Are HFpEF and HFmrEF So Different? The Need to Understand Distinct Phenotypes.

Alberto Palazzuoli,Matteo Beltrami

doi:10.3389/fcvm.2021.676658

Abstract

Traditionally, patients with heart failure (HF) are divided according to ejection fraction (EF) threshold more or <50%. In 2016, the ESC guidelines introduced a new subgroup of HF patients including those subjects with EF ranging between 40 and 49% called heart failure with midrange EF (HFmrEF). This group is poorly represented in clinical trials, and it includes both patients with previous HFrEF having a good response to therapy and subjects with initial preserved EF appearance in which systolic function has been impaired. The categorization according to EF has recently been questioned because this variable is not really a representative of the myocardial contractile function and it could vary in relation to different hemodynamic conditions. Therefore, EF could significantly change over a short-term period and its measurement depends on the scan time course. Finally, although EF is widely recognized and measured worldwide, it has significant interobserver variability even in the most accredited echo laboratories. These assumptions imply that the same patient evaluated in different periods or by different physicians could be classified as HFmrEF or HFpEF. Thus, the two HF subtypes probably subtend different responses to the underlying pathophysiological mechanisms. Similarly, the adaptation to hemodynamic stimuli and to metabolic alterations could be different for different HF stages and periods. In this review, we analyze similarities and dissimilarities and we hypothesize that clinical and morphological characteristics of the two syndromes are not so discordant.

Highlights

Despite the last ESC guidelines introducing a new category for heart failure (HF) classification including those patients with mild ejection fraction (EF) reduction ranging from 40 to 49%, this subtype is still underdetermined and poorly represented in most clinical trials [1]
Current gaps arise from the recent introduction of this HF class and the indeterminate profile between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) that probably account for different phenotypes
heart failure with midrange EF (HFmrEF) represents a mixed model between HFpEF and HFrEF

Summary

INTRODUCTION

Despite the last ESC guidelines introducing a new category for heart failure (HF) classification including those patients with mild ejection fraction (EF) reduction ranging from 40 to 49%, this subtype is still underdetermined and poorly represented in most clinical trials [1]. A small proportion of patients enrolled in the HFmrEF group are considered with “recovered LVEF,” and interestingly, NT-proBNP, Gal-3, and hs-TnT are lower than in patients with persistent EF reduction, suggesting a different biomarker profile in this phenotype In both HFpEF and HFmrEF, inflammatory markers at admission are both predictive for all-cause mortality and rehospitalization [26]. Some processes are more relevant at the extremities (HFrEF myocyte death vs HFpEF inflammation or fibrosis), and in this spectrum, HFmrEF represents a continuum without a predominant underlying pathophysiology [32, 33] In this era in which a new precision phenotype is emerging in patients with HF, knowledge of different pathophysiologic pathways and of the laboratory profile of each patient may contribute to therapeutic decision and prognostic stratification (Table 2)

LIMITATIONS

CONCLUSIONS

Findings

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