Timing of acute decompensated heart failure in patients with heart failure and mildly reduced ejection fraction

Heart and Vessels https://doi.org/10.1007/s00380-024-02505-3 ORIGINAL ARTICLE Timing of acute decompensated heart failure in patients with heart failure and mildly reduced ejection fraction Henning Johann Steffen1 · Noah Abel1 · Felix Lau1 · Alexander Schmitt1 · Marielen Reinhardt1 · Muharrem Akin2 · Thomas Bertsch3 · Jonas Rusnak4 · Kathrin Weidner1 · Michael Behnes1 · Ibrahim Akin1 · Tobias Schupp1 Received: 9 October 2024 / Accepted: 4 December 2024 © The Author(s) 2025 Abstract This study investigates the prognosis of acute decompensated heart failure (ADHF) on admission (i.e., primary ADHF) as compared to ADHF onset during course of hospitalization (i.e., secondary ADHF) in patients hospitalized with heart failure with mildly reduced ejection fraction (HFmrEF). Limited data regarding the prognostic impact of the timing of onset of ADHF is available. Consecutive patients with HFmrEF and ADHF were retrospectively included at one institution from 2016 to 2022. Patients with primary ADHF were compared to patients with secondary ADHF with regard to the primary endpoint all-cause mortality at 30 months. Kaplan–Meier, uni- and multivariable Cox proportional regression analyses were applied for statistics. From a total of 484 patients hospitalized with HFmrEF and ADHF, 67.98% (n = 329) were admitted with primary ADHF. Patients with secondary ADHF had higher rates of concomitant acute myocardial infarction, alongside with a higher extend of coronary artery disease. The risk of all-cause mortality at 30 months was not affected by the timing of ADHF (hazard ratio (HR) = 0.853; 95% confidence interval (CI) 0.653–1.115; p = 0.246). However, patients with primary ADHF were associated with a higher risk of HF-related rehospitalization at 30 months (HR = 2.513; 95% CI 1.555–4.065; p = 0.001), which was still evident after multivariable adjustment (HR = 2.347; 95% CI 1.418–3.883; p = 0.001). The timing of onset of ADHF was not associated with long-term mortality in HFmrEF, however primary ADHF was associated with a higher risk of HF-related rehospitalization. Keywords Heart failure with mildly reduced ejection fraction · HFmrEF · Acute decompensated heart failure · ADHF Introduction * Tobias Schupp 1 Medical Faculty Mannheim, Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Heidelberg University, Theodor‑Kutzer‑Ufer 1‑3, 68167 Mannheim, Germany 2 Department of Cardiology, St. Josef-Hospital, Ruhr-Universität Bochum, 44791 Bochum, Germany 3 Institute of Clinical Chemistry, Laboratory Medicine and Transfusion Medicine, Nuremberg General Hospital, Paracelsus Medical University, 90419 Nuremberg, Germany 4 Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, 69120 Heidelberg, Germany The characterization of patients with heart failure with mildly reduced ejection fraction (HFmrEF) has gained more importance following their introduction and upgrade within the 2016 and 2021 European guidelines of heart failure (HF) [1, 2]. HFmrEF, which is characterized by a left ventricular ejection fraction (LVEF) between 41 and 49% and has been recognized as a unique subtype of HF, sharing patterns with both HF with reduced (i.e., HFrEF) and HF with preserved LVEF (i.e., HFpEF) [3–7]. Related to the limited number of randomized controlled trials including patients with HFmrEF, guideline-based treatment recommendations in HFmrEF are scarce. Acute decompensated heart failure (ADHF) encompasses a diverse range of clinical scenarios characterized by the intensification of manifestations and symptoms associated with heart failure (HF). It constitutes the predominant presentation of acute HF. ADHF can manifest Vol.:(0123456789) Heart and Vessels either as the initial presentation of HF or as an acute exacerbation in the setting of chronic HF [8, 9]. Although ADHF was recently shown to impair long-term prognosis in HFmrEF [10], data regarding the characteristics and prognostic impact of concerning timing of ADHF, such as ADHF on admission (i.e., primary ADHF) compared to ADHF during hospitalization (i.e., secondary ADHF) remains scarce. Prior studies primarily focused on ADHF in patients with HFrEF and HFpEF, resulting in a lack of comprehensive research including patients with HFmrEF, emphasizing the need for focused research efforts to enhance the understanding and clinical management of ADHF across the range of HF phenotypes.[11–23]. The present study sought to investigate the prognosis of patients with primary versus secondary ADHF, including consecutive patients hospitalized with HFmrEF from 2016 to 2022. Methods Study patients, design and data collection: For the present study, patients hospitalized with HFmrEF and ADHF at a tertiary university medical center were included from January 2016 to December 2022, as recently published [24]. The electronic hospital information system facilitated the comprehensive documentation of relevant clinical data related to the index event. This included baseline characteristics, vital signs upon admission, prior medical history, previous medical interventions, duration of the index hospitalization, and intensive care unit (ICU) stay, as well as laboratory values. Furthermore, noninvasive and invasive cardiac diagnostic information, such as echocardiogram results, coronary angiography findings, and data from existing or newly implanted cardiac devices, were systematically recorded. The monitoring extended beyond the index hospitalization to encompass subsequent outpatient clinic visits, echocardiographic assessments, HF-related rehospitalizations, and adverse cardiac events until the end of 2022. This investigation originated from the "Heart Failure With Mildly Reduced Ejection Fraction Registry" (HARMER), which is a retrospective single-center registry that included consecutively enrolled patients with HFmrEF at the University Medical Center Mannheim (UMM), Germany (clinicaltrials.gov identifier: NCT05603390). Ethical standards were upheld in accordance with the principles of the Declaration of Helsinki and received approval from the Medical Ethics Committee II of the Medical Faculty Mannheim, University of Heidelberg, Germany (ethical approval code: 2022-818). Inclusion and exclusion criteria For the present study, patients hospitalized with HFmrEF and ADHF from 2016 until 2022 were included. Patients without ADHF either at index admission or during index hospitalization, as well as patients under 18 years of age were excluded. The diagnosis of HFmrEF was performed in accordance with the "2021 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure" [2]. Patients with a LVEF ranging from 41 to 49%, accompained with symptoms and/or signs of HF, were included. The presence of elevated amino-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels and other indicators of structural heart disease strengthened the diag (...truncated)