Cardio-kidney-metabolic overlap in patients with severe heart failure: data from the HELP-HF registry

Background: Cardiovascular, kidney, and metabolic (CKM) conditions frequently coexist in patients with heart failure (HF), potentially compounding their risk. However, their prevalence and prognostic impact in patients with severe HF remain underexplored. Objectives: To evaluate the impact of CKM overlap in patients with severe HF. Methods: We analysed data from 1149 patients enrolled in the multicenter HELP-HF registry, which includes individuals with severe HF identified by the "I NEED HELP" markers. CKM conditions were assessed across three domains: atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD) (eGFR <60 mL/min/1.73 m²), and metabolic disorders (obesity or type 2 diabetes). Patients were grouped by number of CKM conditions (0-3). The primary endpoint was a composite of 1-year all-cause death or HF hospitalization. Secondary endpoints included all-cause death, cardiovascular death, and first HF hospitalization. Results: CKM conditions were highly prevalent: 85.5% of patients had at least one condition, and 22.3% had all three conditions. ASCVD was the most common (58.7%), followed by CKD (56.5%) and metabolic disorders (48.9%). An increasing number of CKM conditions was associated with worse outcomes, even after multivariable adjustment. The risk of the primary endpoint increased progressively with each additional CKM condition (1: HR 1.92, 95% CI 1.33-2.78; 2: HR 2.11, 95% CI 1.47-3.02; 3: HR 2.52, 95% CI 1.74-3.65; all p<0.001 vs. 0 conditions). Similar trends were observed for mortality and HF hospitalization alone. Conclusions: CKM overlap is highly prevalent among patients with severe HF and is independently associated with worse clinical outcomes. These findings underscore the importance of CKM profiling in HF risk stratification.