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Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

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.

e17003 Background: Accurate ascertainment of prostate cancer (PCa) disease states—biochemical recurrence (BCR), castration-sensitive prostate cancer (CSPC), and castration-resistant prostate cancer (CRPC)—is critical for automated clinical trial enrollment, quality improvement initiatives, and real-world evidence generation. Essential information for disease state ascertainment resides in unstructured EHR data, requiring labor-intensive manual abstraction that is inconsistent and not scalable. We developed an automated hybrid AI framework using large language models to identify PCa disease states from real-world EHR data. Methods: This retrospective study included patients with histopathologically confirmed PCa (2017-2022) and ≥3 years follow-up. Sequential EHR data—including PSA and testosterone levels, clinical notes, pathology and radiology reports—were retrieved across temporal points. BCR was identified using rule-based algorithms (post-radical prostatectomy [RP]: PSA ≥0.2 ng/mL ×2; post-radiation therapy [RT]: nadir + 2 ng/mL ×2). CRPC was determined using androgen deprivation therapy (ADT) timing, PSA kinetics, testosterone < 50 ng/dL, and radiographic progression per PCWG/EAU-ASCO criteria. GPT-4o with structured parametrized prompts extracted metastatic status and radiographic progression. Independent clinicians performed manual annotation for validation. The framework was developed on 10% of data with evaluation on 90%. External validation used a held-out cohort of clinical trial patients. Results: Among 200 PCa patients (median age 66 years [IQR 60-71]; 91% White, 93% non-Hispanic), the framework demonstrated high accuracy: PCa diagnosis (92%), RP dates (94%), RT dates (93%), and ADT initiation (92%). For disease state identification, BCR detection achieved 90% accuracy, castration status 93%, and metastatic state (M0/M1) 87%. External validation on trial-enrolled patients confirmed robust performance: 26/31 (84%) CRPC trial patients and 26/27 (96%) CSPC trial patients were correctly classified, validating the framework’s reliability for clinical trial matching. Conclusions: This hybrid LLM-based framework accurately identifies PCa disease states using real-world EHR data with minimal manual intervention. The system offers a scalable, reproducible approach for automated disease state identification, enabling streamlined clinical trial matching and enhanced real-world data curation in oncology.

e16502 Background: Accurate postoperative risk stratification in localized clear-cell renal cell carcinoma (ccRCC) informs prognosis, surveillance intensity, and eligibility for adjuvant systemic therapy. Although validated prognostic models (Leibovich 2018, SSIGN, and UISS) exist, they are inconsistently applied in routine practice due to workflow and documentation barriers. Using AI assisted tools within the electronic medical record (EMR) may enable rapid, standardized risk assessment and improve clinical use. Methods: We retrospectively analyzed 92 patients with localized ccRCC undergoing radical nephrectomy and postoperative oncology evaluation (December 2021–September 2025) across three Mayo Clinic sites. Pathology reports and oncology notes were extracted via structured SQL queries. Clinical and pathologic variables were parsed using a zero-shot GPT-4o pipeline. Gold-standard prognostic risk classification and adjuvant therapy eligibility were established by an expert oncology clinician using validated prognostic calculators and KEYNOTE-564 eligibility criteria. AI-generated outputs and novice manual abstraction by two first-year fellows were compared against expert assessment using accuracy, precision, recall, and F1 score. Leibovich and SSIGN were evaluated as three-class models (low/intermediate/high), and UISS as binary risk stratification (high vs non-high). Results: Among 92 patients with localized ccRCC (median age 64 years [range 41–78]), AI-generated outputs demonstrated near-perfect agreement with expert assessment for KEYNOTE-564 adjuvant immunotherapy eligibility (accuracy 97%, precision 100%, recall 97%, F1 score 98%). For three-class prognostic stratification, AI achieved perfect agreement for Leibovich disease-free survival risk (accuracy, precision, recall, and F1 all 100%), outperforming novice abstraction. For SSIGN, AI demonstrated strong multi-class performance (accuracy 91%, precision 91%, recall 93%, F1 score 92%), compared with novice abstraction (accuracy 92%, F1 score 90%). For binary UISS risk stratification, AI achieved 81% accuracy, precision 74%, recall 100%, and F1 score 85% showing a tendency towards false positives. Conclusions: This study demonstrates AI can use existing prognostic and systemic therapy eligibility to accurately risk stratify and identify patients eligible for adjuvant systemic immunotherapy post nephrectomy. For our next steps, we plan to develop a multimodal AI platform integrating pathologic, radiologic, and clinical data to improve prognostication for outcomes and predictive capabilities for patients who would benefit from adjuvant systemic therapy for more personalized medicine.

ABSTRACT Background Sodium‐glucose cotransporter‐2 (SGLT2) inhibitors improve glycemic and cardiovascular outcomes in type 2 diabetes mellitus (T2DM). However, their impact on quality of life (QoL) and patient‐reported outcomes (PROs) has not been systematically evaluated. We conducted a systematic review and meta‐analysis to assess the effect of SGLT2 inhibitors on QoL in patients with T2DM. Methods MEDLINE, Embase, Scopus, Cochrane and ClinicalTrials.gov were searched until 18 August 2025 for randomised controlled trials and post hoc analyses of SGLT2 inhibitors reporting validated QoL or PRO outcomes in adults with T2DM. A random‐effects model was used to estimate mean differences (MD) or odds ratios (OR) with 95% CIs. Subgroup analyses compared SGLT2 inhibitors with placebo and active comparators. Risk of bias was assessed using the Cochrane RoB‐2 tool. Results Ten studies including 5294 patients (SGLT2i: 2807; control: 2487) were included. SGLT2 inhibitors significantly improved: EQ‐5D Index score versus placebo (MD: 0.04, p = 0.008), DTR‐QoL against active comparators (MD: 6.99; p = 0.0006), DTSQ compared to active comparators (MD: 0.54; p = 0.006) and IWQoL (MD: 1.44; p = 0.005) versus placebo. Improvements were also observed in SHIELD WQ‐9 overall QoL (OR: 2.11; p = 0.005), emotional health (OR: 2.16; p = 0.006), self‐esteem (OR: 2.26; p = 0.006) and work performance (OR: 1.99; p = 0.04) compared with placebo. Conclusion Randomised evidence suggests SGLT2 inhibitors enhance EQ‐5D Index score, diabetes‐specific QoL and several PROs in T2DM, particularly in physical, emotional and treatment satisfaction domains, supporting their earlier use in this population.

703 Background: The association of circulating tumor DNA (ctDNA) reduction with treatment response has been investigated across multiple malignancies. This study aims to assess the impact of ctDNA response on survival outcomes in patients receiving enfortumab-pembrolizumab (EV-P). Methods: We identified 32 patients with advanced urothelial carcinoma who received EV-P and had ≥2 ctDNA assessments with ≥1 detectable level. Deep molecular response was defined as >2-log reduction from highest ctDNA detection. Radiographic progression was determined from radiology reports documenting progression by RECIST criteria. Kaplan Meier analyses were performed to compute Hazard Ratios (HR) with 95% confidence intervals (CI) for radiographic progression free survival (rPFS), defined as time from treatment start to radiographic progression or death and overall survival (OS) defined as time from treatment start to death were computed. Log-rank tests were performed to compare PFS and OS in patients with deep molecular response to those without response. A p-value <0.05 indicated a statistically significant association with response. Results: Thirty-two patients were included (median age 71 years; range 39–90). Median follow-up was 10.6 months. At cutoff (10/1/2025), 26 patients were alive and 6 had died. Seventeen (53%) achieved a ≥2-log ctDNA reduction (responders), while 15 (47%) did not (non-responders). Progression-free survival was significantly longer in responders (log-rank P < 0.001); median PFS was 5.9 months (95% CI 2.4–NR) in non-responders and not reached in responders (HR 0.09, 95% CI 0.02–0.44; P = 0.0026). Median overall survival was 12.7 months (95% CI 10.0–NR) in non-responders versus not reached in responders (log-rank P = 0.011; HR 0.11, 95% CI 0.01–0.88; P = 0.037). At cutoff, 94% of responders and 67% of non-responders were alive. Conclusions: Achieving a >2-log decrease in ctDNA during EV + Pembrolizumab therapy was significantly associated with improved progression free and overall survival. These findings support ctDNA kinetics as a potential early biomarker of response warranting prospective validation. Clinical outcomes by >2-log ctDNA reduction status. Endpoint > 2-log drop (n = 17 ≤ 2-log drop (n = 15) Log-rank p Median (mo) ≤ 2-log > 2-log HR (95% CI) P C-index PFS 2 events (12%) 10 events (67%) 0.0002 5.9 (2.4–NA) NR 0.09 (0.02–0.44) 0.0026 0.77 OS 1 event (6%) 6 events (40%) 0.011 12.7 (10.0–NA) NR 0.11 (0.01–0.88) 0.037 0.73

Abstract Background Ventricular arrhythmias (VAs) are a proximate mechanism of sudden cardiac death, yet national patterns in place of death (POD) and their determinants remain sparsely described. We quantified 25-year trends and factors associated with POD among UAs decedents in the United States. Methods We analyzed CDC WONDER Multiple Cause of Death data (1999–2024) for adults ≥25 years with ventricular arrhythmias (ICD-10 I47.2, I49.0) as underlying cause. POD was categorized as inpatient, outpatient/emergency department (ED), home, hospice/nursing, or other/unknown. Covariates included age, sex, race, Hispanic origin, and urbanization. We calculated Annual and Average Annual Percent Changes (AAPCs and APC) using Age-Adjusted Mortality Rates (AAMRs), and fit multinomial logistic regression (reference = inpatient) to obtain adjusted odds ratios (ORs, 95% CIs). Results Among 433,988 ventricular arrhythmia (VA) deaths, POD was inpatient 62.0%, outpatient/ED 18.1%, home 11.1%, hospice/nursing 5.8%, other 3.1%. Inpatient deaths increased from 57.8% (1999) to 66.1% (2024). AAMRs declined sharply from 13.3 per 100,000 in 1999 to 6.3–6.5 during 2010–2019, then rose to 7.4 in 2021 and fell to 6.8 in 2024. In home vs inpatient: ≥85 years, medium/small metropolitan counties and rural counties had higher odds of VA deaths, whereas younger age groups, females, Black, American Indian, Asian/Pacific Islander individuals and Hispanic individuals had lower odds. In outpatient/ED vs inpatient: 25–44 years, 45–64 years, males, Black, American Indian and Asian/Pacific Islander individuals had higher odds, whereas ≥85 years and females had lower odds. In hospice/nursing facilities: ≥85 years, females, Whites, non-Hispanic individuals, medium/small metropolitan counties and rural counties had higher odds of VA deaths, whereas younger age groups, Black, American Indian, Asian/Pacific Islander individuals and Hispanic individuals had markedly lower odds. Conclusion From 1999–2024, VA deaths shifted toward hospitals. Persistent disparities by age, sex, race/ethnicity, and rurality highlight the need to expand equitable advance care planning and device deactivation discussions.

Despite advances in percutaneous coronary procedures, in-stent restenosis remains a significant challenge. Although sirolimus- and paclitaxel-coated balloons are promising alternatives, their comparative safety and efficacy remain uncertain. PubMed, Embase, and Cochrane databases were searched using relevant keywords from inception until August 2025. A total of 11 studies (7 randomized controlled trials and 4 observational cohort studies) were included, comprising 3633 participants overall. The primary outcomes assessed were target lesion revascularization and target lesion failure. Meanwhile, the Secondary outcomes included stent thrombosis, all-cause mortality, myocardial infarction, major adverse cardiovascular events, survival, binary restenosis, and angiographic endpoints (acute gain, diameter stenosis, in-segment late lumen loss, in-lesion late lumen loss, and in-segment minimal lumen diameter). Interstudy heterogeneity was assessed using I ² and X ² statistics ( I ²>50% = significant heterogeneity). Interstudy heterogeneity was low for most outcomes, including all primary clinical endpoints, with moderate heterogeneity observed only for select angiographic measures (notably in-segment late lumen loss and diameter stenosis). Statistical analysis was conducted using R software and RStudio (version 4.4.2), with a P value of < 0.05 indicating statistical significance. This meta-analysis examined studies that compared paclitaxel-coated balloon (PCB) versus standard balloon [sirolimus-coated balloon (SCB)] angioplasty. Regarding primary outcomes, there were no notable variations in target lesion failure [risk ratio (RR), 1.08, 95% CI, 0.90–1.29, P = 0.36] or target lesion revascularization (RR, 1.16, 95% CI, 0.98–1.37, P = 0.08). With all aggregated estimates being nonsignificant, secondary outcomes such as stent thrombosis, all-cause mortality, myocardial infarction, major adverse cardiovascular events, and survival were similar between groups. Angiographic endpoints revealed no discernible variations in late lumen loss (in-lesion and in-segment), acute gain, or diameter stenosis. Nonetheless, the SCB group’s minimal lumen diameter was significantly smaller than that of the PCB group (MD, −0.08 mm, 95% CI, −0.14 to −0.01, P = 0.02). In treating coronary in-stent restenosis, SCB and PCBs show similar overall safety and effectiveness; lesion-specific angiographic variations indicate that customized selection may improve patient outcomes.

Abstract Aims Heart failure (HF) continues to be a major cause of morbidity and mortality worldwide, placing a significant burden on healthcare systems. Differences in the outcomes of HF hospitalizations for adults in teaching vs. non-teaching hospitals in urban settings are uncertain. We evaluated outcomes of HF hospitalizations in patients hospitalized in urban teaching vs. non-teaching hospitals in the United States. Methods and results HF hospitalizations were abstracted from the 2016 through 2022 Nationwide Readmissions Database and stratified into urban teaching vs. urban non-teaching hospital settings. Propensity-score matching was used to control for baseline differences between teaching and non-teaching hospital cohorts. Logistic regression and lognormal models were estimated to assess differences in inpatient mortality, length of stay (LOS), total costs, complications, and 30-day and 90-day all-cause readmissions. A total of 7 558 299 weighted HF hospitalizations were included in the analysis, of which 76.3% involved urban teaching hospitalizations. Compared to urban non-teaching, HF hospitalizations in urban teaching hospitals were associated with significantly higher odds of inpatient mortality (OR 1.19, 95% confidence interval [CI]: 1.16–1.22), complications including cardiogenic shock, cardiac arrest, Intra-aortic balloon pump, cardiopulmonary resuscitation, extracorporeal membrane oxygenation and mechanical ventilation use as well as more extended hospital LOS, higher total costs, palliative care consultation and readmissions rates (all P &lt; 0.001). 30-day and 90-day all-cause readmission rates were also statistically higher in teaching hospitals, though the difference was clinically non-significant. Conclusion HF hospitalizations in urban teaching hospitals were associated with higher inpatient mortality, complication rates, resource utilization, and palliative care consult rates than urban non-teaching hospitals.