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Abstract Background Nearly 40,000 people in the U.S. experience recurrent pericarditis with up to 90% of cases having no identifiable cause, often making the journey to diagnosis arduous. Understanding the challenges that patients and health care professionals (HCP) face will help address gaps and barriers in patient diagnosis and care. In addition, the lack of U.S. based guidelines for recurrent pericarditis clinical care, coupled with the time lapse from the last published European guideline, has created an opportunity to discover workflow solutions for U.S. based healthcare professionals. Purpose The American Heart Association’s (AHA) Addressing Recurrent Pericarditis Initiative is a three-year effort utilizing a quality improvement approach to address gaps/barriers in patient care, educate HCPs, and develop patient education resources to improve diagnosis, treatment, and quality of life. To accomplish this, the lived experiences and challenges patients face on their journey to diagnosis was integrated into the qualitative research process. Methods To assess quality improvement opportunities, the AHA engaged HCPs with recurrent pericarditis experience from 15 diverse health systems to participate in a learning collaborative strategy for quality improvement and implementation to share successful strategies, provide input on professional education topics, and participate in process mapping. Data collection strategies include 1:1 consultations, quarterly learning collaborative calls, surveys and questionnaire completion. To assess patient education needs, the AHA Market Research Team held 1-hour video interviews with ten diverse patients. Results AHA-led HCP interviews produced process maps of clinical workflows and identified opportunities for standardization to improve clinical workflow and patient outcomes (Figure 1). From these data collection methods, preliminary results include care coordination across clinical settings, exploring treatment options, standardization of follow-up cadence, and provider awareness of misdiagnoses/underdiagnosis rates. The patient interviews revealed that there is a lack of symptom recognition, persistent rate of misdiagnosis, delay in accurate diagnosis and treatment, and discrepancies in diagnosis and treatment for various demographics including female and younger adult patients (Figure 2). Conclusion(s) In Year 2 of this three-year initiative, we will continue to refine identified areas of opportunities to improve patient outcomes by creating and disseminating educational materials and launch awareness campaigns, while also producing a national education series for HCPs that provide guidance for system-level quality improvement to emphasize consistency in care and reductions in health inequities. Key findings from this study highlight the care coordination involved in the treatment of patients with recurrent pericarditis and the need to provide multidiscipline educational approaches to achieve this goal.Figure. 1 Summary of care pathway Figure. 2 Summary of patient interviews

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.

Resistant hypertension (RH) is a high-risk phenotype characterized by blood pressure readings ≥130/80 mmHg despite maximally tolerated therapy with three antihypertensive agents, including a diuretic, or controlled blood pressure requiring four or more medications. The diagnosis of RH requires a structured evaluation that confirms accurate blood pressure measurement, excludes pseudoresistance—particularly nonadherence and white coat hypertension—and identifies secondary causes such as obstructive sleep apnea, primary aldosteronism, renovascular disease, pheochromocytoma, and Cushing syndrome. RH arises from overlapping mechanisms, including activation of the renin–angiotensin–aldosterone system (RAAS), sympathetic overactivity, arterial stiffness, volume expansion, and immune-mediated pathways. Management begins with lifestyle modification and optimized triple therapy, followed by mineralocorticoid receptor antagonists as the preferred fourth-line treatment. Emerging pharmacological options, such as sodium–glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, endothelin receptor antagonists, aldosterone synthase inhibitors, and angiotensin receptor and neprilysin inhibitors (ARNIs), offer additional therapeutic potential; meanwhile, device-based interventions, including renal denervation and baroreflex activation therapy, have shown sustained blood pressure reductions in selected patients. Future directions highlight precision medicine, digital health technologies, and artificial intelligence as methods to improve diagnosis, guide individualized therapy, and enhance long-term blood pressure control.

Background: Cardiac CT acquired during the acute stroke imaging protocol is an emerging diagnostic modality to detect cardiac thrombi. We aimed to determine its diagnostic yield in a large, international, multicenter study. Methods: We performed an individual patient data meta-analysis by pooling prospective and retrospective observational data of patients with acute ischemic stroke (AIS) who underwent cardiac CT (ECG-gated or non-ECG-gated) as part of the acute imaging protocol between May 2018 and June 2024. We excluded patients with a TIA or stroke mimic. The primary outcome was the proportion of patients with a cardiac thrombus detected on cardiac CT. Secondary outcomes were additional scan time and radiation dose, comparison of yield with echocardiography, and 90-day mortality and recurrent ischemic stroke rates. Results: We included 3940 patients from 4 hospitals (median age 74 [IQR 63-82], 58.0% male, median NIHSS 6 [IQR 3-12], median time onset to hospital arrival 100 minutes [IQR 62-185]). Atrial fibrillation at baseline was present in 23.1% patients, and 29.6% had a large vessel occlusion. Cardiac CT was non-diagnostic in 17 (0.4%) patients. In total, cardiac CT detected 254 cardiac thrombi in 243/3923 (6.2%) patients. Thrombi were located in the left atrial appendage (n=193), left atrium (n=19), and left ventricle (n=42). Of 95/243 (39.1%) patients with a cardiac thrombus that underwent echocardiography (median interval cardiac CT-echocardiography: 2 days), transthoracic echocardiography detected a thrombus in 18/92 (19.6%) patients and transesophageal echocardiography in 2/5 (40.0%) patients. The diagnostic yield in patients that underwent both modalities was higher for cardiac CT (OR 7.5 [CI 4.0-15.3], p<0.001). Median additional scan time was 6 minutes (IQR 5-7) for ECG-gated and 17 seconds (IQR 15-63) for non-ECG-gated cardiac CT. Median additional radiation dose was 5.4mSv (IQR 3.0-7.6). Patients with a cardiac thrombus on cardiac CT had higher 90-day mortality than those without a thrombus (33.3% vs 14.6%, p<0.001). We found no difference in 90-day recurrent stroke rate (5.4% vs 4.4%, p=0.50). Conclusion: Routine cardiac CT performed during the acute stroke imaging protocol detects a cardiac thrombus in 1 out of 16 patients with AIS, with a 7-times higher yield than routine echocardiography. Mortality rate was doubled in patients with a cardiac thrombus, but 90-day stroke recurrence risk did not differ.

Background: The rate of intracardiac thrombus detection in the hyperacute phase of stroke varies from 5% to 12% between studies. Our aim was to compare the thrombus detection rate between ECG-gated and non-ECG-gated cardiac CT protocols in acute stroke patients, using data from a large, international, multicentre registry. Methods: We conducted an individual patient data meta-analysis by pooling prospective and retrospective observational data from stroke patients assessed at four comprehensive stroke centres who underwent either ECG-gated or non-ECG-gated cardiac CT (extended CT angiography or two-phase non-ECG-gated cardiac CT) as part of the acute stroke imaging protocol between May 2018 and June 2024. The primary outcome was the proportion of patients with a cardiac thrombus in gated vs non gated techniques. Results: Of 3,940 patients, 1,474 (37.4%) underwent ECG-gated and 2,466 (62.6%) non-ECG-gated cardiac CT. Patients in the ECG-gated group were younger (median age 72 [IQR 62–81] vs. 74 [IQR 64–82] years, p = 0.000) and had a lower NIHSS at baseline (median 5 [IQR 2–12] vs. 6 [IQR 3–13], p < 0.00). There was a higher rate of thrombus detection with ECG-gated CT compared to non-gated CT (7.5% vs. 5.5%, p = 0.011. The association remained significant after adjusting for age, sex, baseline NIHSS score, and baseline atrial fibrillation (adjusted OR 1.87, 95% CI 1.42–2.47, p = 0.000). ECG-gated CT was associated with lower radiation dose (3.6 vs. 6.3 mSv, p = 0.000) but longer acquisition time (5.8 vs. 0.28 min, p = 0.000). Conclusion: ECG-gated cardiac CT has a higher detection rate for intracardiac thrombus detection compared to non-ECG-gated CT in patients with acute ischemic stroke.

INTRODUCTION: A Model for End-Stage Liver Disease-lactate (MELD-LA) score is an independent predictor of inpatient mortality and organ failure validated in more than 8,600 patients across diverse settings. However, its utility in sepsis, particularly when combined with lactate clearance (LA clearance), has not been fully evaluated. In this study, we examined the dynamic role of MELD-LA with 24-hour LA clearance as a predictor of 30-day mortality in critically ill patients with cirrhosis and sepsis. METHODS: We analyzed cirrhosis patients with sepsis admitted to the intensive care unit (ICU) in a large US healthcare system (20 hospitals) from 2014 to 2022, examining MELD-LA and LA clearance within 24 hours as predictors of 30-day mortality. We externally validated our findings in the Asian Pacific Association for the Study of the Liver-acute-on-chronic liver failure Research Consortium, a multinational Asian cohort (31 centers) from 2009 to 2019. RESULTS: A total of 3,879 cirrhosis patients with sepsis were admitted to the ICU (43.2% female, 20.5% Hispanic, 12.4% on dialysis; mean initial LA 4.5 mmol/L, MELD 20.8, MELD-LA 17.6). Survivors showed a median lactate change of −1.04 (35% clearance) compared with −0.4 (12%) for nonsurvivors. LA clearance within 24 hours was influenced by the presenting MELD-LA. In the North American cohort, ≥35% LA clearance was associated with improved 30-day survival (odds ratio 0.41, 95% CI 0.31–0.53; P < 0.001). Similarly, in the Asian Pacific Association for the Study of the Liver cohort (n = 1,259), ≥35% clearance was linked to a 60% reduction in mortality (odds ratio 0.42, 95% CI 0.28–0.62; P < 0.001). When stratified by LA clearance, patients with LA clearance of ≥35% had a higher percentage of early administration of resuscitative measures than those with LA clearance of < 10% especially regarding early antibiotic administration (82.5% vs 67.6%; P value <0.001). DISCUSSION: Early reduction in initial LA by one-third predicts 30-day mortality and may indicate treatment response in cirrhosis patients with sepsis in the ICU. Combining MELD-LA and LA clearance early enables better risk stratification and informs management.

Background: Sinonasal undifferentiated carcinoma (SNUC) is an extremely rare, high-grade, and aggressive tumor of the sinonasal tract. Due to the rarity of this malignancy, current treatment guidelines are based on small and often/mainly single-center retrospective datasets. In the absence of a universally accepted standard of care for SNUC, treatment approaches vary across countries and institutions, reflecting real-world clinical practice. The primary aim of this study was to describe real-world treatment and outcomes for patients with confirmed SNUC. Methods: This was an international, multi-center, retrospective, observational cohort study that pooled patients into the largest SNUC dataset to date. Fifteen centers were enrolled to contribute data, including seven from Europe, four from the United States, three from the United Kingdom, and one from Canada. In the absence of a universally accepted standard of care for SNUC, treatment approaches varied across countries and institutions, reflecting real-world clinical practice. Patients included were those with histologically confirmed SNUC who were treated between 1997 and 2021. Results: This study yielded 485 patients treated for SNUC. The median age at diagnosis was 55.6 years (IQR: 44.5–67.6), and 63.7% were male. Most cases presented at advanced stages, with 70.8% as T4a or T4b. Overall survival (OS) outcomes were available for 412 patients, with a median follow-up of 26.0 months. The 5- and 10-year OS were 47.2% (95% CI: 40.8–53.3%) and 39.6% (95% CI: 32.5–46.6%), respectively. Advanced age, dichotomized T-stage (T4a/b vs. T1–3), M-stage, and orbital involvement were significant poor prognostic factors on univariable analysis (p’s < 0.01). On multivariable analysis, orbital involvement (HR: 2.73, 95% CI: 1.42–5.27, p = 0.003) and distance metastasis stage (HR: 3.00, 95% CI: 1.25–7.21, p = 0.014) were both independently associated with worse OS. Conclusions: This observational study presents the largest multi-center cohort analysis of SNUC to date, providing new insights into prognostic factors for a rare cancer treated at global centers of excellence. Orbital involvement and the presence of metastases are candidate independent risk factors associated with poorer OS.

373 Background: Recent studies have demonstrated encouraging outcomes with neoadjuvant ICIs in pts with localized deficient mismatch repair (dMMR) and/or microsatellite instability-high (MSI-H) GEC, prompting discussions around the feasibility of nonoperative management (NOM). However, current evidence is largely from phase 1 and 2 clinical trials with limited sample sizes. Thus, the efficacy and safety of neoadjuvant ICI in this pt population remain subject to ongoing debate. Methods: We conducted a systematic review and meta-analysis of prospective and retrospective studies evaluating neoadjuvant ICIs in pts with localized dMMR/MSI-H GEC according to the PRISMA guidelines. The primary outcomes were pathological complete response (pCR) and complete clinical response (cCR) rates. cCR was defined as no evidence of residual disease on tumor-specific imaging and on endoscopy with biopsy. Secondary outcomes included major pathologic response (MPR) rates and the incidence of grade 3–4 immune-related adverse events (irAEs). Proportions with 95% confidence intervals (CI) were used to pool event rates for occurrence of cCR, pCR, MPR and grade 3-4 irAEs. The DerSimonian and Laird random-effects model was used. NOM was assessed as part of the qualitative analysis. Results: 20 studies comprising 396 pts treated with neoadjuvant ICIs were included. Three studies utilized double ICI blockade (PD-1/ PD-L1 inhibitor plus CTLA-4 inhibitor), while the remaining studies primarily utilized monotherapy with a PD-1 inhibitor, with or without chemotherapy. Overall, 320 (81.0%) underwent surgical resection. The pooled pCR rate was 41.6% (95% CI, 33.1%–50.8%), cCR 63.8% (95% CI, 45.6%–78.8%), and MPR 64.2% (95% CI, 49.1%–76.9%). The pooled incidence of grade 3–4 irAEs was 5.1% (95% CI, 0.6%–12.2%). Subgroup analysis showed higher pCR with ≥3 months versus <3 months of ICI (50.2% [95% CI 42.2–58.3] vs 28.4% [18.9–40.2]; χ²=8.69, p=0.003). Forty-four pts were managed with NOM, two experienced early local regrowth over median follow-up ranging from 11.5 to 28 months. Conclusions: Neoadjuvant ICI therapy appears to be a safe and effective therapeutic strategy for pts with localized dMMR/MSI-H GEC. Neoadjuvant ICI exposure for ≥3 months seems to yield higher pCR rates than <3 months. The high and prolonged cCR rates support the nonoperative strategy in selected patients with dMMR/MSI-H GEC.

334 Background: Sarcopenia, or decreased skeletal muscle mass, has been associated with worse surgical and oncologic outcomes across multiple malignancies. This study investigates the impact of sarcopenia on outcomes after multimodal therapy for esophageal cancer. Methods: Retrospective observational cohort study including adult patients who underwent neoadjuvant therapy followed by esophagectomy for primary esophageal cancer from January 2000 - December 2021. A fully automated abdominal segmentation using deep convolutional neural network was utilized to calculate skeletal muscle index (SMI) from preoperative CT scans performed at our institution. Males with SMI <52.4 cm 2 /m 2 and females with SMI <38.5 cm 2 /m 2 at any point before surgery were classified as sarcopenic. The relationship between sarcopenia and patient demographics, operative details, and complications were explored using chi-square tests. The relationship between sarcopenia and disease-free survival and overall survival were investigated using parsimonious multivariable analysis retaining variables with p-value <0.05 using backward selection method. Results: We identified 200 patients meeting the study criteria with 142 (71%) having sarcopenia at any time prior to surgery. Patients with sarcopenia were significantly older [65.2 (59.6, 71.2) vs 63 (53.6, 67.5), p = .023] and more likely to have had open surgery [129 (90.8%) vs 46 (79.3%), p = .034]. There were no significant differences in sex, history of diabetes, coronary artery disease, renal disease, smoking, cancer type, cancer stage, tumor size, tumor location, or margin status between sarcopenic groups ( p > .05). Sarcopenic patients were significantly more likely to require blood transfusion ≥3 units after esophagectomy [79 (55.6%) vs 8 (13.8%), p < .001] or to experience complications requiring surgical intervention [36 (24.6%) vs 7 (12.1%), p = .048]. Multivariate analysis revealed that sarcopenia was associated with disease-free and overall survival (Table). Conclusions: Sarcopenia is a prognostic factor in patients undergoing multimodal therapy for esophageal cancer. Interventions that aim to prevent decreases in SMI after initiating neoadjuvant therapy should be investigated. Multivariate analysis with sarcopenia predicting outcomes. Disease free survivalHR (95% CI) p-value Overall survivalHR (95% CI) p-value Age 1.04 (1.02, 1.06) < .001 1.04 (1.02, 1.07) < .001 Epicenter Middle Upper 1.88 (1.21, 2.86)3.16 (1.67, 5.98) .001.005< .001 1.96 (1.26, 3.04)4.00 (1.90, 8.44) < .001.003< .001 Stage Stage II Stage III Stage IV 1.88 (0.95, 3.71)2.90 (1.46, 5.75)16.02 (6.12, 41.93) < .001.069.002< .001 1.65 (0.83, 3.25)2.76 (1.37, 5.55)10.14 (4.03, 25.53) < .001.151.005< .001 Cancer type - - 1.76 (1.03, 3.02) .039 Transfusion > 3 pRBC - - 1.54 (0.99, 2.40) .057 BMI prior to cancer diagnosis - - 0.98 (0.94, 1.01 .208 Sarcopenic 1.76 (1.16, 2.67) .007 1.64 (1.04, 2.60) .033