure (98.4% vs. 98.8%, P = 0.39) or complications (1.1% vs. 1.5%, P = 0.41). Compared with the conventional fluoroscopy approach, the zero-fluoroscopy approach provided similar outcomes without compromising the safety or efficacy of the procedure. CONCLUSION: The completely zero-fluoroscopy approach demonstrated safety and efficacy comparable to a conventional fluoroscopy approach for catheter ablation of supraventricular tachycardia, and mitigated radiation exposure to both patients and operators. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03042078; first registered February 3, 2017; retrospectively registered.

Effects of mir-21 on Cardiac Microvascular Endothelial Cells After Acute Myocardial Infarction in Rats: Role of Phosphatase and Tensin Homolog (PTEN)/Vascular Endothelial Growth Factor (VEGF) Signal Pathway.

BACKGROUND This study investigated how miR-21 expression is reflected in acute myocardial infarction and explored the role of miR-21 and the PTEN/VEGF signaling pathway in cardiac microvascular endothelial cells. MATERIAL AND METHODS We used an in vivo LAD rat model to simulate acute myocardial infarction. MiR-21 mimics and miR-21 inhibitors were injected and transfected into model rats in order to alter miR-21 expression. Cardiac functions were evaluated using echocardiographic measurement, ELISA, and Masson staining. In addition, lenti-PTEN and VEGF siRNA were transfected into CMEC cells using standard procedures for assessing the effect of PTEN and VEGE on cell proliferation, apoptosis, and angiogenesis. MiR-21, PTEN, and VEGF expressions were examined by RT-PCR and Western blot. The relationship between miR-21 and PTEN was determined by the luciferase activity assay. RESULTS We demonstrated that miR-21 bonded with the 3'-UTR of PTEN and suppressed PTEN expressions. Established models significantly induced cardiac infarct volume and endothelial injury marker expressions as well as miR-21 and PTEN expressions (P<0.05). MiR-21 mimics exhibited significantly protective effects since they down-regulated both infarction size and injury marker expressions by increasing VEGF expression and inhibiting PTEN expression (P<0.05). In addition, results from in vitro research show that lenti-PTEN and VEGF siRNA can notably antagonize the effect of miR-21 on cell proliferation, apoptosis, and angiogenesis (P<0.05). CONCLUSIONS MiR-21 exerts protective effects on endothelial injury through the PTEN/VEGF pathway after acute myocardial infarction.

Effects of VKORC1 Genetic Polymorphisms on Warfarin Maintenance Dose Requirement in a Chinese Han Population.

BACKGROUND VKORC1 is reported to be capable of treating several diseases with thrombotic risk, such as cardiac valve replacement. Some single-nucleotide polymorphisms (SNPs) in VKORC1 are documented to be associated with clinical differences in warfarin maintenance dose. This study explored the correlations of VKORC1-1639 G/A, 1173 C/T and 497 T/G genetic polymorphisms with warfarin maintenance dose requirement in patients undergoing cardiac valve replacement. MATERIAL AND METHODS A total of 298 patients undergoing cardiac valve replacement were recruited. During follow-up, clinical data were recorded. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to detect VKORC1-1639 G/A, 1173 C/T and 497 T/G polymorphisms, and genotypes were analyzed. RESULTS Correlations between warfarin maintenance dose and baseline characteristics revealed statistical significances of age, gender and operation methods with warfarin maintenance dose (all P<0.05). Warfarin maintenance dose in VKORC1-1639 G/A AG + GG carriers was obviously higher than in AA carriers (P<0.001). As compared with patients with TT genotype in VKORC1 1173 C/T, warfarin maintenance dose was apparently higher in patients with CT genotype (P<0.001). Linear regression analysis revealed that gender, operation method, method for heart valve replacement, as well as VKORC1-1639 G/A and 1173 C/T gene polymorphisms were significantly related to warfarin maintenance dose (all P<0.05). CONCLUSIONS VKORC1 gene polymorphisms are key genetic factors to affect individual differences in warfarin maintenance dose in patients undergoing cardiac valve replacement; meanwhile, gender, operation method and method for heart valve replacement might also be correlate with warfarin maintenance dose.

Half versus normal saline irrigation during catheter ablation of outflow tract ventricular arrhythmias (HALF): a multi-center, parallel, open-label, randomized controlled study.

BACKGROUND: Animal studies demonstrated that deeper lesions could be achieved during radio-frequency catheter ablation (RFCA) by using half saline (HS) compared to normal saline (NS) as irrigation. OBJECTIVES: This study sought to compare the efficiency and safety of HS and NS for irrigation during RFCA of idiopathic outflow tract ventricular arrhythmia (OT-VA). METHODS: In this multicenter, randomized controlled study, 167 patients undergoing RFCA of OT-VA were randomized 1:1 to receive HS- or NS-irrigated ablation. Acute success was defined as the absence of induced targeted premature ventricular contraction (PVC) at the end of the procedure. The 6-month success was defined as a ≥ 80% reduction of pre-procedural PVC burden. RESULTS: There were no differences of baseline characteristics between the HS and NS group. Patients in HS group had shorter total ablation time (259.5 ± 155.5 S vs. 355.6 ± 230.7 S, P = 0.04) than that in NS group. The acute and 6-month success rates were similar between the HS and NS group (92.8 vs. 91.7%, P = 0.79; 90.9 vs. 92.1%, P = 0.79, respectively). No significant difference was observed in the incidence of steam pops between the HS and NS group (2.4 vs. 1.2%, P = 0.62). CONCLUSIONS: The ablation using HS irrigation achieved similar success rate and safety compared to that using NS irrigation but was associated with a shorter total ablation time. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200059205).

Sonodynamic therapy combined with phototherapy: Novel synergistic strategy with superior efficacy for antitumor and antiinfection therapy.

Phototherapy (PT), including photodynamic therapy (PDT) and photothermal therapy (PTT), has recently achieved significant advances in antitumor and antiinfection therapy. Sonodynamic therapy (SDT), as a novel noninvasive therapy with a deeper penetration depth (>8 cm), fewer side effects and non-phototoxicity than PT, has drawn much attention in recent years. However, both PT and SDT have intrinsic limitations. By combining PT with SDT, the dualmodel therapy with advanced sensitizers overcome the intrinsic limitations and show higher efficacy than traditional monotherapy. Moreover, the photo-diagnosis modality could be easily integrated into synergistic therapy so that the sensitizer acts as a tracer for fluorescence/photoacoustic imaging, and the treatment process is visualized in a way that SDT combined with other therapies cannot achieve. This review summarizes the advanced sensitizers and the application of combination therapy, and explores the improvement strategies for promoting clinical transformation.

Malignant potential of H22 hepatocarcinoma cells increases after recovery from IFN-γ-mediated inhibition.

IFN-γ (interferon γ) can effectively suppress tumours, but it has also been found to promote tumour progression. However, the underlying mechanisms by which it enhances malignancy have not been fully elucidated. By using a mouse model that expresses IFN-γ locally in muscle, we found that the growth potential of tumours was increased after a quick decrease of IFN-γ. Furthermore, the up-regulation of IRF-2 (IFN regulatory factor 2) and down-regulation of IRF-1 were also found in the tumour cells. Along these lines, IFN-γ led to down-regulated expression of cyclin-D1, Bcl-2 and Bcl-xL and up-regulated expression of p21WAF1 and Bax in tumour cells. Yet, the expression of these genes, as well as activation of ERK (extracellular signal-regulated kinase) and NF-κB (nuclear factor-κB), was also reversed shortly after a decrease in IFN-γ, all of which resulted in increase tumour cell proliferation and apoptosis resistance. These findings indicate that the malignant potential of tumour cells may be suppressed by interfering with IRF-2 signalling pathways during and after decreased IFN-γ in tumour microenvironments.

Association between Serum Adiponectin and Atrial Fibrillation: A Case-Control Study Stratified by Age and Gender.

BACKGROUND: Circulating adiponectin has been suggested to be associated with atrial fibrillation (AF). However, whether the association differs by age and gender remains unknown. We performed a case-control study to evaluate the above association. METHODS: AF patients who underwent 24-hour long-range 12-channel electrocardiogram examination at our center were included in this study, and people with normal sinus rhythm (NSR) were included as controls. All participants underwent echocardiography and heart rate variability tests. Biochemical parameters and adiponectin levels were also evaluated. Receiver operating characteristic (ROC) analyses were used to determine the predictive efficacy of adiponectin for AF, and multivariate logistic regression analysis was performed to evaluate the potential independent predictors of AF. RESULTS: Overall, 84 patients with AF and 84 people with NSR were included. Serum adiponectin was significantly higher in AF patients compared to that in controls (P < 0.001). ROC analysis showed that higher serum adiponectin (>6.098 µg/mL) had predictive efficacy for AF, with an area under the curve of 0.660 (95% confidence interval [CI]: 577-0.742). The results of multivariate logistic regression analysis showed that higher adiponectin was an independent predictor of AF in the overall participants (odds ratio [OR] 1.224, 95% CI 1.018-1.471, P=0.032). Subgroup analysis showed that higher adiponectin was independently associated with AF in women (OR 1.893, 95% CI 1.160-3.089, P=0.011) and in patients aged < 65 years (OR 1.453, 95% CI 1.023-2.064, P=0.037), but not in men or those aged ≥ 65 years. CONCLUSIONS: Higher serum adiponectin level was independently associated with higher odds for AF in women and in participants <65 years old, but not in men or those aged ≥65 years.

Pulsed Field Ablation of Superior Vena Cava: Feasibility and Safety of Pulsed Field Ablation.

Background: Studies have shown that pulsed field ablation (PFA) has excellent effectiveness and safety in pulmonary vein isolation (PVI). However, there are few reports about the application of PFA, especially the alternating current (AC) biphase PFA, in superior vena cava (SVC) isolation, and its effectiveness and safety are still unclear. Objective: To investigate the efficacy and safety of the AC biphase PFA for SVC isolation, and to provide evidence for the clinical use of PFA for SVC. Methods: Eight pigs and two dogs were included in the study. PFA was delivered to these pigs and dogs. Pacing threshold and electrogram data were recorded before and after PFA. Voltage mapping of SCV was obtained before, after, and 3 weeks after PFA. At the end, all animals were euthanatized for gross pathology analysis. Results: For eight pigs, the median pacing threshold was 1.5 (1.4, 2.75) mA before PFA, while > 6.0 mA after PFA for all animals. The average electrogram amplitude reduction was 61.33 ± 24.90% for ablations with the initial amplitude≥0.5 mv. For two dogs, pacing threshold change and electrogram amplitude reduction were also observed. No phrenic palsy or sinus node injury was observed during PFA in any animal. Furthermore, voltage mapping showed that the voltage amplitude was significantly decreased in all animals and this could be kept for more than 3 weeks. Moreover, transmural tissue damage with reserved vessel and nerve were shown, no SVC stenosis was found at 3 weeks after PFA. Conclusion: PFA can effectively isolate SVC. Transmural tissue damage of SVC can be achieved without phrenic palsy, sinus node injury nor SVC stenosis.

Impact of CYP2C19 gene polymorphism on warfarin maintenance doses in patients with non-valvular atrial fibrillation.

BACKGROUND: Pharmacogenetics has provided compelling evidence towards the influence of gene polymorphisms on warfarin therapies. This study aimed to determine the impact of CYP2C19 gene polymorphism on warfarin maintenance doses in patients with non-valvular atrial fibrillation for the progress in overcoming obstacles facing warfarin pharmacogenetics. METHODS: In this study, we utilized polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to investigate the distribution of CYP2C19*2 and *3 gene polymorphism in patients with NVAF. In order to exclude the interference of basic indexes, we compared the association between different genotypes and warfarin maintenance doses. And the comparisons among extensive metabolizer, intermediate metabolizer and poor metabolizer were performed. RESULTS: CYP2C19 mutation accounted for 88.07% of in total NVAF patients, which was 7.38 times of CYP2C19*1/*1 (11.93%). No significant association was observed between different genotypes and basic indexes. The warfarin maintenance dose of patients with CYP2C19*1/*1 was significantly higher than those with other five genotypes (all P<0.05). Besides, the warfarin maintenance doses of patients with CYP2C19*1/*2 and *1/*3 were remarkably higher than those with *2/*2 and *2/*3 (P<0.05). The warfarin maintenance doses of patients with extensive metabolizer were dramatically higher than those with intermediate metabolizer and poor metabolizer (both P<0.05), and also the patients with intermediate metabolizer had higher warfarin maintenance doses than those with poor metabolizer (P<0.05). CONCLUSION: CYP2C19 gene polymorphism can affect maintenance dose of warfarin, with the amount of warfarin dose ranked among different genotypes as follow: CYP2C19*2/*2, CYP2C19*2/*3 and CYP2C19*3/*3

Possible association between serum alkaline phosphatase concentration and thoracicacute aortic dissection.

OBJECTIVES: Alkaline phosphatase (ALP) is an enzyme that catalyzes the hydrolysis of organic pyrophosphate. Accumulating data have demonstrated that the concentration of increased ALP is associated with C-reactive protein (CRP) concentration, and inflammation was complicated in the pathogenesis of acute aortic dissection (ADD). Therefore, the aim of our study was to examine the relationship between serum ALP concentration and thoracic ADD. METHODS: We retrieved demographic data and test results of biochemical data of 68 patients with thoracic ADD and 126 Non-thoracic ADD patients, retrospectively. RESULTS: A total of 194 patients were divided into thoracic ADD groups and non-thoracic ADD groups. Age, creatinine(Cr) and high-density lipoprotein cholesterol (HDL-C) were found to be statistical significance between the two groups. The mean ALP level was significantly higher in patients with thoracic ADD compared with Non-thoracic ADD patients (80.6±23.02 Vs. 65.9±16.49, P=0.001). Stepwise multiple logistic regression analyses revealed a significantly association of ALP with thoracic ADD (OR=1.038, 95% CI: 1.015-1.062, P=0.001). In addition, HDL-C was negative associated with thoracic ADD in multiple logistic regression analyses after adjustment for age, sex and Cr (OR=-0.083, 95% CI: 0.012-0.560, P=0.011). CONCLUSIONS: The present study suggests that the level of serum ALP is associated with thoracic ADD, and serum ALP concentration may be apotential risk factor for thoracic ADD.