Impact of multimorbidity on vulnerable phase outcomes in hospitalized heart failure across ejection fraction: a report from the OPPORTUNITIES registry
L Fazzini, C Giaccherini, F Di Salvo, M Spagnolin, E D'elia, E Chiesa, A Zucchi, A Gavazzi, M Senni, M GoriAbstract
Background
Multimorbidity influences heart failure (HF) outcomes, but how the phenotype of HF (reduced vs preserved ejection fraction (EF), de novo vs worsening) modifies this relationship in hospitalized HF (HHF) remains unknown.
Purpose
We aimed to explore the impact of multimorbidity during the vulnerable phase of HHF at both the individual and population levels.
Methods
Consecutive HHF patients enrolled in the OPPORTUNITIES registry were included. Cox regression models were used to assess associations of comorbidity pairs with the 6-month composite outcome of all-cause death, HF hospitalization, urgent transplant, both at an individual and population level, reported by population-attributable fractions (PAF). Relative excess risk due to interaction (RERI) was explored.
Results
Among 1,052 HHF patients, 760 (72.2%) presented with de novo and 292 (27.8%) with worsening HF (median age 76 years, 62.6% men). In de novo HHF with reduced EF, the multimorbidity associated with the highest individual risk was chronic kidney disease (CKD)/peripheral artery disease (PAD) (HR 2.65, 95% CI 1.34–5.26) (Figure 1), while CKD/coronary artery disease (CAD) showed the largest PAF (30.6%). Significant synergistic interactions were identified for CKD+atrial fibrillation (RERI=1.25) and CKD+PAD (RERI=2.33). In de novo HHF with preserved EF, CKD/obesity (HR 3.94, 95% CI 1.61–9.65) had the highest individual risk (Figure 2), while CKD/diabetes the largest PAF (PAF 47.7%). CKD+diabetes (RERI=2.99), PAD+diabetes (RERI=2.50), and CAD+PAD (RERI=1.24) had synergistic interactions. Multimorbidity showed a neutral impact on outcomes in worsening HF.
Conclusion
Multimorbidity patterns influence short-term outcomes in de novo HHF, as opposed to worsening HF, with distinct profiles across both EF and risk levels (individual/population). These findings highlight the need to prioritize the management of specific comorbidities in HHF.Figure 1For image description, please refer to the figure legend and surrounding text.Figure 2For image description, please refer to the figure legend and surrounding text.