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For these patients, no clinical trial to date has demonstrated clear benefits of therapy 17. HF with reduced EF (HFrEF defined as EF 40%, >45% or ≥45%, or >50% or ≥50%. Until better measurements than the EF are available that meet all the needs for HF characterization, the data described in this Review might be relevant for both clinicians and clinical trialists 6, 14, 15, 16. Nevertheless, EF remains the primary parameter for HF characterization and the primary inclusion criterion for clinical trials of HF. Advanced multivariable analytics (such as machine learning and other methods for patient clustering and phenotyping) as well as other parameters have demonstrated a better calibration and discrimination for survival than the use of EF alone 13. The clinical use of EF has flaws, which are described below in detail. Left ventricular ejection fraction (EF), generally measured by echocardiography, remains the cornerstone of HF diagnosis, characterization, prognosis, patient triage and treatment selection.
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HF is the leading cause of hospitalization among adults, and 1-year mortality is 10–35% in various population-wide registries, and is much higher in patients with advanced HF 9, 10, 11, 12. Despite the availability of effective therapies, the prognosis of patients with HF remains poor 8. As a result, the burden of HF-related hospitalizations and costs are increasing 5, 6, with the total costs for HF in 2012 estimated to be US$30.7 billion, of which more than two-thirds is attributable to direct medical costs, and projections suggesting an increase of 127% by 2030 (ref.
Topcat review drivers#
Drivers of the growing prevalence of HF are ageing of the population, improved survival after myocardial infarction, and improved treatment and survival of patients with HF 1, 2, 3, 4. Heart failure (HF) is a global pandemic with an increasing prevalence. These arguments support the current redefinition of HFmrEF as HF with mildly reduced EF instead of HF with mid-range EF. HFmrEF and HFpEF are milder forms of HF than HFrEF and are associated with a lower risk of cardiovascular and HF events but with a similar or greater risk of non-cardiovascular adverse events.Ĭlinical trials on therapies for HFpEF enrolled patients with an ejection fraction of >40% or ≥45% and did not demonstrate a clear treatment effect however, subgroup and post hoc analyses suggest that some therapies for HFrEF might also be effective in HFmrEF. HFmrEF is an intermediate HF type between HF with preserved EF (HFpEF) and HF with reduced EF (HFrEF) for some characteristics but is more similar to HFrEF for others, especially for the high prevalence of ischaemic heart disease.
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On the basis of contemporary trials and definitions, HFmrEF might be defined as an EF of 41–49%. Heart failure (HF) with mildly reduced ejection fraction (EF) (HFmrEF) has been extensively studied, generally using an EF of 40–49%, and accounts for up to 25% of patients with HF. Although the EF is a continuous measure with considerable variability, in this comprehensive Review we suggest that HFmrEF is a useful categorization of patients with HF and shares the most important clinical features with HFrEF, which supports the renaming of HFmrEF to HF with mildly reduced EF. Evidence from post hoc and subgroup analyses of randomized clinical trials and a trial of an SGLT1–SGLT2 inhibitor suggests that drugs that are effective in patients with HFrEF might also be effective in patients with HFmrEF. By contrast, the risk of non-cardiovascular adverse events is similar or greater in patients with HFmrEF or HFpEF than in those with HFrEF. HFmrEF is milder than HFrEF, and the risk of cardiovascular events is lower in patients with HFmrEF or HFpEF than in those with HFrEF. HFmrEF seems to be an intermediate clinical entity between HFrEF and HFpEF in some respects, but more similar to HFrEF in others, in particular with regard to the high prevalence of ischaemic heart disease in these patients. The prevalence of HFmrEF within the overall population of patients with HF is 10–25%. This category has been largely unexplored compared with heart failure with reduced EF (HFrEF defined as EF <40% in this Review) and heart failure with preserved EF (HFpEF defined as EF ≥50%). The 2016 ESC heart failure guidelines introduced a third EF category for an EF of 40–49%, defined as heart failure with mid-range EF (HFmrEF). Left ventricular ejection fraction (EF) remains the major parameter for diagnosis, phenotyping, prognosis and treatment decisions in heart failure.