The development and long-term maintenance of heart failure with improved ejection fraction after a heart failure hospitalization: how are mortality rates affected?
Authors: Banfi-Bacsardi F , Fuzesi T , Kazay A , Torok G M , Pilecky D , Vamos M , Gergely T G , Forrai Z S , Majoros Z S , Borsanyi T D , Solymossi B , Duray G Z , Kiss R G , Nyolczas N , Muk B 
Published: October 2024

Abstract

Background
According to the current ESC HF Guidelines (GLs), the implementation of the guideline-directed medical therapy (GDMT) is of strategic importance in heart failure (HF) with reduced ejection fraction (HFrEF). In the effect of the successful implementation of the modern GDMT, significant improvement in terms of the left ventricular ejection fraction (LVEF) might be expected in HFrEF. Hence, a new HF category, the improved ejection fraction (HFimpEF), was introduced in the current ESC HF GLs, which has come to the spotlight in the recent years. However, its course and long-term prognosis are still not clearly understood.

Aim
To assess the development and long-term maintenance of the HFimpEF category among a consecutive patient cohort requiring hospitalization due to HFrEF, evaluate its effect on prognosis, and examine the independent predictors of its development.

Patients and methods
A retrospective analysis was carried in a real-world cohort of 270 HFrEF patients (male: 77%, age: 61[49-68]years, coronary artery disease: 47%, diabetes: 30%, hypertension: 60%, atrial fibrillation: 35%, LVEF: 25[20-30]%, eGFR at admission: 59[45-73]mL/min/1.73m², NT-proBNP at admission: 4733[2368-9711]pg/mL, SBP: 120[107-135]mmHg) hospitalized for HF in 2019-2023 at two tertiary cardiac centers. At admission the complex modern GDMT of HFrEF had been already introduced (RASi[ACEi/ARB/ARNI]: 61%, βB: 63%, MRA: 47%, SGLT2i: 6%) in the minority of the cohort.
The improvement to the HFimpEF category was examined after the therapy optimization (OMT). All-cause mortality (ACM) rates were evaluated with Kaplan-Meier method and the predictors of the development to HFimpEF category were assessed with logistic regression analysis.

Results
In the total cohort at discharge, a high proportion of patients received RASis (94%), βBs (90%), MRAs (97%), and SGLT2is (35%). 79 patients (29%) evolved to the HFimpEF category after OMT. During the median 810 [456-1161] days of follow-up (FU), HFimpEF patients had lower, but unquestionably still increased mortality rates (29% vs. 10%, p=0.001; non-HFimpEF vs. HFimpEF patients). At two years of the FU period, based on the available echocardiographies, 98 % of the patients remained in the HFimpEF category.
After performing a multivariate logistic regression analysis, the severity of the LV systolic dysfunction (LVSD) and the „de novo" diagnosis of HFrEF proved to be independent predictors of the development of the HFimpEF category.

Conclusions
In the effect of the implementation of GDMT, a significant proportion (29%) of our multimorbid, hospitalized HFrEF patient cohort improved to the HFimpEF category. The predictors of its development were the severity of the LVSD and "de novo" HFrEF diagnosis. During the FU period, most of the HFimpEF patients remained in this category. However, their persistently elevated mortality rates raise the awareness of the importance of the conscious application and maintenance of GDMT.