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Background The Woven EndoBridge (WEB) device represents an innovative solution for cerebral aneurysm occlusion, particularly for challenging wide-neck bifurcation aneurysms. However, factors affecting sustained occlusion remain poorly understood. We utilized machine learning to attempt to identify predictors of favorable long-term outcomes following WEB treatment. Methods In this multicenter retrospective study, we collected patient demographics, aneurysm characteristics, procedural details, and clinical outcomes. The primary endpoint was improvement in occlusion status, defined as maintained Raymond-Roy Occlusion Classification (RROC) grade 1, or improvement from grade 2 to 1, or from grade 3 to either 2 or 1 on final angiographic follow up. The dataset was split into training (75%) and validation (25%) sets. The CatBoost algorithm was selected based on performance metrics, with Shapley Additive exPlanations (SHAP) values calculated to determine feature importance. Furthermore, a multivariable binomial logistic regression model was performed to validate machine learning findings. Results Among 720 aneurysms from 36 hospitals, 84% showed improvement in occlusion at follow up. Both machine learning and multivariable logistic regression identified aneurysm height as the most consistent correlate of nonimprovement (odds ratio (OR) 0.90 per mm, p = 0.022). In the CatBoost model, the highest-ranking features by SHAP included aneurysm height, patient age, treatment acuity, ACom location, WEB-SLS device, bifurcation anatomy, aneurysm multiplicity, baseline modified Rankin Scale, access route, and partial thrombosis. Conclusions Machine-learning and regression analyses identified consistent predictors of occlusion improvement after WEB treatment, with aneurysm height most strongly linked to nonimprovement. These insights may guide patient selection and follow up. Findings require cautious interpretation and external validation in larger cohorts.

Abstract Purpose: Relapse is a major cause of failure in human papillomavirus–independent head and neck squamous cell carcinoma. Clinicopathologic criteria for adjuvant treatment remain imprecise and have not changed for decades. We investigated whether ctDNA in lymphatic exudate collected via surgical drains (“lymph”) 24 hours after surgery identified molecular residual disease (MRD) and compared its performance with time-matched plasma. Experimental Design: Using an ultra-sensitive tumor-informed sequencing approach, tumor variants were called in lymph and plasma to classify patients as ctDNA positive or ctDNA negative, trained in an initial cohort of 36 patients, and replicated in an independent cohort of 37 patients. Progression-free survival was compared in ctDNA(+) versus ctDNA(–) patients. Results: Lymph identified MRD in two independent multi-site cohorts (initial cohort sensitivity = 76% and specificity = 63%; log-rank P = 0.01; replication cohort sensitivity = 65% and specificity = 70%; log-rank P = 0.04). Lymph performance was enhanced in locoregional relapse (sensitivity = 78% and specificity = 67%; log-rank P = 0.0004) and generalized to early-stage patients. Analysis of matched plasma collected at this early timepoint was not predictive of recurrence (sensitivity = 35% and specificity = 72%; log-rank P = 0.7). In patients with intermediate-risk pathology, lymph ctDNA was associated with recurrence (sensitivity = 88% and specificity = 67%; log-rank P = 0.0008), suggesting an opportunity for improved stratification of patients who may benefit from additional adjuvant treatment. Conclusions: Postoperative lymph is a novel, proximal, and early source of MRD with the potential to introduce more precision into adjuvant therapy decision-making and improve outcomes, especially for patients with intermediate-risk human papillomavirus–independent head and neck squamous cell carcinoma.

Importance The Breast Cancer Index (BCI) previously identified premenopausal patients with tumors in which the ratio of expression of HOXB13 relative to IL17BR (hereafter, BCI [H/I]–low tumors) as likely to derive greatest benefit from ovarian function suppression (OFS)–containing adjuvant therapy in the Suppression of Ovarian Function Trial (SOFT) trial. Objectives To assess BCI as a predictive biomarker of benefit from exemestane plus OFS vs tamoxifen plus OFS and to validate BCI as a prognostic biomarker for premenopausal patients. Design, Setting, and Participants This prognostic study used a prospective-retrospective translational design within the Tamoxifen and Exemestane (TEXT) and SOFT trials (enrolled November 2003 to April 2011). Blinded BCI testing in all available tumor samples was completed in March 2024. Premenopausal women with hormone receptor–positive breast cancer randomized to tamoxifen plus OFS or exemestane plus OFS who had BCI assessed were included. Analysis occurred from March to August 2024. Exposure 5 years of adjuvant tamoxifen plus OFS or exemestane plus OFS. Main Outcomes and Measures The primary outcomes were breast cancer-free interval (BCFI) for predictive analyses and distant recurrence-free interval (DRFI) for prognostic analyses after a median follow-up of 13 years in the TEXT cohort. Secondary objectives examined the predictive performance of BCI (H/I) in the combined TEXT and SOFT cohort overall and in prespecified clinical subgroups. Results Of 1782 patients in the TEXT study, 1034 (58.0%) had BCI (H/I)–low tumors; 915 (51.3%) of patients had N0 disease and 1077 (60.4%) were younger than 45 years. Patients with BCI (H/I)–low tumors had a 6.6% absolute benefit in 12-year BCFI (HR, 0.61; 95% CI, 0.44-0.85) for exemestane plus OFS vs tamoxifen plus OFS, while those with BCI (H/I)–high tumors had a 6.3% absolute benefit (HR, 0.78; 95% CI, 0.57-1.07; P for interaction = .29). Results were consistent in the combined TEXT plus SOFT cohort (2896 patients) and adjusting for clinicopathological variables. Clinical subgroup analyses consistently showed benefit of exemestane plus OFS vs tamoxifen plus OFS for BCI (H/I)–low tumors, and more variable relative treatment effects among BCI (H/I)–high tumors, including by age. Post hoc exploratory time-varying estimates suggested the treatment × BCI associations may differ in years 0 to 5 vs greater than 5 years. BCI and BCI N+ as continuous indices were prognostic for distant recurrence in N0 (HR, 1.27; 95% CI, 1.11-1.44; P < .001) and N1 (HR, 1.58; 95% CI, 1.21-2.05; P < .001) cancers. The 12-year DRFI was 96.3%, 90.3%, and 84.9% for BCI low-, intermediate-, and high-risk N0 cancers, respectively. Conclusions and Relevance In this study of premenopausal women with hormone receptor–positive breast cancer, BCI (H/I) status did not clearly predict greater benefit of adjuvant exemestane plus OFS vs tamoxifen plus OFS for women with BCI (H/I)–low tumors than for those with BCI (H/I)–high tumors; BCI continuous indices were reconfirmed as prognostic for premenopausal women. These findings support prior results of SOFT, which compared tamoxifen-alone vs OFS with either exemestane or tamoxifen, indicating premenopausal patients with BCI (H/I)–low tumors may benefit from more intensive endocrine therapy.

Background: Breast cancer polygenic risk scores (PRS) and traditional risk models (e.g., the Gail model [Gail]) are known to contribute largely independent information, but it is unclear how the overlap varies by ancestry, age, disease type (invasive breast cancer, DCIS), and risk threshold. Methods: In a retrospective case–control study, we evaluated risk prediction performance in 180,398 women (161,849 of European ancestry; 18,549 of Asian ancestry). Odds ratios (ORs) from logistic regression models and the area under the receiver operating characteristic curve (AUC) were estimated. Results: PRS for invasive disease showed a stronger association in younger (<50 years) women (OR = 2.51, AUC = 0.622) than in women ≥ 50 years (OR = 2.06, AUC = 0.653) of European ancestry. PRS performance in Asians was lower (OR range = 1.62–1.64, AUC = 0.551–0.600). Gail performance was modest across groups and poor in younger Asian women (OR = 0.94–0.99, AUC = 0.523–0.533). Age interactions were observed for both PRS (p < 0.001) and Gail (p < 0.001) in Europeans, whereas in Asians, age interaction was observed only for Gail (invasive: p < 0.001; DCIS: p = 0.002). PRS identified more high-risk individuals than Gail in Asian populations, especially ≥50 years, while Gail identified more in Europeans. Overlap between PRS, Gail, and family history was limited at higher thresholds. Calibration analysis, comparing empirical and model-based ROC curves, showed divergence for both PRS and Gail (p < 0.001), which indicates miscalibration. In Europeans, family history and prior biopsies drove Gail discrimination. In younger Asians, age at first live birth was influential. Conclusions: PRS adds value to risk stratification beyond traditional tools, especially in younger women and Asian ancestry populations.

Background: Etripamil nasal spray is a fast-acting, calcium channel blocker in development for the conversion of paroxysmal supraventricular tachycardia (PSVT) outside of a health-care setting. Studies have demonstrated the favorable safety and efficacy of self-administered etripamil in restoring sinus rhythm (SR) and reducing emergency department visits. Purpose: This report analyzes the efficacy, safety, and test-dose tolerability of etripamil across PSVT clinical studies. Methods: We systemically examined randomized, controlled and open-label trials evaluating etripamil in patients with PSVT. Efficacy measures included the proportion of patients converting from PSVT to SR within 30 minutes and the median times to conversion across all Phase 3 studies. Safety data for treatment-emergent adverse events (TEAEs), serious AEs, and test dose tolerability from Phase 2/3 studies were summarized descriptively. Results: NODE-1, NODE-301 Part 1, NODE-301 Part 2 (RAPID, including RAPID Extension, RAPID Open Label, RAPID Open Label Extension periods), NODE-302, and NODE-303 studies were analyzed (Table 1). The Kaplan-Meier estimate of etripamil exposed patients converting to SR within 30 minutes (n= 622) was 59.6% (range, 53.6% to 64.3%) with a median time to conversion of 18.5 minutes (95% CI, 15.7 to 21.0). The proportions of RCT placebo group patients converting from SVT to SR by 30 minutes ranged from 26.7% to 34.7%. Estimates of conversion of SVT to SR with etripamil at 60 minutes for individual studies ranged from 63.2% to 73.5% (Figure). Combined analysis showed mainly the occurrence of mild, transient TEAEs, primarily nasal discomfort, nasal congestion, rhinorrhea, throat irritation, and epistaxis (Table 2). 1,107 patients took at least one etripamil test dose while in SR; no significant change in average baseline heart rate or blood pressure was observed within 45 minutes of administration, and test dose failure occurred in only 16 patients (1.4%). Conclusions: Across multiple clinical studies of acute PSVT management, self-administered etripamil consistently demonstrated robust efficacy and a favorable safety profile for acute PSVT management. Safety data and the low rate of test dose failures indicate favorable tolerability, suggesting no need for a pretreatment test dose. These findings support the potential of etripamil as a patient-administered therapy for PSVT, which may reduce reliance on emergency care.

Background: Atrial arrhythmia recurrence after surgical ablation remains challenging to predict and integrating novel biomarkers may improve risk stratification. Objective: To evaluate whether combining preoperative transthoracic echocardiography (TTE) with artificial intelligence-enabled ECG (AI-ECG) scores enhances prediction of atrial fibrillation/flutter (AF/AFl) recurrence post surgical ablation. Methods: We retrospectively analyzed 1,696 patients undergoing Surgical AF/AFl Ablation between 2006 and 2025 with preoperative TTE and post-blanking ECGs. Clinical variables, TTE indices, and AI-ECG scores (AF probability, ECG-estimated age, HFpEF, LV dysfunction, and aortic stenosis scores) were assessed. The primary outcome was time to AF/AFl recurrence. Univariate/multivariable Cox models and a Random Survival Forest (RSF) model (80:20, training: testing) were developed to identify predictors. Results: Of 1,696 patients (mean age 67.3±10.2 years; 61.7% male) undergoing surgical AF/AFl ablation, 949 (56%) experienced AF/AFl recurrence during a median follow-up of 3.14 years. Patients with recurrence had larger left atria (mean LA area 30.4 vs 24.5 cm 2 , p < 0.001), more diastolic dysfunction (mitral inflow E-wave velocity 1.015 m/s vs 0.896 m/s , p < 0.001), and adverse AI-ECG biomarkers. In multivariable analysis, independent predictors of recurrence included a higher ECG-AF score (p < 1 x 10 -300 ), an older AI-ECG age (p = 0.0002), LA area (p = 0.046), body mass index (p = 0.036), and elevated diastolic blood pressure (HR 1.008 per mmHg, 95% CI 1.002 – 1.014; p = 0.010). The final Cox model achieved a C-index of ~0.67 and stratified patients into risk quartiles with 3-year freedom-from-arrhythmia rates of ~85% (lowest-risk) vs ~43% (highest-risk). An RSF model yielded a slightly higher test C-index (≈0.69), suggesting modest improvement with non-linear modeling. Conclusions: Preoperative AI-ECG biomarkers (AF probability, age discordance) and TTE markers of atrial remodeling independently predicted AF/AFl recurrence after surgical AF/AFl ablation and integration of these metrics improved risk stratification.

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia with prevalence increasing over the last decade. However, data on recent temporal trends in incidence of AF have been inconsistent, with some reports of increasing trends over time and others indicating no change in incidence over time. Therefore, we aimed to determine how the incidence of AF has changed over the last decade in a community in the Midwest USA. Methods: Between 2013 and 2023, adults (aged 18 and older) with incident AF were identified in a 27-county region in the Midwest. AF was identified using diagnostic codes by employing an electronic algorithm requiring 1 inpatient code or 2 outpatient codes separated by >7 days but within 1 year. For total rates, age - and sex-adjusted incidence rates were standardized to the 2010 US total population. Poisson regression was used to calculate the incidence rate ratio of AF for 2023 vs 2013. Results: We identified 44,930 individuals with incident AF from 2013 to 2023. Of these, 56.4% were male, the mean (SD) age was 72.8 (13.5) years, and 95.8% were non-Hispanic white. The age-and sex-adjusted incidence rates (per 1,000) and 95% confidence intervals standardized to the 2010 US total population were 5.24 (5.07-5.41) in 2013, 5.73 (5.56-5.91) in 2018, and 5.44 (5.28-5.61) in 2023. Although a drop in incidence was observed corresponding to the COVID-19 pandemic, a small increase in the overall incidence of AF was observed over time. The overall incidence rate ratio (95% CI) for 2023 vs 2013 was 1.07 (1.02-1.11), P=0.003. The incidence rates were higher in men compared to women and increased with older age ( Figure 1 ). However, differences in AF incidence by sex were greatest in the youngest age group and attenuated with older age (incidence rate ratio (95% CI): 2.18 (2.10-2.28) for ages 18-64 years, 1.76 (1.70-1.83) for ages 65-74 years, 1.38 (1.33-1.42) for ages 75-84 years, and 1.23 (1.18-1.28) for ages 85 years and older). Conclusion: In this 27-county region in the Midwest, although small in magnitude, a statistically significant increase in AF incidence was observed over time from 2013 to 2023. Furthermore, the incidence of AF was higher in men compared with women, especially in younger age groups.

Background: Disease-causative variants in LMNA -encoded lamin A/C cause the laminopathies, a heterogeneous group of diseases variably resulting in arrhythmogenic/dilated cardiomyopathy (ACM/DCM), lipodystrophy, muscular dystrophy, and progeria. The artificial intelligence (AI)-derived electrocardiographic age gap (AI-EAG), determined by the discrepancy between a patient’s artificial AI-enabled electrocardiogram (ECG) predicted biological age versus their chronological age, is accelerated in laminopathy. Thus, we sought to determine if the AI-EAG serves as a prognostic marker in patients with cardiac laminopathy. Methods: Retrospective analysis of 1,049 genotype-positive patients with genetic ACM/DCM was used to identify those with pathogenic/likely pathogenic (P/LP) variants in LMNA . After the exclusion of those who lacked a 12-lead ECG while in sinus rhythm, a previously trained AI-ECG age algorithm was used to determine the AI-EAG by subtracting the patient’s chronological age from the AI-ECG derived biological age. The AI-EAG was then correlated with a combined outcome of major ventricular arrhythmia [sudden cardiac arrest, sustained ventricular tachycardia, and appropriate implantable cardioverter-defibrillator shocks], heart transplantation, and cardiovascular death. Results: Overall, 147/1,049 (14%) patients with genetically-mediated ACM/DCM had a P/LP variant in LMNA . Of these, 80/147 (54%) LMNA variant-positive patients (52% female, mean chronological age 36 ± 15 years) had ECGs suitable for AI-EAG analysis. Most (52/80; 65%) had an AI-EAG >10 years with a mean AI-EAG of 17 ± 13 years. Of note, the AI-EAG was greater in those with a clinical cardiac phenotype (20 ± 14 vs. 13 ± 10 years; p = 0.011). As a continuous variable, an increased AI-EAG was associated with increased risk of the composite outcome at a median follow-up of 20 months (HR 1.036; 95% CI 1.004–1.068; p = 0.026) and AI-EAG > 10 and > 20 years were both associated with elevated risk (HR 4.272; 95% CI 1.388–13.147; p = 0.011 and HR 3.732; 95% CI 1.505–9.255; p = 0.004, respectively). Conclusion: In cardiac laminopathy, an increased AI-EAG was common and correlated with adverse cardiovascular outcomes. Non-invasive ascertainment of electrocardiographic aging by AI may provide a novel prognostic marker in cardiac laminopathy. Future studies are needed to validate this finding and further define the role of the AI-EAG in the risk-stratification of patients with cardiac laminopathy.

Introduction: Infective endocarditis (IE) is a severe intracardiac infection, often requiring intensive care unit (ICU) admission. Despite early surgical intervention, mortality remains high. Data for patients admitted to the cardiac intensive care unit (CICU) is especially limited. Research Question: We aimed to investigate the short and long-term outcomes of patients with IE admitted to the CICU. Methods: We conducted a retrospective cohort study of adult patients admitted to the Mayo Clinic CICU (2007-2018) with confirmed acute IE, identified via database query and manual chart review. Patients were further categorized by cardiac surgery status: performed, indicated but declined, or not indicated. Primary outcomes were all-cause mortality at 30-days and 1-year, analyzed using Kaplan-Meier and Cox proportional-hazard analysis. Models were adjusted for known predictors. Results: Overall, 233 CICU patients met criteria for IE. Median age was 64.0 years; 49 were female. In total, 104 patients had native valve IE; 128 had prosthetic or implantable device-associated IE. Staphylococcus aureus was the most prevalent organism (42.7%) and was present in 72.4% of 30-day deaths. Cardiac surgery was indicated in 182 (78.1%) patients - 129 patients underwent surgery, while 53 declined; 48 patients did not have indications. By 30 days, 58 (24.9%) patients died; significant predictors included older age, higher illness severity scores, and greater need for critical care therapies. The 30-day mortality estimates were markedly higher for patients who declined surgery (60.4%, adj. HR 4.17, 95% CI 2.02-8.52, p <0.001), and lower for those who received surgery vs those without surgical indications (11.9% vs 23.8%, adj. HR 0.44, 95% CI 0.20-0.98, p=0.04) (Figure 1). By 1-year, 93 (39.9%) patients died, including 36 (20.5%) hospital survivors. The 1-year mortality estimates were markedly higher for patients who declined surgery (85.1%, adj. HR 5.46, 95% CI 2.87-10.39, p <0.001), but was similar for patients who received surgery to those without surgical indications (31.8% vs 29.3%, adj. HR 0.94, 95% CI 0.49-1.78, p=0.84) (Figure 2). Conclusion: IE requiring CICU admission carries substantial mortality despite acute management. Higher severity scores, comorbidities, and intensive care interventions predict mortality. Early cardiac surgery improved short-term outcomes, but long-term mortality remains high.

Background: Impella 5.5 is a temporary MCS device FDA-approved for use up to 14 days. Limited data suggest it may be safe beyond this. We aim assess outcomes based on the duration of Impella 5.5 support in heart failure cardiogenic shock (HFCS) patients at our institution. Methods: We retrospectively reviewed all HFCS patients supported with Impella 5.5 at our institution between 2020-2024. Patients supported for >14 days were compared with those supported for ≤14 days. Categorical variables were analyzed with chi-square tests, continuous variables with t-tests or Mann-Whitney U. Logistic regression identified factors linked to clinical outcomes. Results: 154 patients were included: 38 (25%) with support ≤14 days, 116 (75%) with >14 days. Median support duration was 10 (6–12) vs 31 (22–45) days, respectively. Median support duration was 10 (6-12) days for the ≤14 cohort and 31 days (22-45) days for the >14 cohort. Baseline characteristics, comorbidities, LVEF 18% (15-23) and hemodynamics show no statistical differences. Patients supported for >14 days were more likely to undergo heart transplant compared to those supported ≤14 days (91% vs 74%, p=0.009). In contrast, myocardial recovery was more likely in the ≤14 day cohort (8% vs 1%, p=0.018). One patient suffered stroke post-transplant in the ≤14 day group and two had brachial plexus injuries in the >14 days group. Mortality during the impella-supported period was slightly higher in the ≤14 day group (8% vs 5%, p=0.535) but comparable overall, 13% in both groups, p=0.971. Support >14 days was associated with transplant outcome (OR 3.41, 95% CI 1.32–8.84, p=0.012), and remained significant after adjusting for age, gender, GFR, and EF (OR 4.05, 95% CI 1.31–12.54, p=0.015). Support duration <14 days was associated with recovery or LVAD outcomes (OR 5.01, 95% CI 1.49–16.89, p=0.009), and remained significant after adjustment (OR 5.43, 95% CI 1.11–26.45, p=0.036). No association was observed between duration of support and LVAD/mortality outcomes or with EcPella use. Conclusion: Shorter Impella support duration was independently associated with early myocardial recovery or LVAD candidacy, likely reflecting rapid clinical decision-making. Prolonged Impella support was associated with increased likelihood of transitioning to heart transplantation, likely reflecting clinical stabilization over time. Our multidisciplinary, single-center data suggests Impella 5.5 can be used beyond FDA-approved 14 days in HFCS patients.