The Conundrum of HFpEF Definition: Non-Invasive Assessment Uncertainties and Alternative Diagnostic Strategies

Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome including several morphological phenotypes and varying pathophysiological mechanisms. The conventional classification of HF based on left ventricular ejection fraction (LVEF) has created an oversimplification in diagnostic criteria. Although LVEF is a standardized parameter easy to calculate and broadly applied in the large clinical trials, but it is erroneously considered an index of left ventricular (LV) systolic function. Indeed, it is affected by preload and afterload and it has limitations related to reproducibility, reduced sensitivity and scarce prognostic values especially when above 50%. Notably, additional diagnostic parameters have been recently proposed in order to improve diagnostic accuracy and to homogenize the different HFpEF populations. Unfortunately, these algorithms comprise sophisticated measurements that are difficult to apply in the daily clinical practice. Additionally, the scarce diffusion of these diagnostic criteria may have led to neutral or negative results in interventional phase 3 trials. We propose changes to the current HFpEF diagnostic approach mainly based on LVEF stratification measurement aiming towards a more inclusive model taking into consideration an integrative approach starting from the main diseases responsible for cardiac dysfunction through to cardiac structural and functional alterations. Accordingly, with recent universal HF definitions, a stepwise model could be helpful in recognizing patients with early vs. overt HFpEF by the appraisal of specific Doppler echocardiographic variables. Thus, we would encourage the application of new criteria in order to better identify the different phenotypes and to move towards more personalized medicine.