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Abstract Background Left ventricular diastolic function (LVDF) and left bundle branch block (LBBB) are both linked with increased risk of LV systolic dysfunction, heart failure, and mortality. Assessing LVDF, which is typically done through echocardiography, becomes challenging in the presence of LBBB due to the intraventricular conduction delay that disrupts the reliability of tissue Doppler imaging. Recently, we validated an artificial intelligence-enabled electrocardiogram (AI-ECG) model to assess LVDF and filling pressures. Methods We performed a retrospective study among patients with ECG-confirmed LBBB who also underwent comprehensive echocardiography within 14 days of the index ECG between September 2001 and June 2022. Using multivariable survival models, we assessed the risk of all-cause mortality across AI-ECG-derived LVDF grades. Results Of 2,554 patients with LBBB (mean age 72.0+12.6, 54.6% women), 252 (9.8%), 656 (25.7%), and 1,436 (56.2%), and 210 (8.2%) had normal LVDF, G1 LVDF, G2 LVDF, and G3 LVDF, respectively. The median LV ejection fraction (LVEF) was 54% and 49.3% of the patients had heart failure. Worse LVDF was associated with older age, lower LVEF, and higher rates of diabetes, hypertension, chronic pulmonary disease, renal failure, cardiovascular disease, and heart failure (p-of-trend<0.001 for all). During a median follow-up of 2.6 years (interquartile range 0.5-4.0 years), 847 (33.2%) patients died. In multivariable survival analysis, adjusted to multiple risk factors including baseline LVEF and heart failure, worse LVDF was independently associated with a higher risk of death [G1 LVDF: adjusted hazard ratio (aHR) 2.15 (95% confidence interval (95%CI) 0.75-1.77), G2 LVDF: aHR 2.25 (95%CI 1.50-3.38) G3 LVDF: aHR 2.96 (95%CI 1.88-4.65); p<0.001 for both)]. These findings were consistent also in a subgroup of patients with baseline LVEF > 50%. Conclusion Among patients with LBBB, worse LVDF, as derived by a dedicated AI-ECG algorithm is independently associated with all-cause mortality beyond baseline LVEF and clinical heart failure.survival across AI-ECG LVDF grades

Abstract Background Ischemic mitral regurgitation (IMR) is a common complication of coronary artery disease (CAD), often occurring after myocardial infarction (MI). Even when moderate in severity, IMR is associated with adverse outcomes, including a twofold increase in mortality rates. Aim To assess the functional correlates of resting IMR during stress echocardiography (SE) in patients with CAD. Methods This prospective multicenter study included 192 patients with CAD (143 males; mean age 65 ± 10 years) from eight cardiology institutions. Exclusion criteria included a history of coronary artery bypass surgery, more than moderate IMR, and other significant valvular diseases. Patients were divided into two groups based on semiquantitative- quantitative assessment at rest based on EACVI-ASE criteria: Group 1: Patients with moderate IMR, Group 2: Patients without IMR or with trivial IMR. All patients underwent stress echocardiography (SE) using the ABCE protocol. Patients underwent exercise tests, if execise echocardiography was not possible, dobutamine stress tests were performed. At rest and peak SE, we assessed: Left atrial volume index (LAVi), Left ventricular end-diastolic (LV EDV) and end-systolic volumes (LV ESV), ejection fraction (EF), wall motion score index (WMSI), global longitudinal strain (GLS), B-lines (4-site simplified scan), tricuspid annular plane systolic excursion (TAPSE), systolic pulmonary artery pressure (SPAP), LV contractile reserve (LVCR) and heart rate reserve (HRR). Results Despite similar EF at rest, Group 1 patients showed more pronounced functional impairment at rest, which increased during stress. Stress-induced functional worsening affected indices of MR (more frequently becoming severe), ischemic burden (WMSI), diastolic function (LAVI and LVEDV dilation), LV systolic function (LVCR), pulmonary congestion (B-lines), cardiac sympathetic reserve (reduced HRR) and right ventricular/pulmonary artery coupling (reduced TAPSE/SPAP): table 1. Conclusion Compared to CAD patients with absent-to-trivial resting IMR, patients with moderate IMR at rest show a constellation of functional vulnerabilities during SE involving more frequent exercise-induced worsening of MR, blunted LV diastolic and systolic reserve, more pulmonary congestion, impaired cardiac autonomic reserve, and worse right ventricular-pulmonary artery coupling. The individual patient's functional response heterogeneity can be identified with comprehensive exercise SE, possibly a roadmap to personalized and targeted therapeutic interventions.

ABSTRACT Background Immune checkpoint inhibitors (ICIs) have emerged as promising agents for the management of advanced HCC. By reducing tumour burden, ICIs may serve as a downstaging/bridging tool to improve transplant candidacy. The aim of this study was to assess the safety of patients receiving pre‐LT ICIs. Methods Multicenter, retrospective cohort study from January 2018 to December 2024, including 48 patients who received ICIs prior to LT (ICI cohort). A control cohort (non‐ICI cohort) was built (1:3) using propensity score matching including 144 patients who underwent LT for HCC without prior ICI. Results Within the ICI cohort ( N = 48) rejection occurred in 9 patients (18.8%), all biopsy‐proven, with a median onset of 31 days post‐LT (12.0–182.0). The median washout period was 60 days (13–96). Patients experiencing rejection had shorter washout periods ( p = 0.029). All rejection episodes were successfully managed; two were steroid‐resistant, one requiring re‐transplantation. There were no rejection‐related deaths. Of the 5 patients with HCC recurrence, 60% received ICI for < 90 days ( p = 0.027). Comparison between the ICI and non‐ICI cohort revealed no significant differences in rejection rates (18.8% vs. 19.4%, p = 0.916), graft failure, HCC recurrence, or overall mortality. Overall survival (OS) did not differ between ICI and non‐ICI patients ( p = 0.625) or between those with and without rejection ( p = 0.119). Rejection was not associated with increased mortality, with deaths primarily attributed to infection or HCC recurrence. Conclusion Our results demonstrate that rejection rates were similar in patients receiving ICIs pre‐LT and it can be safely managed.

Abstract Background Right ventricular (RV) systolic function is an independent predictor of outcome, but a robust automated method of quantitation is lacking. Purpose To develop and validate a deep learning model for quantifying RV systolic function from 2D echo clips and assess its prognostic value in various loading states and left-heart disease. Methods A deep learning convolutional neural network (CNN) was developed to quantitate RV systolic function using all available apical 4 chamber (A4C) views from 13,039 patients (61,187 A4C video clips) in a US institution. Videos were converted to frames of 256x256 grayscale pixels, with graphics, including the ECG, removed. The model used the S3D architecture, a 3D-CNN with many of the spatial and temporal convolutions separated. RV free wall longitudinal strain (RVFWLS) was used to define RV function: normal (≤-25%); mild (-20% to –24%); moderate (-15% to –19%) and severe RV dysfunction (0% to –14%). The AI-estimate was the average of multiple 32-frame segments for each clip identified as an A4C, including both standard and RV-focused variations. The model was validated in four distinct clinical cohorts from independent data sources: 1) 1365 patients referred to an external diagnostic echocardiography lab in a different US state; 2) 569 patients recruited prospectively with known or suspected pulmonary hypertension (PH); 3) 416 patients with moderate or greater tricuspid valve regurgitation (TR); 4) 872 patients imaged at an Eastern European University with left-sided cardiac diseases (valvular disease, cardiomyopathies, etc.), athletes, or healthy volunteers. Results Model output was strongly correlated with the presence of RV dysfunction by manual measurement [AUC 0.907 (95% CI: 0.888-0.926)] in the internal validation set. Results were similar in an external validation US cohort [N=1365; AUC 0.919 (95% CI: 0.899-0.939)]. When the model was applied to 569 patients with known or suspected PH, presence and severity of the AI measures of RV dysfunction were strongly associated with functional class, 6 min walk distance, NT-proBNP levels and right heart failure (p&lt;0.001). The presence and severity of RV dysfunction (as categorized by the AI model) was strongly associated with all-cause mortality in patients with PH (Figure 1A) and in patients with significant TR (Figure 1B). The European cohort was a geographically and institutionally distinct cohort with a low prevalence of &gt;mild TR (10.8%) or PH (6.4%). In this cohort the AI model predicted a reduced RVEF (&lt; 45%) with an AUC of 0.864 (95% CI: 0.831-0.898) and associated with both all-cause mortality (Figure 2A) and a composite endpoint of heart failure hospitalization or death (Figure 2B). Conclusions A fully automated, AI-based assessment of RV systolic function, using 2D apical 4 chamber echo views alone, is highly feasible and can accurately categorize disease severity and predict outcome across a wide spectrum of cardiovascular conditions.Figure 1 Figure 2

Background Artificial intelligence (AI)–enabled electrocardiography has emerged as a tool for detecting cardiac dysfunction. The prognostic relevance of AI‐enabled electrocardiography–derived diastolic dysfunction (DD) in patients undergoing transcatheter aortic valve replacement had not been assessed. Methods We analyzed 3197 patients undergoing transcatheter aortic valve replacement for severe aortic stenosis between 2010 and 2023 with baseline 12‐lead ECGs processed by a validated AI model to classify diastolic function (grades 0–3). Multivariable Cox models and nested model comparisons assessed associations with all‐cause mortality, including a prespecified analysis in patients with indeterminate echocardiographic grading. Trajectories were defined by change in AI‐enabled electrocardiography DD grade (<2 versus ≥2) from baseline to 30‐day or 1‐year follow‐up. Results At baseline, 21% had grade 3, 57% had grade 2, 8% had grade 1, and 14% had grade 0 AI‐enabled electrocardiography DD. Higher grades were associated with adverse cardiac remodeling and comorbidities. Over a median follow‐up of 3.4 years, grade 3 AI‐enabled electrocardiography DD independently predicted mortality (hazard ratio [HR], 1.80 [95% CI, 1.47–2.20]; P <0.001). AI‐enabled electrocardiography DD improved prognostic discrimination beyond clinical and echocardiographic measures (ΔHarrell concordance statistic, 0.016; Δ χ 2 =57; P <0.001). Among 1259 patients with indeterminate echocardiographic grading, AI‐enabled electrocardiography added prognostic value (ΔHarrell concordance statistic, 0.02; Δ χ 2 =13; P =0.006). Worsening or persistently high‐risk trajectories were associated with increased mortality (HRs, 1.45–1.80; all P <0.05). Conclusions AI‐enabled electrocardiography–derived DD independently predicts mortality after transcatheter aortic valve replacement, adds value beyond echocardiographic grading, and enables dynamic risk stratification through longitudinal tracking.

Background: For women in the United States desiring implant-based breast reconstruction, the maximum volume of commercially available silicone breast implants has, to date, been 800 cc. The authors evaluated the safety of Mentor larger-size MemoryGel Ultra-High Profile breast implants (≥930 cc) in women undergoing postmastectomy breast reconstruction. Methods: This 10-year, multicenter, open-label, prospective, investigational study assessed the safety and effectiveness of larger-volume implants in women undergoing postmastectomy 2-stage primary or revision reconstruction. Three-year Kaplan-Meier curves and multivariable Cox regression analyzed the association between patient and treatment characteristics and surgical outcomes. The BREAST-Q was used to assess effectiveness at 3 years. Results: A total of 400 women were enrolled (225 primary and 175 revision reconstruction). Mean body mass index was 35.8 kg/m 2 ; 81% had a body mass index greater than or equal to 30 kg/m 2 . At 3 years, the cumulative incidence of postoperative complications (excluding rupture) was 63.0% (95% confidence interval, 58.1% to 67.9%). The reoperation rate was 24.5% (95% CI, 20.4% to 29.1%), and the explantation rate was 15.8% (95% CI, 23.5% to 19.9%). Independent predictors of complications included radiation therapy and a history of smoking. There were no significant associations between postoperative complications and implant volume greater than or equal to 1135 cc or less than 1135 cc. BREAST-Q scores at year 3 showed significant improvements from baseline in Satisfaction with Breasts, Psychosocial Well-Being, Sexual Well-Being, and Physical Well-Being (all P < 0.0001). The mean score for Satisfaction with Outcome was 79.9. Conclusions: These 3-year results demonstrate that larger-volume silicone breast implants represent a safe and effective option for patients with larger breasts who are requesting postmastectomy implant-based reconstruction.

Abstract Background JAK inhibitors (JAKi) are small molecules that cross the placenta from early pregnancy.1 Evidence on the safety of in utero JAKi exposure remains limited, particularly regarding pregnancy outcomes, infant infections, vaccine responses, and early development.2, 3 Methods We conducted a multicenter retrospective study within the ECCO CONFER network, including pregnant women with inflammatory bowel disease (IBD) exposed to tofacitinib (TOFA), upadacitinib (UPA), or filgotinib (FILGO). Data were collected from 22 centers across 16 countries and included maternal characteristics, disease activity, medication patterns, and pregnancy and infant outcomes. Results Among 55 JAKi exposed pregnancies, 21 (38.2%) were unplanned and 30 (54.6%) had active disease. Nine women (16.4%) initiated JAKi during pregnancy. Overall, 38 (69.1%) received TOFA, 15 (27.3%) UPA, and 2 (3.6%) FILGO; 39 (70.9%) continued treatment throughout pregnancy. JAKi discontinuation in 1st-2nd trimester led to disease activity in 9/16 cases (56.3%). Maternal complication risk was low: no DVT or (pre) eclampsia occurred; three cases of premature rupture of membranes (GA 34–37) and four required hospitalizations due to infection or other complications. A total of 10 abortions occurred - five spontaneous (9.1%) and five induced (9.1%), including three due to concern about JAKi exposure. Among 45 live births, two infants (3.6%) were preterm, four (7.3%) small for gestational age, and two (3.6%) had Apgar &lt;7 at 5 minutes. No congenital abnormalities were reported. Infant follow-up findings are summarized in Table 1. One-third of breastfeeding women continued JAKi postpartum. A high adherence rate to the national immunization schedule was seen. Eight (19.5%) received the live BCG-vaccine within the first 30 days of life. No adverse events followed live or inactivated vaccines, and no malignancies were observed. Conclusion In this global cohort of JAKi-exposed pregnancies in women with IBD, maternal complication rates were low, and no increased risk of adverse outcomes among live births was identified. While disease activity was common, particularly following discontinuation of JAKi, infant outcomes - including development, infection risk, and vaccine response - were reassuring. These findings provide important preliminary safety data to inform decision-making regarding JAKi use in pregnancy, though prospective studies are needed to confirm long-term safety. References: 1.Fein KC, Arral ML, Kim JS, et al. Placental drug transport and fetal exposure during pregnancy is determined by drug molecular size, chemistry, and conformation. J Control Release 2023;361:29–39. 2.Torres J, Chaparro M, Julsgaard M, et al. European Crohn’s and Colitis Guidelines on Sexuality, Fertility, Pregnancy, and Lactation. J Crohns Colitis 2023;17:1–27. 3.Mahadevan U, Seow CH, Barnes EL, et al. Global Consensus Statement on the Management of Pregnancy in Inflammatory Bowel Disease. J Crohns Colitis 2025;epub ahead of print. Conflict of interest: Julsgaard, Mette: No conflict of interest Baunwall, Simon MD: No conflict of interest Seow, Cynthia: No conflict of interest Duricova, Dana: No conflict of interest Kane, Sunanda: No conflict of interest Zacharias, Neha: No conflict of interest Leong, Rupert: No conflict of interest Cremer, Anneline: No conflict of interest Kok, Klaartje: No conflict of interest Kagramanova, Anna Valeryevna: No conflict of interest Pipek, Barbora: No conflict of interest Candido, Kristina: No conflict of interest Cooney, Rachel: No conflict of interest Filip, Rafal: No conflict of interest Kiudelis, Vytautas: No conflict of interest Konečný, Michal: No conflict of interest Paramsothy, Sudarshan: No conflict of interest Pugliese, Daniela: No conflict of interest Oliveira Santana Silva, Genoile: Honoraria - Abbvie, Johnson & Johnson, Ferring, Takeda. Research - Abivax, Takeda, Johnson & Johnson, Roche, Sanofi, Polpharma. Advisory board - Abbvie, Johnson & Johnson, MSD. Savarino, Edoardo Vincenzo: No conflict of interest Smolovic, Brigita: No conflict of interest Vieujean, Sophie: No conflict of interest Wei, Shu Chen: No conflict of interest Mahadevan-Velayos, Uma: No conflict of interest

Key Points This study reveals the temporal development and progression of senescence in an arteriovenous fistula of uremic mice. Senescent genes including p21 increased 7 days after arteriovenous fistula placement, and p16 and phosphorylated p53 cells accumulate between days 14 and 28. Transcriptomic analyses confirm established genes in arteriovenous fistula failure and suggest a collection of novel genes of interest. Background Hemodialysis therapy for ESKD requires suitable vascular access, most commonly the arteriovenous fistula (AVF). Forty percent of AVFs fail within 1 year, leading to morbidity and care costs. Failure mechanisms remain unclear, and current therapies are inadequate. Cellular senescence may be critical in AVF failure, and ESKD itself may accelerate senescence and subsequent vascular dysfunction. Senescence follows AVF placement in rodents with normal kidney function, but the temporal and spatial features in uremic conditions are unknown. This study aimed to characterize AVF changes in uremic mice over time and versus control vessels. Methods Six- to eight-week-old male C57BL6/J mice underwent five/six nephrectomy. Twenty-eight days later, an AVF was created by cuff anastomosis (right carotid artery to the right jugular vein). Transcriptomic analysis was performed 7 days post-AVF, and further samples were collected at 14 and 28 days post-AVF creation for histologic assessment. Results AVF outflow vein morphometry showed reduced neointimal cell density. Whole transcriptomic analysis of outflow versus control veins at 7 days post-AVF placement revealed 1187 upregulated and 3256 downregulated genes. Differentially expressed genes were significantly enriched in two established senescence-related gene sets, SenMayo (a curated panel of approximately 125 genes validated across species to capture senescence and associated proteins) and SenSig (a broader panel assessed to represent fibrotic and stress-induced cell response). Histologically, senescence markers p16, p21, and phospho53 increased between days 14 and 28. Genes common to our dataset, SenMayo, and SenSig were validated with quantitative reverse transcription PCR. Conclusions These data support established markers of AVF failure, such as matrix-metalloproteinases and monocyte chemokines, and identify potential novel modulators of AVF survival that may inform senolytic strategies to improve patency. In summary, this study reveals for the first time the chronologic progression of vascular senescence in the AVF of uremic mice.

Abstract Background Trials in Lewy body dementia (LBD) rely on scales and measurements created for Alzheimer’s disease and Parkinson’s disease. Industry and regulatory authority stakeholders and LBD triallists have recognised the absence of an LBD‐specific scale as critical unmet need in the drug development pipeline. Heterogeneity in LBD trials design, particularly concerning outcome measures, precludes effective evidence synthesis and data harmonisation. We describe the development of the Lewy Body Dementia‐Domain Rating Scale (LBD‐DRS) and a proposed roadmap for adoption and validation. Method Led by a core working group and steering committee, a three‐round Delphi survey process was used to establish consensus around the conceptual framework and preliminary content of the LBD‐DRS among invited LBD researchers and clinicians. “Consensus” was established when ≥75% of respondents concurred on any survey statement or questions. Result Consensus around the need for an LBD‐specific scale, specifically for use in early LBD, was established. After feedback was received for two early versions of LBD, a third version of LBD‐DRS has been further developed. This third version, and the results of the second Delphi survey round will be presented. A pragmatic approach, favouring an inclusive scoring approach for symptoms has been adopted, recognising that further iterations will be required once field data becomes available. Conclusion After consensus on the conceptual framework and preliminary content is established, the authors will consult with a broader range of stakeholders, including people living with LBD and their care partners, will be required to further develop LBD‐DRS. Engagement with regulatory bodies and the pharmaceutical industry will guide further development before validation studies are pursued.

The treatment landscape for soft tissue sarcomas (STS) is evolving constantly. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for STS specific to surgical management and systemic therapy recommendations for various subtypes.