Does the Measurement of Ejection Fraction Still Make Sense in the HFpEF Framework? What Recent Trials Suggest

Left ventricular ejection fraction (LVEF) is universally accepted as a cardiac systolic function index and it provides intuitive interpretation of cardiac performance. Over the last two decades, it has erroneously become the leading feature used by clinicians to characterize the left ventricular function in heart failure (HF). Notably, LVEF sets the basis for structural and functional HF phenotype classification in current guidelines. However, its diagnostic and prognostic role in patients with preserved or mildly reduced contractile function is less clear. This is related to several concerns due to intrinsic technical, methodological and hemodynamic limitations entailed in LVEF measurement that do not describe the chamber's real contractile performance as expressed by pressure volume loop relationship. In patients with HF and preserved ejection fraction (HFpEF), it does not reflect the effective systolic function because it is prone to preload and afterload variability and it does not account for both longitudinal and torsional contraction. Moreover, a repetitive measurement could be assessed over time to better identify HF progression related to natural evolution of disease and to the treatment response. Current gaps may partially explain the causes of negative or neutral effects of traditional medical agents observed in HFpEF. Nevertheless, recent pooled analysis has evidenced the positive effects of new therapies across the LVEF range, suggesting a potential role irrespective of functional status. Additionally, a more detailed analysis of randomized trials suggests that patients with higher LVEF show a risk reduction strictly related to overall cardiovascular (CV) events; on the other hand, patients experiencing lower LVEF values have a decrease in HF-related events. The current paper reports the main limitations and shortcomings in LVEF assessment, with specific focus on patients affected by HFpEF, and it suggests alternative measurements better reflecting the real hemodynamic status. Future investigations may elucidate whether the development of non-invasive stroke volume and longitudinal function measurements could be extensively applied in clinical trials for better phenotyping and screening of HFpEF patients.