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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.

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.

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: Glucagon-like peptide-1 (GLP-1) agonists have been shown to improve outcomes across various cardiovascular diseases. However, data regarding the effects of GLP-1 agonists in obstructive hypertrophic cardiomyopathy (HCM) is limited. Objective: This study aimed to evaluate the 5-year outcomes of GLP-1 agonists in patients with HCM. Methods: Using TriNetX Analytics Network, we identified patients aged ≥18 years with a diagnosis of obstructive hypertrophic cardiomyopathy between 1/1/2014 and 1/1/2019. Patients were divided into two groups: those treated with GLP-1 agonists for ≥ 1 year and those who were not. Propensity score matching (PSM) was performed using demographics, cardiac medications, and comorbidities. The study outcomes were 5-year all-cause mortality and cardiac adverse events. Results: A total of 52,978 patients with HCM were identified, including 2,654 (5.0%) patients treated with GLP-1 agonists. After PSM, 2,588 patients in each group were analyzed. Patients on GLP-1 agonists were associated with lower odds of all-cause mortality (5.0% vs. 15.6%, p<0.01), all-cause hospitalization (46.3% vs. 67.8%, p<0.01), acute decompensated heart failure ((9.4% vs. 21.4%, p<0.01), cardiac arrest (3.6% vs. 5.4%, p<0.01), cerebrovascular accidents (9.5% vs. 14.1%, p<0.01), and cardiogenic shock (1.4% vs. 3.6%, p<0.01). Additionally, reduced rates of new ICD implantation (3.5% vs. 7.9%, p<0.01) and septal reduction therapy (1.7% vs. 3.5%, p<0.01) were observed in the GLP-1 agonists group. Conclusion: The use of GLP-1 agonists in HCM was associated with improved cardiovascular outcomes. Future clinical trials are needed to validate these potential benefits.

Background: Patients with cardiac implantable electronic devices (CIEDs) undergoing radiation therapy face potential risks of device malfunction. Proton beam therapy (PBT), with its reduced neutron scatter, has emerged as a potentially safer alternative, yet real-world safety data remain scarce. Methods: We conducted a retrospective cohort study of 100 patients with CIEDs (76 pacemakers, 24 ICDs) who underwent PBT from 2016 to 2023 at a quaternary center. Baseline and serial device interrogations were performed before, during, and after treatment to assess lead impedance, capture thresholds, battery function, and arrhythmic events. Patients were stratified by pacemaker dependence and monitored accordingly. Primary outcomes included device malfunction and new-onset arrhythmias during treatment. Secondary outcomes included device parameter changes, one-year arrhythmia incidence, and cardiac-related hospitalizations. Results: No treatment-related deaths or major device failures occurred. Device malfunction was rare (2 pacemaker patients, 2.6%), with no malfunctions in ICD recipients. Transient, non-clinically significant changes in lead impedance and capture thresholds were observed. Arrhythmias during treatment occurred in 26% of pacemaker and 25% of ICD patients, but only 4% developed new arrhythmias. At one year, device-related complications and cardiac outcomes remained comparable across groups. Independent predictors of arrhythmias during treatment included a higher radiation dose per fraction (OR 1.45; p=0.001), a longer treatment duration (OR 1.12; p=0.04), and a higher number of fractions (OR 1.20; p=0.01). Conclusion: Proton beam therapy appears safe in patients with CIEDs, with a low incidence of clinically significant device malfunctions or arrhythmias. These findings support the integration of PBT into routine practice for this population and underscore the importance of structured monitoring protocols and prospective guideline refinement.

Background: Leadless pacemaker has emerged as a promising alternative to traditional transvenous pacemaker (PM) among elderly patients who are at high risk of complications. Objective: This study aims to assess and compare 5-year clinical outcomes of leadless PM versus transvenous single-chamber PM in elderly patients using a multi-national dataset. Methods: Using the TriNetX Analytics Research Network, we included patients aged ≥65 years who underwent leadless versus transvenous single-chamber PM implantation between 1/1/2014 and 1/1/2020. Propensity score matching (PSM) was performed by using patient’s demographic, LVEF, cardiac comorbidities, and medications. The study outcomes included all-cause mortality and adverse cardiovascular events over a 5-year follow-up period. Results: After PSM, 7,501 patients in each group were analyzed. Leadless PM was associated with a significantly lower odds of 5-year all-cause mortality (odds ratio [OR]: 0.534; 95% confidence interval [CI]: 0.497-0.575), heart failure exacerbation (OR: 0.779, 95% CI: 0.721-0.841), major bleeding (OR: 0.666, 95% CI: 0.604-0.734), cardiac arrest (OR: 0.747, 95% CI: 0.646-0.864) and stroke (OR: 0.825, 95% CI: 0.750-0.908) compared to transvenous single-chamber PM. No significant difference was observed between the two groups in all-cause hospitalization (OR: 1.006, 95%CI: 0.938-1.079), cardiac thrombus (OR: 1.077, 95%CI: 0.791-1.465) or venous thromboembolism (OR: 1.028, 95%CI: 0.916-1.153). Conclusion: Leadless PM was associated with significantly improved mortality and cardiovascular outcomes compared to transvenous single-chamber PM in elderly patients. These findings support the strong consideration of leadless pacing as a strategy to reduce mortality and improve clinical outcomes in this high-risk population.

ABSTRACT Background Ventricular tachycardia (VT) is a major contributor to sudden cardiac death among patients with ischemic heart disease (IHD). While catheter ablation reduces the arrhythmic burden, the impact on long‐term outcomes remains uncertain. We assess the efficacy of catheter ablation in patients with IHD. Methods We performed a meta‐analysis by systematically searching electronic databases from inception to April 2025. Pairwise, reconstructed time‐to‐event data meta‐analyses and Trial Sequential analyses were conducted. Results A total of seven studies (1192 participants) were included. Among patients with IHD with ICD, 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). VT ablation showed no significant impact on mortality or VT/VF recurrence compared to either ICD alone or ICD with AADs. Reconstructed Kaplan–Meier analysis for all‐cause mortality showed no significant difference between VT ablation and AAD + ICD. Trial Sequential Analysis provided conclusive evidence for VT/VF recurrence, while further data is required for other outcomes. Conclusion Among patients with IHD with ICD, VT ablation reduces ICD shocks, VT storm, and cardiovascular hospitalizations compared to ICD‐only therapy, but offers no significant advantage over ICD combined with AADs. VT ablation does not impact overall 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.

11pt, fleqn, a4paper, ]LegrandOrangeBook 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. Condensed Abstract Delayed atrial fibrillation (AF) ablation was associated with higher (AF) recurrence in both HFrEF and HFpEF. In HFrEF, delayed ablation led to increased use of re-do ablation, cardioversion and antiarrhythmic drugs (AADs). In HFpEF, only AAD use was significantly higher with delayed ablation. Stroke and mortality rates were similar between early and delayed ablation groups.

ABSTRACT Background Sodium‐glucose cotransporter 2 inhibitors (SGLT2‐Is) are primarily used to manage type 2 diabetes mellitus (T2DM) and heart failure (HF), but their impact on reducing stroke risk in patients with atrial fibrillation (AF) remains underexplored. We aimed to investigate the impact of SGLT2‐Is for stroke risk mitigation in patients with AF. Methods Using the TriNetX database, we performed a retrospective cohort study on patients ≥ 18 years with AF and on anticoagulation. These patients were then classified into two cohorts based on their use of SGLT2‐Is. To balance the baseline demographics, comorbidities, and medication use, propensity score matching (PSM) was used. The primary outcome was ischemic and hemorrhagic strokes, and the secondary outcomes were all‐cause mortality, all‐cause hospitalizations, need for AF cardioversion or antiarrhythmic drug initiation, and cardiac arrest. Adjusted odds ratio (aORs) and hazard ratios (HRs) were estimated for both the primary and secondary outcomes. Results A total of 152,778 patients with 76,389 patients were included in each cohort (SGLT2‐Is users, and non‐users) after PSM. The mean age of both SGLT2‐Is users and non‐users was 72.8 years. For the SGLT2‐Is users, the mean follow‐up period was 317 days, whereas the mean follow‐up period for the non‐users was 306 days. For the primary outcome, we found that SGLT2‐Is users had a lower risk of ischemic stroke (aOR: 0.889; 95% CI: 0.857–0.923) and hemorrhagic stroke (aOR: 0.682; 95% CI: 0.620–0.749) compared to non‐users. Regarding the secondary outcomes, SGLT2‐Is users also had lower risk for all‐cause mortality (aOR: 0.615; 95% CI: 0.595–0.636), all‐cause hospitalizations (aOR: 0.599; 95% CI: 0.587–0.611), need of AF cardioversion (aOR: 0.846; 95% CI: 0.813–0.881), antiarrhythmic drug initiation (aOR: 0.790; 95% CI: 0.766–0.815), and cardiac arrest (aOR: 0.643; 95% CI: 0.601–0.688). Conclusions SGLT2‐I use in patients with AF is associated with lower risks of stroke and other cardiovascular and non‐cardiovascular outcomes. Future prospective research is needed to validate these findings.