HLM Staging and Treatment Benefit of SGLT2i Across Heart Failure Severity

Heart failure (HF) is a complex systemic syndrome for which the HLM staging system has been proposed to better capture disease complexity. This study investigated the prognostic role of HLM staging according to SGLT2i status and the impact of in-hospital SGLT2i therapy across different stages of HF severity. In this prospective, multicenter, observational study, consecutive patients hospitalized for HF between November 2022 and August 2025 were enrolled and stratified according to HLM stage and according to SGLT2i status at discharge. The primary endpoint was the composite of cardiovascular (CV) death or HF hospitalization at 6-month follow-up. A total of 711 patients were included. The primary endpoint occurred in 82 patients with a significant increase across HLM stages (p < 0.001). Increasing HLM stage was associated with higher risk of adverse outcomes (HR = 1.40; 95% CI 1.02-1.90; p = 0.03), regardless of SGLT2i status. SGLT2i therapy initiation within the index hospitalization was independently associated with a lower risk of the composite endpoint (HR = 0.59; 95% CI 0.38-0.92; p = 0.02) across the HLM severity stages. In this cohort of HF patients, the HLM staging system provided potential clinically meaningful risk stratification irrespective of SGLT2i therapy, and SGLT2i therapy was associated with improved outcomes irrespective of HLM severity. These observations suggest a potential role for integrated pathophysiological staging in risk assessment and therapeutic evaluation.