PF787 THE EFFICACY OF ALENDRONATE FOR THE TREATMENT OF THALASSEMIA-ASSOCIATED OSTEOPOROSIS: A RANDOMIZED CONTROLLED TRIAL
Authors: P. Piriyakhuntorn, A. Tantiworawit, M. Phimphilai, S. Srichairatanakool, W. Teeyasoontranon, T. Rattanathammethee, C. Chai-Adisaksopha, E. Rattarittamrong, L. Norasetthada, P. Charoenkwan
Journal: HemaSphere (2019)

Background: The MIOT (Myocardial Iron Overload in Thalassemia) Network was a network of thalassemia and CMR centers built in 2006 in order to assure homogeneous and standardized cardiac iron overload assessment for a significant number of patients. Aims: We describe the impact of this ten-year Network on cardiac iron, complications and deaths in patients with thalassemia major (TM). Methods: 1746 TM patients (911 females; mean age 31.17 ± 9.09 yrs) were enrolled in the MIOT Network. Myocardial iron overload (MIO) was quantified by the multislice multiecho T2∗ technique. Biventricular function was quantified by cine images. Results: 1392 TM patients performed an end-of-study CMR. At the last CMR significantly higher global heart T2∗ values (35.44 ± 10.69 ms vs 29.16 ± 12.02 ms; P < 0.0001) and a significant lower number of patients with global heart T2∗<20 ms (26.3% vs 12.0%; P < 0.0001) were detected. Four patterns of MIO were identified: no MIO (all segments with T2∗≥20 ms), heterogeneous MIO and global heart T2∗≥20 ms, heterogeneous MIO and global heart T2∗<20 ms, and homogeneous MIO (all T2∗<20 ms). Figure 1 shows the frequency of the 4 patterns at both scans. At the last CMR a significant higher frequency of patients with no MIO and a significant lower frequency for the other three patterns indicating MIO were detected. In patients with global heart T2∗<20 ms a significant increase in left ventricular ejection fraction (EF) (difference: 3.2 ± 8.5 %, P < 0.0001) as well as in right ventricular EF (difference: 1.2 ± 8.9 %, P = 0.002) were detected. Based on CMR results the 75% of the patients changed the chelation therapy. At the last CMR the percentage of patients with an excellent/good compliance was significantly higher (94.8% vs 92.2%%; P < 0.0001). The complete history of cardiac complications-CC (heart failure, arrhythmias, pulmonary hypertension, myocardial infarction, angina, myo/pericarditis, peripheral vascular disease) was present for 1062 patients. Out of the 1001 patients with resolved CC or without CC before the enrolment in the project, the 6.6% had a CC before the enrolment in the project. During the study, the frequency of CC was 4.4 %, significantly lower (P = 0.023). In particular, the frequency of heart failure (HF) was significantly lower (3.5% vs 0.8%, P < 0.0001). Forty-six patients died during the study. HF continues to be the leading cause of death (30.4% of all causes), but there was a consistent decline in HF mortality rate, that was 60.2% in an Italian study dated 2004. No patients died for arrhythmias while cancer was the second leading cause of death.Summary/Conclusion: Over a period of 10 years, the continuous monitoring of cardiac iron levels and a tailored chelation therapy allowed a reduction of MIO in the 70% of patients, with consequent improvement of cardiac function and reduction of cardiac complications and mortality from MIO-related HF. So, a national networking was effective in improving the care and reducing cardiac outcomes of TM patients.