Frailty in patients suffering from heart failure with reduced ejection fraction: how are pharmacotherapy and prognosis affected?

Introduction In the care of patients with heart failure (HF), the identification and targeted management of frail HF patients has come to the spotlight in recent years. Literature data suggests that frailty can negatively influence the application of guideline-directed medical therapy (GDMT) and can unfavourably affect prognosis. Aim to assess the occurrence of frailty according to the 2019 ESC HFA definition in a consecutive patient cohort hospitalised for HF with reduced ejection fraction (HFrEF), and to evaluate the effect of frailty on in-hospital implementation and long-term use of GDMT. 1-year prognosis (all-cause mortality [ACM], HF hospitalisation [HFH]) was also assessed in the light of frailty. Patients and methods: We retrospectively analysed data from a consecutive cohort of 237 HFrEF patients hospitalised for HF at our cardiology centre between 2021 and 2024 who had frailty documented (male: 76%, age: 60 [51-70] years, de novo HF: 54%, coronary artery disease: 45%, diabetes: 41%, atrial fibrillation: 42%, eGFR < 60 mL/min/1.73m2: 39%, LVEF: 25 [20-30] %, NT-proBNP at admission: 5538 [2577-10281] pg/mL, systolic blood pressure: 120 [108-137] mm Hg, heart rate: 90 [76-104] min-1; GDMT at discharge: RASi: 98%, βB: 88%, MRA: 97%, SGLT2i: 81%, triple therapy [TT: RASi + βB + MRA]: 86%, quadruple therapy [QT: TT + SGLT2i]: 73%). The four domains of frailty suggested by the 2019 ESC HFA definition were evaluated (clinical-, psycho-cognitive-, functional-, social domain). Patients fulfilling ≥ 2 frailty domains were considered frail in the current analysis. The effect of frailty on the application of GDMT at discharge and at 1 year was assessed. 1-year prognostic differences and the independent predictors of 1-year ACM/HFH were investigated as well. Results The clinical domain was present in 96% of the total cohort (TC), while 24% had fulfilled the psycho-cognitive-, 20% the functional-, and 10% the social domain. 37% of the TC had at least 2 domains. Frail patients were less likely to be treated with GDMT at discharge (βB: 97% vs 72%; SGLT2i: 90% vs 67%; TT: 95% vs 72%; QT: 86% vs 51%; p<0.001; non-frail vs frail patients, respectively). At 1 year, frail patients had significantly lower rates of TT (86% vs 73%, p=0.011) and QT (78% vs 58%, p=0.010). Frail patients had worse 1-year ACM (7% vs 18%, p=0.046) and HFH (7% vs 20%, p=0.009); the composite endpoint of 1-year ACM/HFH was worse in the frail subgroup (14% vs 29%, p=0.008). In the multivariate Cox-regression analysis, CRT (HR: 2.854, 95% CI: 1.281-6.357, p=0.010) and the number of frailty domains (/1 domain, HR: 1.508, 95% CI: 1.026-2.215, p=0.036) increased the risk of 1-year ACM/HFH. Conclusions Frailty was present in a remarkable ratio of hospitalised HFrEF patients. Nothing emphasises the need for frailty screening and targeted care more than the fact that the rate of GDMT was lower, and ACM and HFH were higher among them after 1 year of follow-up.Frailty 1Frailty