Ischemic Heart Disease Modifies the Association of Atrial Fibrillation With Mortality in Heart Failure With Reduced Ejection Fraction

Background The CASTLE - AF (Catheter Ablation versus Standard Conventional Therapy in Patients With Left Ventricular Dysfunction and Atrial Fibrillation) trial recently reported that catheter ablation of atrial fibrillation ( AF ) improves survival in heart failure (HF) with reduced ejection fraction ( HF r EF ). However, established AF was not associated with mortality in trials of contemporary HF r EF pharmacotherapies. We investigated whether HF r EF pathogenesis may influence the conclusions of studies evaluating the prognostic impact of AF . Methods and Results Using a prospective cohort study of 791 patients with HFr EF , with AF determined using 24-hour ambulatory ECG monitoring, univariable and multivariable Cox regression analyses were used to define the association between AF and mode-specific mortality (mean follow-up of 5.4 years). One-year HF-related hospitalization was assessed with binary logistic regression analysis. One-year cardiac remodeling was assessed in a subgroup (n=378) using echocardiography. AF was present in 28.2% of patients, with 9.4% of these being paroxysmal. While AF was associated with increased risk of all-cause mortality (hazard ratio, 1.27; 95% confidence interval 1.03-1.57), with diverging survival curves after 1 year of follow-up, this association was lost in age-sex-adjusted analyses. However, AF was associated with increased risk of age-sex-adjusted all-cause mortality in people with ischemic pathogenesis, with a statistically significant interaction between pathogenesis and AF. This was predominantly attributed to progressive HF deaths. After 1 year, HF hospitalization and cardiac remodeling were not associated with AF , even in people with ischemic pathogenesis. Conclusions AF is associated with increased risk of death in HF r EF of ischemic pathogenesis, predominantly due to progressive HF deaths during long-term follow-up. HF r EF pathogenesis should be considered in trial design and interpretation.