Left bundle branch area pacing (LBBAP) has developed in an effort to improve cardiac resynchronization therapy (CRT). We aimed to compare the long-term clinical outcomes between LBBAP and biventricular pacing (BIVP) in patients with heart failure (HF) and complete left bundle branch block (CLBBB). Consecutive patients with HF and CLBBB requiring CRT received either LBBAP or BIVP were recruited at the Second Affiliated Hospital of Nanchang University from February 2018 to May 2019. We assessed their implant parameters, electrocardiogram (ECG), clinical outcomes at implant and during follow-up at 1, 3, 6, 12, and 24 months. Forty-one patients recruited including 21 for LBBAP and 20 for BIVP. Mean follow-up duration was 23.71 ± 4.44 months. LBBAP produced lower pacing thresholds, shorter procedure time and fluoroscopy duration compared to BIVP. The QRS duration was significantly narrower after LBBAP than BIVP (129.29 ± 31.46 vs. 156.85 ± 26.37 ms, p = 0.005). Notably, both LBBAP and BIVP significantly improved LVEF, LVEDD, NYHA class, and BNP compared with baseline. However, LBBAP significantly lowered BNP compared with BIVP (416.69 ± 411.39 vs. 96.07 ± 788.71 pg/ml, p = 0.007) from baseline to 24-month follow-up. Moreover, patients who received LBBAP exhibited lower number of hospitalizations than those in the BIVP group (p = 0.019). In addition, we found that patients with moderately prolonged left ventricular activation time (LVAT) and QRS notching in limb leads in baseline ECG respond better to LBBAP for CLBBB correction. LBBAP might be a relative safe and effective resynchronization therapy and as a supplement to BIVP for patients with HF and CLBBB.

Whether the presence of SCN5A mutation is a predictor of BrS risk remains controversial, and patient selection bias may have weakened previous findings. Therefore, we performed this study to clarify the clinical characteristics and outcomes of BrS probands with SCN5A mutations. We systematically retrieved eligible studies published through October 2018. A total of 17 studies enrolling 1780 BrS patients were included. Overall, our results found that compared with BrS patients without SCN5A mutations, patients with SCN5A mutations exhibited a younger age at the onset of symptoms and higher rate of the spontaneous type-1 electrocardiogram pattern, more pronounced conduction or repolarization abnormalities, and increased atrial vulnerability. In addition, the presence of SCN5A mutations was associated with an elevated risk of major arrhythmic events in both Asian (odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.07-3.11; P = .03) and Caucasian (OR = 2.24, 95% CI 1.02-4.90; P = .04) populations. In conclusions, patients with SCN5A mutations exhibit more pronounced electrophysiological defects and more severe prognosis.Clinicians should be cautious when utilizing genetic testing for risk stratification or treatment guidance before determining whether the causal relationship regarding SCN5A mutation status is an independent predictor of risk.

The O-linked β-N-acetylglucosamine (O-GlcNAc) modification and autophagy are associated with diabetic myocardial injury, however, the molecular mechanisms between the two processes remain to be fully elucidated. The purpose of the present study was to elucidate the molecular regulation of autophagy by O-GlcNAc-modified synaptosomal-associated protein 29 (SNAP29) in diabetic myocardial injury. A rat model of type I diabetes was established via intraperitoneal injection of streptozotocin (STZ; 55 mg/kg). Significant increases in the O-GlcNAc modification and accumulation of the autophagy markers microtubule-associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction. Subsequently, the selective O-GlcNAcase inhibitor, thiamet G, increased the level of O-GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation. By contrast, 6-diazo-5-oxo-L-norleucine, an inhibitor of glucosamine fructose-6-phosphate aminotransferase isomerizing 1, acted as an O-GlcNAc antagonist and reduced the level of O-GlcNAc modification, which maintained autophagic flux and improved cardiac diastolic function. In vitro, high glucose (25 mM) was used to stimulate primary neonatal rat cardiomyocytes (NRCMs). Consistent with the myocardium of diabetic rats, it was also shown in the NRCMs that O-GlcNAc modification of SNAP29 negatively regulated autophagic flux. The application of the short hairpin RNA interference lysosome-associated membrane protein (LAMP2) and the autophagy inhibitor 3-methyladenine demonstrated that high glucose inhibited autophagy-mediated degradation rather than affected the initial stage of autophagy. Finally, co-immunoprecipitation was used to determine the role of the O-GlcNAc-modified substrate protein SNAP29, which acted as an SNAP29-syntaxin-17 (STX17)-vesicle-associated membrane protein 8 (VAMP8) complex during disease progression. The present study is the first, to the best of our knowledge, to demonstrate that SNAP29 is an O-GlcNAc substrate and that an increase in O-GlcNAc-modified SNAP29 inhibits SNAP29-STX17-VAMP8 complex formation, thereby inhibiting the degradation of autophagy and exacerbating myocardial injury in type I diabetic rats.

Background:The comparative effects of different types of cardiac resynchronization therapy (CRT) delivered by biventricular pacing (BVP), His bundle pacing (HBP), and left bundle branch area pacing (LBBAP) remain inconclusive.Hypothesis: HBP and LBBAP may be advantageous over BVP for CRT.Methods: PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for studies that reported the effects after BVP, HBP, and LBBAP for CRT. The effects between groups were compared by a frequentist random-effects network meta-analysis (NMA), by which the mean differences (MDs) and 95% confidence intervals (CIs) were calculated.Results: Six articles involving 389 patients remained for the final meta-analysis. The mean follow-up of these studies was 8.03 ± 3.15 months. LBBAP resulted in a greater improvement in LVEF% (MD = 7.17, 95% CI = 4.31 to 10.04), followed by HBP (MD = 4.06, 95% CI = 1.09 to 7.03) compared with BVP. HBP resulted in a narrower QRS duration (MD = 31.58 ms, 95% CI = 12.75 to 50.40), followed by LBBAP (MD = 27.40 ms, 95% CI = 10.81 to 43.99) compared with BVP. No significant differences of changes in LVEF improvement and QRS narrowing were observed between LBBAP and HBP. The pacing threshold of LBBAP was significantly lower than those of BVP and HBP. Conclusion:The NMA first found that LBBAP and HBP resulted in a greater LVEF improvement and a narrower QRS duration compared with BVP. Additionally, LBBAP resulted in similar clinical outcomes but with lower pacing thresholds, and may therefore offer advantages than does HBP for CRT.

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