Heart failure subtypes and thromboembolic risk in patients with atrial fibrillation: The PREFER in AF - HF substudy

To assess thromboembolic and bleeding risks in patients with heart failure (HF) and atrial fibrillation (AF) according to HF type.

We analyzed 6170 AF patients from the Prevention of thromboembolic events - European Registry in Atrial Fibrillation (PREFER in AF), and categorized patients into: HF with reduced left-ventricular ejection fraction (HFrEF; LVEF < 40%); mid-range EF (HFmrEF; LVEF: 40-49%); lower preserved EF (HFLpEF; LVEF: 50-60%), higher preserved EF (HFHpEF; LVEF > 60%), and no HF. Outcomes were ischemic stroke, major adverse cardiovascular and cerebral events (MACCE) and major bleeding occurring within 1-year.

The annual incidence of stroke was linearly and inversely related to LVEF, increasing by 0.054% per each 1% of LVEF decrease (95% CI: 0.013%-0.096%; p = 0.031). Patients with HFHpEF had the highest CHA₂DS₂-VASc score, but significantly lower stroke incidence than other HF groups (0.65%, compared to HFLpEF 1.30%; HFmrEF 1.71%; HFrEF 1.75%; trend p = 0.014). The incidence of MACCE was also lower in HFHpEF (2.0%) compared to other HF groups (range: 3.8-4.4%; p = 0.001). Age, HF type, and NYHA class were independent predictors of thromboembolic events. Conversely, major bleeding did not significantly differ between groups (p = 0.168).

Our study in predominantly anticoagulated patients with AF shows that, reduction in LVEF is associated with higher thromboembolic, but not higher bleeding risk. HFHpEF is a distinct and puzzling group, featuring the highest CHA₂DS₂-VASc score but the lowest residual risk of thromboembolic events, which warrants further investigation.