The associations of ECG, ECHO, T2* MRI and ferritin levels with results of these exams were evaluated in patients with β-TM. Cardiac T2* MRI results were within pathological limits (< 20 msec) in 12 (29.27%) patients. All parameters (except JTc interval) in ECG were detected significantly increased in patients with β-TM when compared to the control group of this study. On the other hand, LVM and LVMI were increased in the patient group compared to the control group, and a statistically significant difference was found between the two groups. However, there was not any statistically significant difference in other ECHO findings. When the patients were examined by dividing them into 2 groups according to cardiac T2* score results as < 20 msec and > 20 msec, all findings in except P wave and T peak-end/QT were detected increased in the T2* scores < 20 msec group when compared to T2* >20 msec group. In ECHO findings, IVST, LVPWT, LVM and LVMI were increased in T2* <20 msec group; there was not any difference for other parameters. When the correlation between cardiac T2* and ECG and ECHO findings was reviewed, a negative correlation was found between the heart rate, PR interval, LVM and LVMI and cardiac T2*. On the other hand, a positive correlation was detected between ferritin and QRS interval.
The height, weight and BMI values of patients were lower than the control group in our study. Furthermore, lower haemoglobin level and higher platelet count, WBC count, uric acid level, total bilirubin level and ferritin levels in the patients are considered to develop due to frequent transfusions, and this is a common finding (table 1). Although it is less common in patients receiving regular transfusions, retardation of growth is an expected finding in patients with β-TM. Anemia is not the only cause of growth retardation in these patients. Not using a regular chelator is also one of the factors that cause impairment in growth hormone production. Furthermore, chelators themselves may cause growth retardation. Along with aging, the retardation of growth and development, prominence on the bones of the maxillary region, protrusion on the frontal bones, and a specific facial appearance defined as "thalassemia face" appears [20, 21].
We detected cardiac T2* MRI result of 12 (29.27%) of 41 patients as < 20 msec. The presence of iron overload in 12 patients despite receiving iron chelation therapy regularly is an indicator of how susceptible patients with β-TM are to cardiac complications (table 2). Cardiac iron accumulation is generally increased in patients with β-TM due to frequent transfusions despite chelation therapy, and T2* MRI is used to show cardiac iron load [11, 12, 22, 23]. Therefore, T2* MRI is performed once a year regularly as in our patients. Since biopsy is an invasive procedure to measure myocardial iron accumulation, alternative methods are needed. For this purpose, the cardiovascular T2* MRI which is a non-invasive method has become the gold standard to evaluate the cardiac response to iron chelation therapy in patients with β-TM in order to measure myocardial iron and determine ventricular functions [11, 12, 24, 25].
Cardiac complications caused by excessive iron overload are pericarditis, arrhythmias, and myocardial dysfunction. We had our patients to have ECG at every control in order to detect cardiac rhythm disorders of our patients earlier. As shown in Table 3, all ECG parameters except JTc interval were found significantly prolonged in the patients when compared to the controls. One of the symptoms of cardiac failure is prolongation of PR interval on ECG. Abnormalities of the T wave are a late finding. It is more common in those at older age and higher iron load . Rhythm disorders often start with atrial extra-systoles in the second decade. Ventricular extra-systoles may occur in the middle of the second decade and their frequency gradually increases . If there is a decrease in the ejection fraction (EF) along with resistant arrhythmias, this finding is accepted as a sign that symptomatic cardiac failure will develop within one year. Atrial and ventricular pulses, paroxysmal atrial tachycardia, flutter, and fibrillation may be observed as a result of iron accumulation in the cardiac conduction systems [28, 29]. The conduction system and atria are affected less than ventricles. Patients with mild cardiac dysfunction are usually limited with perinuclear areas, and a few fibre cells are affected. It is observed that a large number of myocardial fibre cells are affected by iron deposition in patients with obvious cardiac dysfunction .
Our patients who are followed up in our centre are evaluated with ECHO once a year in order to detect other cardiac complications and cardiac functions, except rhythm disorders, if any. For this purpose, we evaluated EF, FS, LVEDD, LVESD, IVST and LVPWT by ECHO. LVM and LVMI were significantly higher in patients when compared to the controls. We did not find any statistically significant difference in other ECHO parameters in the patient and control groups. Although it was not statistically significant, IVST measurements were found increased in the patient group when compared to the control group. Iron accumulation in the heart causes hypertrophy, enlargement, and myocardial fibrosis. Heart failure due to iron accumulation in the myocardium often occurs around 20 years of age. The cardiac decompensation caused by iron load is the cause for 70% of deaths [7, 8, 30]. The iron is deposited in myocytes in the cardiac muscle. The free iron atom in the myocyte increases free radical production and causes deterioration in the structure of the mitochondrial respiratory chain .
Twelve of our patients with cardiac T2* result below 20 msec were patients with higher cardiac iron load, and 29 patients were with cardiac T2* result above 20 msec were those with normal cardiac iron load. When ECG findings were considered, all ECG findings except P wave duration and T peak-end/QT ratio were found significantly prolonged in our patients with cardiac T2* results below 20 msec when compared to patients with cardiac T2* results above 20 msec. These results indicate that those with increased cardiac iron load may have more arrhythmia problems. When evaluated according to these results, it is considered that the increase in ECG disorders in the patients may also be related with cardiac iron load when compared to the controls. Previous studies that evaluate the results obtained with cardiac T2* in patients with β-TM found that ECG findings of patients with increased cardiac iron load presented arrhythmic findings [32–34].
Cardiac T2 * results showed that IVST, LVPWT, LVM and LVMI values were higher in patients with results below 20 msec in comparison to patients with cardiac T2* findings above 20 msec. This result shows that our patients with cardiac T2* value below 20 msec started to be affected along with ECHO findings. Although these results are stated in many studies in the literature, they were not emphasized sufficiently in studies conducted on adults [32, 33].
The associations between ECG and ECHO findings as well as cardiac T2* and ferritin results of the patients were examined. The negative correlation of heart rate and PR interval with cardiac T2* result and the positive correlation of QRS interval with ferritin support each other. In addition, a negative correlation was found between the values obtained with LVM and LVMI in ECHO and the cardiac T2 * score. These results indicate that both cardiac T2* and serum ferritin level are important to monitor the development of cardiac complications. There are studies in the literature indicating that ECG findings and cardiac functions are associated with ferritin level and cardiac T2* results. Eghbali et al. did not detect any association between cardiac T2* findings and serum ferritin levels; however, Yuksel et al. found a negative correlation [35, 36].
Our study had some limitations. The first limitation is conduction of the study on a small group of patients. Furthermore, we could not perform a 24-hour ECG monitoring and effort ECG monitoring. Therefore, our study may be insufficient to detect the development of prospective arrhythmic events.