[Correlation between abnormal left atrial appendage function and thrombotic events in patients with non-valvular atrial fibrillation].

Objective: To investigate the association between abnormal left atrial appendage function and thrombotic events in patients with non-valvular atrial fibrillation, and the independent risk factors affecting left atrial appendage function. Methods: Patients with non-valvular atrial fibrillation, who visited the Atrial Fibrillation Center of the First Affiliated Hospital of Xinjiang Medical University from June 1, 2019 to June 1, 2021, were selected. According to left atrial appendage flow velocity (LAAFV), they were divided into normal left atrial appendage function group (297 patients with LAAFV ≥ 40 cm/s) and abnormal left atrial appendage function group (85 patients with LAAFV<40 cm/s). Baseline data and transesophageal echocardiography images were collected from all the patients. The occurrence of thrombotic events was recorded. Univariate and multivariate unconditional logistic regression analyses were conducted to investigate the correlation between abnormal left atrial appendage function and the occurrence of thrombotic events. Results: There were significant differences in gender, type of atrial fibrillation, CHA2DS2-VASc score, anticoagulant therapy, total cholesterol, low-density lipoprotein cholesterol, international normalized ratio (INR), left atrial diameter, proportion of patients with right atrial enlargement, left ventricular ejection fraction, inner diameter, sum of inner diameter, depth, and sum of depth of all angles of the left atrial appendage, and incidence of thrombotic events between the two groups (all P<0.05). After adjusting for confounders, multivariate unconditional logistic regression analyses showed that abnormal left atrial appendage function was closely associated with thrombotic events (ß=1.168 P=0.002), and left atrial diameter (OR=1.084, 95%CI 1.019-1.153, P=0.011) and persistent atrial fibrillation (OR=2.323, 95%CI 1.226-4.403, P=0.010) were independent risk factors affecting left atrial appendage function. Conclusions: Abnormal left atrial appendage function is closely associated with thrombosis. The left atrial diameter and persistent atrial fibrillation were independent risk factors affecting left atrial appendage function.

Pioglitazone Alleviates ß1-Adrenergic Receptor Antibody-Induced Atrial Fibrillation Susceptivity via Mitigation of PPAR-γ-Mediated Metabolic Inflexibility.

BACKGROUND: Beta-1-adrenergic receptor antibodies (ß1-AAbs) function as arrhythmogenic molecules in autoimmune-related atrial fibrillation (AF). This study examined the potential impact of pioglitazone, an agonist for peroxisome proliferator-activated receptor-γ (PPAR-γ), on atrial remodeling induced by ß1-AAbs. METHODS: An in vivo study was performed to confirm the protective effects of pioglitazone on ß1- AAbs-induced atrial remodeling. GW9662, a PPAR-γ antagonist, was employed to identify the potential therapeutic target of pioglitazone. The rats were administered subcutaneous injections of the second extracellular loop peptide for 8 weeks to establish active immunization models. Pioglitazone was then administered orally for 2 weeks. Epicardial electrophysiologic studies, multielectrode array measurements, and echocardiography were conducted to examine atrial remodeling. Glucose metabolism products and key metabolic molecules were measured to evaluate the atrial substrate metabolism. Mitochondrial morphologies and function indices were tested to depict the underlying links between atrial metabolism and mitochondrial homeostasis under the pioglitazone treatment. RESULTS: Pioglitazone significantly reversed ß1-AAbs-induced AF susceptibility, ameliorated atrial structural remodeling, decreased the global insulin resistance reflected in the plasma glucose and insulin levels, and increased the protein expressions of glycolipid uptake and transportation (GLUT1, CD36, and CPT1a). These trends were counterbalanced by the GW9662 intervention. Mechanistically, pioglitazone mitigated the atrial mitochondrial network damage and partly renovated the mitochondrial biogenesis, even the mitochondrial dynamics, which were reversed by inhibiting the PPAR-γ target. CONCLUSION: Pioglitazone effectively reduced the AF vulnerability and recovered the atrial myocardial metabolism and mitochondrial damage. The potential anti-remodeling effect of pioglitazone on the atrium was associated with the moderately increased expression of key membrane proteins related to glucose transporter and fatty acid uptake, which may promote the increased myocardial preference for utilization of FA as the key cardiac oxidative fuel and ameliorate the atrial metabolic inflexibility.