Cardiac Iron Overload Assessed by T2* Magnetic Resonance (CMR) In Thalassemia Major Patients Treated with Different Iron Chelators

Although iron chelation therapy has markedly improved the survival, heart failure due to myocardial iron overload still remains the leading cause of morbidity and mortality in adult thalassemia major (TM) patients. T2* cardiovascular magnetic resonance (CMR) is a non invasive technique that provides rapid and direct assessment of myocardial iron content and its usefulness in monitoring iron chelation has been proved (Wood et al, Circulation 2009). AIM OF THE STUDY. To evaluate the efficacy of different iron-chelation therapies on removal of cardiac iron content assessed by CMR in adult TM patients. PATIENTS AND METHODS. Sixty-seven TM patients (27 males/40 women, mean age 35 ± 6 yrs) treated with different iron chelators underwent repeated cardiac CMR to assess myocardial iron load. Myocardial T2* was assessed at baseline (t₀), after 6–14 months (t₁) (according to clinical conditions and to T2* at baseline), and as second control (t₂) after a mean of 32±7 months from baseline. CMR was performed at Cardiology and CMR Department “A. De Gasperis” at Niguarda Ca' Granda Hospital in Milan, using a 1.5 Tesla MR scanner (Avanto Siemens, Erlangen). Normal cardiac T2* was defined > 20 ms; T2* < 10 ms indicated severe cardiac siderosis and T2* between 10 and 20 ms moderate-to-mild cardiac siderosis. Each patient has to be chelated with the same iron chelation therapy at least for 1 year before the baseline CMR evaluation. Patients were divided based on chelation therapy in 4 groups: group A (n=36, 53.7 %) patients chelated with deferasirox (DFX, mean actual dose 27±7 mg/Kg/die), group B (n=15, 22.4 %) deferoxamine (DFO, actual mean dose 48±9 mg/kg for a median of 6 days/week), group C (n=12, 17,9 %) DFO (mean actual dose 46±7 mg/kg for a median of 4 days/week) plus deferiprone (DFP, mean actual dose 73±7 mg/kg/day) and group D (n=4,6 %) only DFP (mean actual dose 75±0 mg/kg/day). Statistical analysis was performed using a paired Student's t-test. RESULTS. Overall, the pre-transfusional mean hemoglobin (Hb) was 9.7±0.5 g/dl, the median ferritin value was 913 ng/ml (range 229–5934 ng/ml) and the mean iron intake was 0.41±0.12 mg/Kg/day. In the overall population, the baseline myocardial T2* was < 10 ms in 8 patients (11.9 %), between 10 and 20 ms in 22 patients (32.8 %) and ≥ 20 ms in 37 patients (55.2 %). At baseline evaluation, T2* < 10 ms was detected only in 1 patient (1/36: 2.77 %) in group A, in 4 patients (4/15: 26.6 %) in group B and in 3 patients (3/12: 25 %) in group C. In group D all patients showed a myocardial T2* above 20 ms at baseline. Progressive changes in T2* values were observed at t₁ and t₂ for all the groups. Ten patients (10/36: 27.8 %) in group A, 3 patients (3/15: 20 %) in group B, 3 patients (3/12: 25%) in group C, respectively, moved from an abnormal T2* (< 20 ms) to normal values, in 32±7 months (Table 1). T2* values at t₂ improved significantly compared to baseline (p=0.0006) in patients treated with DFX (group A). In patients treated with combination therapy (DFO and DFP), T2* increased more rapidly in those with severe siderosis (T2* < 10 ms) (p=0.006). No significant changes in left ventricular ejection fraction (LVEF) values were observed in all groups of patients: only patients in group A with baseline cardiac T2* between 10 and 20 ms showed a slight improvement in LVEF (p=0.049). No statistically significant reduction in ferritin levels were associated with ameliorating myocardial T2* values. DISCUSSION AND CONCLUSIONS. Our data showed that compliance to chelation therapy at proper doses significantly improve myocardial T2* over 3-year treatment period. Continued treatment with deferasirox significantly increase myocardial T2* over time, showing its efficacy to remove iron from the heart. DFO and DFP combination therapy seems to ameliorate cardiac T2* more rapidly only in patients with T2* < 10 ms at baseline.

No relevant conflicts of interest to declare.