Discussion
The main findings of our study were as follows: (1) Individuals with ERP
had significantly higher LV dimensions, LV wall thickness, RV dimension;
(2) a significant inverse interaction was observed between ERP and GLS;
(3) ERP had an impact on regional longitudinal and circumferential SR
values. The lower longitudinal SRS, SREand SRA were mainly found at the A3C and the lower
circumferential SRS and SRE were mainly
seen in the basal segment of LV. To our knowledge, this is the first
study for demonstrating an important relationship between ERP and both
LV longitudinal and circumferential strain and SR parameters.
ERP is associated with an increased risk of sudden cardiac arrest due to
idiopathic ventricular fibrillation in the general population1,5,17. Unfortunately, these arrhythmic events can be
seen in the young people without cardiac disease such as ischemic heart
diseases, cardiomyopathies 18. However, Trenkwalder et
al. and McNamara et al. showed that the morphological changes of LV
began to be seen in ERP subjects 9,10. In these
subjects, ventricular dysfunction can not be determined with the use of
conventional echocardiographic modalities 18,19. STE
and TDI can clearly detect subtle ventricular dysfunction by calculating
the ventricular strain and SR which are more sensitive indicators than
LVEF 20,21.
In our study, we found that both LV and RV dimensions, and LV wall
thickness were significantly increased in subjects with ERP. In
addition, it was observed that LV mass and RWT were significantly higher
in ERP group. Our results are consistent with the previous studies9,22,23. These results suggest that ERP can lead to LV
structural changes. As we known, LV radius, LV wall thickness and
hemodynamic conditions impose onto LV- wall stress (WS)24. In ERP group, increased LV volumes may lead to
proliferation of LV myocardium to normalize LV- WS. These structural
changes may be accompanied by oxygen demand- supply mismatch which leads
to myocardial systolic dysfunction, even before LVEF reduces.
The most important finding of our study was that ERP participants had a
significantly lower GLS. There are plausible mechanisms for why ERP
produced impaired GLS. Firstly, ERP can mediate impaired GLS through its
effects on LV structural changes. Especially, the increased LVESV and
LVEDV can lead to increased WS followed by impaired GLS. Because,
ventricular strain and SR has been known as WS dependent indicators. In
line with our work, several studies have also reported a significant
inverse relationship between WS and strain and SR parameters25-28. The second mechanism for impaired GLS values
may be that mutations in genes can cause both ion channel dysfunction
and myocardial dysfunction 29,30. Chen et al. showed
that CACNA1C/ DES/ MYPN mutations are the pathogenic substrates for the
clinical manifestation in the hypertrophic cardiomyopathy patients with
ERP 29. ERP could be a heritable condition with
variable penetrance and incomplete phenotypic manifestation. In such
patients, impaired GLS may also guide further genetic analysis. To our
knowledge, our study was the first to evaluate the relationship between
GLS and ERP and also to explain the possible underlying mechanisms for
impaired GLS in ERP subjects. However, unlike to these findings, Gulel
et al. reported that myocardial deformation parameters including
longitudinal and circumferential S/ SR were not affected by ERP31. The main reason for this unexpected result in
Gulel et al. may be due to lower number participants in their study. In
addition, mean age was lower in Gulel’s study. The possibility of ERP
induced morphological and functional changes on the myocardium may
increased with advancing age.
The significantly lower longitudinal SRS,SRE and SRA at the A3C in ERP can be
consistent with the significantly higher IL wall dimension in ERP group
due to WS relationship. In addition, these findings may be consistent
with the animal studies which showed higher levels of transient outward
potassium current (Ito) in the inferior wall and lateral
wall of canine myocardium 32. Because, long non-
coding RNAs which has been known as myocardial K+ channel regulators may
play an important role in subtle myocardial dysfunction in the region
with higher Ito density 33.
The association between ERP and impaired basal segment circumferential
SRS and SRE deserves further comment. We
previously explained that the morphological changes related to ERP could
be affected by ion channel density. The density of potassium (K+)
channel varies from apical segment to basal segment of LV34,35. The density of K+ channel in apical segment is
approximately twice as high as in basal segment 35. In
accordance with our previous findings, in ERP group, the lower frequency
of basal segment ion channel density may be associated with a thinner
wall thickness in basal segment than that in apical segment. In
addition, basal segment has the largest radius as compared to mid and
apical segment of LV. The combined effect of basal segment’s ion channel
density and large radius may cause significantly higher WS in the basal
segment of LV in subjects with ERP than those without ERP, resulting in
the fact that LV basal segment needs more energy for both contraction
and relaxation than mid and apical segment do. Consequently, the
presence of ERP accompanied by worse basal segment circumferential
SRS and SRE.