A systematic review and Bayesian network meta-analysis comparing left bundle branch pacing, his bundle branch pacing, and right ventricular pacing for atrioventricular block.

Background: Although right ventricular pacing (RVP) is recommended by most of the guidelines for atrioventricular block, it can cause electrical and mechanical desynchrony, impair left ventricular function, and increase the risk of atrial fibrillation. Recently, the His-Purkinje system pacing, including His bundle pacing (HBP) and left bundle branch pacing (LBBP), has emerged as a physiological pacing modality. However, few studies have compared their efficacy and safety in atrioventricular block (AVB). Methods and results: The PubMed, Web of Science, Cochrane Library, and ScienceDirect databases were searched for observational studies and randomized trials of patients with atrioventricular block requiring permanent pacing, from database inception until 10 January 2022. The primary outcomes were complications and heart failure hospitalization. The secondary outcomes included changes in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD), pacing parameters, procedure duration, and success rate. After extracting the data at baseline and the longest follow-up duration available, a pairwise meta-analysis and a Bayesian random-effects network meta-analysis were performed. Odds ratios (ORs) with 95% confidence intervals (CIs) or 95% credible intervals (CrIs) were calculated for dichotomous outcomes, whereas mean differences (MDs) with 95% CIs or 95% CrIs were calculated for continuous outcomes. Seven studies and 1,069 patients were included. Overall, 43.4% underwent LBBP, 33.5% HBP, and 23.1% RVP. Compared with RVP, LBBP and HBP were associated with a shorter paced QRS duration and a more preserved LVEF. HBP significantly increased the pacing threshold and reduced the R-wave amplitude. There was no difference in the risk of complications or the implant success rate. The pacing threshold remained stable during follow-up for the three pacing modalities. The pacing impedance was significantly reduced in HBP, while a numerical but non-significant pacing impedance decrease was observed in both LBBP and RVP. LBBP was associated with an increased R-wave amplitude during follow-up. Conclusion: In this systematic review and network meta-analysis, HBP and LBBP were superior to RVP in paced QRS duration and preservation of LVEF for patients with atrioventricular block. LBBP was associated with a lower pacing threshold and a greater R-wave amplitude than HBP. However, the stability of the pacing output of LBBP may be a concern. Further investigation of the long-term efficacy in left ventricular function and the risk of heart failure hospitalization is needed. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=315046], identifier [CRD42022315046].

The Expression of miR-365 in Serum of Hypertension Patients with Left Ventricular Hypertrophy Was Up-Regulated, Which Was Positively Correlated with Left Ventricular Mass Index.

OBJECTIVE: The present study aims to investigate micro ribonucleic acid-365 (miR-365) serum expression and its correlation with left ventricular hypertrophy (LVH) in patients with hypertension (HT). METHODS: Eighty-four patients were selected as study subjects and divided into three groups: the experimental group (n = 28), the observation group (n = 29), and the control group (n = 27). The experimental group included patients with LVH-accompanied HT who were treated in the People's Hospital of Hebei Province between November 2019 and November 2020, the observation group included patients with HT unaccompanied by LVH, and the control group included healthy age and gender-matched subjects who underwent health examinations in our physical examination center. The cardiac echocardiography, 24-h Holter electrocardiogram, and circulating miR-365 levels in all subjects were measured. The differences in circulating miR-365 expression levels among the three groups were compared, and the correlations between the miR-365 expression levels and the blood pressure parameters (24-h mean systolic blood pressure [SBP] and 24-h mean diastolic blood pressure [DBP]), inter-ventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular internal diameter (LVID), left ventricular mass (LVM), LVM index (LVMI), and LVH-related indicators were analyzed. RESULTS: The relative miR-365 expressions in the experimental, observation, and control groups were 2.08 (1.60, 2.34), 0.62 (0.44, 0.83), and 0.66 (0.35, 0.86), respectively. Patient miR-365 expression was significantly higher in the experimental group than in the observation group and the control group; the differences were statistically significant (p < 0.000). Furthermore, miR-365 expression was significantly correlated with SBP, DBP, IVST, LVPWT, LVID, LVM, and LVMI; the greatest correlation was with LVMI. Further univariate linear regression analysis revealed that miR-365 expression was linearly and positively correlated with LVMI and that miRNA-365 expression increased with the LVMI value. CONCLUSION: The miR-365 serum expression in patients with LVH-accompanied HT was increased compared with the observation group and the control group and positively correlated with the LVH degree.

Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease in China (RWE-PCSK study).

BACKGROUND: The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention (PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events (MACE) over six months were compared between two groups. A propensity score-matched (PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE. RESULTS: In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol (LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81% (P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group ( P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE (hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250). CONCLUSIONS: In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.

Cardioprotective effect of anisodamine against ischemia/reperfusion injury through the mitochondrial ATP-sensitive potassium channel.

Previous clinical studies have shown that anisodamine could improve no-reflow phenomenon and prevent reperfusion arrhythmias, but whether this protective effect is related to the antagonism of the M-type cholinergic receptor or other potential mechanisms is uncertain. The aim of the present study was to investigate the role of the mitochondrial ATP-sensitive potassium channel (mitoK ATP ) in cardioprotective effect of anisodamine against ischemia/reperfusion injury. Anisodamine and 5- hydroxydecanoic acid were used to explore the relationship between anisodamine and mitoK ATP . Using a Langendorff isolated heart ischemia/reperfusion injury model, hemodynamic parameters and reperfusion ventricular arrhythmia were evaluated; in addition, changes in myocardial infarct size, cTnI from coronary effluent and myocardial ultrastructure, as well as ATP, MDA and SOD in myocardial tissues, were detected. In the hypoxia/reoxygenation injury model of neonatal rat cardiomyocyte, cTnI release in the culture medium and levels of ATP, MDA and SOD in cardiomyocytes and mitochondrial membrane potential, were analyzed. Overall, anisodamine could significantly improve the hemodynamic indexes of isolated rat heart injured by ischemia/reperfusion, reduce the occurrence of ventricular reperfusion arrhythmia and myocardial infarction area, and improve the ultrastructural damage of myocardium and mitochondria. The in vitro results demonstrated that anisodamine could improve mitochondrial energy metabolism, reduce oxidative stress and stabilize mitochondrial membrane potential. The cardioprotective effects were significantly inhibited by 5-hydroxydecanoic acid. In conclusion, this study suggests that the opening of mitoK ATP could play an important role in the protective effect of anisodamine against myocardial ischemia/reperfusion injury.

Safety and efficacy of intracoronary prourokinase administration in patients with high thrombus burden.

OBJECTIVES: The study was designed to evaluate the effect of low-dose intracoronary prourokinase administration immediately after thrombus aspiration in patients with ST-segment elevation myocardial infarction (STEMI) presenting with a serious thrombus burden. METHODS: Consecutive STEMI patients with high thrombus burden received thrombus aspiration during primary percutaneous coronary intervention (PCI) were randomly assigned to study group (intracoronary prourokinase administration) or control group (intracoronary 0.9% sodium chloride administration). The primary endpoint was complete ST-segment resolution (STR) at 90 min after primary PCI, and the secondary endpoints included angiographic myocardial perfusion indexes. RESULTS: Patients in study group had a higher incidence of complete STR and myocardial blush grade 3 compared with those in control group (56.52% vs. 38.89%, P = 0.017 and 57.61% vs. 38.89%, P = 0.041). The peak cardiac troponin I value and corrected thrombolysis in myocardial infarction frame count were significantly lower in study group (52.16 ± 24.67 ng/mL vs. 60.91 ± 28.81 ng/mL, P = 0.029; and 19.57 ± 9.05 vs. 22.91 ± 10.22, P = 0.020). A significant improvement in left ventricular ejection fraction and major adverse cardiac events (MACEs)-free survival was observed in study group (55.22 ± 10.50% vs. 52.18 ± 9.39%, P = 0.041; 10.87% vs. 22.22%, P = 0.039) at the 6-month follow-up. The bleeding complication was similar in both groups (17.39% vs. 12.22%, P = 0.327). CONCLUSIONS: In STEMI patients with high thrombus burden, low-dose prourokinase intracoronary administered immediately after thrombus aspiration improves myocardial perfusion, cardiac function, and MACEs-free survival with no significant increase in major bleeding.

Research progress of CA125 and BDNF in serum of patients with acute myocardial infarction for predicting acute heart failure.

BACKGROUND: At present, the treatment for acute myocardial infarction has achieved great progress. Reperfusion therapy in the short term can effectively reduce recurrence rates and mortality in patients with acute myocardial infarction. According to a report of a large national registry, the mortality of patients with acute coronary syndrome combined with acute heart failure is 10 times of that of patients without heart failure, and the mortality in nearly 10 years has no significant change. Therefore, people are constantly exploring indicators for acute heart failure prognosis to improve a patient's prognosis. With the constant understanding and exploration of acute myocardial infarction, more and more researches have focused in determining how to predict the occurrence of acute heart failure. The present study focuses on presenting the latest progress of Carbohydrate Antigen-125 (CA125) and Brain Derived Neurotrophic Factor (BDNF) in serum of patients with acute myocardial infarction in predicting acute heart failure.

Predictive value of soluble suppression of tumourigenicity 2 on myocardial reperfusion.

BACKGROUND: High baseline level of soluble suppression of tumourigenicity 2 (sST2) was an independent predictor of cardiovascular death and heart failure in ST-segment elevation myocardial infarction (STEMI). AIMS: To investigate the value of serum sST2 baseline levels in predicting myocardial reperfusion in patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). METHODS: Consecutive STEMI patients who underwent PPCI within 12 h after the onset of chest pain were enrolled, and were divided into Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grading (TMPG) 0/1/2 group and TMPG 3 group based on post-procedural TMPG. Baseline clinical characteristics, lesions and procedural characteristics were compared. Univariate logistic regression and multivariate linear logistic analysis were performed to identify independent predictors of impaired myocardial reperfusion (TMPG 0/1/2). Receiver-operating characteristics curve (ROC) analysis of sST2 was performed to identify the optimum cut-off value for predicting the myocardial reperfusion. RESULTS: A total of 121 patients was enrolled in this study. Univariate logistic regression analysis showed that Killip II-III, high levels of sST2 and brain natriuretic peptide were risk factors of TMPG 0/1/2. Multivariable logistic regression analysis revealed that sST2 was an independent predictor of impaired myocardial reperfusion (odds ratio 12.318, 95% confidence interval 4.567-33.220, P < 0.001). ROC curve analysis showed that the area under curve of sST2 was 0.849, and the best cut-off value was 2.003 ng/mL, with a sensitivity of 89.2% and a specificity of 67.9%. CONCLUSION: The elevated levels of sST2 on admission were associated with impaired myocardial reperfusion in STEMI patients undergoing PPCI.

Catestatin prevents endothelial inflammation and promotes thrombus resolution in acute pulmonary embolism in mice.

Catestatin (CTS), a catecholamine-release inhibitory peptide, exerts pleiotropic cardiac protective effects. Pulmonary embolism caused by deep vein thrombosis involving vascular dysfunction. The present study aims to investigate the effects of CTS on thrombus formation that may inhibit the development of pulmonary embolism and its potential pathway. Acute pulmonary embolism (APE) model was developed as an in vivo model. The effects of CTS on mice with APE were examined. Human pulmonary artery endothelial cells (HPAECs) were pretreated with CTS before thrombin stimulation, and endothelial inflammation and underlying mechanisms were evaluated in vitro. That plasma CTS level was decreased in APE mice, while the number of platelets was significantly increased. The decreased circulating CTS level negatively associated with the number of platelets. CTS administration increased the survival rate of APE mice and protected against microvascular thrombosis in lung. APE-induced the increase in platelets number and plasma von Willebrand factor (VWF) were inhibited by CTS. Platelets from CTS-treated APE mice showed impaired agonist-induced platelets aggregation and spreading. CTS also ameliorated APE-induced the systemic inflammatory response. In in vivo study, thrombin-induced the increase in inflammation, TLR-4 expression and p38 phosphorylation were abrogated by CTS in HPAECs. Furthermore, TLR-4 overexpression inhibited the effect of CTS on VWF release and inflammation in HPAECs. Collectively, CTS increases thrombus resolution by attenuating endothelial inflammation at partially via inhibiting TLR-4-p38 pathway. The present study may provide a novel approach for anti-thrombosis.

Increased Serum CA125 and Brain-Derived Neurotrophic Factor (BDNF) Levels on Acute Myocardial Infarction: A Predictor for Acute Heart Failure.

BACKGROUND This study was conducted to see whether increased values of serum CA125 and BDNF (brain-derived neurotrophic factor) on acute myocardial infarction (AMI) act as predictor for acute heart failure (AHF). MATERIAL AND METHODS Seventy-eight patients with clinically diagnosed cardiac function II-IV; and AHF were considered as the study group of this retrospective study and patients who had cardiac function I (without AHF) were considered the control group (n=82). The values of CA125 and BDNF were measured using enzyme-linked immunosorbent assay (ELISA) for developing the correlation with the Killip classification, and the diagnostic value of AHF. RESULTS Statistically insignificant difference was noticed between baseline information e.g., blood pressure or smoking status of participants in study group and control group (P>0.05). The higher values of CA125 (5.68±1.8 U/mL or BDNF (19.48±5.3 pg/mL) in the study group had advantage over the control after independent sample t-test (P<0.001). A positive correlation was observed between values of the test substances and Killip classifications (I-IV) of cardiac functioning was observed (r=0.745, P<0.001; Spearman's rank correlation coefficient). The sensitivity and specificity of area under the curve (AUC) combined with serum CA125 and BDNF levels in the diagnosis of AHF was 91.02% and 81.63%, respectively. CONCLUSIONS Increased serum level of the test substances indicates severity of AHF-leading AMI. Thus, monitoring is needed to avoid risk of AHF.

Beneficial effect of ticagrelor on microvascular perfusion in patients with ST-segment elevation myocardial infarction undergoing a primary percutaneous coronary intervention.

BACKGROUND: Ticagrelor significantly reduced the incidence of death, myocardial infarction, and stent thrombosis in patients with ST-segment elevation myocardial infarction (STEMI) intended for reperfusion with a primary percutaneous coronary intervention (pPCI). However, the effects of this drug on microvascular perfusion in patients presenting with STEMI have not been evaluated completely. PATIENTS AND METHODS: A total of 298 patients presenting with STEMI were randomized to either ticagrelor 180 mg loading, followed by 90 mg twice daily, or clopidogrel 600 mg loading, followed by 75 mg daily. The primary endpoint was ST-segment resolution at 90 min after pPCI. The secondary endpoints included myocardial blush grade and corrected thrombolysis in myocardial infarction frame count after the procedure. Left ventricular ejection fraction and major adverse cardiac events (MACE) at the 1- and 6-month follow-up time points were also recorded. RESULTS: There were no significant differences between the two groups with respect to baseline characteristics. Ticagrelor administration resulted in a higher rate of completed ST-segment resolution (58.67 vs. 39.86%, P=0.001), higher myocardial blush grade (2.63±0.64 vs. 2.41±0.71, P=0.005), and lower corrected thrombolysis in myocardial infarction frame count (19.68±7.38 vs. 22.35±8.30, P=0.004). At 6 months, left ventricular ejection fraction was higher (55.01±8.44 vs. 52.34±9.05%, P=0.009) in the ticagrelor group. Kaplan-Meier analysis showed that MACE-free survival had also improved in the ticagrelor group during the 1- and 6-month follow-up time points. CONCLUSION: Compared with clopidogrel, ticagrelor improves myocardial perfusion and left ventricular ejection fraction, and reduces the incidence of MACE for STEMI patients undergoing pPCI, with no significant increase in major bleeding.

Clinical efficacy of ticagrelor in patients undergoing emergency intervention for acute myocardial infarction and its impact on platelet aggregation rate.

OBJECTIVE: This study aims to investigate the clinical efficacy of ticagrelor in patients who underwent emergency percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), and its impact on platelet aggregation rate. METHODS: A total of 257 AMI patients who underwent emergency PCI in our hospital were included in the present study. These patients were randomly divided into two groups: ticagrelor group (n = 129), patients took 180 mg of ticagrelor (qd) before the intervention, and subsequently took 90 mg of ticagrelor (bid) for maintenance; clopidogrel group (n = 128), patients took 300 mg of clopidogrel (qd) before PCI, and subsequently took 75 mg of clopidogrel (qd) for maintenance. Patients in both groups took 100 mg of aspirin. The major adverse cardiovascular events (MACE) within one year, changes in LVEF and LVEDD, platelet aggregation rate and drug safety before PCI and at one week and 30 days after PCI were observed in these two groups. RESULTS: The differences in baseline data between these two groups were not statistically significant. Within one year after the intervention, in the ticagrelor group, the total incidence of MACE was lower (P < 0.05), LVEF and LVEDD was improved (P < 0.05), and the decrease in platelet aggregation rate after the intervention was more significant (P < 0.05). Furthermore, the incidence of bleeding events was higher in the ticagrelor group than in the clopidogrel group (P < 0.05). CONCLUSIONS: Compared with clopidogrel, ticagrelor decreases the incidence of adverse cardiovascular events in AMI patients who underwent emergency PCI, does better in improving the fluctuation level of LVEF and LVEDD, and strongly inhibits platelet aggregation. Some patients encountered adverse drug events, but drug withdrawal or medication change did not occur.

Rho kinase inhibition by fasudil has anti-inflammatory effects in hypercholesterolemic rats.

Inhibition of Rho kinase (ROCK) ameliorates many cardiovascular dysfunctions. The aim of the current study is to investigate the anti-inflammatory effects of fasudil, a selective ROCK inhibitor, on high cholesterol diet-induced hypercholesterolemic rats and its possible mechanisms. In hypercholesterolemic rats, we found the serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and several inflammatory markers including interleukin (IL)-8, IL-6, C-reaction protein (CRP) and soluble intercellular adhesion molecule (sICAM)-1 significantly elevated, while those of high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) decreased. Moreover, mRNA expressions of ROCK and nuclear factor-kappa B (NF-κB) and activity of ROCK in thoracic aorta were greatly up-regulated. Remarkably, administrating fasudil (10, 30 mg/kg per day) or simvastatin (10 mg/kg per day) to hypercholesterolemic rats for 2 weeks, activation of ROCK and NF-κB in thoracic aorta were suppressed, status of dyslipidemia were improved and inflammatory markers lowered. From the histopathological examination, fasudil treatment was found to lessen the thickening noted in the aortic intima and media of the hypercholesterolemic rats. These results suggested fasudil-induced inhibition of ROCK may improve lipid metabolism and has anti-inflammatory effect, which might expand the clinical application of fasudil as a new therapy for hypercholesterolemia and preventing the development of atherosclerosis.