Background: Long-term β-adrenergic receptor (β-AR) activation can impair myocardial structure and function. Dapagliflozin (DAPA) has been reported to improve clinical prognosis in heart failure patients, whereas the exact mechanism remains unclear. Here, we investigated the effects of DAPA against β-AR overactivation toxicity and explored the underlying mechanism. Methods and Results: Rats were randomized to receive saline + placebo, isoproterenol (ISO, 5 mg/kg/day, intraperitoneally) + placebo, or ISO + DAPA (1 mg/kg/day, intragastrically) for 2-week. DAPA treatment improved cardiac function, alleviated myocardial fibrosis, prevented cardiomyocytes (CMs) apoptosis, and decreased the expression of ER stress-mediated apoptosis markers in ISO-treated hearts. In isolated CMs, 2-week ISO stimulation resulted in deteriorated kinetics of cellular contraction and relaxation, increased diastolic intracellular Ca²⁺ level and decay time constant of Ca²⁺ transient (CaT) but decreased CaT amplitude and sarcoplasmic reticulum (SR) Ca²⁺ level. However, DAPA treatment prevented abnormal Ca²⁺ handling and contractile dysfunction in CMs from ISO-treated hearts. Consistently, DAPA treatment upregulated the expression of SR Ca²⁺-ATPase protein and ryanodine receptor 2 (RyR2) but reduced the expression of phosphorylated-RyR2, Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), and phosphorylated-CaMKII in ventricles from ISO-treated rats. Conclusion: DAPA prevented myocardial remodeling and cardiac dysfunction in rats with β-AR overactivation via restoring calcium handling and suppressing ER stress-related CMs apoptosis.

The global burden of atrial fibrillation (AF) and atrial flutter (AFL), major contributors to stroke and heart failure, has substantially increased since 1990 due to aging populations and improved chronic disease survival. This study analyzed global, regional, and national trends in AF/AFL prevalence, incidence, mortality, and disability-adjusted life years (DALYs) among those aged ≥ 65 years (1990–2021), stratified by age, sex, and socioeconomic development index (SDI). The Global Burden of Disease (GBD) 2021 dataset provided data on AF/AFL. The analysis included age standardization, average annual percentage change (AAPC) calculations, frontier analysis, and decomposition analysis to quantify the contributions of demographic and epidemiological changes. Global AF/AFL cases in those aged ≥ 65 years increased significantly (1990–2021), with a 203.91% increase in deaths. However, age-standardized rates varied; high-income North America showed the highest prevalence rate in 2021 at 11,815.10 per 100,000. Decomposition analysis showed that the increase was attributable to population aging and growth. Frontier analysis revealed countries with disproportionately high DALYs relative to their SDI. The escalating global burden of AF/AFL in older adults demands targeted interventions and resource allocation to address regional disparities. While demographic changes are primary drivers, further research is crucial to understand the contribution of epidemiological factors and develop effective prevention and management strategies.

Left atrial thrombus (LAT) poses a significant risk for stroke and other thromboembolic complication in patients with atrial fibrillation (AF). This study aimed to evaluate the incidence and predictors of LAT in patients with paroxysmal AF, utilizing machine learning techniques based on data from the Chinese Atrial Fibrillation study. A large-scale multi-center retrospective study was conducted involving patients diagnosed with non-valvular paroxysmal AF. LAT incidence was assessed, and potential risk factors were analyzed. Machine learning algorithms, including decision tree, random forest, AdaBoost, k-Nearest Neighbor, and logistic regression, were employed to develop a predictive model for LAT. Of the 49,515 patients with paroxysmal AF, 1,058 patients (2.1%, 95% CI 2.0%-2.3%) were identified with LAT. Sixty-one variables were initially included to train machine learning models, with the random forest algorithm demonstrating the best predictive performance (AUC 0.833, 95%CI 0.730–0.924). The final model, refined to include nine essential features, achieved an AUC of 0.787 (95%CI 0.670–0.883). Calibration analysis indicated no significant difference between predicted and observed values (p = 0.181). The median predicted probabilities of LAT across quintiles were 2.3%, 7.0%, 11.8%, 16.6%, and 21.5%. This simplified prediction model effectively identifies the risk of LAT in patients with paroxysmal AF, providing a valuable tool for clinical decision-making. Further studies are needed to explore AF management and risk stratification in other AF subtypes.

Background: Data concerning young patients with atrial fibrillation (AF) are currently limited.Hypothesis: This study aimed to assess the clinical characteristics and risk factors for AF recurrence in young patients following catheter ablation (CA).Methods: All AF patients aged ≤ 45 years who underwent CA were identified from the China Atrial Fibrillation Center database between September 2018 and September 2023. Baseline clinical characteristics, procedural details, and follow‐up outcomes were compared between the paroxysmal and non‐paroxysmal cohorts.Results: A total of 6,531 young patients with AF were included in the final analysis, with an average age of 37.7 ± 5.5 years, 77.1% were male, and 65.2% with paroxysmal AF. The primary comorbidities were hypertension (16.2%), heart failure (8.4%), valvular heart disease (3.5%), diabetes mellitus (3.2%), peripheral arterial disease (2.8%), stroke/transient ischemic attack (2.5%), and cardiomyopathy (2.2%). Following CA, the recurrence rate of AF post‐CA was 14.4% across the entire cohort, with a lower recurrence rate in the paroxysmal AF group compared to the non‐paroxysmal AF group (10.6% vs. 19.7%, p < 0.001). Non‐paroxysmal AF (HR 2.34, 95% CI 1.62 to 3.36, p < 0.001) and hypertension (HR 1.69, 95% CI 1.09 to 2.63, p = 0.019) were identified as independent predictors for AF recurrence.Conclusion: Young AF patients who undergo CA exhibit a low recurrence rate and a notable improvement in symptoms post‐CA. Non‐paroxysmal AF and hypertension emerge as primary contributors to AF recurrence following CA in this population.

Primary aldosteronism (PA) is a treatable endocrine cause of secondary hypertension and, rarely, ventricular tachycardia (VT), syncope, or sudden cardiac death. A 59-year-old woman with hypertension presented with recurrent syncope for 30 years, worsening over 2 weeks. Electrocardiogram showed multifocal premature ventricular complexes (PVCs), with one dominant morphology triggering predominantly monomorphic VT, plus corrected QT interval prolongation. Hypokalemia, renal potassium wasting, left ventricular enlargement, and mild systolic dysfunction were also present. Ventricular arrhythmias recurred despite electrolyte repletion, beta-blocker therapy, and radiofrequency catheter ablation. A positive saline infusion test and a 3.6-cm left adrenal adenoma supported PA. After adrenalectomy, potassium normalized, palpitations improved, VT burden decreased, and syncope did not recur at 1 month. PA may present primarily with ventricular arrhythmias and syncope. In patients with ventricular arrhythmias accompanied by hypertension and hypokalemia, PA should be considered as a treatable endocrine-metabolic cause.