Gender Differences in Iron Overload and Left Ventricular Function in a Cohort of Thalassemia Major Patients: A Prospective Study of a Single Italian Center Using Cardiovascular Magnetic Resonance.
Authors: Volpato Elisabetta , Cassinerio Elena , Fasulo Maria Rosaria , Pedrotti Paola , Pedretti Stefano , Dellegrottaglie Santo , Cappellini Maria Domenica , Roghi Alberto 
Published: April 2020

Abstract
Introduction: cardiac failure due to secondary iron overload remains the main cause of death in patients with b-Thalassemia Major (TM). Cardiovascular Magnetic Resonance Imaging (CMR) T2* technique is a new tool to assess myocardial iron concentration that allows to tailor the optimal iron chelation treatment for each patient.
Aim of the study: to assess left ventricular function and myocardial iron overload in a cohort of TM patients, cared at Hereditary Anemia Center in Milan, Italy.
Methods and Results: In 91 TM patients (33 males/58 females, mean age 32 ± 6 yrs) myocardial iron loading was assessed with the use of CMR T2* measurements (CMR Tools, Cardiovascular Imaging Solutions, London, UK). Left ventricular ejection fraction (LVEF) was also assessed with CMR. In the overall group hemoglobin levels were 9.0 ± 1.0 g/dl; the mean serum ferritin levels and iron intake during the six months before CMR evaluation were 1507 ± 1884 ng/ml and 0.34 ± 0.08 mg/kg/die respectively. T2* was significantly different between females and males (24 ± 11 and 32 ± 12 ms, respectively; p &lt; 0.0001), with significant differences in diabetes mellitus prevalence (17% vs 8%, p&lt;0.01) but not in age, serum ferritin, iron intake and hemoglobin levels (Table 1). Seven (7.6%) asymptomatic females showed a severe cardiac iron overload (T2* ≤ 10 ms), 9 patients (9.9%) moderate (T2* between 10.1 and 14 ms), 15 patients (16.4%) mild cardiac iron overload (T2* between 14.1 and 20 ms) and 60 patients (65.9%) had normal T2* (&gt; 20 ms). LVEF was significantly different between females and males (35% vs 57%, p&lt;0.001) with evidence of a significant relationship between iron overload severity and LVEF impairment (r=0.92).
Conclusions: CMR cardiac function and T2* assessment allow to detect pre-symptomatic cardiac iron overload. Females are more at risk for severe iron overload and left ventricular impairment. The prevalence of diabetes mellitus and compliance to chelation therapy could be relevant in explaining the gender differences.
Clinical parameters and T2* values in men and women with thalassemia major Men p Women SD: standard deviation Number of patients (n. of pts) 33 - 58 Age ± SD (years) 33 ± 6 ns 32 ± 6 Hemoglobin levels ± SD (g/dl) 9.0 ± 1.7 ns 9.0 ± 0.8 Ferritin levels ± SD (ng/ml) 964 ± 891 ns 1821 ± 2216 Iron intake ± SD (mg/Kg/die) 0.30 ± 0.07 ns 0.36 ± 0.09 Mean T2* value ± SD (ms) 32 ± 12 &lt;0.0001 24 ± 11 T2*&lt; 10 ms (n. of pts) 0 - 7 T2* between 10.1 and 14 ms (n. of pts) 1 - 8 T2* between 14.1 and 20 ms (n. of pts) 7 - 8 T2* &gt; 20 ms (n. of pts) 25 - 35 T2*&lt; 10 ms (n. of pts) plus LVEF≤ 57 % 0/0 (0%) - 6/7 (85.7%) T2* between 10.1 and 14 ms (n. of pts) plus LVEF≤ 57 % 1/1 (100%) - 3/8 (37.5%) T2* between 14.1 and 20 ms (n. of pts) plus LVEF≤ 57 % 3/7 (42.8%) - 1/8 (12.5%) T2* &gt; 20 ms (n. of pts) plus LVEF≤ 57 % 7/25 (28%) - 5/35 (14.3%)