Myocardial dysfunction is a serious consequence of sepsis and contributes to high mortality. Currently, the molecular mechanism of myocardial dysfunction induced by sepsis remains unclear. In the present study, we investigated the role of gasdermin D (GSDMD) in cardiac dysfunction in septic mice and the underlying mechanism. C57BL/6 wild-type (WT) mice and age-matched Gsdmd-knockout (Gsdmd^-/-) mice were intraperitoneally injected with lipopolysaccharide (LPS) (10 mg/kg) to mimic sepsis. The results showed that GSDMD-NT, the functional fragment of GSDMD, was upregulated in the heart tissue of septic WT mice induced by LPS, which was accompanied by decreased cardiac function and myocardial injury, as shown by decreased ejection fraction (EF) and fractional shortening (FS) and increased cardiac troponin I (cTnI), creatine kinase isoenzymes MB (CK-MB), and lactate dehydrogenase (LDH). Gsdmd^-/- mice exhibited protection against LPS-induced myocardial dysfunction and had a higher survival rate. Gsdmd deficiency attenuated LPS-induced myocardial injury and cell death. Gsdmd deficiency prevented LPS-induced the increase of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum, as well as IL-1β and TNF-α mRNA levels in myocardium. In addition, LPS-mediated inflammatory cell infiltration into the myocardium was ameliorated and activation of NF-κB signaling pathway and the NOD-like receptor protein 3 (NLPR3) inflammasome were suppressed in Gsdmd^-/- mice. Further research showed that in the myocardium of LPS-induced septic mice, GSDMD-NT enrichment in mitochondria led to mitochondrial dysfunction and reactive oxygen species (ROS) overproduction, which further regulated the activation of the NLRP3 inflammasome. In summary, our data suggest that GSDMD plays a vital role in the pathophysiology of LPS-induced myocardial dysfunction and may be a crucial target for the prevention and treatment of sepsis-induced myocardial dysfunction.

Background: Persistent atrial fibrillation may lead to a higher probability of inappropriate shocks in heart failure patients with an implantable cardioverter‐defibrillator ( ICD ). The aim of this study was to evaluate the impact of His‐Purkinje conduction system pacing combined with atrioventricular node ablation in improving heart function and preventing inappropriate shock therapy in these patients. Methods and Results: A total of 86 consecutive patients with persistent atrial fibrillation and heart failure who had indications for ICD implantation were enrolled from January 2010 to March 2018. His‐Purkinje conduction system pacing with ICD and atrioventricular node ablation was attempted in 55 patients, and the remaining patients underwent ICD implantation only. Left ventricular (LV) ejection fraction, LV end‐systolic volume, New York Heart Association ( NYHA ) classification, shock therapies, and drug therapy were assessed during follow‐up. Overall, 31 patients received ICD implantation with optimal drug therapy (group 1). atrioventricular node ablation combined with His‐Purkinje conduction system pacing was successfully achieved in 52 patients (group 2). During follow‐up, patients in group 2 had lower incidence of inappropriate shock (15.6% versus 0%, P <0.01) and adverse events ( P =0.011). Meanwhile, improvement in LV ejection fraction and reduction in LV end‐systolic volume were significantly higher in group 2 than in group 1 (15% versus 3%, P <0.001; and 40 versus 2 mL, P <0.01, respectively). NYHA functional class improved in both groups from a baseline 2.57±0.68 to 1.73±0.74 in group 1 and 2.73±0.59 to 1.42±0.53 in group 2 ( P <0.01). Conclusions: His‐Purkinje conduction system pacing combined with atrioventricular node ablation is feasible and safe with a high success rate in persistent atrial fibrillation patients with heart failure and ICD indication. It can significantly reduce the incidence of inappropriate shocks and improve LV function.

Background: Left bundle branch pacing (LBBP) is a novel physiological pacing and previous studies have confirmed the feasibility and safety of it. The incidence of complications in LBBP is relatively low as reported. Here we present a case of interventricular septal hematoma complicating LBBP lead implantation.Case summary: LBBP was achieved for treatment of high-grade atrioventricular block in a 67-year-old female. Chest pain began 1 h after implantation when the electrocardiogram showed ST-T changes. Then bedside echocardiography confirmed the formation of interventricular septal hematoma. Urgent coronary angiography showed the contrast agent retention and overflow in the interventricular septum. The symptom was relieved half an hour later. Echocardiogram performed 2 h later revealed the size of the hematoma was the same as before. The electrocardiography, coronary angiography and CTA confirmed the resolution of the hematoma at 1-month follow-up. Pacing parameters and cardiac function remained stable during 6-month follow-up.Conclusion: This is the first reported case describing the clinic features and management of interventricular septum hematoma complicating LBBP. The importance of routine echocardiograms after implantation for identifying the hematoma should be highlighted.