Abstract Body (Do not enter title and authors here): INTRODUCTION: The 2022 AHA/ACC/HFSA heart failure (HF) classification newly incorporates cardiac biomarkers to identify patients at risk of HF.

RESEARCH QUESTION: Given shared risk factors between HF and other cardiorenal events, the HF stages may also guide prognosis and management of cardiovascular (CV) and kidney-related events beyond HF.

AIMS: Examine the association of HF stage with CV and kidney events.

METHODS: SCORED was a randomized trial in diabetes with kidney disease comparing sotagliflozin (sota) v. placebo on CV death, hospitalizations for HF, and urgent HF visits. SCORED participants were grouped by HF stage post hoc. Stage A: No HF, normal cardiac biomarkers (NT-proBNP; <125 pg/mL, hs-cTnT; <14 ng/L) and normal cardiac structure/function by echocardiography. Stage B (pre-HF): No HF but elevated NTproBNP, hsTNT or abnormal echocardiography. Stage C/D: symptomatic HF. Endpoints of interest included the primary composite endpoint (CV death and HF-related events), major adverse CV events (MACE), and kidney-related composites (See Figure caption). Using Cox regression, we examined the association between HF stage and these endpoints, and whether the effect of sota v. placebo varied by HF stage.

RESULTS: There were 741 patients in stage A, 6560 in stage B (pre-HF) and 3283 in stage C/D (established HF). The mean NTproBNP and hs-cTnT increased with HF stage. Stepwise increases in HF stage were associated with a 2-4 fold higher incidence of the primary, MACE and kidney endpoints in the placebo group, although the incidence of the kidney-specific composite was similar in stage B and C/D (Figure). The relative risk reduction with sota v. placebo for all endpoints was similar irrespective of HF stage (p-interaction>0.05), with higher absolute benefit in each HF stage (Figure). The absolute benefit for the kidney-specific endpoint was comparable for stage B and C/D.

CONCLUSIONS: Increasing HF stage is associated with higher risk of HF, MACE, and kidney events, but the risk of kidney events is similar in stage B (pre-HF) and stage C/D (established HF). Sota has similar relative benefits for all endpoints, irrespective of HF stage, with a corresponding increase in absolute benefits at higher stages.