Arrhythmias and Sudden Cardiac Death in Beta-Thalassemia Major Patients: Noninvasive Diagnostic Tools and Early Markers

Abstract

Beta-thalassemias are a group of inherited, autosomal recessive diseases, characterized by reduced or absent synthesis of beta-globin chains of the hemoglobin tetramer, resulting in variable phenotypes, ranging from clinically asymptomatic individuals to severe anemia. Three main forms have been described: heterozygotes, homozygotes β+, and homozygotes β°. Beta-thalassemia major (β-TM), the most serious form, is characterized by an absent synthesis of globin chains that are essential for hemoglobin formation, causing chronic hemolytic anemia. Cardiac complications represent a leading cause of mortality in β-TM patients, although an important and progressive increase of life expectancy has been demonstrated after the introduction of chelating therapies. Iron overload is the primary factor of cardiac damage resulting in thalassemic cardiomyopathy, in which diastolic dysfunction usually happens before systolic impairment and overt heart failure (HF). Although iron-induced cardiomyopathy is slowly progressive and it usually takes several decades for clinical and laboratory features of cardiac dysfunction to manifest, arrhythmias or sudden death may be present without signs of cardiac disease and only if myocardial siderosis is present. Careful analysis of electrocardiograms and other diagnostic tools may help in early identification of high-risk β-TM patients for arrhythmias and sudden cardiac death.

Atrial Fibrillation in β-Thalassemia: Overview of Mechanism, Significance and Clinical Management

“…Furthermore, iron overload is involved in block of ryanodine Ca ++ channels and in changes of sarcoplasmic Ca ++ release and reuptake mediated by oxidative stress. All these factors result in electrical heterogeneity, which is the substrate for triggered activity and re-entry circuits, representing the mechanism of origin of arrhythmias [ 32 ].…”

Evaluation of diagnostic accuracy tests of erythrocyte indexes in the differential diagnosis of beta thalassemia minor and iron deficiency anemia: A preliminary report

“…Moreover, the treatment of beta thalassemia is very difficult and despite the treatment, it can lead to disastrous results such as heart failure and sudden death. For all these reasons, the % sensitivity of the index method to be selected should be high enough 20,21 . The Bessman index was found to have a negative Youden Index (%) score (-29.83), and therefore the cut-off value of this index should be reversed (Table 4)…”

Contemporary non-invasive methods for the diagnosis of early cardiac dysfunction in young patients with beta-thalassemia major

“…Отлагането на токсичната форма на свободно желязо в миокарда крие риск от развитие на нарушения и в сърдечния ритъм. Най-честите клинично значими ритъмни нарушения сред възрастните са предсърдното трептене, предсърдно мъждене и интраатриална риентри тахикардия [17], като злокачествените камерни аритмии са специфични за тежка кардиотоксичност. За разлика от възрастните, при децата с БТМ водещи са камерните екстрасистоли [18].…”