Assessing the relationship between left ventricular diastolic and systolic function during exercise in healthy volunteers using a novel individualised stress echocardiography protocol
Authors: Sharma C , Gibb J , Smith M , Williams M , Haywood A J , Emirza Cilbir C , Wadey C A , Stuart A G , Pieles G E , Williams C A , Dorobantu D M 
Published: January 2025

Abstract

Background
Exercise stress echocardiography (ESE) provides a non-invasive estimation of diastolic function during exercise and can provide insight into systolic-diastolic coupling response. Current protocols are confounded by individual variation in fitness and exercise tolerance, which in turn leads to ESE normative data being difficult to define.

Aims
This study aims to use ESE to describe the relationship between diastolic and systolic left ventricular function in healthy volunteers using physiologically defined personalised exercise intensity domains, accounting for individual HR response, exercise intensity and cardiorespiratory fitness.

Methods
Participants underwent resting echocardiography, then a maximal CPET followed by ESE consisting of two 6-minute stages: 1; Moderate intensity (M-Int) at 90% of the work rate at the gas exchange threshold (GET) and 2; High intensity (H-Int) at 40% of the difference between GET and peak exercise. Average (septal and lateral) peak systolic (LV-S’) and diastolic (LV-E’) longitudinal annular velocities as well as early diastolic mitral inflow velocity (E) were measured. E/E’ ratio was calculated to estimate LV diastolic filling pressure. Physical activity (PA) levels were assessed using age-appropriate questionnaires. Random effects linear mixed models were used to analyse exercise test data.

Results
A total of 101 healthy children and adults (mean age 37.8 ± 15.7 years, range 9-65, male 48.5%) were included. Participants’ PA was low in 13%, moderate in 54% and high in 33% and mean peak VO2 was 36.1 ± 7.7 ml/min/kg (range 21.3 to 60.2). LV-S’ increased significantly between rest, M-Int and H-Int, while E/E’ ratio remained constant, after adjusting for heart rate (Figure 1A and B). There was a significant inverse relationship between E/E’ ratio and LV-S’ at rest (b: -0.39, p&lt;0.001), M-Int (b: -0.7, p=0.007) and H-Int (b: -0.65, p=0.03), shown in Figure 2. When adjusted by exercise intensity, HR, age, gender, PA levels and peak VO2, this relationship remained statistically significant for M-Int (b: -0.42, p=0.02) and H-Int, (b: -0.71, p&lt;0.001) but not for rest (b: -0.01, p=0.9). In addition to E/E’ ratio, other factors associated with LV-S’ change during exercise were HR, age, gender and peak VO2 (p&lt;0.1 for all). Older age was associated with overall higher E/E' values (main effect 0.04/year) but not higher relative changes during exercise (interaction with Rest: p&lt;0.001, M-Int: p=0.7, H-Int: p=0.5).

Conclusion
This study shows dynamic changes in systolic-diastolic coupling during exercise, in healthy volunteers, not present at rest. Systolic-diastolic coupling could provide insight into pathological exercise limiting mechanisms, such as in heart failure with preserved ejection fraction. A sub-maximal individualised ESE protocol can be a useful tool to assess this physiological mechanism, without the bias of individual variation in cardiorespiratory fitness affecting current protocols.
Figure 1
Figure 2