The impact of comorbidities on therapy-optimization and their prognostics role among hospitalized patients with heart failure with reduced ejection fraction

Abstract Background The early, accurate diagnosis and proper treatment of comorbidities (CMs) are of strategic importance in heart failure (HF), as stated in the current ESC HF Guidelines. Unquestionably, the presence of CMs is associated with worse prognosis. Moreover, CMs can unfavourably affect the implementation of the guideline-directed medical therapy (GDMT) in heart failure with reduced ejection fraction (HFrEF). Aim To assess the prevalence of the relevant prognosis-modifying CMs among patients requiring hospitalization due to HFrEF, investigate their effect on the implementation and optimization of GDMT, and examine the impact of the presence of CMs on the prognosis in HFrEF. Patients and methods The data of 313 patients requiring hospitalization at our Institution due to HFrEF between 2021-2023 (male: 77%, age: 60[50-70]years, coronary artery disease: 46%, diabetes: 36%, hypertension: 65%, atrial fibrillation: 42%, LVEF: 24[20-30]%, eGFR at admission: 57[46-74]mL/min/1.73m², NT-proBNP at admission: 5035[2376-9369]pg/mL, SBP: 121[110-140]mmHg; GDMT at admission - RASi[ACEi/ARB/ARNI]: 60%, βB: 59%, MRA: 44%, SGLT2i: 14%) were analyzed retrospectively. Based on the number of diagnosed CMs, patients were divided into 3 categories: 0-1 vs. 2-3 vs. ≥4 CMs. The implemented GDMT at discharge was compared among CM categories with Chi-square test, while all-cause mortality (ACM) rates were investigated with Kaplan-Meier method and multivariate Cox-regression analysis. Results During the hospitalization in the total cohort the proportion of patients on GDMT increased significantly (RASi: 91%, βB: 85%, MRA: 96%, SGLT2i: 57%; patients on triple [TT] therapy [RASi+βB+MRA]: 83%, patients on quadruple therapy [TT+SGLT2i]: 52%; p＜0.05). However, among patients with higher rates of CMs, the application of GDMT was less favourable (RASi: 97% vs. 94% vs. 82%; βB: 93% vs. 89% vs. 75%; p＜0.05; 0-1 vs. 2-3 vs. ≥4 CMs), the proportion of patients on TT and QT remained remarkably high even among those with ≥4 CMs (TT: 93% vs. 87% vs. 71%; QT: 65% vs. 52% vs. 45%; p＜0.05). During the median follow-up period of 1.3 year, the ACM of patients with increased burden of CMs was higher (12% vs. 18% vs. 37%, p＜0.001). According to the results of the multivariate Cox-regression analysis, more advanced left ventricular systolic dysfunction (/1%), previously confirmed diagnosis of HFrEF, the growing number of CMs proved to be negative independent predictors of ACM, while the application of TT or QT reduced the risk of ACM significantly (HR: 0.471, 95% CI: 0.271-0.819, p=0.008). Conclusions According to our real-world analysis, although among HFrEF patients with an increased burden of CMs, less favourable prognosis can be expected, the application of modern GDMT is even possible among them, resulting in a significantly improved prognosis. Thus, clinicians should insist on the early, conscious implementation of GDMT among these patients as well.