Atrial fibrillation (AF) is one of the risk factors for dementia. Female sex is an inconsistent risk factor for dementia after adjusting for age in the general population, and there lacks research on its impact in developing dementia in patients with AF. This paper aims to investigate whether female sex is a risk factor for dementia in AF patients. Data of patients with newly diagnosed AF between 2001–2013 were retrieved from Taiwan’s National Health Insurance Research Database. Exclusion criteria were: patients with incomplete demographic data, age < 20 years, rheumatic heart disease, hyperthyroidism, past valvular heart surgery, and a history of dementia. Propensity score matching (PSM) between sexes was performed, including comorbidities, medications and index date stratified by age. The primary outcome was a new diagnosis of dementia at follow-up. A total of 117,517 men and 156,705 women were eligible for analysis. After 1:1 PSM, both 100,065 men and women (aged 72.5 ± 12.5 years) were included for analysis. Dementia risk varied with age in women compared with men. The difference was negligible for ≤55 years (sub distribution HR (SHR) = 0.89, 95% CI 0.73–1.07), but increased between 56–65 years (SHR = 1.13, 95% CI 1.02–1.25), 66–75 years (SHR = 1.14, 95% CI 1.09–1.20), 75–85 years (SHR = 1.11, 95% CI 1.07–1.15) and >85 years (SHR 1.10, 95% CI 1.04–1.16) for females. This study establishes that female sex increases the risk of developing dementia compared to male sex in AF patients aged >56 years. However, the impact of female sex on dementia in AF patients differs between dementia types.

Obstructive sleep apnea syndrome (OSAS) is a significant risk factor for left atrial (LA) remodeling. Intermittent hypoxemia occurs during the sleep cycle in patients with OSAS and plays a crucial role in cardiovascular pathologies such as stroke, arrhythmia, and coronary artery disease. However, there is very little information about the role of intermittent hypoxemia in LA remodeling in patients with OSAS. In total, 154 patients with sleep-related breathing disorders (SRBD) were prospectively recruited for this study. All enrolled SRBD patients underwent polysomnography and echocardiography. Significant OSAS was defined as an oxygen desaturation index (ODI) of ≥10 per hour. Intermittent hypoxia/reoxygenation (IHR) stimulation was used to test the effect of hypoxia on the viability, reactive oxygen species, apoptosis, and inflammation-associated cytokine expression in the HL-1 cell line. To investigate the effect of patients’ exosomes on HIF-1 and inflammation-associated cytokine expression, as well as the relationship between ODI and their expression, exosomes were purified from the plasma of 95 patients with SRBD and incubated in HL-1 cells. The LA size was larger in patients with significant OSAS than in those without. There was a significant association between ODI, lowest SpO₂, mean SpO₂, and LA size (all p < 0.05) but not between the apnea–hypopnea index and LA size. IHR condition caused increased LDH activity, reactive oxygen species (ROS) levels, and apoptosis in HL-1 cells and decreased cellular viability (all p < 0.05). The expression of HIF-1α, TNF-α, IL-6, and TGF-β increased in the IHR condition compared with the control (all p < 0.05). The expression of HIF-1α, IL-1β, and IL-6 increased in the HL-1 cells incubated with exosomes from those patients with significant OSAS than those without (all p < 0.05). There was a significantly positive correlation between ODI and the expression of HIF-1α, TNF-α, IL-1β, IL-6, and TGF-β; a significantly negative correlation between mean SpO₂ and IL-6 and TGF-β; and a significantly negative correlation between the lowest SpO₂ and HIF-1α (all p < 0.05). In conclusion, intermittent hypoxemia was strongly associated with LA remodeling, which might be through increased ROS levels, LDH activity, apoptosis, and the expression of HIF-1α and inflammation-associated cytokines.

A prominent circadian variation is present in atrial fibrillation (AF) attacks that may be related to the expression of circadian clock genes. Little is known about the expression of circadian clock genes in AF. We prospectively enrolled 73 patients who had received pacemaker implantation, in order to define the burden of atrial high-rate episodes (AHREs) accurately. AF was diagnosed clinically in 43 (59%) patients (15 with persistent AF and 28 with paroxysmal AF). The expression levels of circadian clock genes of peripheral blood leukocytes were checked. There were more males and patients with a larger left atrial (LA) size and lower expression levels of BMAL1, CRY2, NR1D1, NR1D2, PER2, RORA, RORC, and TIM genes in persistent AF group than in other groups. There was a significant correlation between higher AHRE burden and larger LA size and between higher AHRE burden and decreased expression of circadian clock genes in patients with AF. LA volume and the expression of CRY1, NR1D1, and RORA are significantly associated with AHRE burden. However, the underlying mechanism needs to be elucidated in further studies.

Obstructive sleep apnea syndrome (OSAS) is an important risk factor for atrial fibrillation (AF). GJA1 gene encoding connexin43, a major protein in cardiac gap junctions, plays a crucial role in the synchronized contraction of the heart and in cardiac arrhythmia. However, little is known regarding the role of GJA1 expression in the incidence of AF in patients with OSAS. All prospectively enrolled OSAS patients underwent polysomnography, electrocardiography, a 24-h Holter test, and echocardiography. Moderate-to-severe OSAS was defined as an apnea-hypopnea index (AHI) ≥ 15. Exosomes were purified from the plasma of all OSAS patients and incubated in HL-1 cells to investigate the effect of exosomes from patients with and without AF on GJA1 expression. A total of 129 patients were recruited for this study; 26 were excluded due to an AHI < 15. Of the 103 enrolled patients, 21 had AF, and 82 did not. Multivariate analysis showed diabetes mellitus, lower sleep efficiency, lower left ventricular ejection fraction, and larger left atrial (LA) size were independent predictors of AF occurrence in OSAS patients. The area under the receiver operating characteristic curve for LA with a size ≥38.5 mm for predicting AF occurrence in OSAS patients was 0.795 (95% confidence interval [0.666, 0.925]); p < 0.001). GJA1 expression in HL-1 cells incubated with exosomes from OSAS patients with AF was lower than that with exosomes from patients without AF after controlling for age and sex and was negatively correlated with the AHI and oxygen desaturation index (ODI), especially during the non-rapid eye movement period (NREM) of OSAS patients with AF (all p < 0.05). LA size was an independent predictor of AF occurrence in OSAS patients. The AHI and ODI in the NREM period of OSAS patients with AF were negatively correlated with GJA1 expression in HL-1 cells, which offers a hint that GJA1 may play a crucial role in the development of AF in patients with OSAS.

A previous study showed that high-glucose (HG) conditions induce mitochondria fragmentation through the calcium-mediated activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) in H9C2 cells. This study tested whether empagliflozin could prevent HG-induced mitochondria fragmentation through this pathway. We found that exposing H9C2 cells to an HG concentration decreased cell viability and increased cell apoptosis and caspase-3. Empagliflozin could reverse the apoptosis effect of HG stimulation on H9C2 cells. In addition, the HG condition caused mitochondria fragmentation, which was reduced by empagliflozin. The expression of mitochondria fission protein was upregulated, and fusion proteins were downregulated under HG stimulation. The expression of fission proteins was decreased under empagliflozin treatment. Increased calcium accumulation was observed under the HG condition, which was decreased by empagliflozin. The increased expression of ERK 1/2 under HG stimulation was also reversed by empagliflozin. Our study shows that empagliflozin could reverse the HG condition, causing a calcium-dependent activation of the ERK 1/2 pathway, which caused mitochondria fragmentation in H9C2 cells.

Shared decision making (SDM) is an interactive process that involves patients and their healthcare professionals reaching joint decisions about medical care through negotiation. As the initiators of medical decision-making in daily routine, physicians should be aware of and concerned about the SDM process. Thus, professional competency development for SDM has become increasingly critical for physicians’ training. Therefore, this study investigates the professional competency and the important competency development aspects/criteria of SDM tasks through expert interviews and literature research. The study adopts the SAA (satisfaction-attention analysis) method to assess the status of competency development aspects/criteria and determine the NRM (network relation map) based on the DEMATEL (decision-making trial and evaluation laboratory) technique. The results demonstrate that the CE (concept and evaluation) aspect is the dominant aspect, and the CR (communication and relationship) aspect is the aspect being dominated. The CE aspect influences the aspects of SP (skill and practice), JM (joint information and decision making) and CR, and the SP aspect affects the aspects of JM and CR. Then, the JM aspect affects the CR aspect. The study also suggests suitable adoption paths of competency development for SDM tasks using the NRM approach. It provides recommendations and strategic directions for SDM competency development and sustainable training programs.