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Background: The effects of conduction system pacing (CSP) compared with conventional biventricular pacing (BVP) on heart function in patients with heart failure remain elusive.Methods: PubMed, Embase, Cochrane’s Library and Web of science databases were searched up to 1 October 2022 for pertinent controlled studies. Random or fixed-effect model were used to synthesize the clinical outcomes. Subgroup analysis was performed to screen the potential confounding factors.Results: Fifteen studies including 1,347 patients were enrolled. Compared with BVP, CSP was significantly associated with shortened QRS duration [WMD -22.51 ms; p = 0.000], improved left ventricular ejection fraction [WMD 5.53%; p = 0.000], improved NYHA grade [WMD -0.42; p = 0.000], higher response rate and lower heart failure rehospitalization rate. CSP resulted in better clinical outcomes in higher male proportion group than lower one compared with BVP. No significant differences of clinical outcomes were observed between left bundle branch area pacing (LBBaP) and his bundle pacing (HBP) except the pacing threshold. The pacing threshold of LBBaP was significantly lower than those in BVP and HBP.Conclusion: This study suggests that CSP might be superior to conventional BVP for HF patients. In a higher male proportion group, CSP may be associated with more benefits than BVP.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022355991; Identifier: CRD42022355991.

BACKGROUND: Enhanced late sodium current (INaL) is reportedly related to an increased risk of atrial fibrillation (AF). Moricizine, as a widely used anti-arrhythmia drug for suppressing ventricular tachycardia, has also been shown to prevent paroxysmal AF. However, the mechanism of its therapeutic effect remains poorly understood. METHODS: Angiotensin II (Ang II) was induced in C57Bl/6 mice (male wild-type) for 4 weeks to increase the susceptibility of AF, and acetylcholine-calcium chloride was used to induce AF. The whole-cell patch-clamp technique was used to detect INaL from isolated atrial myocytes. The expression of proteins in atrial of mice and HL-1 cells were examined by Western-blot. RESULTS: The results showed that moricizine significantly inhibited Ang II-mediated atrial enlargement and reduced AF vulnerability. We found that the densities of INaL were enhanced in Ang II-treated left and right atrial cardiomyocytes. Simultaneously, the Ang II-induced increase in INaL currents density was alleviated by the administration of moricizine, and no alteration in Nav1.5 expression was observed. In normal isolated atrial myocytes, moricizine significantly reduced Sea anemone toxin II (ATX II)-enhanced INaL density with a reduction of peak sodium currents. In addition, moricizine reduced the Ang II-induced upregulation of phosphorylated calcium/calmodulin-dependent protein kinase-II (p-CaMKII) in both the left and right atria. In HL-1 cells, moricizine also reduced the upregulation of p-CaMKII with Ang II and ATX II intervention, respectively. CONCLUSIONS: Our results indicate that Ang II enhances the INaL via activation of CaMKII. Moricizine inhibits INaL and reduces CaMKII activation, which may be one of the mechanisms of moricizine suppression of AF.

Glucose fluctuation is more harmful than sustained hyperglycemia, but the effect on cardiomyocyte apoptosis have not yet been clarified. In this study, we aim to identify the effect of glucose fluctuation on cardiomyocyte apoptosis and explore the underlying mechanism. Sprague-Dawley rats were intraperitoneally injected with streptozotocin (STZ) and divided into three groups: controlled diabetic group (C-STZ); uncontrolled diabetic group (U-STZ) and glucose fluctuated diabetic group (GF-STZ). After twelve weeks, echocardiography, Hematoxylin-eosin (HE) staining, and Masson staining were adopted to assess the cardiac function and pathological changes. TUNEL staining was used to detect apoptotic cells. Expressions of apoptosis-related proteins and key molecules in the endoplasmic reticulum (ER) stress pathway were determined via western blots. Further, primary cardiomyocytes incubated in different glucose conditions were treated with the inhibitor of ER stress to explore the causative role of ER stress in glucose fluctuation-induced cardiomyocyte apoptosis. In vivo, we demonstrated that glucose fluctuation promoted cardiomyocyte apoptosis, and were more harmful to cardiomyocytes than sustained hyperglycemia. Moreover, glucose fluctuation significantly triggered ER stress signaling pathway. In vitro, primary cardiomyocyte apoptosis induced by glucose fluctuation and the activation of ER stress were significantly attenuated by 4-PBA, which is an ER stress inhibitor. Above all, glucose fluctuation can promote cardiomyocyte apoptosis through triggering the ER stress signaling pathway in diabetic rats and in primary cardiomyocytes.

Additional file 2: Table S1. Characteristics of the datasets included in the analysis.