Prognostic impact of cardiovascular-kidney-metabolic overlap among patients with acute heart failure: insights from a real-world multinational cohort

Abstract Introduction Cardiovascular-kidney-metabolic (CKM) multimorbidity is known to be associated with a stepwise increase in the risk of adverse clinical outcomes in chronic heart failure (HF). However, its prognostic impact in patients in an acute HF (AHF) setting remains unknown. Purpose We aimed to assess the prognostic impact of CKM multimorbidity on cardiovascular events, in a real-world cohort of AHF patients enrolled in Kyrgyzstan and Switzerland. Methods We analyzed consecutive patients hospitalized for AHF between 2005 and 2020 at two tertiary-care centers. Patients were categorized based on the number of CKM conditions at baseline in addition to HF (0, 1, 2 or 3 conditions). CKM conditions included prior myocardial infarction (MI), impaired kidney function (defined as an estimated glomerular filtration rate at admission 60 ml/min/m2), and documented type 2 diabetes. The association between the number of CKM conditions and the primary outcome of first HF hospitalization or all-cause death at 1 year, was assessed with Cox proportional hazards models. Results Among 1,745 patients (69% Swiss, 56% male, age 74±13 years, mean left ventricular ejection fraction 43%), at baseline, 18.9% had HF alone, 39.0% had one CKM condition, 30.7% had two, and 11.4% had three. Impaired kidney function was the most prevalent CKM condition (n=1,011), followed by prior MI (n=742), and type 2 diabetes (n=595) (Figure 1). The primary composite outcome occurred in 731 patients (41.9%) at 1 year. Compared with HF alone, an increasing number of CKM conditions was associated with stepwise increases in the risk of the primary outcome, with adjusted hazard ratios of 1.27 (95% confidence interval CI: 1.01–1.59), 1.50 (95% CI: 1.19–1.89), and 2.10 (95% CI: 1.59–2.77) in patients with 1, 2, or 3 CKM conditions, respectively (Figure 2). These associations remained consistent regardless of sex (Pinteraction = 0.57), age (categorized at median: 77 and ≥77 years, Pinteraction = 0.43), and LVEF (40% and ≥40%, Pinteraction = 0.42). Conclusions In this real-world, multinational cohort of patients hospitalized for AHF, CKM multimorbidity was common and associated with a stepwise increase in the risk of adverse clinical outcomes. These findings highlight the prognostic significance of a high CKM burden in an AHF setting, extending beyond its established impact in chronic HF.Figure 1 Figure 2