Left ventricular volume regulation in heart failure with preserved ejection fraction

Abstract

Ejection Fraction (EF) has attained the recognition as indicator of global ventricular performance. Remarkably, precise historical origins promoting the apparent importance of EF are scant. During early utilization EF has been declared a gold standard for the evaluation of the heart as a pump. In contrast, during the last two decades, clinicians have developed a measure of doubt in the universal applicability of EF. This reluctance lead to the introduction of a new and prevalent syndrome in which heart failure (HF) is diagnosed as having a preserved EF (pEF). We examine the existing criticism regarding EF, and describe a novel avenue to characterize ventricular function within the unifying framework of cardiac input–output volume regulation. This approach relates end-systolic volume (ESV) to end-diastolic volume (EDV), and derives for a subgroup matching pEF criteria a distinct pattern in the ESV–EDV domain. In patients with pEF (n = 34), a clear difference (P < 0.0004) in the slope of the regression line for ESV versus EDV was demonstrated compared to control patients with EF < 50% (n = 29). These findings are confirmed by analysis of data presented in two independent publications. The volume regulation approach proposed employs primary end-point determinants (such as ESV and EDV) rather than derived quantities (e.g., the ratio EF or its differential parameter, that is, stroke volume) and confirms a distinct advantage over the classical Starling curve. Application of the ESV-EDV-construct provides the basis and clarifies why some patients present as HFpEF, while others have reduced EF.

Left ventricular volume analysis as a basic tool to describe cardiac function

“…Traditionally, the PV loop depends on the triad, preload (i.e., EDV), afterload (often interpreted as MAP, or ESP), and contractile state. The latter refers to intrinsic contractile properties of the heart muscle and is reflected by the maximum slope (Emax) of the elastance curve, which corresponds with the ratio of LV pressure over volume (11). This line shows an intercept (Vo) with the volume axis.…”

“…This means that, while taking a linear approach, Vo varies along with Emax, depending on the particular region where Emax is determined (3). Also, Vo has no direct physiological meaning, because it just refers to an extrapolation of a linearized approach used to describe systolic elastance in a simplified manner (11). In the nonlinear model, Emax should simply be viewed as the tangent at any particular point under consideration along the full trajectory of ESP-ESV combinations, the so-called end-systolic PV relationship.…”

Left Ventricle–Arterial System Interaction in Heart Failure

“…Experimental studies with volume loading have shown that utilization of Starling’s law is effective in improving LV function in the short term 11,12. Some investigators have shown that the alternative Starling’s law, based on the relation of SV to end-systolic volume (ESV),13,14 is a better indicator of LV function in HF. This may be more effective in identifying the differences between HFpEF and HFrEF patient groups.…”

“…In contrast, diastolic pressures for both the LV and aorta are not significantly different. These one-sided differences contribute to the finding that E max tends to be higher in HFpEF and therefore can be regarded as a cofactor leading to the uncoupling of EF and k 14. A larger pulse pressure (PP) is found in the HFpEF group, which is the consequence of a lower arterial compliance; as C is inversely proportional to PP 4,5…”

The authors’ reply to the letter from Kerkhof et al entitled ‘The importance of (measuring) the end-systolic volume index in predicting survival’

“…Unlike STICH, Kerkhof3 looked at subjects with heart failure with preserved ejection fraction. Additionally, they excluded patients on β-blockers because of the effect on the ejection fraction - end-systolic volume (EF-ESV) relationship, whereas 86% of the STICH population was on β-blockers.…”