“Real-world prognostic performance of different severe and advanced heart failure definitions: Data from the Swedish Heart Failure Registry”

BACKGROUND: A valid definition of severe heart failure (HF) is essential for earlier identification, timely referral for advanced therapies, and to optimize clinical trial design. OBJECTIVES: To assess the prevalence, prognostic performance, and 1-year outcomes associated with different definitions of severe and advanced HF (AdvHF) in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: We included 15,153 patients with EF <40%, HF duration >6 months, and no prior left ventricular assist device or heart transplant, from the Swedish Heart Failure Registry. Several definitions of severe/AdvHF were evaluated: a simplified Heart Failure Association (HFA) definition (NYHA III-IV, EF <30%, ≥2 HF hospitalizations in 12 months), the GALACTIC-Severe-definition (NYHA III-IV, EF <30%, ≥1 hospitalization in 6 months), and variations adding/removing criteria such as NT-proBNP levels and diuretic dose to the HFA-AdvHF definition. Predictive performance and 1-year outcomes were analyzed. RESULTS: The HFA-definition identified 6.4% of patients, with a 1-year cardiovascular death/HF hospitalization risk of 70% and all-cause mortality of 45% (AUC = 0.72). The GALACTIC-Severe definition identified 12.6% of patients with slightly lower but still substantial event rates (59% and 38%, respectively; AUC = 0.73). Definitions incorporating NT-proBNP ≥2000 pg/ml had the highest prognostic accuracy (AUC = 0.75). CONCLUSIONS: The HFA-AdvHF definition selected a smaller, high-risk group, while the GALACTIC-Severe criteria identified a broader population, with a lower, but still high risk. NT-proBNP, HF hospitalization history, and diuretic dose might represent valuable enrichment tools for future trials.