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Importance Primary brain and central nervous system cancer (collectively referred to as CNS cancer) comprises 2% of all human cancers and poses significant health and economic challenges in the United States. Objective To analyze CNS cancer burden in the US, stratified by time, location (state and division), sex, age group, and Sociodemographic Index (SDI). Design, Setting, and Participants This cross-sectional study involved a repeated analysis of Global Burden of Disease Study (GBD) 2021 data in 2024. Using data from 183 sources, CNS cancer metrics in the US were estimated across states and years. US CNS cancer metrics across all sexes and age groups were included in the GBD. Exposure CNS cancer diagnosis. Main Outcomes and Measures Overall and age-standardized estimates of the incidence, prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost, and years lived with disability per 100 000 population, including 95% uncertainty intervals (UIs), and time trends. Results In 2021, for all age groups and sexes across the US, there were 31 780 incident cases (95% UI, 29971.1 to 32843.9). Age-standardized incidence, DALYs, and mortality rates per 100 000 population were 6.91 (95% UI, 6.58 to 7.12), 134.38 (95% UI, 129.83 to 137.95), and 4.1 (95% UI, 3.87 to 4.22), respectively. Despite no significant change observed in the overall incidence between 1990 and 2021, DALY and mortality rates decreased by 15.77% (95% UI, −17.75% to −13.68%) and 8.41% (95% UI, −11.09% to −6.22%), respectively. Substantial geographic variability was noted. Mississippi, Alabama, Kentucky, and Kansas (West North Central and East South Central divisions) and West Virginia faced persistently high burdens over the past 30 years. Sex differences were evident; disease burden was consistently higher in males compared with females. Age-specific estimates showed a bimodal distribution: the youngest group (<5 years) showed a significant decrease in incidence rate (−34.42% to −11.56%), whereas older age groups (>70 years) experienced increasing trends. DALYs and mortality rates were negatively correlated with SDI (ρ = −0.6860 and ρ = −0.6391; P < .001). Conclusions and Relevance These findings provide valuable insights into the CNS cancer burden across the US by age, sex, location, and SDI, enabling better public health status assessments, health care policy restructuring, and resource redistribution for improved care.

Introduction: In patients with type 2 diabetes (T2D) at high cardiovascular risk, glucagon-like peptide-1 receptor agonists (GLP1-RAs) have been shown to reduce major adverse cardiovascular events. However, patients with valvular heart disease, including those undergoing transcatheter aortic-valve implantation (TAVI), have been largely excluded from randomized trials. Hypothesis: We investigated whether GLP1-RA use is associated with improved one-year cardiovascular outcomes in patients with T2D undergoing TAVI. Methods: We conducted a retrospective cohort study using the TriNetX network. Adults (≥18 years) with T2D who underwent TAVI between 2015 and 2023 were included and stratified based on GLP1-RA initiation within 14 days post-TAVI. Baseline characteristics, comorbidities, medications, and laboratory data were balanced using 1:1 propensity score matching (PSM). The primary outcome was a composite of all-cause mortality or hospitalization at 1 year. Secondary outcomes included acute heart failure (HF) exacerbation, acute myocardial infarction (AMI), cardiac arrest, and ischemic stroke. Outcomes were assessed from 1 month to 1 year after TAVI. Survival probabilities were estimated using Kaplan-Meier analysis, and hazard ratios (HRs) were calculated with Cox proportional hazards models. Results: Among 20,454 patients with T2D undergoing TAVI from 2015-2023, 937 received GLP1-RAs. After PSM, 930 patients were included in each cohort, with a mean age of 73 years and 37% female. The mean follow-up duration was 342 days for GLP1-RA users and 325 days for non-users. GLP1-RA cohort exhibited a higher 1-year survival probability (93.8%) compared to non-users (89.5%) (HR 0.573 [95% CI, 0.410-0.801]; p=0.001). GLP1-RA use was also associated lower rates of all-cause hospitalization (HR 0.762 [95% CI, 0.652-0.891]; p=0.001), acute HF exacerbation (HR 0.687 [95% CI, 0.566-0.834]; p<0.001), and cardiac arrest (HR 0.452 [95% CI, 0.213-0.960]; p=0.034). No differences were observed in AMI (HR 1.033 [95% CI, 0.750-1.423]; p=0.844), or ischemic stroke (HR 0.875 [95% CI, 0.659-1.162]; p=0.356). Conclusions: In patients with T2D undergoing TAVI, GLP1-RA use is associated with significant survival benefits and improved cardiovascular outcomes, including reductions in acute HF exacerbation, all-cause hospitalization, and cardiac arrest. These findings highlight the need for prospective clinical trials to confirm these results.

Introduction: Preeclampsia is a multisystem progressive disease of pregnancy, characterized by a new onset of hypertension (≥ 140/90 mm Hg) with proteinuria after the 20th week of gestation. There is a conflict between United States guidelines that recommend Low-dose aspirin (LDA) and United Kingdom guidelines that recommend High-dose aspirin (HDA) for the prevention of preeclampsia in high-risk pregnant women. After the latest study that recommends HDA and the absence of pairwise meta-analyses comparing two doses, we aimed to conduct a comprehensive pairwise meta-analysis to assess whether HDA is better than LDA in the prevention of preeclampsia. Methods: We conducted a systematic search on PubMed, Scopus, Cochrane Central, and Web of Science (WOS) from inception until June 2025. All randomized controlled trials (RCTs) comparing LDA and HDA in high-risk pregnant women were included. Our primary outcome was the incidence of preeclampsia (PE), while secondary outcomes were Placental abruption, Pre-term delivery, and Intrauterine Growth Restriction (IUGR). Using random-effects models, we calculated risk ratios (RR) with 95% confidence intervals (CIs). Results: A total of 8 RCTs with 1,290 patients from the United States, Canada, England, and different Asian countries were included, among whom 642 (49.8%) patients were randomized to HDA. All studies compared HDA (≥ 150 mg) and LDA (75 mg to 81 mg). Patients with LDA had a higher risk of Preeclampsia (RR: 1.71, 95% CI: 1.19 to 2.44, p<0.001) compared to HDA. There was no significant difference between the LDA and HDA regarding Placental abruption, Pre-term delivery, and IUGR. With a pooled RR with a 95% CI (1.8, [0.91 to 3.54], P = 0.09), (1.25, [0.79 to 1.97], P = 0.34), (1.5, [0.93 to 2.42], P = 0.1), respectively. Conclusion: Among high-risk pregnant women, LDA was associated with a 71% higher incidence of preeclampsia than HDA. These results support the use of HDA as a preventive medication for preeclampsia in high-risk pregnant women.

Background: Cardiac amyloidosis (CA) patients with reduced left ventricular ejection fraction (EF) are at increased risk for mortality. The benefit of cardiac resynchronization therapy (CRT) in terms of mortality reduction has not been established in this population. Aim: To evaluate the survival benefit of CRT, either CRT-D or CRT-P, in a large cohort of patients with cardiac amyloidosis and reduced EF. Methods: We retrospectively analyzed patients with confirmed CA and reduced EF (<40%) between 2009 and 2023 across Mayo Clinic sites. Patients were stratified into three groups: no device, CRT with pacemaker function (CRT-P), and CRT with defibrillator function (CRT-D). CRT devices were indicated for low ejection fraction less than 40% and patients who had chronic heart failure with a wide QRS. Kaplan-Meier survival estimates were generated, and log-rank tests were used for comparison. A secondary analysis was conducted combining CRT-P and CRT-D versus no device (EF <40%), and a tertiary analysis compared CRT-P versus CRT-D. Results: Among 184 patients [36 AL (20%), 148 ATTR (80%)], 38 (19%) had no cardiac device and EF <40%, 20 (11%) received CRT-P, and 116 (63%) received CRT-D. The median follow-up was 3.4 years (1.7, 5.0). The probability of survival was significantly higher in the CRT group compared to the no device-EF<40 group (Log Rank p=0.013; figure B). Among patients receiving CRT, there was no significant difference in all-cause mortality between those receiving CRT-P and those receiving CRT-D (Log Rank p=0.5; figure C). Conclusion: In patients with cardiac amyloidosis and reduced EF, CRT is associated with significantly improved survival compared to no device. No mortality difference was observed between CRT-P and CRT-D. Prospective studies are warranted.

Background: We conducted an updated meta-analysis of the routine use of cerebral embolic protection (CEP) devices in Transcathter Aortic Valve Replacement (TAVR). This analysis follows the recent BHF PROTECTED TAVI trial which is the largest randomized controlled trial to date. Methods: Electronic databases were searched through April 2025 for eligible randomized controlled trials (RCTs). The primary outcome was overall incidence of stroke, disabling stroke and non-disabling stroke all reported at 2-5 days and 30 days were primary outcomes for our analyses. Results: 8 RCTs with a total of 11,692 patients were included. No statistically significant difference was found between CEP group and the control group in overall stroke incidence at 2-5 days and 30 days as the following (RR=0.95, 95%CI: [0.75,1.19], p=0.64) and (RR=0.93, 95%CI: [0.57,1.53], p=0.79). Similarly, the pooled analysis revealed no statistically significant difference between the two groups in terms of disabling stroke at 2-5 days (RR=0.70, 95%CI: [0.41,1.18], p=0.18), and at 30 days (RR=1.18, 95%CI: [0.36,3.87], p=0.78). CEP group and control group didn’t show statistically significant difference in non- disabling stroke at 2-5 days and 30 days as the results showed: (RR=1.17, 95%CI: [0.84,1.63], p=0.36) and (RR=0.86, 95%CI: [0.49,1.51], P=0.61) respectively. Conclusion: Our meta-analysis found no statistically significant evidence that cerebral embolic protection (CEP) devices reduce the incidence of stroke—disabling or non-disabling in the 2-5 days following TAVR or after 30 days. Major bleeding, major vascular complication and AKI showed no statistically significant results indicating a neutral safety profile.

Background: Ventricular tachycardia (VT) is a major contributor to death among ischemic heart disease (IHD) patients. In this systematic review and meta-analysis, we evaluate the efficacy of catheter ablation in patients with ischemic cardiomyopathy. Methods: We conducted a meta-analysis by searching the electronic database up to April 2025. Seven studies, including 1192 patients, were identified. A random-effect model was used to estimate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Trial sequential analysis was conducted to assess sample size adequacy. Results: Among Ischemic heart disease patients with ICDs, VT ablation was associated with a significant reduction in ICD shocks (RR = 0.50, 95% CI [0.34–0.74]), a trend toward reduced VT storm (RR = 0.64, 95% CI [0.40–1.04], p = 0.07), and lower rates of cardiovascular hospitalization (RR = 0.73, 95% CI [0.53–1.01], p = 0.06) compared to ICD alone. However, no significant differences were observed when compared to patients receiving ICD plus antiarrhythmic drugs (AADs). Additionally, VT ablation showed no significant impact on mortality or VT/VF recurrence compared to either ICD alone or ICD with AADs. Trial Sequential Analysis provided conclusive evidence for VT/VF recurrence outcomes, while further data are required for other outcomes. Conclusion: Among ischemic heart disease patients with ICD, VT ablation reduces ICD shocks, VT storm, and cardiovascular hospitalizations compared to ICD-only, but offers no significant advantage over ICD combined with antiarrhythmic drugs. VT ablation does not impact mortality or the recurrence of VT/VF. Trial Sequential Analysis confirmed conclusive evidence for VT/VF recurrence, while additional data is needed for other outcomes.

Introduction: Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder caused by pathogenic variants in the COL3A1 gene, often leading to arterial, intestinal, and uterine rupture. While vascular complications are well-documented, the prevalence and characteristics of cardiac arrhythmias in this population remain underexplored. Aim: To assess the prevalence of arrhythmias and conduction abnormalities in patients with confirmed vEDS. Methods: A retrospective cohort study was conducted across all three Mayo Clinic sites. Patients with vEDS were initially identified using an electronic data extraction tool. Each case was subsequently confirmed through detailed chart review. Additional reviews were performed to assess the prevalence of heart blocks and both atrial and ventricular arrhythmias. Statistical analysis was conducted using SPSS to determine the prevalence of each arrhythmia type. Results: A total of 132 patients with confirmed vEDS were included in the study. The mean age was 45.7 ± 13 years. The cohort was predominantly white (93.7%), with 47 males (35.6%) and 85 females (64.4%). Atrial arrhythmias were identified in 15 patients (11.4%), including atrial fibrillation in 14 (10.6%) and atrial flutter in 8 (6.1%). Supraventricular tachycardia (SVT) was observed in 15 patients (11.4%). Conduction abnormalities included first-degree AV block in 8 (6.1%), second-degree AV block in 3 (2.3%), left bundle branch block in 8 (6.1%), and right bundle branch block in 15 (11.4%) patients. Ventricular arrhythmias were observed in 6 patients (4.5%) with sustained ventricular tachycardia, 6 (4.5%) with non-sustained ventricular tachycardia, and 7 (5.3%) with ventricular fibrillation. Postural orthostatic tachycardia syndrome (POTS) or orthostatic hypotension was documented in 18 patients (13.6%). Conclusion: Although arrhythmias are not the most common manifestation of vEDS, their prevalence in this cohort is notably higher than in the general population and tends to occur at a younger age. These findings support the consideration of routine screening for atrial and ventricular arrhythmias in patients with vEDS as part of their long-term cardiovascular management.

Background: Obicetrapib is a next-generation cholesteryl ester transfer protein (CETP) inhibitor. It has emerged as a promising agent for improving lipid parameters and potentially reducing risk of atherosclerotic cardiovascular disease (ASCVD). Methods: A systematic search of databases, including PubMed, Scopus, Embase, Web of Science, Clinical Trials, and Cochrane Library, was conducted to identify relevant randomized controlled trials (RCTs). Outcomes included the assessment of LDL-C reduction, changes in ApoB, non-HDL-C, HDL-C, triglycerides, Lp(a), MACE, as well as the safety and tolerability profile of Obicetrapib in patients with dyslipidemia or ASCVD. Standardized mean differences (SMD) with 95% confidence intervals (CI) were pooled using random-effects. Results: Seven RCTs encompassing 3483 patients were included. Obicetrapib significantly improved lipid parameters. It reduced LDL-C (MSD: –35.43; 95% CI: –40.14 to –30.17; I2 = 93.26%), non-HDL-C (MSD: –36.42; 95% CI: –42.77 to –30.07; I2 = 99.06%), ApoB (MSD: –23.38; 95% CI: –30.68 to –16.08; I2 = 88.56%), and Lp(a) (MSD: –23.95; 95% CI: –35.26 to –12.63; I2 = 77.14%). Obicetrapib also led to a reduction in TG levels (MSD: –0.12; 95% CI: –0.19 to –0.05; I2 = 0.00%). In contrast, favorable increases were observed in HDL-C (MSD: 77.35; 95% CI: 64.56 to 90.13; I2 = 95.82%) and ApoA1 (MSD: 63.93; 95% CI: 53.65 to 74.21; I2 = 81.89%). Despite high heterogeneity, these results support Obicetrapib’s effectiveness in improving atherogenic lipid markers. Obicetrapib demonstrated a safety profile comparable to placebo. The overall risk of any adverse event was slightly reduced in the Obicetrapib group compared to placebo, but the 95% CI included 1, (RR: 0.96; 95% CI: 0.76 to 1.21; I2 = 66.3%; p = 0.01). Specific adverse events such as diarrhea (OR: 1.56; 95% CI: 0.34 to 7.11; I2 = 5.16%; p = 0.57), headache (OR: 1.17; 95% CI: 0.74 to 1.84; I2 = 0.00%; p = 0.50), and back pain (RR: 0.36; 95% CI: 0.11 to 1.16; I2 = 18.3%; p = 0.26) were also not significantly different between groups. Overall, Obicetrapib appears well-tolerated without increased adverse events. Conclusion: Obicetrapib significantly improved lipid parameters, notably reducing LDL-C, non-HDL-C, ApoB, Lp(a), and triglycerides, while increasing HDL-C and ApoA1, with a favorable and comparable safety profile.

Background: Early catheter ablation for atrial fibrillation (AF) improves outcomes, but the optimal timing, especially in heart failure (HF) subtypes, remains unclear. Objective: To evaluate the impact of ablation timing on outcomes in patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Methods: We used the TriNetX database (2010–2024) to identify HF patients with AF who underwent ablation. Patients were classified as early ablation (≤1 year of first AF diagnosis) or delayed ablation (1–3 years), with propensity score matching (PSM) applied to balance the baseline characteristics. The primary outcome was AF recurrence, defined by repeat ablation, direct current cardioversion (DCCV), or antiarrhythmic drug (AAD) use after a 3-month blanking period. Secondary outcomes included stroke, hospitalization, and mortality over 5 years. Results: After PSM, delayed ablation was associated with higher AF recurrence in both HFrEF (HR 1.25, p < 0.001) and HFpEF (HR 1.27, p = 0.01), as seen in multivariate analysis. In HFrEF, delayed ablation was associated with higher incidence of re-do ablation, AAD use, and DCCV, while in HFpEF, higher recurrence with delayed ablation was associated with increased AAD use. Both cohorts had similar stroke and mortality rates between early and delayed ablation. Conclusions: Delayed ablation in HFrEF and HFpEF was linked to higher AF recurrence, driven by increased redo ablations, DCCV, AAD use in HFrEF, and higher AAD use in HFpEF. Stroke and mortality rates were similar, suggesting earlier ablation may enhance rhythm control without affecting long-term survival.

Background: Noncompaction cardiomyopathy (NCCM) is a distinct myocardial disorder associated with a high risk of ventricular arrhythmias and sudden cardiac death. Although implantable cardioverter-defibrillators (ICDs) are frequently used in this population, data on predictors of shock therapy remain limited. Aim: Evaluation of a large cohort of patients with NCCM and ICDs to identify incidence and clinical factors associated with ICD shock Methods: This retrospective cohort study included patients with confirmed NCCM between 2002 and 2023 at all Mayo Clinic sites. Baseline clinical data, genetic findings, cardiac imaging parameters, and device-related outcomes were collected through detailed chart review. Multivariable Logistic regression was used to identify independent predictors. Results: Among 145 patients with NCCM who received ICDs, the median age was 45 years (IQR: 34–56), with 75 (52%) female and 120 (83%) White. The median left ventricular ejection fraction (LVEF) was 35% (IQR: 22.5–47.5%), and the median follow-up from ICD implantation was 6.4 years (IQR: 2.9–11.0). Most ICDs (124, 85.5%) were implanted for primary prevention. Appropriate shocks were observed in 37 patients (25.5%), with 14 (9.8%) experiencing three or more appropriate shocks. Inappropriate shocks occurred in 15 patients (10.3%). Device-related complications were reported in 22 patients (15.2%), including infections in 4 (2.8%), lead fractures or dislodgement in 17 (11.9%), and pneumothorax in 1 (0.7%). Clinical predictors of shocks are illustrated in the figure. Conclusion: ICD therapy for NCCM patients prevented SCD in 25.5% of patients. Syncope, RBBB, troponin T >30 ng/L, and imaging-based apical trabeculations were independently associated with ICD shocks in patients with NCCM. These factors may aid in risk stratification and clinical decision-making.