Improving therapeutic effects of exosomes encapsulated gelatin methacryloyl/hyaluronic acid blended and oxygen releasing injectable hydrogel by cardiomyocytes induction and vascularization in rat myocardial infarction model.

Acute myocardial infarction (AMI) causes acute cardiac cell death when oxygen supply is disrupted. Improving oxygen flow to the damaged area could potentially achieve the to prevent cell death and provide cardiac regeneration. Here, we describe the production of oxygen-producing injectable bio-macromolecular hydrogels from natural polymeric components including gelatin methacryloyl (GelMA), hyaluronic acid (HA) loaded with catalase (CAT). Under hypoxic conditions, the O2-generating hydrogels (O2 (+) hydrogel) encapsulated with Mesenchymal stem cells (MSCs)-derived-exosomes (Exo- O2 (+) hydrogel) released substantial amounts of oxygen for >5 days. We demonstrated that after 7 days of in vitro cell culture, exhibits identical production of paracrine factors compared to those of culture of rat cardiac fibroblasts (RCFs), rat neonatal cardiomyocytes (RNCs) and Human Umbilical Vein Endothelial Cells (HUVECs), demonstrating its ability to replicate the natural architecture and function of capillaries. Four weeks after treatment with Exo-O2 (+) hydrogel, cardiomyocytes in the peri-infarct area of an in vivo rat model of AMI displayed substantial mitotic activity. In contrast with infarcted hearts treated with O2 (-) hydrogel, Exo- O2 (+) hydrogel infarcted hearts showed a considerable increase in myocardial capillary density. The outstanding therapeutic advantages and quick, easy fabrication of Exo- O2 (+) hydrogel has provided promise favourably for potential cardiac treatment applications.

A higher non-HDL-C/HDL-C ratio was associated with an increased risk of progression of nonculprit coronary lesion in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: The ratio of nonhigh-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) has been shown associated with various metabolic diseases and atherosclerosis in primary prevention. However, there is limited evidence on the relationship between the non-HDL-C/HDL-C ratio and progression of nonculprit coronary lesion (NCCL) after percutaneous coronary intervention (PCI). HYPOTHESIS: Our study aimed to investigate the potential association between the non-HDL-C/HDL-C ratio and NCCL progression in patients with acute coronary syndrome (ACS) undergoing PCI. METHODS: We conducted a retrospective analysis of ACS patients who underwent coronary angiography twice at a single center from 2016 to 2022. Lipid measurements, demographic, clinical, and other laboratory data were collected from electronic medical records. NCCLs were evaluated using quantitative coronary angiography. The primary outcome was the progression of NCCL. Patients were categorized based on NCCL progression and tertiles of the non-HDL-C/HDL-C ratio. Associations were analyzed using univariate and multivariate logistic regression analysis. RESULTS: The study included 329 ACS patients who underwent PCI, with a median follow-up angiography of 1.09 years. We found NCCL progression in 95 (28.9%) patients with acceptable low-density lipoprotein cholesterol control (median: 1.81 mmol/L). Patients in the top tertile of the non-HDL-C/HDL-C ratio had a higher risk of NCCL progression. After adjusting for potential confounding factors, the non-HDL-C/HDL-C ratio remained a significant predictor for NCCL progression (adjusted odds ratio: 1.45; 95% confidence interval: 1.14-1.86; p < 0.05). CONCLUSIONS: The non-HDL-C/HDL-C ratio predicts NCCL progression in ACS patients following PCI, providing a valuable tool for risk assessment and enhancing secondary prevention of atherosclerotic cardiovascular disease.

Long-term outcomes of high-risk percutaneous coronary interventions under extracorporeal membrane oxygenation support: An observational study.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) offers hemodynamic support for patients undergoing high-risk percutaneous coronary interventions (PCIs). However, long-term outcomes associated with VA-ECMO have not previously been studied. AIM: To explore long-term outcomes in high-risk cases undergoing PCI supported by VA-ECMO. METHODS: In the present observational cohort study, 61 patients who received VA-ECMO-supported high-risk PCI between April 2012 and January 2020 at the Sixth Medical Center of Chinese People's Liberation Army General Hospital were enrolled. The endpoint characteristics such as all-cause mortality, repeated cardiovascular diseases, and cardiac death were examined. RESULTS: Among 61 patients, three failed stent implantation due to chronic total occlusions with severely calcified lesions. One patient showed VA-ECMO intolerance because of high left ventricular afterload. PCI was successfully performed in 57 patients (93.4%). The in-hospital mortality was 23.0%, and the overall survival was 45.9%, with a median follow-up period of 38.6 (8.6-62.1) mo. CONCLUSION: VA-ECMO can be used as a support in patients undergoing high-risk PCI as it is associated with favorable long-term patient survival.

AngioJet rheolytic thrombectomy in patients with thrombolysis in myocardial infarction thrombus grade 5: an observational study.

The aim of this study was to evaluate the effectiveness and safety of AngioJet rheolytic thrombectomy among patients with high thrombus burden. Routine manual thrombus aspiration in patients with ST-segment elevation myocardial infarction (STEMI) does not improve clinical outcomes and was associated with an increased rate of stroke. However, the safety of mechanical thrombus aspiration is still unknown. This was a retrospective, single-center study involving 621 patients with Thrombolysis In Myocardial Infarction thrombus grade 5. The primary outcome was the composite of major adverse cardiovascular events (MACE) within 12 months. The safety outcome was stroke within 1-year. Propensity matching score was calculated due to the significant baseline differences between the AngioJet rhelytic thrombectomy group and the routine treatment group. AngioJet rheolytic thrombectomy was performed in 117 patients. After propensity-score matching, there was no significant difference both in the incidence of MACE (11.1% vs 17.9%, hazard ratio, 1.641; 95% confidence interval [CI] 0.822 to 3.277, p = 0.161) and the incidences of stroke (1.7% vs 2.6%, hazard ratio 1.522; 95% confidence interval [CI] 0.254 to 9.107, p = 0.646) between two groups at 1-year follow-up. In patients with Thrombolysis In Myocardial Infarction thrombus grade 5, AngioJet rheolytic thrombectomy did not improve clinical outcomes at 1 year. However, AngioJet rheolytic thrombectomy did not increase the risk of stroke in patients with high thrombus burden.

[Screening of LDLR gene mutations in nine patients with familial hypercholesterolemia].

OBJECTIVE: To screen for LDLR gene mutations in 9 patients with familial hypercholesterolemia (FH). METHODS: All exons of the LDLR gene and flanking intronic sequences were amplified by PCR and subjected to automatic DNA sequencing. For patients with homozygous or compound heterozygous mutations, parental DNA sequencing or T cloning sequencing was carried out to determine the parental origin of the mutant alleles. RESULTS: Direct sequencing of PCR products revealed 8 LDLR variants in 7 patients, which included c.259T>G, c.513delC, c.530C>T, c.682G>T, c.763C>T, c.1187-10G>A, c.1948delG, and c.1730G>A, among which c.1948delG was novel. Four patients have carried heterozygous mutations, two carried homozygous mutations, and one carried compound heterozygous mutations. The patients with biallelic mutations presented with a more severe phenotype compared those carrying heterozygous mutations. CONCLUSION: LDLR mutations were identified in 7 out of 9 patients with FH. Among the 8 identified LDLR mutations, c.1948delG was firstly reported. Above findings have expanded the mutation spectrum of LDLR gene.

Prevalence and composition of CHD at different altitudes in Tibet: a cross-sectional study.

BACKGROUND: The prevalence of CHD has been well described worldwide except in Tibet. This study aimed to illustrate the prevalence and composition of CHD in Tibetan children according to altitude. Methods and results In the first part, we prospectively recruited 7088 unselected Tibetan children (4-17 years) from south-west Tibet. The total prevalence of CHD increased from 4.6/1000 below 4200 m to 13.4/1000 above 4700 m, with a female-to-male ratio of 1.3:3.1. The total prevalence and female prevalence of patent ductus arteriosus increased more than 10-fold. Females living above 4700 m had exceptionally high prevalence of patent ductus arteriosus (14.9/1000). The prevalence of atrial septal defect was comparable among different altitudes (3.3-3.8/1000). The prevalence of ventricular septal defect was 1.3/1000 below 4700 m, and no cases were found above this altitude. In the second part, we retrospectively reviewed the clinical data of 383 CHD children in Tibet and 73 children at lower altitudes. The percentage of isolated ventricular septal defect decreased from 54.8 to 3.1%, and the percentage of isolated patent ductus arteriosus increased from 8.2 to 68.4% with elevation. Children living below 4200 m (10.4-13.7%) had a larger proportion of complex CHD than those above this altitude (2.0-3.1%). Of the 20 Tibetan children with complex CHD, 14 (70.0%) lived below 4200 m. CONCLUSIONS: A wide variation in CHD prevalence and composition existed in Tibetan children among different altitudes.

Transthoracic contrast echocardiography using vitamin B6 and sodium bicarbonate as contrast agents for the diagnosis of patent foramen ovale.

To evaluate the utility of transthoracic contrast echocardiography (cTTE) using vitamin B6 and sodium bicarbonate as contrast agents for diagnosing right-to-left shunt (RLS) caused by patent foramen ovale (PFO) compared to that of transesophageal echocardiography (TEE). We investigated 125 patients admitted to our neurology department with unexplained cerebral infarction and migraine. All patients underwent cTTE using vitamin B6 and sodium bicarbonate as contrast agents, after which they underwent transthoracic echocardiography. The Doppler signal was recorded during the Valsalva maneuver, and TEE examinations were performed. The feasibility, diagnostic sensitivity, and safety of cTTE and TEE for PFO recognition were compared. Evidence of PFO was found in 49 (39.20%) patients with cTTE, more than were detected with TEE (39, 31.20%) (χ2=5.0625, P=0.0244). cTTE had a sensitivity of 92.31% and a specificity of 84.88% for diagnosing PFO, showing high concordance with TEE for PFO recognition (κ=0.72). Further, results of a semi-quantitative evaluation of PFO-RLS by cTTE were better than those with TEE (Z=-2.011, P=0.044). No significant adverse reaction was discovered during cTTE examination. cTTE using vitamin B6 and sodium bicarbonate as contrast agents has relatively good sensitivity and specificity for diagnosing RLS caused by PFO when compared with those for TEE. Using vitamin B6 and sodium bicarbonate as contrast agents to perform cTTE is recommended for detecting and diagnosing the PFO due to its simplicity, non-invasive character, low cost, and high feasibility.

High-Performance Personalized Heartbeat Classification Model for Long-Term ECG Signal.

Long-term electrocardiogram (ECG) has become one of the important diagnostic assist methods in clinical cardiovascular domain. Long-term ECG is primarily used for the detection of various cardiovascular diseases that are caused by various cardiac arrhythmia such as myocardial infarction, cardiomyopathy, and myocarditis. In the past few years, the development of an automatic heartbeat classification method has been a challenge. With the accumulation of medical data, personalized heartbeat classification of a patient has become possible. For the long-term data accumulation method, such as the holter, it is difficult to obtain the analysis results in a short time using the original method of serial design. The pressure to develop a personalized automatic classification model is high. To solve these challenges, this paper implemented a parallel general regression neural network (GRNN) to classify the heartbeat, and achieved a 95% accuracy according to the Association for the Advancement of Medical Instrumentation. We designed an online learning program to form a personalized classification model for patients. The achieved accuracy of the model is 88% compared to the specific ECG data of the patients. The efficiency of the parallel GRNN with GTX780Ti can improve by 450 times.

Resting Myocardial Contrast Echocardiography for the Evaluation of Coronary Microcirculation Dysfunction in Patients With Early Coronary Artery Disease.

BACKGROUND: Coronary microcirculation dysfunction can occur in patients with chest pain suggestive of coronary artery disease (CAD). The present study aimed to determine the diagnostic value of resting myocardial contrast echocardiography (MCE) for early CAD with myocardial microcirculation dysfunction by evaluating the continuous imaging time, peak time, and peak intensity. HYPOTHESIS: Resting MCE is an effective and noninvasive method for evaluation of coronary microcirculation dysfunction in patients with early coronary artery disease. METHODS: The present study included 20 consecutive patients without obvious clinical evidence of early CAD and 20 healthy volunteers. Resting MCE was performed to evaluate the myocardial microcirculation perfusion, and the follow-up evaluation of myocardial microcirculation perfusion was performed with technetium 99 m 2-methoxy-isobutyl-isonitrile ((99m) Tc-MIBI) single-photon emission computed tomography (SPECT). RESULTS: Peak intensity was significantly lower in patients with high risk of CAD than in controls (P < 0.0001). The peak time and continuous imaging time were significantly higher in patients with high risk of CAD than in controls (P < 0.0001). None of the 40 subjects experienced discomfort, such as cough and chest tightness, during the resting MCE procedure, and the heart rate and blood pressure showed no abnormalities during the entire procedure. SPECT imaging showed reversible myocardial perfusion reduction in 80% (16/20) of the patients with high risk of CAD. Abnormalities of heart rate and blood pressure and adverse reactions were noted during the process of SPECT examination. CONCLUSIONS: Resting MCE is an effective and noninvasive method for detecting abnormalities of coronary microcirculation and can help in the clinical analysis, risk assessment, and treatment of early occult CAD.

Prevalence and predictors of decreased glomerular filtration rate in tibetan children with congenital heart disease.

OBJECTIVES: To assess the prevalence of decreased glomerular filtration rate (GFR) in Tibetan children with congenital heart disease (CHD) and its associated risk factors. METHODS: A total of 207 Tibetan children attending authors' center for treatment of CHD from May 2012 through November 2012, were included in the study. GFR was estimated with the Schwartz formula (eGFR). RESULTS: The mean eGFR was 104.3±16.6 mL/min/1.73 m2, and decreased in 21 children (10.1%). In the cyanotic category, eGFR was decreased only in severely cyanotic individuals. In the acyanotic category with left ventricular overload, children with decreased eGFR were younger, more commonly lived in areas above 4,700 m, and had higher left ventricular internal dimensions indexed by body surface areas (LVID/BSA) (53.8±6.9 vs. 40.1±6.8 mm/m2, P<0.001) compared with those with normal eGFR. Multivariate analysis identified LVID/BSA as the only independent predictor for decreased eGFR (OR: 1.329, 95% CI: 1.177~1.501, P<0.001). Receiver operating characteristic analysis showed the area under curve for LVID/BSA was 0.921 (95% CI: 0.863 ~ 0.980, P<0.001), with the optimal cutoff value of 49.8 mm/m2 (sensitivity: 75.0%, specificity: 93.9%). In the remaining category, decreased eGFR was only observed in those living above 4,700 m. CONCLUSIONS: One tenth of Tibetan children with CHD had decreased eGFR. The risk factors included severe cyanosis, younger age, living above 4,700 m and higher LVID/BSA.

Prevalence of symptomatic congenital heart disease in Tibetan school children.

The prevalence of congenital heart disease (CHD) in Tibet has not been fully investigated. The aim of this study was to illustrate and compare the prevalence of symptomatic CHD and its major subtypes in Tibetan children at different altitudes. A total of 5,790 children from regions at altitudes of 3,500 to 4,100 m (group L) and 4,548 children from 4,200 to 4,900 m (group H) were compared for CHD prevalence. Group H had greater prevalence of total CHD (12.09 vs 4.32 per 1,000, p <0.001), patent ductus arteriosus (PDA, 7.70 vs 1.38 per 1,000, p <0.001), and atrial septal defect (ASD, 3.52 vs 2.25 per 1,000, p = 0.23) than group L. The differences were more remarkable in women (CHD, 18.63 vs 4.88 per 1,000, p <0.001; PDA, 11.53 vs 1.74 per 1,000, p <0.001; ASD, 5.32 vs 2.79 per 1,000, p = 0.15). No significant difference was observed in the prevalence of ventricular septal defect between the 2 groups (0.44 vs 0.35 per 1,000, p >0.05). The most common cardiac defect was ASD (52.0%) in group L compared with PDA (63.6%) in group H. In group L, women had slightly and insignificantly greater prevalence of total CHD, PDA, and ASD than men. In contrast, the prevalence was almost threefold greater in women than men in group H. In conclusion, the CHD prevalence and composition differed significantly between populations of school children living above and below 4,200 m.