Heart Failure: The Dilemma of the 40-50% Ejection Fraction Range
Authors: Henein Michael , Lindmark Krister , Coats Andrew , Lindqvist Per 
Published: February 2018

The common pathophysiology contributing to fluid retention and dyspnoea in heart failure is a non-compliant and stiff myocardium with raised left ventricular end-diastolic pressure. With the rapid development of newer imaging technologies, particularly echocardiography, our understanding of the syndrome of heart failure has significantly changed. The most important imaging sign in the early eighties was reduced ejection fraction (HFrEF), with low values being used as an explanation for the development of signs and symptoms.  In the early 2000s, similar Doppler echocardiographic signs became frequently recognised in patients with heart failure symptoms and signs who proved to have  a relatively maintained ejection fraction (EF) of >40%, hence the description of the syndrome of “diastolic heart failure”.  This was later rephrased as heart failure with normal ejection fraction (HFnEF) and more recently as heart failure with preserved ejection fraction (HFpEF). Since then, HFpEF has attracted the interest of many cardiologists and scientists worldwide, searching for specific features and treatment options for the syndrome. As for the features, two important findings have now been established, the first showed that LV systolic function mainly at the subendocardial level was abnormal in HFpEF, particularly manifesting during stress/exercise when the increase in heart rate was not associated with a commensurate increase in stroke volume and a second observation of a significant impairment of left atrial function (i.e. myocardial strain) and emptying fraction associated with increased left atrial pressures and the potential development of atrial arrhythmia in HFpEF. Such atrial abnormalities have been shown to be commonly associated with cavity enlargement and poor compliance. The latter observation has similarly been reported in patients with reduced EF.  Despite the above similarities in cardiac physiology between HFpEF and HFrEF, treatments of the two conditions differ markedly. When comparing HFrEF and HFpEF, we can easily see that some patients fall into the grey area on the EF spectrum with values fluctuating above and below 40%, suggesting that the substrate for the expected drug effect may differ, possibly explaining the lack of consistent response in these patients.. In addition, it should not be forgotten that most heart failure medications work on the circulation rather than the heart itself, hence the need for shared circulatory disturbances between the two conditions before we can reasonably expect identical treatment benefits when using the same medications in different clinical settings.  Therefore, it is clear that classifying heart failure patients according to a single measure of LV function i.e. ejection fraction fails to help at least 50% of patients presenting with this syndrome. In contrast, aggregating such patients based on clear evidence for raised LA pressures, irrespective of EF, might show evidence for a more consistent response to vasodilators and conventional heart failure therapy, particularly those patients currently described as HFpEF.