Electrocardiographic consequences of cardiac iron overload in thalassemia major

Abstract

Background Iron cardiomyopathy is a leading cause of death in transfusion dependent thalassemia major (TM) patients and MRI (T2*) can recognize preclinical cardiac iron overload, but, is unavailable to many centers. Design and Methods We evaluated the ability of 12-lead electrocardiography to predict cardiac iron loading in TM. 12-lead electrocardiogram and cardiac T2* measurements were performed prospectively, with a detectable cardiac iron cutoff of T2*less than 20 ms. Patients with and without cardiac iron were compared using two-sample statistics and against population norms using age and gender-matched Z-scores. Results 45/78 patients had detectable cardiac iron. Patients having cardiac iron were older and more likely female but had comparable liver iron burdens and serum ferritin. Increased heart rate (HR) and prolonged corrected QT interval (QTc) were present, regardless of cardiac iron status. Repolarization abnormalities were the strongest predictors of cardiac iron, including QT/QTc prolongation, left shift of T-wave axis, and interpretation of ST/T-wave morphology. Recursive partitioning of the data for females using T-axis and HR and for males using QT, HR and T-axis produced algorithms with AUROC’s of 88.3 and 87.1 respectively. Conclusions Bradycardia and repolarization abnormalities on 12-lead electrocardiography were the most specific markers for cardiac iron in thalassemia major. Changes in these variables may be helpful to stratify cardiac risk when cardiac MRI is unavailable. However, diagnostic algorithms need to be vetted on larger and more diverse patient populations and longitudinal studies are necessary to determine reversibility of the observed abnormalities.

Deferiprone (GPO‐L‐ONE®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

“…Both patients had normal LVEF (>56%) at baseline and there was no deterioration of cardiac function after 1 year of treatment. Because of overall cardiac iron evaluation by T2*, in our patients was normal, we observed no abnormal electrocardiographic findings found to be associated with cardiac iron overload as described by Detterich et al [30] during the study period. All baseline echocardiography parameters research article American Journal of Hematology Figure 2.…”

Cardiac complications in beta-thalassemia: From mice to men

“…42 Cardiac arrhythmias, including premature ventricular contraction, ST-T changes, QT prolongation, and second-and third-degree atrioventricular block have been reported in iron overload beta-thalassemia patients. [43][44][45][46] In view of cardiac complications, serum ferritin concentrations have been shown to correlate poorly with all stages of cardiac dysfunction. 35,47 Non-transferrin-bound iron (NTBI) seems to be the most accurate parameter among serum iron markers; however, it is commonly used only in research studies.…”

Cardiovascular Function and Treatment in β-Thalassemia Major

“…90 Electrocardiographic changes most specifically associated with cardiac iron include repolarization abnormalities and relative bradycardia. 91 It is not known whether progressive alterations in electrocardiographic tracings occur before HF develops.…”