No Association of Genetic Markers with Carotid Intimal Medial Thickness in β-Thalassemia Major Patients

AbstractRegular transfusion leads to cardiac siderosis resulting in cardiac complications that account for more than 71% of the total mortality in thalassemia patients. We aimed to study the variants of matrix metalloproteinase-9 (MMP9), matrix Gla protein (MGP), and estrogen receptor α(ERα), which might be contributing to atherosclerosis, leading to heart failure in thalassemia major. One hundred and five thalassemia patients on regular transfusion and iron chelation therapy were enrolled for the study. Carotid artery intimal medial thickness (CIMT) measurement was done to check for atherosclerosis. MMP9 (C1562T), MGP (T138C), and ERα gene (PvuII (rs2234693T > C) and XbaI (rs9340799A > G) polymorphism were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. CIMT values were within the normal range (<0.90 mm) in all patients. There was no difference in mean CIMT values between males and females (0.56 ± 0.11 versus 0.56 ± 0.12, p = 0.928). There was no correlation of CIMT with age, body surface area, and body mass index as well as with serum ferritin levels. No statistically significant difference in frequency of MMP9, MGP, and ERα genotypes was seen in two dichotomized groups of CIMT (CIMT < 0.56 and CIMT ≥ 0.56). Variants of MMP9, MGP, and ERα have a reserved influence on cardiac disease pathogenesis, and the disease phenotype in thalassemia patients may be more strongly impacted by other factors.

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Impact of the period of the day on mortality and major cardiovascular complications after vascular surgeries

European Heart Journal ◽

10.1093/ehjci/ehaa946.3213 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

F.A.M Cardozo ◽

T Artioli ◽

B Caramelli ◽

D Calderaro ◽

P.C Yu ◽

...

Keyword(s):

Multivariable Analysis ◽

Total Mortality ◽

Mortality Rates ◽

Cardiovascular Complications ◽

Cardiac Complications ◽

Funding Source ◽

Confounding Variables ◽

Significant Difference ◽

One Year ◽

Night Period

Abstract Introduction Patients submitted to arterial vascular surgeries are at a high risk of postoperative cardiac and non-cardiac complications, therefore developing strategies to lower perioperative complications is essential to optimize outcomes for this subgroup. Recent studies have suggested that the period of the day in which surgeries are performed may influence postoperative major cardiovascular complications but there is still no evidence of this association in vascular surgeries. Purpose Our goal is to evaluate whether the period of the day in which surgeries are performed may influence mortality and cardiovascular outcomes in patients undergoing non-cardiac vascular procedures. Methods Patients who underwent non-cardiac vascular surgeries between 2012 and 2018 were prospectively included at our cohort. For this analysis, subjects were categorized into two groups: those who underwent surgery in the morning (7am - 12am) and those who underwent surgery in the afternoon/night (12:01pm - 6:59am). The primary endpoints were to compare the incidence of major adverse cardiac events (MACE - acute myocardial infarction, acute heart failure, arrhythmias, and cardiovascular death) and total mortality between morning and afternoon/night surgeries within 30 days and one year. The secondary endpoint was the incidence of perioperative myocardial injury (PMI) in both groups. PMI was defined as an absolute elevation of high-sensitivity cardiac troponin T (hs-cTnT) concentrations ≥14ng/L. Multivariable analysis using Cox proportional regression (with Hazard Ratio – HR and Confidence Interval – 95% CI) was performed to adjust for confounding variables, including emergency and urgent surgeries. Results Of 1267 patients included, 1002 (79.1%) underwent vascular surgery in the morning and 265 (20.9%) in the afternoon/night. After adjusting for confounding variables, the incidence of MACE at 30 days was higher among those who underwent surgery in the afternoon/night period (37.4% vs 20.4% – HR 1.43, 95% CI: 1.10–1.85; p=0.008). Mortality rates were also elevated in the afternoon/night group (21.5% vs 9.9%, HR 1.59, 95% CI: 1.10–2.29; p=0.013). After one-year of follow-up the worst outcomes persisted in patients operated in the afternoon/night: higher incidence of MACE (37.7% vs 21.2%, HR 1.37, 95% CI: 1.06–1.78; p=0.017) and mortality (35.8% vs 17.6%, HR 1.72, 95% CI 1.31–2.27; p<0.001). There was no significant difference in the incidence of PMI between groups (p=0.8). Conclusions In this group of patients, being operated in the afternoon/night period was independently associated with increased mortality rates and incidence of MACE. Mortality and MACE at one year Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): FAPESP - Fundação de Amparo a Pesquisa do Estado de São Paulo

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MRI evaluation of hepatic and cardiac iron burden in pediatric thalassemia major patients: spectrum of findings by T2*

Egyptian Journal of Radiology and Nuclear Medicine ◽

10.1186/s43055-019-0044-5 ◽

2019 ◽

Vol 50 (1) ◽

Cited By ~ 1

Author(s):

Samar M. Shehata ◽

Mohamed I. Amin ◽

El Sayed H. Zidan

Keyword(s):

Chelation Therapy ◽

Statistical Significance ◽

Iron Chelation ◽

Good Method ◽

Thalassemia Major ◽

Local Magnetic Field ◽

Cardiac Complications ◽

Liver Iron ◽

Cross Sectional ◽

Signal Decay

Abstract Background Iron deposition distorts the local magnetic field exerting T2* signal decay. Biopsy, serum ferritin, echocardiography are not reliable to adjust iron chelation therapy. Quantified MRI signal decay can replace biopsy to diagnose iron burden, guide treatment, and follow up. The objective of this study is to evaluate the role of T2* in quantification of the liver and heart iron burden in thalassemia major patients. This cross-sectional study included 44 thalassemia patients who were referred to MRI unit, underwent T2* MRI. Results Twenty-one male (47.7%) and 23 female (52.3%) were included (age range 6–15 years, mean age 10.9 ± 2.9 years). Patients with excess hepatic iron show the following: 11/40 (27.5%) mild, (13/40) 32.5% moderate, and (14/40) 35% severe liver iron overload. High statistical significance regarding association between LIC and liver T2* (p = 0.000) encountered. Cardiac T2* values showed no relationship with age (p = 0.6). Conclusion T2* is a good method to quantify, monitor hepatic and myocardial iron burden, guiding chelation therapy and prevent iron-induced cardiac complications.

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A randomized trial of amlodipine in addition to standard chelation therapy in patients with thalassemia major

Blood ◽

10.1182/blood-2016-06-721183 ◽

2016 ◽

Vol 128 (12) ◽

pp. 1555-1561 ◽

Cited By ~ 22

Author(s):

Juliano L. Fernandes ◽

Sandra R. Loggetto ◽

Monica P. A. Veríssimo ◽

Kleber Y. Fertrin ◽

Giorgio R. Baldanzi ◽

...

Keyword(s):

Chelation Therapy ◽

Combined Treatment ◽

Iron Chelation ◽

Thalassemia Major ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Cardiac Siderosis ◽

Key Points ◽

Effective Reduction

Key Points In thalassemia patients with cardiac siderosis, amlodipine combined with iron chelation resulted in more effective reduction of cardiac iron. The combined treatment did not have any effect on serum ferritin and left ventricular ejection fraction.

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Significant Improvement of Survival By T2* Cardiovascular Magnetic Resonance in Thalassemia Major

Blood ◽

10.1182/blood.v126.23.4567.4567 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4567-4567

Author(s):

Alessia Pepe ◽

Antonella Meloni ◽

Giovanni Carlo Del Vecchio ◽

Maria Antonietta Romeo ◽

Maria Rita Gamberini ◽

...

Keyword(s):

Heart Failure ◽

Cardiovascular Magnetic Resonance ◽

Magnetic Resonance ◽

Survival Data ◽

Cox Model ◽

Thalassemia Major ◽

Rank Test ◽

Cardiac Siderosis ◽

Kaplan Meier ◽

Significant Difference

Abstract Background: In 2004 seven Italian centers reported survival data for patients with thalassemia major (TM) and showed that heart disease due to iron overload was the most common cause of death (Borgna et al Haematologica 2004). In the same years the accurate and noninvasive assessment of cardiac siderosis was made possible in Italy by the introduction of the T2* cardiovascular magnetic resonance (CMR). Purpose: We aimed to evaluate if the deployment of T2* CMR had an impact on the mortality rate. Methods: Four centers contributed to the present study, updating the data of the enrolled patients until August 31, 2010. For the patients who died, the date of the death represented the end of the study. 577 patients (264 females and 313 males) were included. Results: One-hundred and fifty-nine (27.6%) patients died, 124 of whom (77.9%) died before the year 2000. The Table shows the comparison between dead patients and survivors. Dead patients were significantly younger and they were more frequently males. Dead patients started chelation therapy significantly later. HIV, arrhythmias and heart failure were significantly more frequent in dead patients. According to the Cox model, the following variables were identified as significant univariate prognosticators for the death: male sex (HR=1.87, 95%CI=1.34-2.60, P<0.0001), HIV (HR=2.55, 95%CI=1.25-5.20, P=0.010) and heart failure (HR=8.86, 95%CI=6.37-12.31, P<0.0001). MRI was not performed in 406 patients (70.4%) and no patient had been scanned before his/her death. Among the survivors, MRI was not performed in the 59% of the cases (P<0.0001). The absence of an MRI scan was a significant univariate prognosticator for death (HR=43.25, 95%CI=11.32-165.33, P<0.0001). The study was restricted to the patients dead after 2004 (19/159=12%) or followed until August 2010 (N=357). In this subgroup of 376 patients, MRI was not performed in the 52.4% of the survivors and in all dead patients (P<0.0001). The absence of a MRI exam was reconfirmed as a strong predictive factor for death (HR=49.37, 95%CI=1.08-2263.24, P=0.046). The Kaplan-Meier curve is showed in Figure 1. The log-rank test revealed a significant difference in the curves (P<0.0001). Conclusions: Our data suggests that the use of T2* CMR, that enables individually tailored chelation regimes reducing the likelihood of developing decompensated cardiac failure, allowed the reduction of cardiac mortality in chronically transfused TM patients. Table 1. Table 1. Figure 1. Figure 1. Disclosures Pepe: Novartis: Speakers Bureau; Chiesi: Speakers Bureau; ApoPharma Inc: Speakers Bureau.

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Serum Uric Acid As a Predictor Factor of the Response to Deferasirox Therapy for Patients with b-Thalassemia Major

Blood ◽

10.1182/blood.v118.21.5306.5306 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5306-5306

Author(s):

Efthimia Vlachaki ◽

Vasileios Perifanis ◽

Antonia Kondou ◽

Nikolaos Neokleous ◽

Aikaterini Teli ◽

...

Keyword(s):

Uric Acid ◽

Serum Uric Acid ◽

Research Funding ◽

Iron Chelation ◽

Thalassemia Major ◽

Iron Chelator ◽

Beta Thalassemia ◽

Positive Correlation ◽

Significant Difference ◽

Predictor Factor

Abstract Abstract 5306 Serum uric acid of patients with beta-thalassemia major (b-MA), despite the hyperuricosuria observed in these patients, is usually in the upper normal levels or increased due to excessive catabolism of the red blood cells (ineffective erythropoiesis). Deferasirox a new oral iron chelator with potential nephrotoxicity is recently used as iron overload treatment in patients with b-MA. Aim: Aim of the study is to investigate the effect of deferasirox on uric acid levels of patients with homozygous b-MA. Material-Method: 53 patients were enrolled to the present study with b-MA major, (aged 22.4 ± 14.7 years, range 4–12 years) 36 adults and 17 children, 32 females and 21 male. All the patients were transfusion-dependent with pretransfusional haemoglobin 9gr/dl and treated with iron chelation. The comparison was made between two different time points' measurements of uric acid and ferritin, at the beginning before Deferasirox, and one year later. The blood was taken from the patients early at mornings before the transfusion. Also uric acid was measured in 24 hour urine of patients under deferasirox, or other iron chelation therapy or after weekly discontinuation of deferasirox. Patients taken allopurinol or thiazide or with abnormal kidney function were excluded. Results: There is statistically significant difference (p< 0.001) between the mean annual value of serum uric acid (before 5.2 ± 1.3mg/dl) and ferritin (before 1653,4 ± 1026,3 ng/dl) before and after the start of deferasirox (uric acid after 4.2 ± 1.3 mg/dl and ferritin after 1529,07 ± 1137,44 ng/dl). Also, statistically significant positive correlation between the levels of serum uric acid and ferritin was found during the treatment with deferasirox. However, comparing the uric acid in urine of patients, it was not reported any statistically significant difference between treatment with deferasirox (859,75 ± 122), other iron chelators or without iron chelation for one week (844,32 ± 146). Conclusion: The mechanism of uric acid reduction in patients with b-MA major treated with deferasirox is not clear. However, it does not seem to be associated with excess of excretion by urine. The positive correlation between uric acid level and ferritin, allow us to consider uric acid as a predictor factor of the response to deferasirox therapy. Disclosures: Vlachaki: Novartis Hellas S.A.C.I.: Research Funding. Oikonomou:Novartis Hellas S.A.C.I.: Research Funding.

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Longitudinal Changes in Iron Overload Parameters and Iron Chelation Therapy in Young Patients with Thalassemia Major,

Blood ◽

10.1182/blood.v118.21.3202.3202 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3202-3202

Author(s):

Antonis Kattamis ◽

Konstantinos Stokidis ◽

Polyxeni Delaporta ◽

Kyriakopoulou Dimitra ◽

Theoni Petropoulou ◽

...

Keyword(s):

Iron Overload ◽

Chelation Therapy ◽

Iron Concentration ◽

Young Patients ◽

Iron Chelation ◽

Thalassemia Major ◽

Time Points ◽

Cardiac Siderosis ◽

Iron Load ◽

Oral Chelators

Abstract Abstract 3202 Background: New modalities for the assessment of iron overload and the availability of new oral chelators have led to important changes in the iron load status and its treatment for patients with thalassemia major (TM). The goals of this retrospective analysis were to evaluate the changes that occurred in regards to the degree of iron overload, as well as to the therapeutic regimen of iron chelation over the last decade in young patients with TM. Methods: All patients with TM followed in our unit, who were <18 years at certain time points, were included in this study. Group A included all patients who were younger than 18 years old on 1/1/2001, while group B, C, D, E and F on 1/1/2003, 1/1/2005, 1/1/2007, 1/1/2009, and 1/1/2011, respectively. Liver iron concentration (LIC) and cardiac siderosis (T2*) were evaluated by MRI. Cardiac iron concentration (CIC) was calculated based on the recently prescribed formula CIC= 45 × (T2*Heart)−1.22.The closest MRI, which was <12 months from the time point, was recorded for each patient at each group. The therapeutic regimen for iron chelation, being deferoxamine (DFO), deferiprone (DFP), combination therapy of DFO and DFP (DFO+DFP) and deferasirox (DFX), used at the different time points were also recorded. Results: The results of the analysis are shown in the following table: Ferritin levels did not change significantly over the last decade (p>0.05). There was a trend for decreasing values of LIC (Independent Samples Kruskal-Wallis test, p=0.075) with the mean LIC of group E and F being significantly lower than group C (Mann-Whitney test, p<0.05). Similarly, there was a trend for improvement in the indexes of cardiac iron load. Of note is, that cardiac overload was not documented in this group of patients. None of the patients has significant (T2*<10 msec), and only 3 patients had moderate cardiac siderosis (T2*>10 <20 msec). Conclusions: A steady decrease in the number of young patient with thalassemia has been observed, reflecting the efficacy of the thalassemia prevention program. As expected, the utilization of MRI to evaluate iron overload has increased significantly especially in the second part of the last decade, but it remains limited mainly to older children and teenagers. Oral chelation has become the preferable mode of treatment of hemosiderosis in young patients with TM. While DFX is, currently, the most used iron chelator, the use of DFO is becoming limited as an additive therapy to DFP. Despite presumed better compliance with oral chelation therapy, the iron overload indexes have not improved dramatically. This may reflect the short period of using the oral chelators or/and the need for further treatment intensification. Disclosures: Kattamis: Novartis Oncology: Honoraria, Research Funding, Speakers Bureau; Apopharma: Honoraria.

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Monitoring Cardiac Siderosis in Patients with Beta-Thalassemia Major on Various Chelation Regimens,

Blood ◽

10.1182/blood.v118.21.3177.3177 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3177-3177

Author(s):

Srikanth R. Ambati ◽

Rachel Randolph ◽

Kevin Mennitt ◽

Dorothy A Kleinert ◽

Patricia Giardina

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Iron Concentration ◽

Iron Chelation ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Liver Iron ◽

Beta Thalassemia Major ◽

Cardiac Siderosis ◽

Hepatic Iron Overload

Abstract Abstract 3177 Background: Patients with Beta-thalassemia major develop progressive iron overload in various organs. Cardiac siderosis is a major cause of mortality and morbidity in these patients, and also poses a significant treatment challenge. Methods: We have reviewed 101 beta-thalassemia major patients 39 Male (M) 62 Female (F) with a mean age of 27.9 (range: 2 to 60 years). All received regular transfusions to maintain pre transfusion Hb levels of 9 to10 gm/dl and all received iron chelation initially with deferoxamine (DFO) and subsequently treated with deferasirox (DFX) or deferiprone (DFP) in combination with DFO. Each patient was monitored yearly for iron excess by hepatic and cardiac magnetic resonance imaging (MRI) T2*. They were also assessed with monthly evaluations for liver and renal function (Bili, AST, ALT, BUN, Creatinine), serum ferritin, CBC (or weekly if on DFP), and urinalysis. Annual EKG, ECHO, hearing and vision testing and endocrine evaluations were also performed. The patients were grouped according to the severity of cardiac siderosis. Mild to moderate cardiac siderosis was defined as a T2* 12–20 msec and severe cardiac siderosis T2*≤ 11 msec. Annual studies were compared using paired student T test and repeated measures Analysis Of Variance (ANOVA) when necessary. Patient population: Twenty one of the 101 patients (7M and 14F) with a mean age of 30.6 yr, age range 15 to 56 yr, had abnormal cardiac T2* of <20 msec and three or more subsequent annual cardiac T2* measurements. Thirteen patients, 3 M 10 F with a mean age of 33 (range: 19 to 60), had severe cardiac siderosis and 8 patients, 3 M 5 F with mean age of 38 (range: 25 to 49), had mild-moderate cardiac siderosis. During the course of the observation their iron chelation therapy was optimized to reduce serum ferritin levels < 1500 μg/dl and to reduce or maintain liver iron concentration (LIC) ≤ 7 mg/gm dw. Data analysis: At the time of their first annual MRI study (baseline), 8 patients were on DFO of which 6 were switched to DFX, 13 patients were on DFX, 11 patients were dose escalated on DFX, and 4 patients were switched to combination chelation with DFO and DFP. At baseline, patients with severe cardiac siderosis had a mean cardiac T2* level = 7.4 ± 0.47 SEM (range: 4.6 to 11msec). Over the treatment course of 6 years annual cardiac T2* levels consistently improved and by 6 years cardiac T2* reached a mean level =14.3 ±1.5 SEM (range: 12 to 17 ms) (Fig 1). Those patients who at baseline had a mild to moderate cardiac siderosis with mean cardiac T2* of 14.6 ± 1.02 SEM (range: 12 to 19 msec) improved by 3 years of treatment when they achieved a mean cardiac T2* of 26.3 ± 3.4 SEM (range of 16 to 42 msec) (Fig 2). Liver iron concentration (LIC) was measured annually by MRI. Initially the majority, 16 out of 21 of patients, had hepatic iron overload LIC ≤ 10 mg/ gm dw of whom 56% (9 of the 16) had severe cardiac siderosis. 5 of 21 patients had a LIC > 15 mg/ gm dw of whom 80% (4 out of 5) patients had severe cardiac siderosis (Fig 3). Patients with LIC ≤10 mg/ gm dw had ferritin levels ranging from 166 to 3240 μg/ dl and patients with LIC >15 mg/ gm dw had elevated serum ferritin levels of 1180 to 17,000 μg/ dl. Patients with severe cardiac siderosis had mean MRI ejection fraction (EF)= 55.8% (range: 31 to 70%) while patients with mild to moderate cardiac siderosis had mean MRI EF= 60% (range: 53 to 66%). One patient with severe cardiac siderosis was recovering from symptomatic congestive heart failure. Conclusion: Cardiac siderosis can be noninvasively diagnosed utilizing MRI T2* techniques and subsequently to monitor treatment. The majority of patients improve cardiac T2* over time with optimal chelation therapy. Severe cardiac siderosis occurs even with mild to moderate hepatic iron overload. Left ventricular EF may not predict severe cardiac siderosis. Therefore it is important to annually monitor cardiac siderosis with MRI T2*. Disclosures: No relevant conflicts of interest to declare.

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Combination iron chelation therapy with deferiprone and deferasirox in iron-overloaded patients with transfusiondependent β-thalassemia major

Clinics and Practice ◽

10.4081/cp.2017.912 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 10

Author(s):

Hossein Karami ◽

Mehrnoush Kosaryan ◽

Arash Hadian Amree ◽

Hadi Darvishi-Khezri ◽

Masoomeh Mousavi

Keyword(s):

Combination Therapy ◽

Cardiac Mri ◽

Iron Concentration ◽

Iron Chelation ◽

Thalassemia Major ◽

Liver Mri ◽

Duration Of Treatment ◽

Liver Iron ◽

Significant Difference ◽

Before And After

There are few papers on the combination therapy of deferiprone (DFP) and deferasirox (DFX) in iron-overloaded patients with transfusion-dependent β-thalassemia major (β-TM). A total of 6 patients with β-TM (5 males and 1 female) with a mean age of 23.8±5.8 years (ranging from 17 to 31) used this treatment regimen. The mean doses of DFP and DFX were 53.9±22.2 and 29.3±6.8 mg/kg/day, respectively. The duration of treatment was 11.5±4.6 months. Their serum ferritin levels were measured to be 2800±1900 and 3400±1600 ng/mL before and after treatment, respectively (p<0.6). Their cardiac magnetic resonance imaging (MRI) T2* values were 16.69±15.35 <em>vs</em> 17.38±5.74 millisecond (ms) before and after treatment, respectively (p < 0.9). Although there was no significant difference between their cardiac MRI T2* values before and after treatment statistically, the values improved after combination therapy with DFP and DFX in most of the patients. Liver MRI T2 * values were changed from 2.12±0.98 to 3.03±1.51 ms after treatment (p < 0.01); Further, their liver T2* values and liver iron concentration (LIC) were improved after treatment. Our study found that cardiac MRI T2* values, liver MRI T2* values, and LIC were improved after combination therapy with DFP and DFX in β-TM patients and that DFP and DFX combination therapy could be used to alleviate cardiac and liver iron loading.

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

Blood ◽

10.1182/blood.v116.21.4275.4275 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4275-4275

Author(s):

Elena Cassinerio ◽

Alberto Roghi ◽

Patrizia Pedrotti ◽

Francesca Brevi ◽

Laura Zanaboni ◽

...

Keyword(s):

Chelation Therapy ◽

Iron Chelation ◽

Thalassemia Major ◽

Iron Chelators ◽

Iron Chelation Therapy ◽

Myocardial Iron ◽

Cardiac Siderosis ◽

Group A ◽

Group B ◽

Group D

Abstract Abstract 4275 Introduction. 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. Disclosures: No relevant conflicts of interest to declare.

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