Empagliflozin Reduces Risk of Atrial Fibrillation in Patients with Heart Failure with Preserved Ejection Fraction

Presenter: Andrew Nguyen

Heart failure with preserved ejection fraction (HFpEF) is a common cause of atrial fibrillation (AF), and while empagliflozin has been shown to reduce cardiovascular events in this population, its effect on AF risk remains unclear. This retrospective cohort study using the TriNetX global federated health research network evaluated patients with HFpEF treated with empagliflozin versus those receiving no SGLT2 inhibitor.

After matching, 108,661 patients were included in each group with a median follow-up of 363 days. Empagliflozin was associated with a significantly lower risk of atrial fibrillation compared to the control group (9.0% vs 15.2%; RR 0.59, 95% CI 0.57–0.61; p<0.001), corresponding to a 41.1% relative risk reduction. It was also associated with significantly lower risks of all-cause mortality (RR 0.41, 95% CI 0.39–0.41; p<0.001), hospitalization (RR 0.57, 95% CI 0.56–0.58; p<0.001), stroke (RR 0.55, 95% CI 0.52–0.57; p<0.001), and myocardial infarction (RR 0.57, 95% CI 0.55–0.59; p<0.001).

These findings suggest that empagliflozin substantially reduces the risk of atrial fibrillation and adverse cardiovascular outcomes in patients with HFpEF.

Role of Dual Therapies with Sacubitril/Valsartan and SGLT-2 Inhibitors in Reduced Arrhythmic Clinical Events and Hospitalisations in Patients with Implantable Cardioverter Defibrillator

Presenter: Yap-Hang Chan

Sacubitril/valsartan and SGLT2 inhibitors are both known to provide protection in heart failure, however, the impact of their combined use on arrhythmia-related hospitalisations in patients with implantable cardioverter-defibrillators (ICDs) has not been well studied. This territory-wide retrospective cohort study included 3,834 patients with ICD implants (mean age 61.6±14.2 years; 24% female) and evaluated the effect of dual therapy on arrhythmia outcomes.

Over a mean follow-up of 1386±1579 days, arrhythmia-related hospitalisations occurred in 35.3% of patients (n=1352). Kaplan–Meier analysis showed that dual therapy with sacubitril/valsartan and SGLT2 inhibitors was associated with a significantly lower risk of arrhythmia-related hospitalisations (log-rank=23.1, p<0.001). In multivariable Cox regression analysis, dual therapy was independently associated with reduced risk of arrhythmia-related hospitalisations (HR 0.56, 95% CI 0.38–0.81; p=0.002) as well as the co-primary composite endpoint of incident atrial fibrillation, ventricular tachyarrhythmias, arrhythmia-related hospitalisations, and all-cause mortality (HR 0.69, 95% CI 0.55–0.88; p=0.002).

These findings suggest that combined use of sacubitril/valsartan and SGLT2 inhibitors may reduce arrhythmia-related hospitalisations and improve arrhythmia-related outcomes in patients with ICDs.

Outcomes of DOACs in First-Time Sepsis-Associated Paroxysmal Atrial Fibrillation: A Propensity-Matched Retrospective Analysis

Presenter: Preet Doshi

This retrospective cohort study using the TriNetX Global Collaborative Network evaluated patients aged >65 years with hypertension (CHA₂DS₂-VASc ≥2) who developed first-time paroxysmal atrial fibrillation (PAF) within 1 day before or up to 30 days after sepsis. After excluding patients with prior AF or pulmonary embolism and performing propensity-score matching across 43 variables, 2,568 patients were included in each of the direct oral anticoagulants (DOAC) and non-DOAC groups. Average age was 76.3 years, with a predominance of males (52.57%).

No significant differences were observed between groups in the incidence of acute ischemic stroke, hemorrhagic stroke, or major bleeding at 30 days, 1 year, and 2 years. However, DOAC use was associated with significantly lower all-cause mortality at 30 days (HR 0.75, 95% CI 0.65–0.87), 1 year (HR 0.80, 95% CI 0.70–0.92), and 2 years (HR 0.66, 95% CI 0.57–0.77).

These findings suggest that while DOAC use did not impact stroke or major bleeding outcomes, it was associated with reduced all-cause mortality in elderly hypertensive patients with sepsis-associated new-onset PAF, highlighting the need for further prospective evaluation.

Effect of Sodium-Glucose Transporter 2 Inhibitors on Ventricular Arrhythmic Burden in Heart Failure Patients with Cardiac Implantable Electronic Device Monitoring: A Systematic Review and Meta-Analysis

Presenter: Muhammad Abdullah Nizam,

Patients with heart failure (HF) and cardiac implantable devices are at high risk for malignant ventricular arrhythmias. While sodium-glucose co-transporter 2 inhibitors (SGLT2i) are known to improve HF outcomes, their impact on arrhythmic burden in this population is not well established. This meta-analysis, conducted according to PRISMA guidelines, included studies from EMBASE and PubMed up to May 2025 and evaluated outcomes including ventricular arrhythmias, appropriate shocks, VT/NSVT, and any arrhythmia.

A total of 12 studies (33,287 person-years; 40.2% female; mean follow-up 1.2±0.7 years) were included. SGLT2i use was associated with a 37% reduction in any ventricular arrhythmia (IRR 0.63, 95% CI 0.41–0.97; I²=92%) and a 35% reduction in appropriate shocks (IRR 0.65, 95% CI 0.43–0.97; I²=48%). VT/NSVT was reduced by 23% (IRR 0.77, 95% CI 0.37–1.6; I²=93%), and any arrhythmia was also lower (IRR 0.64, 95% CI 0.45–0.91; I²=92%).

These findings suggest that SGLT2 inhibitors have an association with reduced ventricular arrhythmic burden and fewer device therapies in patients with HF and cardiac implantable devices.

Impact of Sodium Glucose Cotransporter-2 Inhibitors on Ventricular Arrhythmia in Patients with Implantable Cardioverter-Defibrillators: A Meta Analysis

Presenter: David Song,

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are known to improve outcomes in heart failure, but their effect on arrhythmias, particularly in high-risk patients with implantable cardioverter-defibrillators (ICDs), remains unclear. This systematic review and meta-analysis of 1,605 participants from PubMed, Scopus, and Cochrane databases up to August 19, 2025 found that SGLT2 inhibitor therapy was associated with a lower risk of ventricular arrhythmias (MD 3.09; 95% CI 1.87–4.31), discrete ventricular tachycardia (MD 3.09; 95% CI 1.87–4.31), and sustained ventricular tachycardia (MD 1.67; 95% CI 0.31–3.03). Secondary analysis showed that patients receiving SGLT2 inhibitors were more likely to remain free from supraventricular tachycardia events (RR 0.67; 95% CI 0.47–0.95) and had a reduction in ICD shocks (RR 2.76; 95% CI 1.28–5.95). No significant difference was observed for non-sustained ventricular tachycardia (MD 29.99; 95% CI 56.88–116.87; p=0.50).

These findings suggest that SGLT2 inhibitors may reduce ventricular arrhythmias and related device therapies in patients with ICDs, although no significant effect was observed for non-sustained ventricular tachycardia.

One-Year Ventricular Arrhythmia and Ablation Burden in Ischemic Versus Non-Ischemic Dilated Cardiomyopathy

Presenter: Isadora Guarino

Ventricular arrhythmias (VA) are a major cause of morbidity and sudden death in cardiomyopathy, but contemporary comparisons between ischemic cardiomyopathy (ICM) and non-ischemic dilated cardiomyopathy (NICM) are limited. This study used the TriNetX U.S. Research Network to identify adults with a first diagnosis of ICM or NICM between 2014 and 2024, with matching performed to compare outcomes. Incident ventricular tachycardia (VT), ventricular fibrillation (VF), and VT catheter ablation within 1 year were evaluated.

After matching, 53,687 patients were included in each group (mean age 66.0±13.7 years in ICM vs 65.4±15.5 years in NICM; 39% female). ICM was associated with a higher 1-year incidence of ventricular arrhythmias, with VT occurring in 2.89% vs 2.03% (RR 1.42, 95% CI 1.32–1.54; p<0.001) and VF in 0.69% vs 0.29% (RR 2.38, 95% CI 1.99–2.85; p<0.001). VT catheter ablation was also more frequent in ICM (0.38% vs 0.18%; RR 2.07, 95% CI 1.65–2.61; p<0.001), although absolute rates remained below 1% in both groups.

These findings indicate that ischemic cardiomyopathy is associated with a higher burden of ventricular arrhythmias and greater use of catheter ablation compared with non-ischemic cardiomyopathy, despite overall low ablation rates.

Catheter Ablation Versus Anti-Arrhythmic Drug Therapy for Atrial Arrhythmias in Hypertrophic Cardiomyopathy: A Real-World Cohort Study

Presenter: Revanth Reddy Bandaru

Atrial arrhythmias are common in hypertrophic cardiomyopathy (HCM) and are associated with adverse outcomes, while rhythm control with anti-arrhythmic drugs (AADs) is often limited. This retrospective cohort study using the TriNetX database (2015–2025) compared outcomes with catheter ablation versus AAD therapy in HCM patients, with a follow-up of three years. Patients were divided into ablation and AAD groups, and propensity score matching was performed.

After matching, 10,243 patients were included in each group, with similar mean age (67.8±13.9 vs 68.0±14.2 years; p=0.594). Catheter ablation was associated with significantly lower all-cause mortality (HR 0.566, 95% CI 0.478–0.671; p<0.0001). There was no significant difference in atrial arrhythmia recurrence (HR 0.970, 95% CI 0.940–1.001; p=0.057). Ablation was also associated with lower risks of all-cause hospitalization (HR 0.530, 95% CI 0.506–0.555), heart failure hospitalization (HR 0.724, 95% CI 0.695–0.753), and ischemic stroke (HR 0.801, 95% CI 0.709–0.904), all p<0.0001.

In patients with hypertrophic cardiomyopathy and underlying atrial arrhythmias Catheter ablation was associated with a reduction in all-cause mortality, all-cause hospitalization, hospitalization related to heart failure, and ischemic stroke. There was no statistically significant difference in the recurrence of atrial arrhythmias post ablation.

ACC 2026, March 28 – 30, New Orleans, LA