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Background Individuals with schizophrenia spectrum disorders are at increased risk of cardiometabolic complications, largely due to antipsychotic-associated metabolic effects. Effective management strategies remain limited. Semaglutide, a glucagon-like peptide-1 receptor agonist, has shown metabolic benefits in the general population, but its role in this population remains unclear. Objective To evaluate the efficacy and safety of semaglutide compared with placebo in individuals with schizophrenia spectrum disorders receiving antipsychotic therapy and experiencing metabolic abnormalities. Design Systematic review and meta-analysis of randomized controlled trials. Data Sources and Methods: A systematic review and meta-analysis was conducted following PRISMA guidelines. PubMed, Cochrane Library, Embase, and ScienceDirect were searched from inception to February 2026. Randomized controlled trials comparing semaglutide with placebo were included. The longest follow-up time point from each study was used for pooled analysis. Mean differences (MD) and odds ratios (OR) with 95% confidence intervals (CIs) were calculated using RevMan 5.4. The certainty of evidence for critical outcomes was assessed using the GRADE framework. Results Three randomized controlled trials (n = 258) were included. Semaglutide was associated with reductions in body weight (MD: -11.01 kg), BMI (MD: -3.63 kg/m 2 ), and waist circumference (MD: -6.33 cm). Improvements were also observed in body composition. No significant differences were found in lipid or glycemic parameters except HbA1c which showed a significant reduction. Psychiatric outcomes remained unchanged. Gastrointestinal adverse particularly nausea and vomiting events were more frequent with semaglutide. Conclusion Semaglutide appears to improve anthropometric outcomes without worsening psychiatric symptoms in individuals receiving antipsychotic therapy. However, evidence is limited, and larger, long-term trials are required. According to the GRADE framework, the certainty of evidence ranged from moderate for key anthropometric and safety outcomes to low or very low for several metabolic and psychiatric outcomes, highlighting the need for larger, long-term randomized trials.

ABSTRACT Background Disparities in management of atrial fibrillation in rural and urban hospitals across the U.S. have been reported. However, studies investigating disparities regarding outcomes and complications after left atrial appendage occlusion (LAAO) based on hospital location are lacking. Objective To evaluate differences in outcomes and complications related to LAAO among rural and urban hospitals. Methods The National Inpatient Sample was used to identify patients who underwent LAAO implantations in the U.S. from 2016−2020. Study endpoints assessed included inpatient complications, outcomes, and resource utilization after LAAO procedures among rural and urban hospitals. Results From 2016−2020, there were a total of 87 315 and 1985 LAAO device placements in urban and rural hospitals, respectively. Baseline characteristics were similar among both groups, with a few exceptions. After multivariable adjustment for confounders, odds of inpatient complications and mortality were similar among both groups. However, rural LAAO recipients experienced greater rates of discharge to an acute care facility (3.3% vs 2.4%, p = 0.01), as well as lower costs (aOR: 0.58, 95% CI: 0.49–0.69) and length of stay (aOR: 0.89, 95% CI: 0.81–0.98). Conclusions A majority of LAAO implantations occurred in urban hospitals in the U.S. Baseline characteristics and adjusted odds of inpatient complications and mortality were similar in rural and urban recipients. However, important differences were described regarding resource utilization and disposition. Further investigation into the specific factors driving these inequities is encouraged to promote improved access to and outcomes of cardiovascular care for rural residents.

Over 37% of pregnant women report excessive daytime sleepiness or hypersomnia during the first trimester, and commonly throughout the remaining trimesters of pregnancy and the postpartum period. The clinical presentation and symptoms of central disorders of hypersomnolence (CDH) such as narcolepsy, idiopathic hypersomnia, or excessive daytime sleepiness secondary to shift work or obstructive sleep apnea may be confounded by physiological changes in sleep architecture and hormonal fluctuations occurring during pregnancy. These overlapping features may cause delays in diagnosis and treatment, impacting quality of life, maternal functioning, and overall health. Management of CDH during pregnancy and lactation requires careful consideration of maternal benefits, potential side effects of medications and fetal and neonatal safety. Here, we present a case of idiopathic hypersomnia and detail management and outcomes during pregnancy and lactation. We briefly review the existing literature on prevalence, pathophysiological mechanisms, diagnostic challenges, objective findings, and risks posed by CDH in pregnancy and lactation. In this narrative review for primary care clinicians, we also summarize currently available evidence regarding the efficacy, teratogenic and other risks of pharmacologic agents used in the treatment of CDH in pregnancy and lactation. Lastly, we provide a clinical algorithm for management of CDH during pregnancy and lactation.

ABSTRACT Background Patients with end‐stage renal disease (ESRD) undergoing dialysis have an increased risk of pacemaker‐related complications due to limited vascular access and increased susceptibility to infection. Leadless pacemakers (LPMs) may mitigate these risks compared with conventional transvenous pacemakers (TPMs), but long‐term comparative data in this population remain limited. Methods We conducted a retrospective cohort study using the TriNetX Research Network, including adults (≥ 18 years) with ESRD on dialysis who underwent LPM or TPM implantation between May 2016 and December 2020. Propensity score matching (1:1) was performed using demographics and comorbidities. Outcomes assessed over up to 5 years included all‐cause hospitalization, heart failure hospitalization, device re‐intervention, device‐related complications, infection‐related hospitalization, pacemaker‐induced cardiomyopathy, and all‐cause mortality. Results After matching, 901 patients were included in each group with well‐balanced baseline characteristics. LPM implantation was associated with a significantly lower risk of device re‐intervention compared with TPM (4.1% vs. 9.3%; hazard ratio [HR] 0.44; 95% confidence interval [CI] 0.28–0.69; p < 0.01). There were no significant differences between groups in all‐cause hospitalization (65.5% vs. 68.3%; p = 0.22), heart failure hospitalization (26.9% vs. 30.2%; p = 0.13), all‐cause mortality (37.5% vs. 35.3%; p = 0.34), device‐related complications (14.5% vs. 14.3%; p = 0.94), infection‐related hospitalization (1.6% vs. 2.1%; p = 0.35), or pacemaker‐induced cardiomyopathy (9.0% vs. 8.6%; p = 0.66). Conclusion In a large, propensity‐matched cohort of patients with ESRD on dialysis, LPMs were associated with fewer device re‐interventions and comparable long‐term clinical outcomes compared with TPMs.

ABSTRACT Background Atrial fibrillation (AF) is common in patients with hypertrophic cardiomyopathy (HCM) and is associated with increased morbidity, heart failure (HF) exacerbations, and adverse long‐term outcomes. Although catheter ablation is an established rhythm‐control strategy, data comparing its long‐term clinical outcomes with anti‐arrhythmic drug (AAD) therapy in patients with HCM remain limited. Objective To compare long‐term clinical outcomes of catheter ablation versus medical therapy with AADs in patients with HCM and AF. Methods We conducted a retrospective cohort study using the TriNetX Research Network, a global federated database of electronic health records. Adult patients with HCM and AF between January 2010 and December 2020 were identified and stratified according to treatment with catheter ablation or AAD therapy. Outcomes included all‐cause mortality, HF exacerbations, AAD‐related adverse events, all‐cause hospitalization, ischemic stroke, repeat ablation, need for cardioversion, need for long‐term AAD use, and atrioventricular nodal ablation. A 1:1 propensity score matching (PSM) analysis was performed to balance baseline characteristics. Kaplan–Meier survival analysis and Cox proportional hazards models were used to estimate hazard ratios (HRs). Results After PSM, 3144 patients were included (1572 in each cohort) with a mean follow‐up of approximately 3.4 years. Catheter ablation was associated with lower all‐cause mortality compared with AAD therapy (9.5% vs. 14.8%; HR: 0.60; 95% CI: 0.49–0.74; p < 0.001). Ablation was also associated with reduced risk of HF exacerbations (38.4% vs. 43.3%; HR: 0.79; 95% CI: 0.71–0.88; p < 0.001) and fewer AAD‐related adverse events (8.4% vs. 11.2%; HR: 0.71; 95% CI: 0.55–0.93; p = 0.011). Rates of all‐cause hospitalization (HR: 0.93; p = 0.11) and ischemic stroke (HR: 0.78; p = 0.10) were similar between groups. Conclusion In this large real‐world cohort of patients with HCM and AF, catheter ablation was associated with lower mortality, reduced HF hospitalizations, and decreased AAD therapy‐related adverse events, as compared with medical therapy. These findings suggest that catheter ablation may provide meaningful clinical benefits in selected patients with HCM and AF, although prospective studies are needed to confirm these observations.

Objectives This study aims to compare the reliability and accuracy of three large language models (LLMs) (Claude, Gemini and GPT) in assessing the risk of bias of nonrandomised studies using the ROBINS-I tool. Methods and analysis We conducted a secondary analysis of 171 nonrandomised studies previously assessed with Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool by two independent human review teams. Only studies with concordant human domain-level ratings were included. Each study was independently assessed twice by Claude, Gemini and Generative Pre-trained Transformer (GPT) using agent-based structured implementations of the ROBINS-I tool. Reliability (agreement between two runs of the same LLM) was evaluated using percent agreement and Gwet’s AC1. Accuracy (agreement with human reviewers) was assessed only for studies with consistent LLM ratings, using the same metrics. Results Claude demonstrated high reliability across all domains (79.5–98.0% agreement, AC1=0.729–0.975). Gemini showed moderate-to-high reliability (agreement 76.7–100%, AC1=0.680–1.0). GPT exhibited lower reliability overall, though domain-level agreement ranged from 70.9–95.6% (AC1=0.596–0.944). In terms of accuracy, Claude showed overall poor agreement with human reviewers (14.4–68.5% agreement; low AC1 values). Gemini demonstrated moderate-to-high accuracy in several domains, including deviations from intended interventions (79.6%, AC1=0.848) and measurement of outcomes (73.9%, AC1=0.702), with the highest overall agreement (40.0%, AC1=0.672). GPT showed variable accuracy, with the highest in measurement of outcomes (62.8%, AC1=0.571) and classification of interventions (57.8%, AC1=0.498), but poor performance in selection (14.3%, AC1 = −0.041) and overall agreement (23.0%, AC1=0.267). Conclusions Claude was internally consistent but poorly aligned with human reviewers. Gemini achieved both high reliability and moderate-to-high accuracy, whereas GPT had lower reliability and mixed accuracy. Current off-the-shelf LLMs cannot reliably perform ROBINS-I risk of bias assessments.

ABSTRACT Introduction Frailty is increasingly recognized as an important determinant of outcomes in cardiovascular disease, yet its population‐level impact among patients hospitalized with cardiac implantable electronic device (CIED) infections remains incompletely defined. We examined the prevalence of frailty and its association with clinical outcomes and utilization of transvenous lead removal (TLR) in a contemporary national cohort. Methods and Results We analyzed the National Readmissions Database from 2016–2021 to identify adults hospitalized for CIED infections. Frailty was defined using the Johns Hopkins adjusted clinical groups frailty‐defining diagnoses. Of 288,402 patients hospitalized with CIED infections, 25.1% were classified as frail. Frail patients experienced significantly higher in‐hospital mortality (10.8% vs. 4.6%), 30‐day mortality (9.2% vs. 5.5%), complications, longer length of stay, lower rates of discharge home, and higher 30‐day readmissions compared with non‐frail patients (all p < 0.01). TLR was performed less frequently in frail patients (10.8% vs. 13.4%; adjusted odds ratio [aOR] 0.80, 95% CI 0.76–0.83). On adjusted analyses, TLR was independently associated with lower in‐hospital mortality, 30‐day mortality, and 30‐day readmissions in both frail and non‐frail patients. Conclusion Among patients hospitalized with CIED infections, TLR was independently associated with lower mortality and readmissions in both frail and non‐frail patients, despite lower utilization in frail individuals. Frailty was common (25.1%) and independently associated with significantly worse outcomes. These findings highlight important associations between frailty, treatment patterns, and outcomes that warrant prospective evaluation.

ABSTRACT Background Transvenous lead removal (TLR) in patients with a history of mediastinal radiation poses unique challenges due to potential radiation‐induced fibrosis, vascular changes, and anatomical distortion, which may increase procedural complexity and complication risk. However, contemporary data on clinical outcomes in this population remain limited. Methods We analyzed the National Readmissions Database (2016–2021) to identify adults (≥ 18 years) undergoing TLR. Patients were stratified by prior mediastinal radiation. Baseline characteristics were compared using standard statistical tests. Multivariable logistic regression was used to evaluate the association between prior mediastinal radiation and in‐hospital outcomes, 30‐day mortality, and 30‐day readmissions after adjustment for demographics and comorbidities. Results A total of 48,985 patients underwent TLR, of whom 735 (1.5%) had a history of mediastinal radiation. Compared with patients without radiation, those with prior radiation were older (70.1 vs. 66.2 years, p < 0.01), were more frequently females (38.2% vs. 31.6%, p < 0.01), and had higher rates of valvular heart disease, atrial fibrillation, and peripheral vascular disease. Adjusted analyses demonstrated no increased risk of in‐hospital mortality (2.3% vs. 3.4%; adjusted odds ratio [aOR] 0.65, 95% confidence interval [CI] 0.41–1.18, p = 0.29) or major complications, including cardiac arrest, pericardial complications, vascular injury, pulmonary complications, or embolic events. Similarly, (3.6% vs. 5.3%; aOR 0.76, 95% CI 0.48–1.43, p = 0.35) and 30‐day all‐cause readmissions (8.7% vs. 9.1%; aOR 0.81, 95% CI 0.64–1.28, p = 0.70) were not significantly different between groups. Subgroup analyses by indication for TLR (infection vs. mechanical complication) revealed no differences in outcomes. Conclusion Despite theoretical concerns, prior mediastinal radiation was not associated with excess procedural risk or worse short‐term outcomes after TLR. These findings may inform procedural planning and risk counseling in clinical practice.

ABSTRACT Background Early catheter ablation for atrial fibrillation (AF) improves outcomes, but the optimal timing, especially in heart failure (HF) subtypes, remains unclear. Objective To evaluate the impact of ablation timing on outcomes in patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Methods We used the TriNetX database (2010–2024) to identify HF patients with AF who underwent ablation. Patients were classified as early ablation (≤ 1 year of first AF diagnosis) or delayed ablation (1–3 years), with propensity score matching (PSM) applied to balance the baseline characteristics. The primary outcome was AF recurrence, defined by repeat ablation, direct current cardioversion (DCCV), or antiarrhythmic drug (AAD) use after a 3‐month blanking period. Secondary outcomes included stroke, hospitalization, and mortality over 5 years. Results After PSM, delayed ablation was associated with higher AF recurrence in both HFrEF (HR = 1.28, p < 0.001) and HFpEF (HR = 1.21, p = 0.02), as seen in multivariate analysis. In HFrEF, delayed ablation was associated with higher incidence of re‐do ablation, AAD use, and DCCV, while in HFpEF, higher recurrence with delayed ablation was associated with increased AAD use. Both cohorts had similar stroke and mortality rates between early and delayed ablation. Conclusions Delayed ablation in HFrEF and HFpEF was linked to higher AF recurrence, driven by increased redo ablations, DCCV, AAD use in HFrEF, and higher AAD use in HFpEF. Stroke, HF hospitalization and mortality rates were similar, suggesting earlier ablation may enhance rhythm control over other outcomes.

Background: Ventricular tachycardia (VT) is a major contributor to death among ischemic heart disease (IHD) patients. In this systematic review and meta-analysis, we evaluate the efficacy of catheter ablation in patients with ischemic cardiomyopathy. Methods: We conducted a meta-analysis by searching the electronic database up to April 2025. Seven studies, including 1192 patients, were identified. A random-effect model was used to estimate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Trial sequential analysis was conducted to assess sample size adequacy. Results: Among Ischemic heart disease patients with ICDs, VT ablation was associated with a significant reduction in ICD shocks (RR = 0.50, 95% CI [0.34–0.74]), a trend toward reduced VT storm (RR = 0.64, 95% CI [0.40–1.04], p = 0.07), and lower rates of cardiovascular hospitalization (RR = 0.73, 95% CI [0.53–1.01], p = 0.06) compared to ICD alone. However, no significant differences were observed when compared to patients receiving ICD plus antiarrhythmic drugs (AADs). Additionally, VT ablation showed no significant impact on mortality or VT/VF recurrence compared to either ICD alone or ICD with AADs. Trial Sequential Analysis provided conclusive evidence for VT/VF recurrence outcomes, while further data are required for other outcomes. Conclusion: Among ischemic heart disease patients with ICD, VT ablation reduces ICD shocks, VT storm, and cardiovascular hospitalizations compared to ICD-only, but offers no significant advantage over ICD combined with antiarrhythmic drugs. VT ablation does not impact mortality or the recurrence of VT/VF. Trial Sequential Analysis confirmed conclusive evidence for VT/VF recurrence, while additional data is needed for other outcomes.