Cardiovascular-Kidney-Metabolic Overlap in Patients Hospitalized for Heart Failure

Importance Among patients with heart failure (HF) in contemporary US clinical practice, the burden of overlapping cardiovascular-kidney-metabolic (CKM) conditions and the associated impact on outcomes remain poorly characterized. Objective To evaluate the prevalence of CKM multimorbidity and the impact on clinical outcomes in patients hospitalized for HF across the spectrum of ejection fraction (EF). Design, Setting, and Participants This was a retrospective cohort study of patients hospitalized for HF at US hospitals participating in the Get With The Guidelines–Heart Failure (GWTG-HF) registry. The analysis included patients hospitalized for HF in the GWTG-HF registry between 2019-2025 and Medicare beneficiaries hospitalized for HF in the GWTG-HF registry between 2019-2023. Exposures Presence of up to 4 additional CKM conditions including atherosclerotic cardiovascular disease, chronic kidney disease, diabetes, and obesity (body mass index ≥30; calculated as weight in kilograms divided by height in meters squared). Main Outcomes and Measures In-hospital mortality, 1-year postdischarge all-cause mortality, and 1-year postdischarge HF readmission. Results This study included 725 205 patients (median [IQR] age, 72.0 [61.0-82.0] years; 386 886 male [53.3%]) hospitalized for HF between 2019 and 2025 and 123 271 Medicare beneficiaries (median [IQR] age, 80 [73-87] years; 64 375 female [52.2%]) hospitalized for HF between 2019 and 2023. Among 725 205 patients hospitalized for HF, 521 739 (71.9%) had 2 or more overlapping CKM conditions, and a minority of patients (48 732 [6.7%]) had HF only. CKM overlap was greatest in HF with preserved EF (HFpEF). Compared with HF only, increasing number of overlapping CKM conditions was associated with stepwise increases in in-hospital mortality (4 CKM conditions: HF with reduced EF [HFrEF] adjusted odds ratio [aOR], 5.08; 95% CI, 4.43-5.83; HF with mildly reduced EF [HFmrEF] aOR, 2.37; 95% CI, 1.68-3.34; HFpEF aOR, 2.05; 95% CI, 1.77-2.38), and this association was strongest in HFrEF ( P for interaction <.001). Among Medicare beneficiaries hospitalized for HF, compared with HF only, increasing CKM multimorbidity was associated with increasing risks of postdischarge all-cause mortality (4 CKM conditions: HFrEF adjusted hazards ratio [aHR], 2.10; 95% CI, 1.93-2.29; HFmrEF aHR, 1.38; 95% CI, 1.17-1.63; HFpEF aHR, 1.09; 95% CI, 1.03-1.17) and HF readmission (4 CKM conditions: HFrEF aHR, 2.33; 95% CI, 2.12-2.56; HFmrEF aHR, 2.20; 95% CI, 1.82-2.66; HFpEF aHR, 1.91; 95% CI, 1.77-2.06), with steepest increases in risk among patients with HFrEF ( P for interaction <.001). Conclusions and Relevance In this contemporary cohort of US patients hospitalized for HF, most patients had multiple additional overlapping CKM conditions. Increasing CKM multimorbidity was independently associated with stepwise increases in mortality and readmission risk. Although these associations spanned the EF spectrum, the prognostic impact of CKM multimorbidity was greatest in HFrEF and least in HFpEF.