Citations

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.

e16443 Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with KRAS mutations present in approximately 90% of cases. Patients with advanced or metastatic PDAC who have progressed after standard chemotherapy face limited treatment options, with historical outcomes showing objective response rates (ORR) below 10% and median progression-free survival (PFS) and overall survival (OS) of approximately 2-4 months and 6-8 months, respectively. The development of covalent KRAS G12C inhibitors—including sotorasib, adagrasib, garsorasib, glecirasib, and divarasib—has opened new therapeutic options for this molecularly defined subset of PDAC patients. Methods: We conducted a systematic review and meta-analysis of clinical trials evaluating KRAS G12C inhibitor monotherapy in patients with advanced/metastatic pancreatic ductal adenocarcinoma. Data were extracted from 3 studies (Strickler 2022, Li J 2025, and Tanios 2023) encompassing a total of 91 patients with KRAS G12C-mutant PDAC who had received 1-2 prior lines of chemotherapy. Pooled estimates were calculated using random-effects meta-analysis models (DerSimonian-Laird method). For proportion outcomes (ORR and DCR), standard errors were calculated using binomial distribution, and for continuous outcomes (PFS and OS), inverse-variance weighting was employed. Heterogeneity was assessed using the I² statistic and Cochran's Q test. All confidence intervals were calculated at the 95% level. Results: The pooled analysis revealed clinically meaningful efficacy across all endpoints. The pooled objective response rate (ORR) was 32.9% (95% CI: 17.0% to 48.9%), with moderate heterogeneity (I² = 64.0%). The pooled disease control rate (DCR) was substantially higher at 88.3% (95% CI: 80.5% to 96.1%), with low heterogeneity (I² = 27.7%), indicating consistent disease stabilization across studies. For survival outcomes, the pooled median progression-free survival (PFS) was 4.98 months (95% CI: 3.62 to 6.34 months), with low heterogeneity (I² = 32.3%). The pooled median overall survival (OS) was 8.73 months (95% CI: 6.07 to 11.39 months), though with substantial heterogeneity (I² = 77.0%). Conclusions: KRAS G12C inhibitor monotherapy demonstrates clinically significant and durable efficacy in pretreated adults with advanced/metastatic PDAC harboring the KRAS G12C mutation. The pooled ORR of approximately one-third, together with a DCR near 90%, indicates substantial tumor control in a population with historically poor outcomes. Median PFS of approximately 5 months and OS of nearly 9 months represent clinically relevant improvements over standard salvage therapies, supporting KRAS G12C inhibitors as a viable option after chemotherapy failure.

ABSTRACT Background Patients with end‐stage renal disease (ESRD) undergoing dialysis have an increased risk of pacemaker‐related complications due to limited vascular access and increased susceptibility to infection. Leadless pacemakers (LPMs) may mitigate these risks compared with conventional transvenous pacemakers (TPMs), but long‐term comparative data in this population remain limited. Methods We conducted a retrospective cohort study using the TriNetX Research Network, including adults (≥ 18 years) with ESRD on dialysis who underwent LPM or TPM implantation between May 2016 and December 2020. Propensity score matching (1:1) was performed using demographics and comorbidities. Outcomes assessed over up to 5 years included all‐cause hospitalization, heart failure hospitalization, device re‐intervention, device‐related complications, infection‐related hospitalization, pacemaker‐induced cardiomyopathy, and all‐cause mortality. Results After matching, 901 patients were included in each group with well‐balanced baseline characteristics. LPM implantation was associated with a significantly lower risk of device re‐intervention compared with TPM (4.1% vs. 9.3%; hazard ratio [HR] 0.44; 95% confidence interval [CI] 0.28–0.69; p < 0.01). There were no significant differences between groups in all‐cause hospitalization (65.5% vs. 68.3%; p = 0.22), heart failure hospitalization (26.9% vs. 30.2%; p = 0.13), all‐cause mortality (37.5% vs. 35.3%; p = 0.34), device‐related complications (14.5% vs. 14.3%; p = 0.94), infection‐related hospitalization (1.6% vs. 2.1%; p = 0.35), or pacemaker‐induced cardiomyopathy (9.0% vs. 8.6%; p = 0.66). Conclusion In a large, propensity‐matched cohort of patients with ESRD on dialysis, LPMs were associated with fewer device re‐interventions and comparable long‐term clinical outcomes compared with TPMs.

ABSTRACT Background Atrial fibrillation (AF) is common in patients with hypertrophic cardiomyopathy (HCM) and is associated with increased morbidity, heart failure (HF) exacerbations, and adverse long‐term outcomes. Although catheter ablation is an established rhythm‐control strategy, data comparing its long‐term clinical outcomes with anti‐arrhythmic drug (AAD) therapy in patients with HCM remain limited. Objective To compare long‐term clinical outcomes of catheter ablation versus medical therapy with AADs in patients with HCM and AF. Methods We conducted a retrospective cohort study using the TriNetX Research Network, a global federated database of electronic health records. Adult patients with HCM and AF between January 2010 and December 2020 were identified and stratified according to treatment with catheter ablation or AAD therapy. Outcomes included all‐cause mortality, HF exacerbations, AAD‐related adverse events, all‐cause hospitalization, ischemic stroke, repeat ablation, need for cardioversion, need for long‐term AAD use, and atrioventricular nodal ablation. A 1:1 propensity score matching (PSM) analysis was performed to balance baseline characteristics. Kaplan–Meier survival analysis and Cox proportional hazards models were used to estimate hazard ratios (HRs). Results After PSM, 3144 patients were included (1572 in each cohort) with a mean follow‐up of approximately 3.4 years. Catheter ablation was associated with lower all‐cause mortality compared with AAD therapy (9.5% vs. 14.8%; HR: 0.60; 95% CI: 0.49–0.74; p < 0.001). Ablation was also associated with reduced risk of HF exacerbations (38.4% vs. 43.3%; HR: 0.79; 95% CI: 0.71–0.88; p < 0.001) and fewer AAD‐related adverse events (8.4% vs. 11.2%; HR: 0.71; 95% CI: 0.55–0.93; p = 0.011). Rates of all‐cause hospitalization (HR: 0.93; p = 0.11) and ischemic stroke (HR: 0.78; p = 0.10) were similar between groups. Conclusion In this large real‐world cohort of patients with HCM and AF, catheter ablation was associated with lower mortality, reduced HF hospitalizations, and decreased AAD therapy‐related adverse events, as compared with medical therapy. These findings suggest that catheter ablation may provide meaningful clinical benefits in selected patients with HCM and AF, although prospective studies are needed to confirm these observations.

ABSTRACT Introduction Frailty is increasingly recognized as an important determinant of outcomes in cardiovascular disease, yet its population‐level impact among patients hospitalized with cardiac implantable electronic device (CIED) infections remains incompletely defined. We examined the prevalence of frailty and its association with clinical outcomes and utilization of transvenous lead removal (TLR) in a contemporary national cohort. Methods and Results We analyzed the National Readmissions Database from 2016–2021 to identify adults hospitalized for CIED infections. Frailty was defined using the Johns Hopkins adjusted clinical groups frailty‐defining diagnoses. Of 288,402 patients hospitalized with CIED infections, 25.1% were classified as frail. Frail patients experienced significantly higher in‐hospital mortality (10.8% vs. 4.6%), 30‐day mortality (9.2% vs. 5.5%), complications, longer length of stay, lower rates of discharge home, and higher 30‐day readmissions compared with non‐frail patients (all p < 0.01). TLR was performed less frequently in frail patients (10.8% vs. 13.4%; adjusted odds ratio [aOR] 0.80, 95% CI 0.76–0.83). On adjusted analyses, TLR was independently associated with lower in‐hospital mortality, 30‐day mortality, and 30‐day readmissions in both frail and non‐frail patients. Conclusion Among patients hospitalized with CIED infections, TLR was independently associated with lower mortality and readmissions in both frail and non‐frail patients, despite lower utilization in frail individuals. Frailty was common (25.1%) and independently associated with significantly worse outcomes. These findings highlight important associations between frailty, treatment patterns, and outcomes that warrant prospective evaluation.

Background: Vitamin C is a vital nutrient that functions as an antioxidant and is important as a co-factor and regulator of several immune system pathways. The role of vitamin C in the treatment of COVID-19 is largely debatable. We conducted this meta-analysis to evaluate the efficacy and safety of vitamin C in the treatment of COVID-19. Methods: We searched several electronic databases from inception to March 2023 to retrieve randomized controlled trials on the use of vitamin C for COVID-19. RevMan 5.4 was used to calculate risk ratios (RRs) and mean differences (MDs) along with confidence intervals (95% CI) using a random-effects model. Results: We included nine randomized controlled trials in our meta-analysis. Vitamin C did not reduce the all-cause mortality in patients with COVID-19 compared to the standard treatment (RR 0.92, 95% CI: 0.83–1.02; I 2 = 1%). Vitamin C was found to be associated with a similar incidence of ventilation in COVID-19 patients when compared to standard treatment (RR 0.98, 95% CI: 0.87–1.11, I 2 = 0%). There were no significant differences between both groups regarding the incidence of hospitalization (RR 1.00, 95% CI: 0.98–1.02; I 2 = 0%), incidence of recovery (RR 1.57, 95% CI: 0.45–5.50; I 2 = 52%), hospital mortality (RR 0.68, 95% CI: 0.44–1.06; I 2 = 0%) and length of hospital stay (MD −0.63, 95% CI: −3.04 to 1.78; I 2 = 81%). Conclusion: Vitamin C administration did not reduce all-cause mortality in COVID-19 patients. Additional studies are required to evaluate the role of vitamin C in the prevention and treatment of COVID-19 especially in ICU patients.

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.

Abstract Background The COVID-19 pandemic saw a worrisome rise in mucormycosis cases in India, especially among those receiving corticosteroid therapy. While corticosteroids are essential for managing severe COVID-19 cases, their immunosuppressive action appears to augment infection risk. Clinically, prolonged steroid use may result in severe forms of mucormycosis; however, this requires rigorous systematic evaluation. Methods We conducted an exhaustive analysis of 327 mucormycosis cases and 596 COVID-19 controls, all of whom were treated during the second wave in India. Exposure to steroids was carefully categorized by duration into three groups: short-term (1-5 days), standard-term (5-10 days), and long-term ( &gt; 10 days). Each case was biopsy-proven, with further radiographic confirmation of disease extent. Special emphasis was laid on intracranial extension as a marker of severity, along with tracking treatment outcomes and survival. Statistical modeling was used to correct for important confounders, including diabetes status, glycemic control, and concurrent use of other immunomodulators. Results The results were striking. Those receiving steroid treatment for more than ten days of duration had a nearly fourfold higher incidence of intracranial mucormycosis compared with short-term-treated patients (38.2% vs. 12.5%, p&lt; 0.001). Each day of steroid use accounted for a 12% increase in associated risk. While mortality rates were equal, patients receiving prolonged treatment had a considerably increased number of surgical procedures (35.3% vs. 16.7%, p=0.02) as well as more complicated hospitalization. Those with diabetes were especially sensitive to such effects of prolonged treatment. Conclusion The study highlights the role of cautious use of corticosteroids in the management of COVID-19. Our work gives strong evidence for the importance of compliance with guideline-based recommendations for corticosteroid duration, especially for high-risk populations. This study empowers healthcare practitioners with unequivocal evidence to provide optimal COVID-19 treatments while avoiding the risk of severe fungal infection. Disclosures All Authors: No reported disclosures

Abstract Introduction FD Ibr+Ven is approved as first-line (1L) treatment (tx) for CLL/SLL in 78 countries across Asia, Europe, the Middle East, and South America, plus Australia, Canada, and New Zealand. Clinical trials with up to 5.5 years (yrs) of follow-up have demonstrated progression-free and overall survival benefits of 1L FD Ibr+Ven in pts with CLL/SLL (Wierda WG, ASH 2024; Jacobs R, EHA 2024). Despite established clinical benefits, there is a lack of RW evidence on the effectiveness and tolerability of FD Ibr+Ven outside of clinical trial settings. Here we present pooled data from REALITY-WW and REALITY-2 to understand the usage, factors for therapy decision, clinical response, and safety of FD Ibr+Ven in routine clinical practice. Methods REALITY-WW and REALITY-2 are prospective observational cohort studies. REALITY-WW is an international study; REALITY-2 is conducted in Germany. Both included previously untreated pts with CLL/SLL from hospitals and medical institutions where Ibr+Ven was routinely used. The decision to start FD Ibr+Ven was made prior to and independent of pt enrollment. Pts aged ≥18 yrs with a confirmed diagnosis of CLL/SLL requiring 1L tx per iwCLL 2018 criteria received 3 cycles of Ibr, followed by 12 cycles of FD Ibr+Ven orally (Ibr, 420 mg/d; Ven, 5-week ramp-up to 400 mg/d). Primary end point was overall response rate (ORR) per iwCLL 2018 criteria. Secondary end points and outcomes of interest included tx-emergent adverse events (TEAEs), tumor lysis syndrome (TLS) risk, and factors associated with physician decision to initiate FD Ibr+Ven in routine clinical practice. Results At data cutoff (REALITY-WW: May 2025; REALITY-2: March 2025), 129 pts from both studies received FD Ibr+Ven (REALITY-WW, 81; REALITY-2, 48). The median (range) time on study was 6.4 (0.1-19.0) months (mo). Median (range) age was 65.0 (37.0-87.0) yrs, with 46.5% of pts aged &lt;65 yrs and 53.5% of pts aged ≥65 yrs; 62.8% were male. Median (range) time from diagnosis to FD Ibr+Ven initiation was 38.1 mo (0.1-238.0) and median (range) duration of tx was 6.0 mo (0.1-15.9) for Ibr and 3.2 mo (0.1-8.4) for Ven. A Cumulative Illness Rating Scale score of &gt;6 was observed in 12.6% of pts, with a higher score in pts aged ≥65 vs &lt;65 yrs (18.0% vs 6.9%). TP53 mutations were seen in 7.4% of pts; 52.8% had an unmutated IGHV status. ORR was assessed in the 44 pts with ≥ 1 post-baseline assessment in REALITY-WW. Of these, 39 showed a response by the end of 6 tx cycles (3 cycles of Ibr + 3 cycles of FD Ibr+Ven) and 5 had stable disease. ORR at 6 mo per iwCLL 2018 criteria (partial response [PR] with lymphocytosis [PR-L] or better) was 88.6% (95% CI, 79.3-98.0), including complete responses in 29.5%, PR in 34.1%, and PR-L in 25.0% pts. Among 129 treated pts, TEAEs were reported in 61.2%; diarrhea was the most common TEAE (14.0%). Serious TEAEs and grade 3/4 TEAEs were reported in 12.4% and 8.5% of pts, respectively. The most common grade 3/4 TEAE was myocardial infarction (1.6%). Dose reduction was observed in 13.2% (Ibr) and 2.3% (Ven) of pts, mainly due to tx-associated TEAE/toxicity/TLS. Rates of TEAEs leading to discontinuation, dose reduction, and interruption of ≥1 study tx were 4.7%, 10.9%, and 20.9%, respectively. At baseline (n=129), 18.6%, 45.0%, and 14.7% of pts had high, intermediate, and low TLS risk, respectively, while 20.2% were not assessed and 1.6% had missing data. After the 3-cycle Ibr lead-in, the distribution shifted to 9.3%, 24.8%, and 24.0%, respectively, with 14.7% not assessed and 27.1% missing. There were no TEAEs of TLS and no hospitalizations due to TLS. Seven pts (6 aged ≥65 yrs and 1 &lt;65 yrs) were hospitalized prophylactically for TLS. Prophylactic hospitalization was observed in 8.5% (11/129) of pts with high or medium TLS risk and impaired renal function for whom the Ven ramp-up was initiated; no pts were hospitalized due to laboratory/clinical TLS during the Ven ramp-up period. Physician questionnaire responses (n=126) indicated the most common factors associated with decision to initiate FD Ibr+Ven were administration route advantage (91.3%), overall health status (87.3%), anticipated superior efficacy of tx (84.1%), and general risk factors such as high tumor burden/genetic risk factors (81.0%). Conclusions Overall findings suggest that FD Ibr+Ven is an effective and safe tx for pts with CLL/SLL in a RW population, including those aged ≥65 yrs. Data with longer follow-up will be presented at the meeting.