Citations

BACKGROUND: Greater left atrial size is associated with a higher incidence of cardiovascular disease and mortality, but the full spectrum of diagnoses associated with left atrial enlargement in sex-stratified clinical populations is not well known. Our study sought to identify genetic risk mechanisms affecting left atrial diameter (LAD) in a clinical cohort. METHODS: Using Vanderbilt deidentified electronic health record, we studied 6163 females and 5993 males of European ancestry who had at least 1 LAD measure and available genotyping. A sex-stratified polygenic score was constructed for LAD variation and tested for association against 1680 International Classification of Diseases code–based phenotypes. Two-sample univariable and multivariable Mendelian randomization approaches were used to assess etiologic relationships between candidate associations and LAD. RESULTS: A phenome-wide association study identified 25 International Classification of Diseases code–based diagnoses in females and 11 in males associated with a polygenic score of LAD (false discovery rate q<0.01), 5 of which were further evaluated by Mendelian randomization (waist circumference [WC], atrial fibrillation, heart failure, systolic blood pressure, and coronary artery disease). Sex-stratified differences in the genetic associations between risk factors and a polygenic score for LAD were observed (WC for females; heart failure, systolic blood pressure, atrial fibrillation, and WC for males). By multivariable Mendelian randomization, higher WC remained significantly associated with larger LAD in females, whereas coronary artery disease, WC, and atrial fibrillation remained significantly associated with larger LAD in males. CONCLUSIONS: In a clinical population, we identified, by genomic approaches, potential etiologic risk factors for larger LAD. Further studies are needed to confirm the extent to which these risk factors may be modified to prevent or reverse adverse left atrial remodeling and the extent to which sex modifies these risk factors.

Introduction: Artificial intelligence applied to electrocardiograms (ECG-AI) enables early and efficient detection of cardiovascular disease. The technical and clinical impact of different approaches to designing ECG-AI remains under-explored. We consider left ventricular hypertrophy (LVH) and examine the impact of disease-specific labeling of minority etiologies of left ventricular wall thickening- hypertrophic cardiomyopathy (HCM) and cardiac amyloidosis (CA) - on ECG-AI performance. Hypothesis: ECG-AI designed to detect HCM or CA outperforms ECG-AI broadly trained to identify LVH due to differences in attention to key ECG features associated with HCM or CA. Methods: Independent neural networks were trained to identify HCM, CA, and LVH. HCM and CA patients were identified using the full depth of EHR data and validated via clinician adjudication (N = 3,025 and 4,251 patients, respectively). Moderate and severe LVH patients (N = 98,144) were identified using echocardiogram results and international LVH criteria. We compared the ability of disease-specific ECG-AI vs. LVH ECG-AI to detect HCM (or CA) by examining model performance within each of the three test sets. Results: 52.6% of HCM patients and 49.5% of CA patients met LVH criteria. Within the HCM test set, the AUROC, sensitivity, specificity, and positive predictive value (PPV) of the HCM ECG-AI were 0.94, 0.88, 0.85, and 60%, respectively, whereas the same for LVH ECG-AI were 0.83, 0.83, 0.64, and 37%. Within the CA test set, CA ECG-AI achieved AUROC, sensitivity, specificity, and PPV of 0.94, 0.81, 0.91, and 69%, respectively, whereas the same for LVH ECG-AI were 0.75, 0.73, 0.68, and 31%. ECGs positive for HCM exhibited higher P wave area, QRS deflection and R wave amplitude compared to LVH-positive ECGs (Cohen's D > 0.75). ECGs positive for CA exhibited lower R wave amplitude/area, QRS deflection and QRS areas (Cohen's D > 0.6). Conclusion: Models trained using carefully labeled HCM or CA identify distinct signals associated with the diseases, resulting in improved disease discrimination compared to a model trained to identify echocardiographic left ventricular thickening. Labeling choices should be communicated transparently to clinicians to ensure safe and effective use of ECG-AI.

Introduction: The combination of local impedance (LI), a direct measure of electrical resistance at the catheter tip, and contact force (CF) may facilitate treatment of atrial fibrillation (AF). This trial is designed to examine the safety and effectiveness of a novel RF catheter that allows measurement of both LI and CF. Hypothesis: Demonstrate the safety and effectiveness of a novel radiofrequency catheter with LI and CF for treatment of drug refractory, recurrent, symptomatic Paroxysmal AF (PAF). Methods: NEwTON AF is a multi-center, global, prospective, single arm study. Patients received index treatment for PAF with the study catheter. The present 6-month endpoint analysis was prospectively planned. Results: The study treated 299 patients at 45 sites in North America, Europe, and Asia. Patients were 39.5% female with a mean age of 62yrs (±12), and had a mean LVEF of 59% and an LA diameter of 3.9cm. Procedure time, LA dwell, and fluoroscopy times were 166, 136, and 15 minutes, respectively. High-power short-duration (HSPD, 45-50W) was exclusively used in 210 cases, which had notably shorter procedure times than the 82 cases that used conventional power, 148 vs 208 min, respectively. Acute procedural success was observed in 98.3% of cases. As of 6 months, freedom from documented recurrence of any atrial arrhythmia was 79.9% (Figure). Recurrence in relation to LI shows that pts with a 20Ω LI drop (in at least 60% of lesions) had better 6m outcomes (84.2% vs 73.3, p=0.04). The freedom from safety event rate at 30d was 96.0%; events included pericarditis (6), access complications (2), pulmonary edema (2), embolism (2), cerebrovascular accident (1), tamponade (1). Pericarditis was higher in pts with a history of COVID at enrollment, 16.3% vs 5.9%, p=0.025. Conclusions: This data suggests that patient outcomes and safety for this novel catheter are promising. Further data from this study, including 12m outcomes, and detailed analysis of local impedance data are forthcoming.

AbstractRelapsed and refractory B‐cell acute lymphoblastic leukemia (B‐ALL) is an aggressive B‐cell neoplasm associated with poor outcomes. Conventional multiagent chemotherapy and bispecific antibody therapy may induce remission; however, relapse rates remain high and overall survival is poor. Chimeric antigen receptor T‐cell (CAR‐T) therapy provides durable, deep complete remission, and long‐term cures in relapsed and refractory B‐ALL. However, with this new treatment modality, 10%–30% of patients do not achieve remission, and over 50% experience relapse after therapy. Currently, there are two approved CD19‐specific CAR‐T cell constructs in B‐ALL, Tisagenlecleucel and Brexucabtagene Autoleucel by the United States Food and Drug Administration, and the European Medicines Agency (EMA). In this review, we discuss patients, disease, and CAR‐T predictors of outcomes in B‐ALL. We describe the two approved CD19‐directed CAR‐T cell products, review the current literature, and discuss factors associated with high risks of therapy failure and future direction in CAR‐T cell therapy for B‐ALL.

Background Cervicofacial arteriovenous malformations (AVMs) are a significant source of morbidity. Endovascular embolization has emerged as a promising treatment technique for these lesions. However, current literature on cervicofacial AVM embolization mostly consists of single-agent oriented case series, and to date, no comprehensive study has compared the outcomes of available embolic agents. Purpose To investigate the performance of different embolic agents in the management of cervicofacial AVMs. Methods We systematically searched Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials Scopus, and Web of Science. Studies providing data for the endovascular treatment of cervicofacial AVMs were included. The data regarding complication and cure rates were collected for each embolic agent. Pooled event rates were presented as descriptive statistics. Results Eleven studies comprising 204 patients were included in the review. The overall complete and partial cure rates were 62.2% (127/204) and 36.2% (74/204), respectively. Embolization failed to achieve significant improvement in only 1.6% (3/204) of the patients. The complete cure rates were 87.5% (75–100%) for n-Butyl cyanoacrylate (NBCA, glue), 80.5% (61–100%) for Onyx (Medtronic, MN, USA), and 51.5% (18–85%) for ethanol. The overall complication rate was 30% (61/204). The complication rates were 33% (12.5–53%) for ethanol, 14% (0–28%) for Onyx, and 0% for NBCA. Conclusions Our systematic review supports that endovascular embolization is an effective treatment option for cervicofacial AVMs. In our review, the use of Onyx and NBCA was associated with consistently high complete cure rates and a promising safety profile. However, more research is needed to investigate the use of different embolic agents in the treatment of cervicofacial AVMs.

ImportancePostoperative radiation therapy for close surgical margins in low- to intermediate-grade salivary carcinomas lacks multi-institutional supportive evidence.ObjectiveTo evaluate the oncologic outcomes for low- and intermediate-grade salivary carcinomas with close and positive margins.Design, Setting, and ParticipantsThe American Head and Neck Society Salivary Gland Section conducted a retrospective cohort study from 2010 to 2019 at 41 centers. Margins were classified as R0 (negative), R1 (microscopically positive), or R2 (macroscopically positive). R0 margins were subclassified into clear (&amp;gt;1 mm) or close (≤1 mm). Data analysis was performed from June to October 2023.Main Outcomes and MeasuresMain outcomes were risk factors for local recurrence.ResultsA total of 865 patients (median [IQR] age at surgery, 56 [43-66] years; 553 female individuals [64%] and 312 male individuals [36%]) were included. Of these, 801 (93%) had parotid carcinoma and 64 (7%) had submandibular gland carcinoma, and 748 (86%) had low-grade tumors and 117 (14%) had intermediate-grade tumors, with the following surgical margins: R0 in 673 (78%), R1 in 168 (19%), and R2 in 24 (3%). Close margins were found in 395 of 499 patients with R0 margins (79%), for whom margin distances were measured. A total of 305 patients (35%) underwent postoperative radiation therapy. Of all 865 patients, 35 (4%) had local recurrence with a median (IQR) follow-up of 35.3 (13.9-59.1) months. In patients with close margins as the sole risk factor for recurrence, the local recurrence rates were similar between those who underwent postoperative radiation therapy (0 of 46) or observation (4 of 165 [2%]). Patients with clear margins (n = 104) had no recurrences. The local recurrence rate in patients with R1 or R2 margins was better in those irradiated (2 of 128 [2%]) compared to observed (13 of 64 [20%]) (hazard ratio [HR], 0.05; 95% CI, 0.01-0.24). Multivariable analysis for local recurrence found the following independent factors: age at diagnosis (HR for a 10-year increase in age, 1.33; 95% CI, 1.06-1.67), R1 vs R0 (HR, 5.21; 95% CI, 2.58-10.54), lymphovascular invasion (HR, 4.47; 95% CI, 1.43-13.99), and postoperative radiation therapy (HR, 0.10; 95% CI, 0.04-0.29). The 3-year local recurrence-free survivals for the study population were 96% vs 97% in the close margin group.Conclusions and RelevanceIn this cohort study of patients with low- and intermediate-grade major salivary gland carcinoma, postoperative radiation therapy for positive margins was associated with decreased risk of local recurrence. In isolation from other risk factors for local recurrence, select patients with close surgical margins (≤1 mm) may safely be considered for observation.