Coronary sinus signal amplitude: A predictor of the atrial substrate and low voltage areas.

BACKGROUND: Low voltage areas (LVA) are pivotal in atrial fibrillation (AF) pathogenesis, influencing local left atrial LA excitation and perpetuating AF occurrences. While pulmonary vein isolation (PVI) with cryo-balloon (CB) ablation is effective for AF, it doesn't provide insights into the LA substrate or detect LVA, which affects ablation success rates. This study examines whether LA voltage and LVAs can be anticipated by analyzing the voltage signal amplitude at the coronary sinus (CS) catheter, which is standard in CB and radiofrequency ablation procedures. METHODS: A retrospective analysis of 284 patients with recurrent AF undergoing RF catheter ablation was conducted at a high-volume EP center in Germany. The correlation between LA voltage and LVA with the CS signal was explored. RESULTS: The signal amplitude in the CS significantly correlated with voltage in LA walls, particularly in the proximal CS (correlation coefficient ρ = 0.81, p < 0.001). A CS signal cut-off of 1.155 mV effectively predicted severe atrial LVAs (>40%) with a sensitivity of 90.7% and a specificity of 100%. While a threshold of 1.945 mV identified patients with no significant atrial LVAs (<5%) with a sensitivity of 88% and a specificity of 50% (AUC: 0.81, 95% CI: 0.71-0.89, p < 0.001). CONCLUSION: The CS signal amplitude is associated with the LA voltage. Due to its potential as a diagnostic tool for atrial LVAs, the signal amplitude in the CS could provide valuable information about the LA substrate, especially when 3D mapping is not feasible.

Unraveling the interplay: early-stage atrial functional mitral regurgitation and left atrial electrical substrate in atrial fibrillation patients.

Background: Atrial fibrillation (AF) triggers atrial remodeling, impacting atrial function and ablation efficacy. This remodeling leads to atrial cardiomyopathy and dilatation, linked to mitral regurgitation, forming atrial functional mitral regurgitation (aFMR). Our study explores the relationship between early-stage-aFMR and the atrial electrical architecture, focusing on left atrial bipolar voltage and low-voltage areas (LVAs) in AF patients. Methods: We enrolled 282 patients undergoing redo-PVI after AF recurrence post-PVI. Echocardiography was performed prior to ablation, and only patients with no, mild, or mild-to-moderate aFMR were included. Ablation used radiofrequency and a 3D mapping system, with atrial voltage documented on each atrial wall. LVAs were calculated using high-density maps, and patients were followed for 15 months. Results: Significant differences in left atrial voltage and LVA extent were observed based on aFMR severity. Patients with aFMR 1 + had significantly lower atrial voltage compared to no-aFMR, but no significant increase in LVAs. Patients with aFMR 2 + showed lower voltage amplitudes in all atrial regions and larger LVAs compared to no-aFMR patients. AF recurrence was significantly higher in the aFMR group (62.9% vs. 48.3%, p = 0.027) within 1 year. aFMR was associated with AF recurrence after adjusting for sex, age, and AF types (HR: 1.517, 95% CI: 1.057-2.184, p = 0.025). Conclusion: aFMR in AF patients may indicate progressive atrial remodeling and left atrial cardiomyopathy, characterized by reduced atrial voltage and increased LVAs. aFMR is linked to PVI outcomes, suggesting its consideration in AF therapy decision-making.

Methylation Patterns of the FKBP5 Gene in Association with Childhood Maltreatment and Depressive Disorders.

Childhood maltreatment is an important risk factor for adult depression and has been associated with changes in the hypothalamic pituitary adrenal (HPA) axis, including cortisol secretion and methylation of the FKBP5 gene. Furthermore, associations between depression and HPA changes have been reported. This study investigated the associations of whole-blood FKBP5 mRNA levels, serum cortisol levels, childhood maltreatment, and depressive symptoms with the whole-blood methylation status (assessed via target bisulfite sequencing) of 105 CpGs at the FKBP5 locus using data from the general population-based Study of Health in Pomerania (SHIP) (N = 203). Both direct and interaction effects with the rs1360780 single-nucleotide polymorphism were investigated. Nominally significant associations of main effects on methylation of a single CpG site were observed at intron 3, intron 7, and the 3'-end of the gene. Additionally, methylation at two clusters at the 3'-end and intron 7 were nominally associated with childhood maltreatment × rs1360780 and depressive symptoms × rs1360780, respectively. The results add to the understanding of molecular mechanisms underlying the emergence of depression and could aid the development of personalised depression therapy and drug development.

Maternal exercise conveys protection against NAFLD in the offspring via hepatic metabolic programming.

Maternal exercise (ME) during pregnancy has been shown to improve metabolic health in offspring and confers protection against the development of non-alcoholic fatty liver disease (NAFLD). However, its underlying mechanism are still poorly understood, and it remains unclear whether protective effects on hepatic metabolism are already seen in the offspring early life. This study aimed at determining the effects of ME during pregnancy on offspring body composition and development of NAFLD while focusing on proteomic-based analysis of the hepatic energy metabolism during developmental organ programming in early life. Under an obesogenic high-fat diet (HFD), male offspring of exercised C57BL/6J-mouse dams were protected from body weight gain and NAFLD in adulthood (postnatal day (P) 112). This was associated with a significant activation of hepatic AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor alpha (PPARα) and PPAR coactivator-1 alpha (PGC1α) signaling with reduced hepatic lipogenesis and increased hepatic ß-oxidation at organ programming peak in early life (P21). Concomitant proteomic analysis revealed a characteristic hepatic expression pattern in offspring as a result of ME with the most prominent impact on Cholesterol 7 alpha-hydroxylase (CYP7A1). Thus, ME may offer protection against offspring HFD-induced NAFLD by shaping hepatic proteomics signature and metabolism in early life. The results highlight the potential of exercise during pregnancy for preventing the early origins of NAFLD.