Association of anti-catecholaminergic antiarrhythmic drugs with survival in sepsis-associated new-onset atrial fibrillation

Abstract

Abstract Sepsis-induced new-onset atrial fibrillation (NOAF) is a potentially life-threatening arrhythmogenic complication, partially driven by catecholamine-mediated atrial remodeling. While β-adrenergic receptor blockers may mitigate this pathophysiology through sympatholytic and rate-controlling mechanisms, their association with patient survival remains incompletely characterized due to heterogeneous evidence. To elucidate the association between the administration of anti-catecholaminergic antiarrhythmic drugs and all-cause mortality in critically ill patients with sepsis-induced NOAF.This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care-IV database. We included adult patients admitted to a tertiary academic medical center between 2008 and 2019 who fulfilled the Sepsis-3 criteria and developed NOAF during their ICU stays.Based on the initial antiarrhythmic drug administration within 24 h following time-zero, patients were categorized into either β-blocker group or alternative antiarrhythmic drug group. The matched cohort comprised 560 patients (mean age 74.1 [SD 11.5] years; 64.6% male), among whom 280 were assigned to the β-blocker group and 280 to the alternative antiarrhythmic drug group. The β-blocker group demonstrated significantly lower 28-day mortality (36.1 vs. 51.1%; adjusted HR, 0.53; 95% CI, 0.41–0.67; P < .001) and 1-year mortality (50.7 vs. 63.6%; adjusted HR, 0.68; 95% CI, 0.55–0.85; P = .001). ICU mortality was also reduced in the β-blocker group (22.1 vs. 42.5%; P < .001). Furthermore, this group had more vasopressor-free days (median [IQR], 24.0 [18.0–26.0] vs. 16.0 [0.0–23.0]) and ventilator-free days (24.0 [18.0–26.0] vs. 17.0 [0.0–24.0]) (both P < .001). Safety outcomes included less bradycardia (12.5 vs. 20.0%; P = .016) but more hypotension (26.4 vs. 18.6%; P = .039). Subgroup and mediation analyses suggested greater benefit in high-risk patients, partially mediated (15.92%) by reduced vasopressor requirements. In critically ill patients with sepsis-induced NOAF, early β-blocker therapy was associated with markedly lower 28-day and 1-year mortality, along with decreased organ-support burden, warranting prospective trials are warranted to confirm these survival benefits.