Clinical Efficacy of Catheter Ablation in the Treatment of Vasovagal Syncope.

Catheter ablation of ganglionated plexi (GPs) performed as cardioneuroablation in the left atrium (LA) has been reported previously as a treatment for vasovagal syncope (VVS). However, the efficacy and safety of catheter ablation in the treatment of VVS remains unclear. The objective of this study is to explore the efficacy and safety of catheter ablation in the treatment of VVS and to compare the different ganglion-mapping methods for prognostic effects. A total of 108 patients with refractory VVS who underwent catheter ablation were retrospectively enrolled. Patients preferred to use high-frequency stimulation (HFS) (n = 66), and anatomic landmark (n = 42) targeting is used when HFS failed to induce a positive reaction. The efficacy of the treatment is evaluated by comparing the location and probability of the intraoperative vagal reflex, the remission rate of postoperative syncope symptoms, and the rate of negative head-up tilt (HUT) results. Adverse events are analyzed, and safety is evaluated. After follow-up for 8 (5, 15) months, both HFS mapping and anatomical ablation can effectively improve the syncope symptoms in VVS patients, and 83.7% of patients no longer experienced syncope (<0.001). Both approaches to catheter ablation in the treatment of VVS effectively inhibit the recurrence of VVS; they are safe and effective. Therefore, catheter ablation can be used as a treatment option for patients with symptomatic VVS.

MicroRNA-494-3p Exacerbates Renal Epithelial Cell Dysfunction by Targeting SOCS6 under High Glucose Treatment.

BACKGROUND: Diabetic nephropathy is a common complication of the kidneys induced by diabetes and is the main cause of end-stage renal disease. MicroRNA-494-3p was reported to be upregulated in renal tissues collected from db/db mice, but its specific role in diabetic nephropathy was still unclear. This study aimed to explore the effect of miR-494-3p on renal fibrosis using an in vitro cell model of diabetic nephropathy. METHODS: After human renal tubular epithelial cells (HK-2) were treated with high glucose (HG), the viability and apoptosis of cells were examined by CCK-8 assays and flow cytometry analyses. Additionally, protein levels of fibronectin, collagen I, collagen III, collagen IV, and epithelial-mesenchymal transition (EMT) markers in HG-induced HK-2 cells were quantified by Western blotting. miR-494-3p expression in HK-2 cells was detected by reverse-transcription quantitative polymerase chain reaction. The binding relation between miR-494-3p and the messenger RNA suppressor of cytokine signaling 6 (SOCS6) was detected by luciferase reporter assays. RESULTS: HG reduced cell viability and enhanced cell apoptosis in a time- or concentration-dependent manner. Additionally, HG induced collagen accumulation and triggered the EMT process. miR-494-3p was upregulated in HG-treated HK-2 cells. miR-494-3p inhibition alleviated HG-induced cell dysfunction. Mechanistically, miR-494-3p bound with SOCS6 and negatively regulated SOCS6 expression. Moreover, silencing SOCS6 rescued the suppressive effect of miR-499-5p inhibition on HG-induced cell dysfunction. CONCLUSION: miR-494-3p aggravates renal fibrosis, EMT process, and cell apoptosis by targeting SOCS6, suggesting that the miR-494-3p/SOCS6 axis may become a potential strategy for the treatment of diabetic nephropathy.

Perillaldehyde improves cognitive function in vivo and in vitro by inhibiting neuronal damage via blocking TRPM2/NMDAR pathway.

BACKGROUND: Vascular cognitive dysfunction in patients with vascular dementia (VD) is a kind of severe cognitive dysfunction syndrome caused by cerebrovascular diseases. At present, effective drugs to improve the cognitive function of VD patients still need to be explored. Transient Receptor Potential Melastatin 2 (TRPM2) channel is a nonspecific cation channel that plays a key role in the toxic death of neurons. Perillaldehyde (PAE) has the protective effect of epilepsy and insomnia and other central nervous system diseases. The aim of this study is to explore whether PAE improves cognitive function in VD rats and to investigate the potential mechanisms in vivo and vitro. METHODS: VD rats were induced by bilateral common carotid arteries occlusion (2-vessel occlusion [2VO]) and treated with PAE for 4 weeks. The neuroprotective effects of PAE was subsequently assessed by the Morris water maze, hematoxylin-eosin (HE) staining, Golgi staining, electron microscopy, Neuron-specific nuclear protein (Neu N) staining, and TdT-mediated dUTP nick end labeling (TUNEL) staining. After primary hippocampal neurons were isolated, cell viability was detected by MTT assay and intracellular Ca2+ concentration was detected by calcium imaging assay. The content of Nitriteoxide (NO), Malondialdehyde (MDA) and Superoxide dismutase (SOD) activity in serum of rats were observed by Enzyme Linked Immunosorbent Assay (ELISA). Immunohistochemistry, Western blot, and Confocal laser scanning were used to detect the expression levels of N-methyl-D-asprtate receptor-2B (NR2B) and TRPM2. RESULTS: The results showed that PAE can improve the number and activity of neurons, increase the length and number of dendrites in hippocampus, decrease the Vv value and PE value of neuronal nucleus and mitochondrial structure significantly, increase the s value and L value in nucleus structure, decrease the s value and L value in mitochondrial structure, and improve the learning and memory ability of rats significantly. And PAE can strengthen the ability of antioxidant stress confirmed by increasing the activity of SOD and reducing the production of MDA. The results of western blot, immunohistochemistry and immunofluorescence showed that PAE could reduce the level of TRPM2 and increase the expression of NR2B. CONCLUSIONS: Taken together, our findings provide evidence that the neuroprotective effects of PAE in VD rats maybe through TRPM2 inhibition and subsequent activation of NMDAR signaling pathway.

Floralozone protects endothelial function in atherosclerosis by ameliorating NHE1.

Endothelial dysfunction is the pathological basis of atherosclerosis. Incomplete understanding of endothelial dysfunction etiology has impeded drug development for this devastating disease despite the currently available therapies. Floralozone, an aroma flavor, specifically exists in rabbit ear grass. Recently, floralozone has been demonstrated to inhibit atherosclerosis, but the underlying mechanisms are undefined. The present study was undertaken to explore whether floralozone pharmacologically targets endothelial dysfunction and therefore exerts therapeutic effects on atherosclerosis. The Na+/H+ exchanger 1 (NHE1), a channel protein, plays a vital role in atherosclerosis. Whether NHE1 is involved in the therapeutic effects of floralozone on endothelial dysfunction has yet to be further answered. By performing oil red staining and hematoxylin-eosin staining, vascular functional study, and oxidative stress monitoring, we found that floralozone not only reduced the size of carotid atherosclerotic plaque but also prevented endothelial dysfunction in atherosclerotic rats. NHE1 expression was upregulated in the inner membrane of carotid arteries and H2O2-induced primary rat aortic endothelial cells. Inspiringly, floralozone prevented the upregulation of NHE1 in vivo and in vitro. Notably, the administration of NHE1 activator LiCl significantly weakened the protective effect of floralozone on endothelial dysfunction in vivo and in vitro. Our study demonstrated that floralozone exerted its protective effect on endothelial dysfunction in atherosclerosis by ameliorating NHE1. NHE1 maybe a drug target for the treatment of atherosclerosis, and floralozone may be an effective drug to meet the urgent needs of atherosclerosis patients by dampening NHE1.

Clinical Features of Patients Undergoing the Head-Up Tilt Test and Its Safety and Efficacy in Diagnosing Vasovagal Syncope in 4,873 Patients.

Background: The head-up tilt test (HUTT) is a useful diagnostic tool in patients with suspected vasovagal syncope (VVS). Objectives: We aimed to investigate the direct drug-potentiated HUTT in patients with recurrent syncope or precursor syncope and to assess the diagnostic value of the direct drug-potentiated HUTT. Methods: The medical history and direct drug-potentiated HUTT records of patients who complained of syncope or precursor syncope and who visited The Xianyang Central Hospital from January 2016 to December 2020 were retrospectively reviewed. Results: A total of 4,873 patients (age = 43.8 ± 17.6 years; male = 2,064 [42.4%]) were enrolled in our study. Overall, 2,343 (48.1%) showed positive responses as follows: 1,260 (25.9%) with the mixed type, 34 (0.7%) with the cardioinhibitory type, 580 (11.9%) with the vasodepressor type, 179 (3.7%) with postural tachycardia syndrome (POTS), and 290 (6.0%) with orthostatic hypotension (OH). The study showed that prior to syncope or near-syncope symptoms, patients first presented an increase in heart rate (HR), followed by decreases in blood pressure (BP) and HR successively. Among the patients in the syncope group, the sensitivity of the HUTT was 65.9%, which was significantly higher than a sensitivity of 44.8% for patients in the non-syncope group (P < 0.01). The sensitivity of the HUTT was higher for females than males in both the syncope group (52.6% in males and 77.9% in females, P < 0.01) and the non-syncope group (36.5% in males and 50.6% in females, P < 0.01). Within the four age groups (<20, 21-40, 41-60, and >60 years old), the sensitivities were 74.7%, 67.7%, 45.6%, and 31.2%, respectively. And all gender, age and symptom (whether suffered from a syncope or not) significantly affected the positive responses of HUTT. There were two adverse events and no deaths during the HUTT in this study. Conclusion: The direct drug-potentiated HUTT is a safe and highly sensitive tool with which to diagnose VVS. Patients with precursor syncope symptoms without syncope should undergo a HUTT, especially young females presenting with weakness and sweating, which can decrease the probability of a misdiagnosis or a missed diagnosis.

Clinical characteristics of patients with atrial fibrillation suffering from pulmonary vein stenosis after radiofrequency ablation.

OBJECTIVE: Pulmonary vein stenosis (PVS) is a serious complication in patients with atrial fibrillation (AF) receiving radiofrequency catheter ablation (RFCA). We therefore examined these patients' clinical characteristics in relation to PVS occurrence. METHOD: We retrospectively analyzed the clinical symptoms, diagnostic procedures, and treatment strategies in patients with AF who developed PVS after RFCA. RESULTS: Among 205 patients with AF who underwent RFCA, five (2.44%) developed PVS (all men; age 44-64 years; AF history 12-60 months; 2 paroxysmal AF, 3 persistent AF). One patient underwent two RFCA sessions and the others received one. The time to PVS diagnosed by pulmonary vein computed tomography angiography (CTA) was 3 to 21 months. PVS symptoms included dyspnea and hemoptysis. Nine pulmonary veins developed PVS. Single mild PVS occurred in two asymptomatic patients and multiple PVS or single severe PVS in three symptomatic patients who underwent pulmonary vein angiography and stent placement. Symptoms in the three patients significantly improved after stent implantation; however, stent restenosis occurred 1 year later in one case. CONCLUSION: PVS is a rare complication of RFCA for AF that can be diagnosed by CTA. Pulmonary vein stent implantation can remarkably improve the symptoms, but stent restenosis may occur.

Comparison in Prevalence, Predictors, and Clinical Outcome of VSR Versus FWR after Acute Myocardial Infarction: The Prospective, Multicenter Registry MOODY Trial-Heart Rupture Analysis.

BACKGROUND: Differences in the predictors between ventricular septal rupture (VSR) and free wall rupture (FWR) have not been fully studied. Data on the prevalence and clinical outcome of heart rupture are limited. HYPOTHESIS: This study aimed to investigate heart rupture incidence and clinical results in patients with acute myocardial infarction (AMI). METHODS: Of 9265 AMI patients in the MOODY registry between March 1999 and October 2016, a total of 146 were studied. The primary clinical endpoint was rupture prevalence and in-hospital mortality. Independent factors of heart rupture were analyzed using Cox proportional model and were compared between patients with VSR and those with FWR. RESULTS: Of 9265 AMI patients, 146 (1.58%) patients had a heart rupture (FWR, 94 (1.02%)) and VSR (52 (0.56%)). All patients with FWR died during hospitalization, and in-hospital mortality was recorded in 37 (71.2%) patients with VSR, who had an extremely longer time delay from AMI onset to the first medical contact (FMC) (~20 h). FWR usually occurred in patients with ST-elevation myocardial infarction (STEMI) patients with a FMC ≥ 3 h, for whom primary reperfusion was not performed. Percutaneous repair at 1-2 weeks following AMI was associated with less mortality, and 9 of 38 patients who underwent non-primary reperfusion died post procedure. CONCLUSION: This study demonstrated the importance of shortening FMC to prevent VSR and of early primary reperfusion in STEMI patients to reduce FWR. Urgent closure of rupture is necessary to reduce in-hospital and 1-year mortality. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.org, identifier: No. NCT03051048.

Relationship between the endothelial glycocalyx and the extent of coronary atherosclerosis.

OBJECTIVE: To investigate the correlation between the EG and the severity of coronary atherosclerosis. METHODS: A total of193 subjects were divided into two groups. A SDF video microscope with a glycocalyx thickness measurement system was used to visualize the sublingual microcirculation. The levels of HA in the peripheral circulation and coronary circulation were determined via enzyme-linked immunosorbent assay. The number of coronary artery lesions and the Gensini score were used to evaluate the severity of the coronary atherosclerosis. RESULTS: EG thickness in the coronary heart disease (CHD) group (242.18 ± 10.10 nm) was lower than that in the NON-CHD group (251.78 ± 10.59 nm, P < 0.001). There was a negative correlation between the EG thickness and the number of coronary lesions and the Gensini score. The level of intracoronary HA in the CHD group (48.60, 126.27) was higher than that in the NON-CHD group (20.60, 34.45, P < 0.001), and it was positively correlated with the number of coronary lesions and the Gensini score. CONCLUSIONS: EG damage was correlated with the occurrence and development of coronary atherosclerosis. The EG thickness in the capillaries of the oral submucosa and the intracoronary HA level can be used as auxiliary indexes to assess the severity of coronary atherosclerosis.

Intravascular ultrasound-guided drug-eluting stent implantation is associated with improved clinical outcomes in patients with unstable angina and complex coronary artery true bifurcation lesions.

Stenting coronary artery bifurcation lesion is associated with suboptimal clinical results. Clinical improvement by intravascular ultrasound (IVUS) guided bifurcation stenting is controversial because small-side-branch (SB), low-risk patients and false bifurcations were included in previous studies that had no exact IVUS criteria for optimal stent expansion. We sought determine whether IVUS guidance is superior to angiography guidance for patients with true and complex bifurcation lesions. Between July 2006 and July 2012, 1465 patients with unstable angina and Medina 1,1,1 or 0,1,1 coronary bifurcation lesions were prospectively studied. 310 patients in the IVUS guidance (defined as stent symmetry index > 0.7, stent expansion index > 0.9, well apposition, and no Type B/C dissection) group were paired with 620 patients in the angiography group by propensity score-matching. The primary endpoint was the rate of composite major adverse cardiac events (MACE) (cardiac death, myocardial infarction (MI), or clinically-driven target vessel revascularization) at 1-year and at the end of study after indexed procedure. Use of IVUS guidance was mainly driven by stenting technique selection and identification of lesions' specificities. IVUS criteria for optimal stent expansion were achieved in 82.9% of patients which contribute to IVUS group data assessment and the rest did not meet optimal criteria. MACE occurred in 10.0% of patients at 1-year follow-up and 15.2% at the 7-year follow-up in the IVUS group, significantly different from 15.0% (p = 0.036) and 22.4% (p = 0.01) in the angiography group, respectively. Compared to angiography guidance, IVUS guidance also resulted in a lower 7-year cardiac death rate (6.5 versus 1.3%, p = 0.002) and MI (8.4 versus 2.3%, P < 0.001). Any revascularization was also statistically lower in the IVUS group through whole study period, compared to the angiography group. Lower MACE rates were observed in IVUS guidance group in a 7-year follow-up compared with angiography guidance alone.