The Role of TRPM4 in Cardiac Electrophysiology and Arrhythmogenesis.

The transient receptor potential melastatin 4 (TRPM4) channel is a non-selective cation channel that activates in response to increased intracellular Ca2+ levels but does not allow Ca2+ to pass through directly. It plays a crucial role in regulating diverse cellular functions associated with intracellular Ca2+ homeostasis/dynamics. TRPM4 is widely expressed in the heart and is involved in various physiological and pathological processes therein. Specifically, it has a significant impact on the electrical activity of cardiomyocytes by depolarizing the membrane, presumably via Na+ loading. The TRPM4 channel likely contributes to the development of cardiac arrhythmias associated with specific genetic backgrounds and cardiac remodeling. This short review aims to overview what is known so far about the TRPM4 channel in cardiac electrophysiology and arrhythmogenesis, highlighting its potential as a novel therapeutic target to effectively prevent and treat cardiac arrhythmias.

Relationship between epicardial adipose tissue measured by computed tomography and premature ventricular complexes originating from different sites.

AIMS: This study aims to explore the association between the features of epicardial adipose tissue (EAT) in different zones and premature ventricular complexes (PVCs) originating from different sites by computed tomography (CT). METHODS AND RESULTS: A total of 136 patients who underwent radiofrequency ablation for PVCs were incorporated in this study. One hundred and thirty-six matched controls were included in this study using the case-control method (1:1 matching). PVCs were classified into four subgroups: (1) right ventricular outflow tract (RVOT-PVCs), (2) non-RVOT of the right ventricle (RV-PVCs), (3) left ventricular outflow tract (LVOT-PVCs), and (4) non-LVOT of the left ventricle (LV-PVCs). The volume and density of EAT were quantified by CT. Patients with PVCs had a significantly higher volume and lower density of EAT than the controls (P < 0.001). The LVOT-PVCs and LV-PVCs had a higher left ventricle periventricular EAT volume (LV-EATv) proportion (P < 0.05). The right ventricle periventricular EAT volume (RV-EATv) proportion was higher in ROVT-PVCs and LVOT-PVCs (P < 0.05). RVOT-PVC patients had a higher volume ratio and a smaller density differential (P < 0.05). Patients with LVOT-PVCs had a lower volume ratio and the LV-PVCs showed a greater density differential (P < 0.05). CONCLUSION: Higher volume and lower density of EAT were significantly associated with frequent PVCs. The RVOT-PVC patients had a higher volume ratio and a smaller density differential. The LVOT-PVCs had a lower volume ratio and the LV-PVCs showed a greater density differential. These suggest a link between EAT structural properties and PVCs and a potential role for regional EAT in the development of PVCs.

Self-reported sleep pattern and recurrence of atrial fibrillation after catheter ablation.

BACKGROUND: Increasing evidence has shown the relationship between sleep and the recurrence of atrial fibrillation (AF). However, the association of different sleep patterns with AF recurrence after catheter ablation was rarely studied. We aimed to assess the role of different sleep behaviors in the risk of AF recurrence after catheter ablation. METHODS AND RESULTS: A total of 416 consecutive participants from Zhongda hospital of Southeast University were finally analyzed. Sleep patterns were defined by chronotype, sleep duration, insomnia, snoring, and daytime sleepiness. A total of 208 patients (50.0%) had a healthy sleep pattern within a mean follow-up of 32.42 ± 18.18 months. The observed number of patients with AF recurrence was 10 (50.0%), 80 (42.6%), and 40 (19.2%) in unhealthy, intermediate and healthy sleep groups, respectively (p < .01). After adjusting covariates, unhealthy sleep pattern was significantly associated with AF recurrence [hazard ratio = 3.47 (95% confidence interval CI: 1.726-6.979, p < .001)]. Sleep disorders such as inadequate sleep time (time <7 h or >8 h), insomnia and excessive sleepiness during daytime were associated with a higher risk of recurrence. Otherwise, improvement in sleep seemed to be associated with decreased risk of AF recurrence. CONCLUSION: This retrospective study indicates that adherence to a healthy sleep pattern is associated with a lower risk of AF recurrence. Also, improved sleep before ablation is associated with a lower risk of AF recurrence.

Effects of Chronic Remote Ischemic Conditioning on Atrial Fibrillation Burden in Patients with Permanent Pacemakers.

This study aimed to evaluate the effects of chronic remote ischemic conditioning (CRIC) on atrial fibrillation burden in patients with an implanted pacemaker. Sixty-six patients with permanent pacemakers were randomly divided into the CRIC group and control group after 4 weeks of screening. CRIC treatment was performed twice daily for 12 weeks. The remote ischemic conditioning protocol consisted of 4 × 5 minutes inflation/deflation of the blood pressure cuff applied in the upper arm to create intermittent arm ischemia. Sixty-one patients (31 patients in the CRIC group and 30 patients in the control group) completed the study. CRIC was well tolerated by patients after 12 weeks of treatment. The burden of atrial fibrillation (AF) in the CRIC group decreased significantly at 4 weeks compared with that at 0 weeks (14.7% ± 18.5% versus 17.0% ± 20.7%, P < 0.001), which further decreased at 12 weeks compared with that at 0 weeks (8.6% ± 10.2% versus 17.0% ± 20.7%, P < 0.001) and that at 4 weeks (8.6% ± 10.2% versus 14.7% ± 18.5%, P < 0.001), which was not observed in the control group. AF burden also reduced significantly after 12-week CRIC compared with that in the control group (8.6% ± 10.2% versus 17.6% ± 19.5%, P = 0.013). Repeated measurement ANOVA showed that the changes in AF burden were associated with CRIC instead of time (P < 0.01). In addition, there were trends that the longest duration of AF and cumulative numbers of atrial high-rate episodes (AHREs) reduced after 12-week CRIC. This study suggests that a 12-week course of CRIC treatment could reduce AF burden in patients with permanent pacemakers, supporting the widespread use of CRIC in the daily lives of these patients, which needs to be verified in the future.

WiSE CRT Is Beneficial for Heart Failure Patients as a Rescue Therapy: Evidence From a Meta-Analysis.

Background: Leadless endocardial left ventricular (LV) pacing resynchronization therapy is a novel solution for patients with heart failure (HF) in whom conventional cardiac resynchronization therapy (CRT) failed. Methods: PubMed and the Cochrane Library were searched for relevant cohort studies. Clinical outcomes of interest such as ejection fraction (EF), QRS duration (QRSd), and left ventricular end-systolic volume (LVESV) were extracted and analyzed. Results: Five studies involving 175 HF patients for WiSE CRT were included, and patients were followed-up for 6 months. The implanted success rate ranged from 76.5 to 100%. WiSE CRT resulted in significantly narrower QRSd [mean difference (MD): -38.21 ms, 95% confidence interval (CI): -44.36 to -32.07, p < 0.001], improved left ventricular ejection fraction (MD: 6.07%, 95% CI: 4.43 to 7.71, I2 = 0%, p < 0.001), reduced left ventricular end-systolic volume (MD: -23.47 ml, 95% CI: -37.18 to -9.13, p < 0.001), and reduced left ventricular end-diastolic volume (MD: -24.02 ml, 95% CI: -37.01 to -11.03, p = 0.02). Conclusion: Evidence from current studies suggests that leadless endocardial LV pacing resynchronization is effective for HF patients who failed conventional CRT or needed a device upgrade, and it may be an interesting rescue therapy.

Multifunctional Liposomes Enable Active Targeting and Twinfilin 1 Silencing to Reverse Paclitaxel Resistance in Brain Metastatic Breast Cancer.

Paclitaxel (PTX) is a first-line chemotherapeutic drug for breast cancer, but PTX resistance often occurs in metastatic breast cancer. In addition, due to the poor targeting of chemotherapeutic drugs and the presence of the blood-brain barrier (BBB), it is hard to effectively treat brain metastatic breast cancer using paclitaxel. Thus, it is urgent to develop an effective drug delivery system for the treatment of brain metastatic breast cancer. The current study found that TWF1 gene, an epithelial-mesenchymal transition-associated gene, was overexpressed in brain metastatic breast cancer (231-BR) cells and was associated with the PTX resistance of 231-BR cells. Knockdown of TWF1 by small interference RNA (siRNA) in 231-BR cells could effectively increase the sensitivity of brain metastatic breast cancer cells to paclitaxel. Then, a liposome-based drug delivery system was developed for PTX delivery across BBB, enhancing PTX sensitivity and brain metastases targeting via BRBP1 peptide modification. The results showed that BRBP1-modified liposomes could effectively cross the BBB, specifically accumulate in brain metastases, and effectively interfere TWF1 gene expression in vitro and in vivo, and thus they enhanced proliferation inhibition, cell cycle arrest, and apoptosis induction, thereby inhibiting the formation and growth of brain metastases. In summary, our results indicated that BRBP1-modified and PTX- and TWF1 siRNA-loaded liposomes have the potential for the treatment of brain metastatic breast cancer, which lays the foundation for the development of a new targeted drug delivery system.

Targeted NIRF/MR dual-mode imaging of breast cancer brain metastasis using BRBP1-functionalized ultra-small iron oxide nanoparticles.

Tumor metastasis to brain is the main clinical manifestation of patients with advanced breast cancer, leading to poor survival prognosis. In order to detect the early incidence of brain metastasis, it is urgent to develop hypersensitive contrast agents for multimode imaging. In this study, PEG-phospholipids coated, a phage play derived peptide, BRBP1 peptide modified ultra-small iron oxide nanoparticles were prepared for targeted NIRF and MR imaging of breast cancer brain metastasis. The nanoparticles showed 10 nm core-shell, high relaxivity values and photon emission efficiency in vitro. The nanoparticles offered a T2 contrast imaging effect and near-infrared fluorescent signal enhancement. Compared with control peptide modified nanoparticles, the MR/NIRF imaging signal of BRBP1-modified nanoparticles in tumor tissue was significantly enhanced, which should be induced by the targeting ability of BRBP1 peptide. These results indicated that BRBP1-SPIO@mPEG (DiR) nanoparticles could be applied as an effective targeted delivery system for diagnosis of breast cancer brain metastasis.