Definitions of Stage D heart failure and outcomes among outpatients with heart failure and reduced ejection fraction

Background: An operational consensus definition of Stage D heart failure (HF) is currently lacking. Methods: We evaluated 512 outpatients (median age, 63 years; 35.0% women; 45.5% white and 45.9% black; median ejection fraction was 25%; 67.4% had coronary artery disease) with HF and reduced (≤40%) ejection fraction. We applied 3 hypothetical definitions for Stage D: (1) designation as “Stage D” or “advanced” HF by treating physician; (2) INTERMACS profiles, defining Stage D as profiles 2–6; and (3) European Society of Cardiology Heart Failure Association (ESC-HFA) criteria. Results: Physicians, INTERMACS profiles, and ESC-HFA criteria identified 64 (12.5%), 93 (18.2%), and 67 (13.1%) patients, respectively, as Stage D, with modest concordance between definitions (κ = 0.37). After a median of 3.1 years, 97 patients died (3-year mortality 20.4%). Among patients identified as Stage D by physicians, 3-year mortality was 43.7% vs. 17.0% for non-Stage D patients (age-adjusted hazard ratio [HR] 3.17; 95%CI 1.94–5.18; P < 0.001). The corresponding mortalities for the INTERMACS-based definition were 41.0% vs. 16.2% (HR 3.28; 95%CI 2.11–5.11; P < 0.001) and for ESC-HFA criteria 33.5% vs. 18.6% (HR 2.02; 95%CI 1.22–3.33; P = 0.006); the INTERMACS-based definition provided the best prognostic separation. Results were similar with an alternative INTERMACS-based definition considering only profiles 2–5 as Stage D HF. The INTERMACS-based definition best separated all-cause and HF-specific hospitalization and composite endpoint risk between Stage D and non-Stage D patients also. Conclusions: INTERMACS profiles provide a practical alternative for the identification of Stage D HF in ambulatory populations with systolic HF. The ESC-HFA criteria offer limited prognostic information.