Discussion:
In the current study, systolic and diastolic dysfunctions determined by echocardiographic parameters were found similar with the healthy subjects. However, TD evaluation showed significant myocardial dysfunction. Although various studies declared that global cardiac functions were reserved and evaluated as normal by conventional echocardiographic findings in thalassemia major, regional wall abnormalities were shown by TD measurements.8,9,11-13
When we measured Em, Am and Sm velocities from three different regions of the myocardium, only Sm velocity were found significantly impaired in left ventricular and septal walls compared to the controls. However, these velocity measurements were not different from the controls in the right ventricular wall (p>0.05). This result showed that systolic functions in the left ventricle and septum were impaired in our patients. In addition to that, in the septal region Am velocity was different from controls. Agha et al.14, Yüksel et al.15, Balcı et al.16 and Ragap et al.17 were found only diastolic dysfunction according to velocities. But the another studies were found both diastolic and systolic dysfunctions.8,18-20 Interestingly Marci et al.21 were found Sm abnormalities, and ıt was correlated onset of adverse cardiac event. Mean age was 32 in this study. Although we found normal functions of the right ventricle, according to velocities, abnormalities were detected in the other studies.13,14,16,19 These studies were not same and there were many differences between them. For example; age groups studied, measured areas and TD parameters evaluated were different. In addition, some studies were correlated the results with BNP, ferritin or T2* MRI. Since the studies are not homogeneous, it is difficult to compare with each other.
In our study, we evaluated not only Em, Am and Sm velocities, but also time intervals such as ET, IVRT and indexes such as MPI and IVA. Limited data was found evaluated time intervals and indexes.17,20,22 Arı et al.20 found IVCT abnormality in left ventricle and septum, but ET, MPI and IVRT were normal. Uçar et al.22 found MPI and ET abnormality three different area, but IVRT was normal in the septum. Ragap et al.17 found MPI, ET and IVRT abnormality in the septum and lateral wall. These studies’ mean ages were under our study. We found MPI abnormality in the all three area, ET was only abnormal in the left ventricle. IVRT abnormality was found in left and right ventricle. We found a negative correlation between MPI-septal and T2*MRI scores (r:-0.343, p=0.05, Figure 2). In the Uçar et al.22study, MPI was found correlate BNP, but not was used MRI, and they reported that MPI was important for seeking early impairment. Also Arı et al.20 found correlation with MPI and T2* MRI result in the iron overload group. We found another positive correlation in the iron overloaded group was ET-septal and MRI results.
In the current data, we calculated IVA index. This parameter was very important in determining myocardial acceleration during isovolumetric contraction (early systolic phase) which was resistant to physiologic load changes.10 Our study was the second study evaluating IVA in thalassemia patients. Cheung at al.23 found similar IVA compared with controls in the resting, but during exercises, changes in the IVA was found low from controls. It was showed impaired contractile reserve in this patients. All of them had no cardiac co-morbidities, no Arrhythmias or bundle branch block. Like MPI, we found IVA abnormalities in all region, and in non iron-loaded patients compared with controls.
In thalassemia patients, the mean T2*MRI scores did not change according to serum ferritin levels (p>0.05). Neither TD nor T2*MRI measurements were correlated with serum ferritin level (p>0.05). Various studies also supported this finding that serum ferritin levels in thalassemia patients were not a reliable marker in estimating myocardial iron overload.3,18,22
We compared with according to T2*MRI result, only MPI-septal measurement was different between iron load or non-load group. There are a limited number of studies to evaluate comparisons. Arı et al.20, found Sm, Em and Am abnormalities in the left ventricular wall and detected Sm, MPI and IVCT abnormalities in the septal wall between iron load and non-load group. Agha et al.14 evaluated only velocities from three region and found tricuspid annular A and E/A abnormalities between iron load and non-load group. Vogel et al.8 was found 87% wall motion abnormalities in patient with T2*MRI<20 ms, versus found 35% wall motion abnormalities in patient with T2*MRI≥20 ms.
In our study, the septal measurements of Sm, Am and Em velocities, MPI, ET, IVRT were found similar with the controls in thalassemia patients with non-load group (T2*MRI≥20 ms.). Interestingly, when they were measured from left and right ventricular walls, they were found significantly impaired compared to the controls (Table III). When we searched the literature, only Agha et al.14 evaluated velocities from three region and found tricuspid annular A´ and E´/A´ abnormalities between non-iron load and control group. But there was no data comparing TD time intervals or indexes between healthy subjects and non-iron overloaded thalassemia patients. This patients who are T2*MRI result is ≥20 ms are usually considered as patients with no cardiac complications. T2* MRI shows myocardial iron load measured from septal region.4 Iron accumulation and its toxic effect are not evenly distributed in myocardium, regional differences can occur.24-26 Our data determined that only T2*MRI evaluating was insufficient to cardiac status in this group. Therefore, we strongly suggested to obtain TD measurements from right and left ventricular walls in thalassemia patients with T2*MRI≥20ms especially elder patients.