Heart failure with mildly reduced ejection fraction is not all alike: the importance of disease trajectory
Authors: Ferreira J , Coelho R , Quintal J , Pohle C , Goncalves S , Duarte T , Costa C , Caria R 
Published: November 2023

Abstract

Background
Heart failure with mildly reduced ejection fraction (HFmrEF) is a relatively recent category whose prognosis is described in the literature as intermediate between preserved and reduced ejection fraction (EF). However, this group of patients can be quite heterogeneous, particularly in what concerns their place in HF disease trajectory, since it includes both patients with newly-diagnosed HFmrEF and those who improve from reduced EF to mildly reduced EF.

Purpose
To compare the phenotype and prognosis of patients with mildly reduced EF at diagnosis and those who initially had reduced EF, which later improved to mildly reduced.

Methods
We conducted a retrospective study including all consecutive patients assessed in our HF Clinic between 2018 and 2020 who had mildly reduced EF [41-49%]. Participants were divided into two groups: HFmrEF if EF was consistently between 41-49% and imp-HFmrEF if EF had previously been &lt;40%. We compared HF etiology, comorbidities, ECG patterns, blood markers and echocardiogram results between the two groups. The primary endpoint was a composite of death and hospitalizations for HF or ventricular arrhythmias.

Results
We included 102 patients with a median age of 68 years observed in our HF clinic between 2018 and 2020. The sample was well balanced between HFmrEF (51%) and imp-HFmrEF (49%). Baseline characteristics and comorbidities were similar between the groups, except for a more frequent history of myocardial infarction among HFmrEF patients (45% vs 24%, p = 0.026).
For both groups, the most common HF etiology was ischemic heart disease, although tendentially more dominant for HFmrEF patients compared with imp-HFmrEF (56% vs 37%, p = 0.055). On the contrary, a toxic etiology was more frequent among imp-HFmrEF patients (16% vs 2%, p = 0.015). Left ventricular volumes did not differ between the groups, nor did NT-proBNP values. However, as expected, patients with imp-HFmrEF were under more neurohormonal medication compared with HFmrEF.
At a median follow-up of 2.3 years, imp-HFmrEF was associated with lower rates of death or hospitalization for HF or ventricular arrhythmias (14% vs 31%; log-rank test: p = 0.037), with a hazard ratio of 0.403 (95% CI 0.166-0.980). Additionally, there was also a tendency towards higher rates of worsening EF to &lt; 40% among HFmrEF patients (16% vs 6%, not reaching statistical significance).

Conclusions
This study confirms that among HF patients with mildly reduced EF, different phenotypes with differing disease trajectories coexist. It also suggests that clinical prognosis (and, probably, the risk of EF deterioration) of patients diagnosed with HFmrEF is worse, compared with those who improve from reduced EF to mildly reduced EF. Further research with larger groups is required to identify predictors of EF deterioration and assess the potential role of intensification of neurohormonal modulation in preventing it.Table 1ResultsHospitalization-free survival