5.
Discussion
In this study, we evaluated the relationship between echo parameters of
subclinical myocardial dysfunction, endothelial dysfunction parameters,
and MRI T2 * values which is the gold standard for cardiac iron
deposition.
Among the measured variables, all LVEF values obtained with 2DE were
normal (≥50%) and not significantly associated with MRI T2* values.
This finding is in agreement with previous studies which indicates its
inefficiency in predicting abnormal cardiac iron deposition (14). This
is likely due to limitations of 2DE compared to 3DE for measuring LVEF
which lead to systematic overestimation of volumes and LVEF2D (15). On
the other hand, since echocardiographic measurement of LVEF with 2DE may
be inaccurate in patients with regional wall motion abnormalities or
mechanical dyssynchrony, precence of heart failure can not be ruled out
even with normal LVEF2D (15).
In our study, in contrast to other published studies (16,17), levels of
serum ferritin were significantly different between two groups and
negatively correlated with MRI T2*. Our finding is similar to Wahidiyat
et al. -large-scale population-based- study which found statistically
significant correlation between serum ferritin level and liver and
cardiac T2* (18). This may indicate an ongoing remodeling process even
in patients with preserved LVEF2D and it is important to identify
patients while their cardiomyopathy is still reversible.
In the present study, while LVEF2D was preserved and not significantly
associated with MRI T2*, LVEF3D, SDI12 and SDI16 was significantly
different between two groups and negatively correlated with MRI T2*
findings. These relationships suggest that iron overload may play an
important role in the pathogenesis of ventricular dyssynchrony (19,20).
In light of evidence, we know that ventricular dysynchrony has an
independent mechanism of decrease in left ventricular systolic function
and is an important parameter in determining patients with severely
decreased left ventricular systolic function (21-23). Furthermore Bae et
al. demonstrated a significant improvement of ventricular dysynchrony
after the antihypertensive treatment when compared to the baseline
ventricular dysynchrony in hypertensive patients with preserved LV
systolic function (24). These findings show importance of properly
assessment of cardiac function particularly in this population.
While heart disease is the main cause of death in β-TM, vascular
endothelial pathologies as well as myocardial parenchymal injury has
been reported as the one of the main cause of cardiovascular
complications (25,26). Its known
that, vascular bed function and integrity were affected by chronic
hemolysis because both hemolysis and iron overload are the main causes
of oxidative damage in β-TM patients. Plasma-free hemoglobin, released
as a result of chronic intravascular hemolysis, directly causes the
formation of reactive oxygen species that catalyze oxidative damage in
vascular cellular structures. In addition, it has been observed that
free hemoglobin reacts with NO, causes NO deactivation and limits NO
diffusion from the endothelium to smooth muscle cells (27). Similarly,
the release of erythrocyte arginase during intravascular hemolysis may
limit the cellular availability of L-arginine, a substrate for NO
synthesis, and cause insufficient NO production (28). This imbalance
between NO production and consumption causes a decrease in NO
bioavailability and ultimately leads to the development of endothelial
dysfunction by inhibiting vasodilation (29). Endothelial dysfunction
probably contributes in part to the increase in arterial stiffness. Not
surprisingly, flow-mediated dilatation of the brachial artery and aortic
strain are important research tools for assessing vascular biology and
endothelial function and detects early stages of atherosclerosis.
(30,31). In the present study we found that FMD and aortic strain values
were significantly different between two groups and negatively colerated
with T2* values. Stakos et al. (32) showed in their study that, patients
with β-TM and normal cardiac iron levels documented by T2* and no
clinical signs of cardiac dysfunction, have also increased aortic
stiffness compared with normal control subjects. FMD was found
significantly impaired in patients with β-TM compared with healty
control group in another study (33). While our findings may lead to the
hypothesis that the aorta and peripheral arteries exhibit an accelerated
aging rate in negative correlation with cardiac T2 values, this group of
patients, including patients with normal T2 findings, may undergo a
lifelong process of vascular remodeling. Knowledge about the complexity
of the underlying mechanisms can help prevent or treat potential
complications.