Benign Cardiac Effects of Hemoglobin H Disease

2016 ◽  
Vol 135 (4) ◽  
pp. 200-207
Author(s):  
Claire Sheeran ◽  
Donald K. Bowden ◽  
Sant-Rayn Pasricha ◽  
Ken Cheng ◽  
Giovanni Romanelli ◽  
...  
Keyword(s):  
Ferritin Level ◽  
Left Ventricular ◽  
Iron Loading ◽  
Myocardial Iron ◽  
Normal Range ◽  
Liver Iron ◽  
Imaging Results ◽  
History Of ◽  
Hbh Disease ◽  
Left Atrial Dilatation

Background/Aims: Hemoglobin H (HbH) disease is associated with iron overload, but whether this results in serious cardiac or vascular sequelae is unresolved. Methods: We identified 39 adult subjects (age 42 ± 12 years, 13 men) with HbH disease who had undergone echocardiography, 27 of whom had also undergone cardiac and liver magnetic resonance assessment of iron loading using T2*-weighted imaging. Results: None of the subjects had a history of heart failure or arrhythmias. There were 13/39 subjects with a ferritin level within the sex-based normal range and only 4/39 had ferritin >1,000 ng/ml. Left ventricular (LV) and left atrial dilatation was common, but LV ejection fraction was normal (≥55%) in all subjects. Age was positively correlated with log ferritin in the 27 nontransfused subjects (r = 0.43) and was inversely correlated with the transmitral E wave and E/A ratio (r = -0.69 and r = -0.79, respectively), but no relation of log ferritin with E or E/A was evident. The peak tricuspid regurgitation velocity was normal in 24/29 subjects for whom this was obtained, and it was no more than mildly elevated in the other 5. None of the tested subjects had an abnormal cardiac T2* reading, but half had evidence of liver iron loading. Conclusion: No myocardial iron loading or serious cardiac or vascular sequelae were identified in this cohort with HbH disease.

History of myocardial iron loading is a strong risk factor for diabetes mellitus and hypogonadism in adults with β thalassemia major

2014 ◽  
Vol 92 (3) ◽  
pp. 229-236 ◽  
Author(s):  
Ai Leen Ang ◽  
Ploutarchos Tzoulis ◽  
Emma Prescott ◽  
Bernard A. Davis ◽  
Maria Barnard ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factor ◽  
Thalassemia Major ◽  
Iron Loading ◽  
Myocardial Iron ◽  
Strong Risk Factor ◽  
History Of

Myocardial T2* in Patients with Cardiac Failure Secondary to Iron Overload.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3838-3838 ◽  
Author(s):  
Mark A. Tanner ◽  
John B. Porter ◽  
Mark A. Westwood ◽  
Sunil V. Nair ◽  
Lisa J. Anderson ◽  
...  
Keyword(s):  
Heart Failure ◽  
Iron Overload ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Iron Loading ◽  
Myocardial Iron ◽  
Thalassaemia Major ◽  
Ventricular Ejection Fraction ◽  
Symptomatic Heart Failure ◽  
Increased Risk

Abstract Introduction: Myocardial iron overload is a well established cause of heart failure in a number of haematological disorders and is the leading cause of death in β-thalassaemia major (TM). Once overt heart failure develops prognosis is very poor and it would therefore be desirable to identify patients at risk, prior to the development of symptomatic heart failure. Myocardial iron can now be rapidly and reproducibly assessed using a validated cardiac magnetic resonance (CMR) T2* technique. Left ventricular ejection fraction has been demonstrated to relate to myocardial T2* (normal >20ms), and accordingly iron overloaded patients with symptomatic heart failure are likely to have a low T2* but there are no reports of the myocardial T2* level in newly presenting patients with heart failure and the threshold for increased risk is also unknown. Purpose: To establish the distribution of myocardial T2* values in patients presenting with symptomatic heart failure secondary to iron overload. Methods: Database records of CMR T2* assessments over a 5 year period were reviewed to identify iron overloaded patients presenting with heart failure. Results: 28 patients (median age 29y, 11–79) with iron overload and documented heart failure were identified. 22 patients had thalassaemia major, 3 hereditary haemochromatosis, and 3 had miscellaneous transfusion dependent anaemias. The mean myocardial T2* in all groups was 6.8+/− 2.2ms reflecting severe iron loading by clinical criteria. See figure 1. Myocardial T2* values were similar between sub-groups as follows: TM patients 6.7+/− 2.4ms, haemochromatosis 7.7ms (6.7–7.4ms), miscellaneous 6.8ms (4.8–9.1ms). Conclusion: In this database review, the patients developing heart failure secondary to iron overload all had abnormal myocardial T2*, and overall 89% of heart failure patients had values less than 10ms, which reflects severe myocardial iron loading. This data suggests a myocardial T2* <10ms should be considered a threshold for risk of heart failure (with its attendant high mortality) and such patients should be treated aggressively with increased iron chelation. It also suggests that clinical heart failure occurs nearly exclusively in patients with severe myocardial iron loading. Distribution of myocardial T2+ values in symptomatic heart failure (n=28) Distribution of myocardial T2+ values in symptomatic heart failure (n=28)

Inter-Site Validation of a Single Breath Hold T2* MR Technique for Heart and Liver Iron Measurement.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3830-3830 ◽  
Author(s):  
Paul Kirk ◽  
Lisa J. Anderson ◽  
Mark A. Tanner ◽  
Renzo Galanello ◽  
Gildo Matta ◽  
...  
Keyword(s):  
Coefficient Of Variation ◽  
Breath Hold ◽  
Iron Loading ◽  
Myocardial Iron ◽  
Thalassaemia Major ◽  
Liver Iron ◽  
Single Breath ◽  
Single Breath Hold ◽  
Average Coefficient ◽  
Siemens Sonata

Abstract Background Approximately 60,000 people are born with thalassaemia major every year. The average life expectancy of thalassaemia major patients is 35 years due to iron overload Cardiomyopathy. The cardiomyopathy is reversible when treated early, but once heart failure is established it is often rapidly progressive, and unresponsive to treatment. The single breath hold (SBH) T2* technique has been validated as the most robust and reproducible non-invasive measurement of myocardial and iron load. Our aim in this study was to validate the transferability and reproducibility of this technique in different scanners worldwide. Methods We aim to compare the reproducibility in six different sites worldwide as part of an NIH funded grant (R01-DK66084-01). So far, two of these sites have been validated: Singapore (Siemens Sonata, 1.5T scanner) and Cagliari, Italy (GE Signa, 1.5 T scanner). At both validation sites, 10 patients were scanned for heart and liver T2*, and scans were repeated for interstudy reproducibility. All patients then flew to London to be rescanned on our reference Siemens Sonata scanner. Results Of the 20 patients scanned, 70% had myocardial iron loading (T2* <20ms) and in 10% the myocardial iron loading was severe. Liver iron loading was present in 65% of patients and in 30% this was severe. The coefficient of variation (COV) for the heart T2* measurements between the local sites and London was 5.9% and 4.9% yielding an average coefficient of variation across both sites of 5.4% (figure 1). The coefficient of variation (COV) for the liver T2* measurements between the local sites and London was 11.3% and 3.9% yielding an average coefficient of variation across both sites of 7.6% (figure 2). There was no significant correlation between liver and myocardial loading. Conclusion These are the first data demonstrating the transferability of the SBH T2* technique and the clinical validation from the 2 collaborating centers were excellent for both heart and liver measurements. Further MR sites confirmed for validation include Children’s Hospital of Philadelphia (USA); Ramathibodi Hospital, Bangkok (Thailand); and Chinese University Hong Kong. Figure 1 Figure 1. Figure 2 Figure 2.

A T2* MRI Prospective Survey on Heart and Liver Iron In Thalassemia Major Patients Treated with Sequential Deferipron–Desferrioxamine versus Deferasirox

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5165-5165
Author(s):  
Alessia Pepe ◽  
Giuseppe Rossi ◽  
Antonella Meloni ◽  
Dell'Amico Maria Chiara ◽  
D'Ascola Domenico Giuseppe ◽  
...  
Keyword(s):  
Iron Overload ◽  
Conflicts Of Interest ◽  
Ferritin Level ◽  
Thalassemia Major ◽  
Mean Difference ◽  
Quantitative Mri ◽  
Cardiac Complications ◽  
Myocardial Iron ◽  
Liver Iron ◽  
Multi Centre Study

Abstract Abstract 5165 Introduction: Most deaths in thalassemia major (TM) result from cardiac complications due to iron overload. No data are available in literature about possible different changes in cardiac and liver iron in TM patients treated with sequential deferiprone–deferoxamine (DFP-DFO) versus deferasirox (DFX). Magnetic Resonance (MR) is the unique non invasive suitable technique to evaluated quantitatively this issue. The aim of this multi-centre study was to assess prospectively in the clinical practice the efficacy of the DFP-DFO vs DFX in a cohort of TM patients by quantitative MR. Methods: Among the first 739 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, 253 patients performed a MR follow up study at 18 ± 3 months according to the protocol. We evaluated prospectively the 25 patients treated with DFP-DFO versus the 44 patients treated with DFX between the 2 MR scans. Myocardial and liver iron concentrations were measured by T2* multislice multiecho technique. Results: The doses of the sequential treatment were DFP 70±14 mg/kg/d for 4 d/w and DFO 42±8 mg/kg/d for 3 d/w, the dose of DFX was 26±6 mg/kg/d. Excellent/good levels of compliance were similar in the 2 groups (DFP-DFO 96% vs DFX 100%; P = 0.36). At baseline the 2 groups were homogeneous for cardiac and liver iron. Among the patients with no significant myocardial iron overload at baseline (global heart T2* 3 20 ms), there were no significant differences between groups to maintain the patients without myocardial iron overload (DFP-DFO 95% vs DFX 96%; P = 1.0). Among the patients with myocardial iron overload at baseline (global heart T2* < 20 ms), only in the DFX group there was a significant improvement in the global heart T2* value (11 ± 5 ms at baseline versus 16 ± 8 at 18 ± 3 months, P = 0.0001) and in the number of segment with a normal T2* value (P = 0.003). The improvement in the global heart T2* was not significantly difference in the DFP-DFO versus the DFX group (mean difference global heart T2* 2.2 ± 4.1 ms versus 4.6 ± 4.8 P = 0.2). The changes in the mean serum ferritin level were not significantly different between groups. In patients with liver iron overload at baseline (liver T2* < 5.1 ms), the change in the liver T2* was not significant between groups (mean difference liver T2* 0.9 ± 2.1 ms vs 2.4 ± 5.2; P = 0.3). Conclusions: Prospectively in the clinical setting over 15 months we did not find significant differences on cardiac and liver iron by quantitative MRI in TM patients treated with sequential DFP–DFO versus the TM patients treated with DFX. Disclosures: No relevant conflicts of interest to declare.

Prospective Survey on Heart and Liver Iron and Heart Function in Thalassemia Major Patients Treated with Sequential deferiprone–desferrioxamine Versus Deferiprone and Desferrioxamine in Monotherapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5298-5298
Author(s):  
Alessia Pepe ◽  
Antonella Meloni ◽  
Giuseppe Rossi ◽  
Anna Spasiano ◽  
Domenico Giuseppe D'Ascola ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Iron Overload ◽  
Heart Function ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
The Other ◽  
Hepatic Iron ◽  
Myocardial Iron ◽  
Liver Iron ◽  
Biventricular Function

Abstract Abstract 5298 Introduction: Magnetic Resonance (MR) is the unique non invasive suitable technique to evaluate quantitatively the changes in cardiac and hepatic iron and in cardiac function in thalassemia major (TM) patients under different chelation regimens. This study aimed to prospectively assess the efficacy of the sequential deferiprone–deferrioxamine (DFP-DFO) versus deferiprone (DFP) and deferrioxamine (DFO) in monotherapy in a large cohort of TM patients by quantitative MR. Methods: Among the first 1135 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, 392 patients performed a MR follow up study at 18±3 months. We evaluated prospectively the 35 patients treated with DFP-DFO versus the 39 patients treated with DFP and the 74 patients treated with DFO between the 2 MR scans. Iron concentrations were measured by T2* multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Results: Excellent/good levels of compliance were similar in the DFP-DFO (97.1%) versus DFP (94.9%) and DFO (95.9%) groups. No significant differences were found in the frequency of side effects in DFP-DFO (15.6%) versus DFP group (9.4%). The percentage of patients who maintained a normal global heart T2* value (≥20 ms) was comparable between DFP-DFO (96%) versus DFP (100%) and DFO (98.1%) groups. Among the patients with myocardial iron overload (MIO) at baseline (global heart T2*<20 ms), in all three groups there was a significant improvement in the global heart T2* value (DFO-DFP: P=0.004, DFP: P=0.015 and DFO: ms P=0.007) and a significant reduction in the number of pathological segments (DFO-DFP: P=0.026, DFP: P=0.012 and DFO: P=0.002). In DFO-DFP and DFP groups there was a significant increment in the left ventricular (LV) ejection fraction (EF) (P=0.035 and P=0.045, respectively) as well as in the right ventricular (RV) EF (P=0.017 and P=0.001, respectively). The improvement in the global heart T2* and in biventricular function were not significantly different in DFO-DFP compared to the other groups (Table 1). Among the patients with hepatic iron at baseline (T2*<9.2 ms), only in DFO group there was a significant improvement in the liver T2* value (2.0±3.5 ms P=0.010). Liver T2*changes were not significantly different in DFO-DFP versus the other groups. Conclusions: Prospectively we did not find significant differences on cardiac and hepatic iron or in cardiac function in TM patients treated with sequential DFP–DFO therapy versus the TM patients treated with DFO or DFP in monotherapy. Disclosures: Pepe: Novartis: Speakers Bureau; Apotex: Speakers Bureau; Chiesi: Speakers Bureau. Off Label Use: Association of two chelators commercially available in order to obtain a higher efficacy. Lai:Novartis: Honoraria, Research Funding.

scholarly journals A Randomized, Placebo-Controlled, Double-Blind Trial of the Effect of Combined Therapy With Deferoxamine and Deferiprone on Myocardial Iron in Thalassemia Major Using Cardiovascular Magnetic Resonance

Circulation ◽  
2007 ◽  
Vol 115 (14) ◽  
pp. 1876-1884 ◽  
Author(s):  
M.A. Tanner ◽  
R. Galanello ◽  
C. Dessi ◽  
G.C. Smith ◽  
M.A. Westwood ◽  
...  
Keyword(s):  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Ejection Fraction ◽  
Endothelial Function ◽  
Thalassemia Major ◽  
Iron Chelator ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Iron Loading ◽  
Myocardial Iron

Background— Cardiac complications secondary to iron overload are the leading cause of death in β-thalassemia major. Approximately two thirds of patients maintained on the parenteral iron chelator deferoxamine have myocardial iron loading. The oral iron chelator deferiprone has been demonstrated to remove myocardial iron, and it has been proposed that in combination with deferoxamine it may have additional effect. Methods and Results— Myocardial iron loading was assessed with the use of myocardial T2* cardiovascular magnetic resonance in 167 patients with thalassemia major receiving standard maintenance chelation monotherapy with subcutaneous deferoxamine. Of these patients, 65 with mild to moderate myocardial iron loading (T2* 8 to 20 ms) entered the trial with continuation of subcutaneous deferoxamine and were randomized to receive additional oral placebo (deferoxamine group) or oral deferiprone 75 mg/kg per day (combined group). The primary end point was the change in myocardial T2* over 12 months. Secondary end points of endothelial function (flow-mediated dilatation of the brachial artery) and cardiac function were also measured with cardiovascular magnetic resonance. There were significant improvements in the combined treatment group compared with the deferoxamine group in myocardial T2* (ratio of change in geometric means 1.50 versus 1.24; P =0.02), absolute left ventricular ejection fraction (2.6% versus 0.6%; P =0.05), and absolute endothelial function (8.8% versus 3.3%; P =0.02). There was also a significantly greater improvement in serum ferritin in the combined group (−976 versus −233 μg/L; P <0.001). Conclusions— In comparison to the standard chelation monotherapy of deferoxamine, combination treatment with additional deferiprone reduced myocardial iron and improved the ejection fraction and endothelial function in thalassemia major patients with mild to moderate cardiac iron loading.

Vitamin D Deficiency Is Associated with Cardiac Iron Loading in Thalassemia Major.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 574-574
Author(s):  
John C. Wood ◽  
Susan Claster ◽  
Susan Carson ◽  
Khanna Rachna ◽  
Thomas Hofstra ◽  
...  
Keyword(s):  
Vitamin D ◽  
Multivariate Analysis ◽  
Vitamin D Deficiency ◽  
Transferrin Saturation ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Iron Loading ◽  
Liver Iron ◽  
Cardiac Iron

Abstract Vitamin D deficiency is epidemic in the United States and is associated with decreased calcium absorption and metabolism, leading to bone loss, muscle weakness, and impaired pancreatic function. Many thalassemia major patients, as a result of decreases sunlight exposure and increased metabolic demand, are vitamin D deficient. We hypothesized that vitamin D deficiency might be associated with cardiac siderosis and impaired cardiac function through its modulation of calcium signaling in these patients. Methods: Permission for review of medical records was obtained from the Committee on Clinical Investigation at Children’s Hospital Los Angeles. We compared vitamin D25-0H and D1-25 levels in our thalassemia major patients with cardiac R2* (1/T2*) and left ventricular ejection fraction (LVEF) from the patient’s most recent cardiac MRI. Time difference between the exams was 2.8 ± 3.3 months with a range of 0.2 to 9.4 months. Other parameters recorded included age, gender, ferritin, liver iron (by MRI) and transferrin saturation. Univariate and multivariate regression was performed using JMP 5.1 (SAS, Cary, NC). Results: Twenty four patients had records suitable for review. There were 11 women and 13 men with a mean age of 14.7 ± 7.6 years [1.4 – 25.8]. Population was moderately iron overloaded with ferritin values of 2089 ± 1920 ng/ml [246 – 8230], liver iron 13.7 ± 11.4 mg/g dry wt [2–39.5], cardiac R2* 65 ± 61 Hz [19.8 – 229], and transferrin saturation 84 ± 18% [36%–106%]. Vitamin D25-OH levels were markedly depressed, 17.1 ± 8.5 pg/ml [1–33], with 13/24 values below the lower limit of 20 ng/ml. Surprisingly, vitamin D1-25OH levels were normal or elevated in all patients, 59.9 ± 19.5 pg/ml [32–103] with four patients exceeding the upper limit of normal of 71 pg/ml. There was no correlation between D25-0H and D1-25OH levels. D25-OH levels (but not D1-25OH levels) fell sharply with age (r2 = 0.48) and were negatively associated with liver iron (r2 = 0.20). Figures 1 and 2 demonstrated cardiac R2* and LVEF as functions of D25-OH levels. Cardiac R2* was log-linearly correlated with D25-OH level (r2 = 0.44, p=0.0001; levels below 13 ng/ml were associated with severe cardiac iron loading. Multivariate analysis of D25-OH, D1-25, HIC, ferritin, age, and transferrin saturation demonstrated that D25-0H and ferritin are the sole predictors of abnormal cardiac R2*, accounting for 38% and 5% of the variability respectively. LVEF was also negatively related to D25-OH levels (r2 = 0.35, p = 0.002). In multivariate analysis, vitamin D250H and vitamin D1-25OH levels accounted for 50% of the LVEF variability, independent of cardiac R2*. Conclusion Vitamin D deficiency is common in thalassemia major patients and strongly associated with cardiac iron uptake and ventricular dysfunction. Figure Figure Figure Figure

Comparison of Deferasirox, Deferiprone, and Desferrioxamine Effectiveness on Myocardial Iron Concentrations and Biventricular Function by Quantitative MR in Beta-Thalassemia Major

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3872-3872
Author(s):  
Alessia Pepe ◽  
Brunella Favilli ◽  
Vincenzo Positano ◽  
Paolo Cianciulli ◽  
Anna Spasiano ◽  
...  
Keyword(s):  
Iron Status ◽  
Group Versus ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Beta Thalassemia ◽  
Myocardial Iron ◽  
Liver Iron ◽  
Biventricular Function ◽  
Iron Concentrations

Abstract Despite dramatic gains in life expectancy in the desferrioxamine era for thalassemia major patients, the leading cause of death for this young adult’s population remains iron-induced heart failure. For this reason, strategies to reduce heart disease by improving chelation regimens have the highest priority in this phase. These strategies include development of novel oral iron chelators to improve compliance. Oral deferipron was proved more effective than subcutaneous desferrioxamine in removing cardiac iron. The novel oral one-daily chelator deferasirox has been recently commercially available but its long-term efficacy on myocardial iron concentrations and cardiac function is unknown. Aim of this study was to compare in thalassemia major patients the effectiveness of deferasirox, deferipron, and desferrioxamine on myocardial and liver iron concentrations and bi-ventricular function by quantitative magnetic-resonance imaging (MRI). Among the 550 thalassemic subjects enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network between September 2006 and September 2007, we selected patients receiving one chelator alone for longer than one year. MIOT is an Italian network of six MR sites where the cardiac and liver iron status is assessed by validated and homogeneous standard procedures. We identified three groups of patients: 24 treated with deferasirox, 42 treated with deferipron and 89 treated with desferrioxamine. The three groups were matched for gender, Hb pre-transfusion levels, age of starting chelation, and good compliance to the treatment. The deferasirox group was significantly younger (26±7 years) than the deferipron (32±9 years) and desferioxamine group (33±8 years) (P=0.0001) and showed significantly higher mean serum ferritin levels (2516±2106 ng/ml) than the deferipron (1493±1651 ng/ml) and the desferrioxamine group (987±915 ng/ml) (P=0.0001). Myocardial iron concentrations and distribution were measured by MRI T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine-dynamic MRI images. Liver iron concentrations were measured by MR T2* multiecho technique. Written informed consent was obtained from all subjects. The global heart T2* value was significantly higher in the deferipron group (34±11 ms) versus the deferasirox (21±12 ms) and the desferrioxamine group (27±11 ms) (P=0.0001), as showed in Figure A. The T2* in the mid ventricular septum was significantly higher in the deferipron (36 ± 12 ms) versus the deferasirox (20 ± 12 ms) and the desferrioxamine group (28 ± 13 ms) (P = 0.0001). The number of segments with normal T2* value was significantly higher in the deferipron and the desferrioxamine group versus the deferasirox group (14 ± 2 versus 11 ± 6 versus 7 ± 7 segments; P = 0.0001). Among the biventricular function parameters, we found higher left ventricular ejection fractions in the deferipron and the desferrioxamine group versus the deferasirox group (64 ± 7 versus 62 ± 6 versus 58 ± 7 %; P = 0.005), as showed in Figure B. Liver T2* values were significantly higher in the desferrioxamine group versus the deferipron and the deferasirox group (10 ± 9 versus 6 ± 6 versus 5 ± 5 segments; P = 0.002). In conclusion, Oral deferipron seems to be more effective than oral deferasirox and subcutaneous desferrioxamine in removal of myocardial iron with concordant positive effect on left global systolic function. Figure Figure

Improved Endothelial Function with Combined Chelation Therapy in Thalassaemia Major.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1770-1770 ◽  
Author(s):  
Mark A. Tanner ◽  
Renzo Galanello ◽  
Carlo Dessi ◽  
Annalisa Agus ◽  
Gillian C. Smith ◽  
...  
Keyword(s):  
Placebo Group ◽  
Ejection Fraction ◽  
Endothelial Function ◽  
Chelation Therapy ◽  
Combined Treatment ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Iron Loading ◽  
Myocardial Iron ◽  
Ventricular Ejection Fraction

Abstract Background: In β-thalassemia major (TM) myocardial iron toxicity is the dominant cause of ventricular dysfunction, with heart failure responsible for the majority of deaths. Abnormal endothelial function has also been described in these patients and could further contribute to cardiovascular complications. Endothelial function can be determined by measurement of flow mediated dilatation of the brachial artery (FMD). This can be assessed reproducibly by cardiovascular magnetic resonance (CMR). Aims: To report the changes in endothelial function, LV ejection fraction and ferritin from a randomized placebo controlled trial comparing combined chelation therapy (deferiprone and deferoxamine) with deferoxamine monotherapy. Methods: 65 patients (male 27, female 38, age 28.7+/−4.8years) with mild-moderate myocardial iron loading (heart T2* 8–20ms) were randomized to receive either deferoxamine with placebo (placebo group), or deferoxamine with deferiprone (combined group). FMD was assessed at baseline and after 12 months. Results: There were significant improvements in endothelial function in the combined treatment group compared with the placebo group (+8.8% vs 3.1% p=0.013). This was in accord with improvements in the combined group in left ventricular ejection fraction (+2.4% vs +0.6%, p=0.02), and serum ferritin (−870 vs −194 μg/L; p<0.001). These findings were in accord with improved myocardial T2* in the combined group (+43% vs +23%, p=0.017), Conclusion: In patients with mild-moderate cardiac iron loading, the combined therapy of deferiprone and deferoxamine is superior to deferoxamine alone in improving endothelial function, cardiac function and ferritin, as well as reducing myocardial iron.

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