Discussion
There are significant gaps in the understanding of myocardial augmentation and its relationship with exercise performance. This study addresses these by demonstrating that systolic and (to a lesser extent) diastolic myocardial velocities increase incrementally as exercise work rate increases in a linear fashion, in contrast to parameters that are measured throughout systole (LVEF, SV, GLS) which show a plateau after low intensity exercise. We provide ranges for the expected augmentation in healthy young adults both at low intensity and at peak exercise. We demonstrate that systolic velocities are very closely linked to VO2 throughout exercise and, in our study, systolic velocities during exercise are a better predictor of exercise performance than LVEF, SV or GLS; and we define a new parameter (SES) equivalent to the slope of this relationship that can predict exercise capacity.
Although the augmentation of normal and pathological heart function has been measured this is usually at the start, at some fixed point, during or after the cessation of exercise. This makes comparison complex. We found a 14% increase in LVEF during exercise with the majority of the increase happening during the initial bout of exercise which is very comparable with the existing literature which suggests that LVEF beyond the ventilatory threshold show a slightly plateau response12. In normal individuals, in an upright position, EDV slightly increases with incremental exercise, with either no change or small decrease in ESV 13,14. However body position effects the change in EDV and ESV during exercise. In a recumbent position EDV remains unchanged during exercise and an increase in seen in ESV 15. We used a semi-recumbent cycle ergometer and found a similar response to volumes.
GLS is a more advanced method of measuring LV function. Wang et al.(2014)16 showed a significantly increase in GLS and S’ during exercise in healthy control patients, our data showed a 25% increase in GLS and 89% increase in S’, which is a similar. However GLS is more problematic to measure at peak exercise because high heart rates may lead to speckle misregistration, although anecdotally higher than recommended heart rates are tolerated by the software. Cifra et al. , (2016) described a linear relationship between HR and GLS during exercise and showed that S’ obtained using colour Doppler tissue imaging showed excellent inter-and intra-observer variability. GLS measurements were more challenging to obtain during exercise due to lung interference and more excessive cardiac motion. However although peak systolic strain values showed higher interobserver variability it was still considered acceptable for clinical use 17.
There is limited data on the relationship between myocardial augmentation and exercise performance. We have previously published that peak systolic velocity and VO2 are closely correlated across a very wide range of diagnoses 5,18. This data, while an interesting proof of concept, does not resolve the question of whether the heart is behaving differently, or whether those with less severe disease are simply achieving more exercise and hence more myocardial augmentation. This central weakness, the confounding effect of exercise ability, runs through much of the contractile reserve literature. Attempts to resolve this by imaging at submaximal exercise are vulnerable to an incomplete understanding of the pattern of augmentation for each measured parameter.
The use of a semi-recumbent cycle ergometer allows the combination with CPET and echocardiography to be combined, providing additional insight into any observed changes in heart function. There have been limited attempts to relate changes on myocardial function on echocardiography with changes in VO2. In a study of 31 patients (12 with HF, 15 with preserved LVEF and 16 with reduced LVEF and 15 controls); they demonstrated an increase in S’ and E’ from baseline, to the ventilatory threshold up to maximal effort, a result similar to the data in a healthy cohort. GLS and LVEF also augmented but the relationship was weaker, as did the additional measures of the RV and circumferential strain 19. Resting LVEF is not able to predict VO2peak 4,20,21. However obtaining LVEF during exercise does have incremental prognostic value. HF patients who are able to increase LVEF by more than 5% have a better prognosis than those we do not 22. Evaluating GLS at rest is an independent and incremental prognostic tool regarding long-term risk in cardiovascular morbidity and mortality 23. However GLS at exercise requires more investigation.
In our study, we selected S’ as our principle long axis evaluation parameter as it is a reproducible measurement during exercise2. Mechanistically longitudinal S’ has previously shown to be an early indicator for ventricular dysfunction, as it is one of the principle engines of systole, and a fall often precedes a subsequent fall in LVEF24 during disease; unlike other parameters of both volumetric and longitudinal function S’ augmentation remained linear during exercise. In the analysis S’ was more predictive of VO2peak than EF or GLS both at 5 minutes of exercise, when all parameters showed augmentation and at peak exercise, when EF and GLS had plateaued. It is easily forgotten that strain and velocity measure different aspects of systolic performance and cannot be considered interchangeable. Work by Gu et al. (2017) looking at the first phase EF, during which with, normal activation, peak velocity is reached, has demonstrated that within systole the initial phase of contraction is the most important25. This provides a rationale for the superiority of systolic velocity over the whole systolic measures EF and GLS. Our study confirms the very tight relationship between VO2 and S’ throughout the whole of exercise, making it a very useful surrogate for VO2 and suggesting that the processes that increase myocardial velocity are central to determine exercise function.
By inference therefore variation in, or changes to, cardiac function would result in different relationships between VO2 and S’. This is important because of the potential that augmentation of S’ is simply reflecting a longer exercise time or greater workload making the relationship tautological. To understand the relationship between VO2 and S’ in greater detail we hypothesised that the individual ratios of S’ to VO2 (the amount of myocardial augmentation required to increase VO2 by a single unit) would be able to predict VO2peak values. We devised the term the Systolic Efficiency Slope (SES) to describe this. There was a relationship between the SES and VO2peak suggesting that this relationship may be important. But given that peak exertion can be heavily effort dependent we also looked at OUES (a well validated submaximal measure known to be highly related to VO2peak). Again there was a significant relationship. This contraction / metabolic coupling relationship has not been previously described in this way. The SES slope; a slope that does not require a pre-specified heart rate or maximal exercise to be achieved. While the data is not strong enough to suggest this as a clinical tool, we propose these may be suitable methods for future research.