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.