Prognostic impact of prior LVEF in patients with heart failure with mildly reduced ejection fraction

Clinical Research in Cardiology https://doi.org/10.1007/s00392-024-02443-0 ORIGINAL PAPER Prognostic impact of prior LVEF in patients with heart failure with mildly reduced ejection fraction Alexander Schmitt1 · Michael Behnes1 · Kathrin Weidner1 · Mohammad Abumayyaleh1 · Marielen Reinhardt1 · Noah Abel1 · Felix Lau1 · Jan Forner1 · Mohamed Ayoub2 · Kambis Mashayekhi3 · Ibrahim Akin1 · Tobias Schupp1 Received: 5 January 2024 / Accepted: 25 March 2024 © The Author(s) 2024 Abstract Aims As there is limited evidence regarding the prognostic impact of prior left ventricular ejection fraction (LVEF) in patients with heart failure with mildly reduced ejection fraction (HFmrEF), this study investigates the prognostic impact of longitudinal changes in LVEF in patients with HFmrEF. Methods Consecutive patients with HFmrEF (i.e. LVEF 41–49% with signs and/or symptoms of HF) were included retrospectively in a monocentric registry from 2016 to 2022. Based on prior LVEF, patients were categorized into three groups: stable LVEF, improved LVEF, and deteriorated LVEF. The primary endpoint was 30-months all-cause mortality (median follow-up). Secondary endpoints included in-hospital and 12-months all-cause mortality, as well as HF-related rehospitalization at 12 and 30 months. Kaplan–Meier and multivariable Cox proportional regression analyses were applied for statistics. Results Six hundred eighty-nine patients with HFmrEF were included. Compared to their prior LVEF, 24%, 12%, and 64% had stable, improved, and deteriorated LVEF, respectively. None of the three LVEF groups was associated with all-cause mortality at 12 (p ≥ 0.583) and 30 months (31% vs. 37% vs. 34%; log rank p ≥ 0.376). In addition, similar rates of 12- (p ≥ 0.533) and 30-months HF-related rehospitalization (21% vs. 23% vs. 21%; log rank p ≥ 0.749) were observed. These findings were confirmed in multivariable regression analyses in the entire study cohort. Conclusion The transition from HFrEF and HFpEF towards HFmrEF is very common. However, prior LVEF was not associated with prognosis, likely due to the persistently high dynamic nature of LVEF in the follow-up period. Alexander Schmitt and Michael Behnes contributed equally. * Michael Behnes 1 First Department of Medicine, Section for Invasive Cardiology, University Medical Centre Mannheim (UMM), Medical Faculty Mannheim, Heidelberg University, Theodor‑Kutzer‑Ufer 1‑3, 68167 Mannheim, Germany 2 Division of Cardiology and Angiology, Heart Centre University of Bochum, Bad Oeynhausen, Germany 3 Department of Internal Medicine and Cardiology, Mediclin Heart Centre Lahr, Lahr, Germany Vol.:(0123456789) Clinical Research in Cardiology Graphical Abstract Keywords Heart failure with mildly reduced ejection fraction · HFmrEF · LVEF · Prognosis · Mortality, longitudinal changes of LVEF Introduction Within the last decades, the prevalence of heart failure (HF) has steadily increased due to ongoing demographic changes related to an overall ageing population [1, 2]. Global estimates have shown that approximately 64 million people are affected by HF and data from the United States suggests that total health care expenditure for the management of HF could rise to 70 billion US-dollars by 2030 [3, 4]. Even though HF can be described through a variety of parameters, clinical signs, or symptomatology, it is most commonly classified by left ventricular ejection fraction (LVEF) [5, 6]. Until recently, patients were either divided into the category of HF with reduced (HFrEF) or preserved ejection fraction (HFpEF). However, within the past years, the European and American HF guidelines have introduced an additional category of HF with an LVEF of 41–49%, the so-called heart failure with mildly reduced ejection fraction (HFmrEF) [5, 6]. This category accounts for 16–24% of patients with HF [7, 8]. Furthermore, the category of HF with improved ejection fraction (HFimpEF) has been defined in a widely accepted position paper on the universal definition and classification of HF [9]. This classification aims to consider the potential prognostic implications of longitudinal changes of LVEF. According to this position paper, HFimpEF should be defined by a baseline LVEF ≤ 40% and a second measurement of LVEF > 40% with a ≥ 10% increase from baseline LVEF. Recent evidence from the ESC Heart Failure Long-Term Registry suggests that despite improvements in medical management, mortality of HF remains high with 1-year mortality rates of 8.8%, 7.8%, and 6.4% for HFrEF, HFmrEF, and HFpEF, respectively [7]. Within the same registry, Chioncel et al. were able to demonstrate a nearly linear increase in mortality and HF-related rehospitalization across every decile of reduced LVEF [7, 10]. However, since LVEF is a dynamic parameter, prognostic implications of LVEF changes over time must be considered to properly guide medical management of patients. As previous studies have demonstrated, improvement of LVEF in patients suffering from HFrEF is associated with favourable outcomes compared to patients with persistently reduced LVEF and maybe even those with stable HFpEF [11, 12]. Accordingly, deterioration of LVEF over time was observed to coincide with a worse prognosis [13–15]. Despite the importance of longitudinal changes in LVEF, there is limited evidence regarding the prognostic impact of prior LVEF in patients with HFmrEF. Since the category of HFmrEF was recently introduced, evidence guiding clinical decision-making for this cohort remains limited and the few guideline recommendations currently available are predominantly based on Clinical Research in Cardiology post hoc analyses of prior trials enrolling patients within the LVEF range of HFmrEF (e.g. CHARM-Preserved [16], TOPCAT [17], or PARAGON-HF [18]). Therefore, the present study investigates the prognostic impact of prior LVEF in consecutive patients hospitalized with HFmrEF within a large-scaled retrospective registrybased analysis. Methods Study patients, design, and data collection For the present study, all consecutive patients hospitalized with HFmrEF at one University Medical Centre were included from January 2016 to December 2022, as recently published [19]. Using the electronic hospital information system, all relevant clinical data related to the index event were documented, such as baseline characteristics; vital signs on admission; prior medical history; prior medical treatment; length of index hospital and intensive care unit (ICU) stay; laboratory values; data derived from all noninvasive or invasive cardiac diagnostics and device therapies, such as echocardiographic data, coronary angiography, and data being derived from prior or newly implanted cardiac devices. Every re-visit at the outpatient clinic or rehospitalizations related to HF or adverse cardiac events were documented until the end of the year 2022. The present study is derived from the “Heart Failure With Mildly Reduced Ejection Fraction Registry” (HARME (...truncated)