In this study cardiac pathologies of patients with CD were tried to be determined by electrocardiographic and echocardiographic evaluations. In current study, consistent with the literature [3], high E/e' ratio, low E/A ratio, low mitral e' velocity, low tricuspid e' velocity and low MAPSE, low TAPSE values with impaired left ventricular systolic function, and impaired left ventricular diastolic function with impaired right ventricular systolic function were detected in cystinosis patients. These patients have an increased risk of tachyarrhythmia, sudden death, as well as ventricular dysfunction.
Cardiovascular system damage in CD is due to accumulation of cystine in myocardial tissue [4], increased free oxygen radicals as a result of altered ATP metabolism [29], damage caused by uremic toxins due to kidney damage [30], impaired kidney function and calcium metabolism, and vasculopathy as a result of disorder in cholesterol metabolism [31], and also it may develop due to damage as a result of inflammation and fibrosis in the myocardium as a result of changes in renin-aldosterone metabolism [32]. There are few studies in the literature regarding the cardiovascular system evaluation of cystinosis patients [3, 5–7].
Although the values of IVSd, LVPWd and, LVEDd were similar in our study, the significantly higher values of LVmass-i and RWT in the CD group support concentric hypertrophy of cardiac remodeling [27].
In this study, the absence of fractional QRS complexes in the ECGs of the CD group patients and the QRS duration and QRS-d values were similar to those of the control group, indicating that there was no depolarization pathology in the CD group [11]. No abnormalities in depolarization have been reported in patients with cystinosis.
The left ventricular myocardium consists of three layers: endocardial, midmyocardial, and epicardial. The electrophysiological properties of the three layers were different. The action potential duration was the shortest in the epicardial layer and longest in the mid-myocardial layer. Increased repolarization time and repolarization dispersion times are risk factors, especially for reentrant arrhythmias. In this study, increased QTc, QT-d, Tpe, and Tpe/QT values in the CD group showed that the CD group was at a risk of increased ventricular tachyarrhythmias. In addition, the increase in Tpe/QRS ratio and QTc/QRS ratio in the CD group, which are among the iCEB parameters, indicates that they are at high risk for increased ventricular tachyarrhythmias. iCEB, which has been used in recent years, is the ratio of the repolarization or repolarization dispersion time to the depolarization time. iCEB must be at a critical value. An increase or decrease in iCEB can cause torsadogenic or non-torsadogenic tachyarrhythmias, respectively. The study showed that iCEB provided more information than Tpe/QT ratio in predicting ventricular arrhythmia [17]. This study is the first to evaluate repolarization abnormalities and iCEB in the CD group.
In our study, the correlation between eGFR and ventricular systolic and diastolic parameters, repolarization dispersion, and iCEB parameters suggests that the possible pathology may have resulted from myocardial damage resulting from the accumulation of myocardial cystine cysts, uremic toxins, and free oxygen radicals. We believe that more comprehensive studies on this subject will help predict possible cardiovascular effects in the early period and to regulate treatments in this respect. This may worsen the existing findings with increasing deterioration in kidney function. This suggests that patients with cystinosis should be followed more closely in terms of cardiac monitoring and that the preservation of renal function tests may also provide protection against cardiac effects.
The small number of patients and the single-center design are the main limitations of our study. Second, leukocyte cystine, blood renin, and angiotensin levels were not measured during the study. The lack of coronary imaging data is another limitation of this study. We believe that performing coronary imaging studies by excluding vasculopathy by measuring leukocyte cystine levels, blood renin, and angiotensin levels, and performing coronary imaging in patients will provide more information on elucidating the mechanism of cardiovascular system pathology and may provide a possibility to develop treatment for a possible pathological mechanism.