Heart failure classification schemes now incorporate cardiac biomarkers to identify patients at risk before symptoms develop, guiding therapy timing in high-risk populations like those with diabetes and renal impairment.
The SCORED trial randomized patients with type 2 diabetes and moderate chronic kidney disease to sotagliflozin versus placebo, evaluating cardiovascular death, heart failure hospitalizations, and urgent heart failure visits as the primary composite endpoint. The results were published in the Circulation: Heart Failure. Investigators conducted a post-hoc analysis classifying 10,584 participants into 2022 AHA/ACC/HFSA stages using NT-proBNP, high-sensitivity cardiac troponin T, and cardiac imaging: stage A represented no heart failure with normal biomarkers and structure; stage B indicated pre-heart failure with elevated biomarkers or abnormalities but no symptoms; stage C/D encompassed established symptomatic heart failure. 
Endpoints included the primary composite, major adverse cardiovascular events, and kidney composites comprising 50% or greater eGFR decline, kidney failure, or kidney death. Competing-risk proportional hazards models assessed stage-specific risks and sotagliflozin benefits.
Risk Escalates Steadily by Stage
Stage distribution revealed 741 patients (7%) in stage A, 6560 (62%) in asymptomatic stage B, and 3283 (31%) in symptomatic C/D. Median NT-proBNP and hs-cTnT rose progressively across stages, reflecting worsening subclinical pathophysiology. In the placebo arm, advancing stage associated with two- to four-fold higher primary outcome and major adverse cardiovascular event rates, underscoring biomarker-driven staging utility.
Pre-HFpEF Stage Drives Kidney Risk
The kidney composite risk increased five-fold from stage A to B but plateaued between B and C/D, highlighting stage B as a critical window for renal protection where structural changes precede overt heart failure.
Sotagliflozin Benefits Uniform Across Stages
Sotagliflozin reduced the primary outcome versus placebo with hazard ratio 0.74 and 95% confidence interval 0.63 to 0.88, without interaction by stage (P=1.00). Absolute risk reductions scaled with stage advancement (P-trend=0.002), delivering greater event savings in higher-risk groups. Kidney endpoint benefits remained comparable between stages B and C/D.
Stage-Guided Therapy for Diabetes Clinics
These findings validate universal heart failure staging in diabetes care, identifying stage B patients for aggressive intervention despite lacking symptoms. Sotagliflozin offers consistent risk mitigation, supporting its use from earliest detectable cardiac risk through established disease.