Impaired preload reserve is an important haemodynamic characteristics that discriminates between physiological ageing and overt heart failure with preserved ejection fraction
Authors: Shono A , Matsumoto K , Yamada N , Kusunose K , Suzuki M , Sumimoto K , Tanaka Y , Yamashita K , Shibata N , Yokota S , Suto M , Dokuni K , Tanaka H , Hirata K 
Published: February 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Ageing process per se is a major risk factor for heart failure (HF). In fact, the incidence of HF with preserved ejection fraction (HFpEF) dramatically increases with age. Although ageing plays a central role in the development of HFpEF, not all the elderly patients develop clinical HFpEF. Multiple abnormalities in the cardiovascular system have been proposed to contribute to the development of HFpEF. However, the pathophysiology that discriminates between physiological ageing and overt HFpEF is incompletely understood.

Purpose
The purpose of this study was to assess the effects of ageing on the cardiac structures and haemodynamics. Moreover, we evaluated the determinant factor that discriminates between physiological ageing and overt HFpEF by non-invasive preload increasing manoeuvre using leg-positive pressure (LPP) stress echocardiography.

Methods
A total of 91 subjects were prospectively recruited in this study: 22 patients with HFpEF and 69 healthy controls. Normal controls were further stratified into 3 age groups: young (n = 19, 20-40 years of age), middle-aged (N = 25, 40-65 years) and elderly (n = 25, &gt;65 years). All subjects underwent LPP stress with a continuous external pressure of 90 mmHg around both lower limbs using dedicated airbags (Fig.).

Results
The left ventricular mass index (LVMI; young, 68 ± 19 g/m²; middle-age, 70 ± 18 g/m²; elderly, 84 ± 21 g/m²) and also the relative wall thickness (RWT; young, 0.34 ± 0.09; middle-age, 0.41 ± 0.06; elderly 0.55 ± 0.10) increased with ageing, which was accelerated in HFpEF (LVMI: 111 ± 32 g/m², RWT; 0.63 ± 0.19, ANOVA P &lt; 0.001, respectively). Although baseline LV ejection fraction and cardiac output were quite comparable between groups, E/e’ ratio significantly increased with with ageing (ANOVA P &lt; 0.001, Fig.). During LPP stress, E/e’ ratio significantly increased in the middle-aged and elderly groups (from 8.8 ± 2.7 to 9.7 ± 3.3, and from 11.4 ± 2.4 to 13.0 ± 2.2, P &lt; 0.05, respectively), which was further deteriorated in HFpEF (from 16.8 ± 5.8 to 18.0 ± 7.6, P &lt; 0.05). On the other hand, stroke volume index (SVi) significantly increased in each healthy group during LPP stress (young; from 45 ± 10 to 50 ± 11 mL/m², middle-age; from 39 ± 7 to 44 ± 6 mL/m² and elderly; from 37 ± 7 to 43 ± 8 mL/m², all P &lt; 0.001), while SVi failed to increase in the HFpEF group (from 45 ± 13 to 45 ± 14 mL/m², P = 0.60). In a multivariate logistic regression analysis, LVMI (hazard ratio; HR 1.055, P &lt; 0.05), baseline E/e’ (HR 1.444; P &lt; 0.05), and ΔSVi (HR 0.755; P &lt; 0.05) during LPP stress were the independent parameters that characterised overt HFpEF.

Conclusions
Striking parallels between structure-function alterations were observed in the physiological cardiovascular ageing process, which was further accelerated in patients with HFpEF. Not only structural remodeling and impaired diastolic function, but also impaired systolic reserve during preload stress is important haemodynamic feature that characterise the pathophysiology of HFpEF.
Abstract Figure.