Ejection fraction at hospital admission stratifies mortality risk in HFmrEF patients aged ≥ 70 years: a retrospective analysis from a tertiary university institution

Aging Clinical and Experimental Research (2023) 35:1679–1693 https://doi.org/10.1007/s40520-023-02454-3 ORIGINAL ARTICLE Ejection fraction at hospital admission stratifies mortality risk in HFmrEF patients aged ≥ 70 years: a retrospective analysis from a tertiary university institution Andrea Sonaglioni1 · Chiara Lonati2,4 · Marta Teresa Behring2 · Gian Luigi Nicolosi3 · Michele Lombardo1 · Sergio Harari2,4 Received: 13 May 2023 / Accepted: 24 May 2023 / Published online: 5 June 2023 © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023 Abstract Background During the last few years, increasing focus has been placed on heart failure with mildly reduced ejection fraction (HFmrEF), an intermediate phenotype from preserved to reduced ejection fraction (EF). However, clinical features and outcome of HFmrEF in elderly patients aged ≥ 70 yrs have been poorly investigated. Methods The present study retrospectively included all consecutive patients aged ≥ 70 yrs discharged from our Institution with a first diagnosis of HFmrEF, between January 2020 and November 2020. All patients underwent transthoracic echocardiography. The primary outcome was all-cause mortality, while the secondary one was the composite of all-cause mortality + rehospitalization for all causes over a mid-term follow-up. Results The study included 107 HFmrEF patients (84.3 ± 7.4 yrs, 61.7% females). Patients were classified as “old” (70–84 yrs, n = 55) and “oldest-old” (≥ 85 yrs, n = 52) and separately analyzed. As compared to the “oldest-old” patients, the “old” ones were more commonly males (58.2% vs 17.3%, p < 0.001), with history of coronary artery disease (CAD) (54.5% vs 15.4%, p < 0.001) and significantly lower EF (43.5 ± 2.7% vs 47.3 ± 3.6%, p < 0.001) at hospital admission. Mean follow-up was 1.8 ± 1.1 yrs. During follow-up, 29 patients died and 45 were re-hospitalized. Male sex (HR 6.71, 95% CI 1.59–28.4), history of CAD (HR 5.37, 95% CI 2.04–14.1) and EF (HR 0.48, 95% CI 0.34–0.68) were independently associated with all-cause mortality in the whole study population. EF also predicted the composite of all-cause mortality + rehospitalization for all causes. EF < 45% was the best cut-off value to predict both outcomes. Conclusions EF at hospital admission is independently associated with all-cause mortality and rehospitalization for all causes in elderly HFmrEF patients over a mid-term follow-up. Keywords Elderly · Ejection fraction · Heart failure · HFmrEF · Outcome Introduction * Chiara Lonati 1 Division of Cardiology, IRCCS MultiMedica, Milan, Italy 2 Division of Internal Medicine, IRCCS MultiMedica, Milan, Italy 3 Division of Cardiology, Policlinico San Giorgio, Pordenone, Italy 4 Department of Clinical Sciences and Community Health, Università Di Milano, Milan, Italy Heart failure with mildly reduced ejection fraction (HFmrEF), defined as symptoms and signs of heart failure (HF) with an ejection fraction (EF) between 41 and 49%, has been formally classified as a new phenotype of HF in 2016 European Society of Cardiology (ESC) guidelines [1]. According to the 2021 ESC guidelines, increased serum levels of natriuretic peptides and other evidence of structural heart disease make HFmrEF diagnosis more likely but are not mandatory if there is certainty regarding EF measurement [2]. Based on recent clinical trials and registries, HFmrEF accounts for ~ 13–24% of HF cases [3, 4]. The primary recognized cause of HFmrEF is coronary artery disease (CAD); accordingly, from an etiological point of view, patients with HFmrEF 13 Vol.:(0123456789) 1680 are more similar to those with heart failure with reduced ejection fraction (HFrEF) rather than those with preserved ejection fraction (HFpEF) [5]. According to literature data [6], HFmrEF patients are likely to be heterogeneous and may not have a single pathophysiological substrate. Given that EF is a dynamic index and may increase or decrease during the course of HF, HFmrEF may occur either as a recovery from HFrEF or a deterioration from HFpEF [7]. To date, several studies [5, 8–13] have evaluated epidemiology, pathophysiology and clinical outcomes of HFmrEF patients. However, the majority of individuals included in those studies were 70 years old or younger and only few studies [10, 14] were specifically focused on the assessment of HFmrEF in elderly patients. Because of the growing ageing of the population worldwide, HFmrEF patients aged ≥ 70 yrs will be more frequently encountered in contemporary clinical practice [15]. Accordingly, the present study was designed to investigate the main clinical, laboratory and echocardiographic features of HFmrEF patients aged ≥ 70 yrs, categorized in the two age subgroups of “old” (70–84 yrs) and “oldest-old” (≥ 85 yrs), and to evaluate the independent prognostic indicators of “all-cause mortality”, over a medium-term follow-up. Methods Study population This retrospective observational study included all consecutive patients aged ≥ 70 yrs discharged from Internal Medicine Division of San Giuseppe MultiMedica Hospital (Milan), a tertiary university institution, with a main diagnosis of HFmrEF, between January 1st, 2020, and November 30th, 2020. The present study group was selected from a larger population of HF patients, object of another clinical investigation focused on the prevalence and clinical outcome of main echocardiographic and hemodynamic HF phenotypes [16]. HFmrEF diagnosis was established according to the 2021 ESC guidelines [2] and based on: (1) symptoms (dyspnea, fatigue, or decreased exercise capacity); (2) signs (edema or rales on chest auscultation); (3) a mildly reduced EF (41–49%) on transthoracic echocardiography (TTE) examination performed at admission to the Internal Medicine Division. Exclusion criteria were: HFpEF (EF ≥ 50%), HFrEF (EF ≤ 40%), age < 70 yrs, hemodynamic instability requiring spoke-to-hub transfer, lacking of two-dimensional (2D) TTE performed during hospital stay, poor echocardiographic windows, lacking of a complete laboratory panel. Although this study was performed during the COVID-19 pandemic, COVID-19 patients were excluded from this retrospective 13 Aging Clinical and Experimental Research (2023) 35:1679–1693 analysis, to avoid the risk of bias related to concomitant COVID-19 disease. HFmrEF patients were stratified in two major groups, according to their age: (1) HFmrEF patients aged 70–84 years (the “old” group); (2) HFmrEF patients aged ≥ 85 years (the “oldest-old” group). This cut-off was derived from previous studies conducted on elderly HF patients [17–19]. On the basis of the underlying etiology, following predominant clinical subtypes of HFmrEF were identified: (1) HF due to acute/chronic CAD; (2) HF due to acute/chronic valvular heart disease (VHD); (3) HF due to hypertensive cardiomyopathy; (4) HF due to acute/chronic pulmonary hypertension [2]. Main etiology of HF and both echocardiographic and clinical categories of HF (...truncated)