Highly Transfused MDS Patients Often Have Cardiac Iron Overload, as Shown by MRI Assessment

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2906-2906
Author(s):  
Laurent Pascal ◽  
Odile Beyne Rauzy ◽  
Sabine Brechignac ◽  
Dominique Vassilieff ◽  
Olivier Ernst ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Cardiac Failure ◽  
Cardiac Disease ◽  
Cardiac Mri ◽  
Iron Content ◽  
Cardiac Iron ◽  
Cardiac Symptoms ◽  
Cardiac Iron Overload ◽  
The Impact

Abstract Abstract 2906 Background: Cardiac complications of transfusional iron overload are well documented in various inherited anemias. In regularly transfused MDS, the deleterious role of iron overload on cardiac disease is more disputed, due in particular to frequent concomitant causes of cardiac failure. Cardiac MRI T2* allows accurate and specific measurement of iron content. Methods: We prospectively evaluated in 4 centers of the GFM by standardized and transferable MRI methods both cardiac T2* according to Anderson (Eur Heart J. 2001Dec;22(23):2171-9) and liver iron content (LIC) according to Gandon (Lancet. 2004 Jan 31;363(9406):357-62), as well as cardiac function by routine echocardiography or MRI in regularly transfused MDS patients. Results: From Dec 2005 to March 2010, 73 patients (pts) were included (14 of them had more than one MRI evaluation over time): 38 M/35F, Median age 68 (24-86); WHO : RA=5, RARS=33, RMCD-RS=3, RMCD=1, RAEB1=9, RAEB2=5, RAEB-T/AML=1, 5q- syndrome=8 and unclassified=8; Karyotype: fav n=50, Int n=9, unfav n=4, failure n=10; IPSS: low n=29, Int-1 n=28, Int-2 n=5 and High n=1, unknown n=10. Median interval from MDS diagnosis and MRI T2* assessment was 49 months (range 0–324). Median serum ferritin at MRI assessment was 1750 ng/ml (range 282–7339) and 54/73 pts were on chelation therapy (CT) (median duration of CT prior to first MRI: 18 months, range 1–125). 37/73 pts had cardiac symptoms and 28 were on cardiac therapy. At first MRI T2* analysis, the median number of RBC units transfused was 68 (range 5–574). Median LIC was 330 micromoles/g/dw (range 40–908). Median Cardiac T2* was 27 ms (range 6–74). 14/73 pts had cardiac iron overload defined by MRI T2* ≤20 ms (19%) and among them 3/73 (4%) had severe cardiac iron overload (T2*≤ 10 ms). LVEF was below normal (55%) in 13/59 cases evaluated. A correlation was found between cardiac T2*and the number of RBC units transfused (Pearson correlation =-0.342, p=0.004) but not with LIC (p= 0.65) and serum ferritin (p=0.21). Cardiac overload was seen in 1/19 (5.5%) pts transfused <50 RBC units, 4/37(12.1%) pts transfused 50–150 units, 9/17 (52.9%) pts transfused >150 units (p= 0.0005). Those 3 pt subgroups also differed in median LIC (μmoles/g/dw) (<50 units= 250, 50–150 units=340, > 150 units=414) (p=0.044 Kruskall-Wallis' test), but not significantly in serum ferritin (p= 0.085). No significant correlation was found between decreased LVEF (< 55%) and cardiac T2* <20 ms (p=0.5), or T2*≤10 ms (p=0.23). In particular, 5/13 pts (38%) with LVEF <55% had T2*<20ms, vs versus 8/46 pts (17%) with LVEF >55% (p= 0.13). However, 1/14, 0/30 and 3/12 pts having received <50, 50–150 and > 150 RBC units had severe cardiac failure (ie LVEF≤35%)(p=0.012). 3/4 pts with severe cardiac failure had T2*< 20ms,compared to 8/54 pts without severe cardiac failure (p=0.023). 14 pts had another cardiac MRI 6 to 34 months (median 18) after the first. All were on CT and had received a median of 60 and 214 PRBC units at first and last MRI, resp. Median Cardiac T2* was 21.6 ms (range 8.5–35.3) and. 28 ms (range 6.4–41) at last and at first assessment, respectively (p=0.3) Conclusions: Moderate and severe post transfusional cardiac iron overload was seen in 19% and 4% of regularly transfused MDS, respectively. The level of cardiac iron overload was well correlated to the number of RBC transfused. The impact of cardiac overload on LVEF was unclear except in pts with severe cardiac impairment (LVEF <35%), possibly suggesting that iron overload is only one of the factors responsible for cardiac disease in many of those elderly patients. Disclosures: No relevant conflicts of interest to declare.

Clinical Relevance of Cardiac Iron Overload Estimated by MRI T2* in Regularly Transfused Low Risk MDS.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2666-2666 ◽  
Author(s):  
C. Ferte ◽  
O. Ernst ◽  
O. Beyne-Rauzy ◽  
M.P. Chaury ◽  
S. Brechignac ◽  
...  
Keyword(s):  
Iron Overload ◽  
Cardiac Mri ◽  
Iron Content ◽  
Clinical Signs ◽  
Left Ventricular ◽  
Low Risk ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Cardiac Symptoms ◽  
Cardiac Iron Overload

Abstract Background: Cardiac iron overload is the first cause of mortality in thalassemia. In MDS, a causal relationship between cardiac iron overload and death is not as well established and heart complication may be of intricate origins in these elderly pts. Cardiac MRI T2* allows accurate measurement of heart iron and is influenced by iron content only (and not by other cardiac diseases). T2* value < 20ms is clearly associated with cardiac iron overload. A few reports (Winder et al ASH 2005, Chacko J BJH2006;133: supp1) showed no cardiac iron overload by T2* in small numbers of multitransfused MDS. We performed a similar analysis in our transfused low risk MDS pts. Methods: We prospectively evaluated by MRI both cardiac T2* according to Anderson (Eur Heart J 2001) and liver iron content (LIC ) according to Gandon (Lancet 2004) and cardiac function by echocardiography in multitransfused low risk MDS pts. Cardiac MRI T2* was also assessed in 33 controls. Results: 21 MDS were analyzed, 9M/12F. Median age: 75 years ( 50–83); FAB : RA= 3, RAS=13, RAEB = 3, CMML n=1, unclassified n=1. Karyotype: fav n= 1, Int n= 18, failure n=1. IPSS: low n= 10, Int I n= 10, unavailable n=1. Median interval from MDS diagnosis and first transfusion was 40 and 24 months respectively. At inclusion, median number of RBC units transfused was 81 (range 6–282, and greater than 100 in 8 pts). Median serum ferritin level was 2152 ng/ml and 11 patients were on chelation therapy (CT). 9/21 pts had cardiac symptoms and were on cardiac therapy. LVEF was below normal (55%) in 3/21 cases. Left ventricular telediastolic diameter LVTD was above normal (normal 53 mm) in 6/14 pts evaluated. Median LIC was 350 micromoles/g/dw (95–898 ). Median Cardiac T2* was 27 ms (8–74) and did not differ significantly from controls (T2*=27ms+/−6.4). No correlation was found between cardiac T2* and ferritin, LIC, LVEF, time from MDS diagnosis. However 3/21 pts had cardiac iron overload with T2* < 20 (18ms,15ms,8ms respectively). LVEF and number of RBC units transfused of these pts was respectively 69%,51%,33% and 119,150,282 RBC units. Two of them were on iron CT, one of them since 8 years. The last 2 pts had clinical signs of cardiac failure unexplained by other causes and both had increased LVTD. Conclusions: Although cardiac T2* did not differ significantly in transfused MDS and in controls, 3 heavily transfused (all in the 8 patients who had received >100 RBC units) had clear cardiac iron overload, clinically relevant in 2 of them and not correlated with higher liver iron overload. Differences between our study and previous studies could be due to the higher number of transfused RBC units in our pts with abnormal T2*, as compared to a median of 50 in the study of Winder, but further studies are required to confirm this finding.

T2* MRI Provides No Evidence for Myocardial and Pancreatic Iron Overload in Multitransfused Patients with Sickle/β-Thalassemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1422-1422 ◽  
Author(s):  
Hussam Ghoti ◽  
Orly Goitein ◽  
Elie Konen ◽  
Ariel Koren ◽  
Carina Levin ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Content ◽  
Transferrin Saturation ◽  
Left Ventricular ◽  
Iron Deposition ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Cardiac Iron Overload ◽  
T2 Mri

Abstract Introduction: Transfusion-dependent hemolytic anemias particularly thalassemia major (thal.m) and also sickle cell disease (SCD) result in iron deposition in the reticuloendothelial system in major organs, mainly in the liver and also in the heart and endocrine glands. However, liver iron levels in patients with thal.m measured by other techniques were found to have no predictive values for the extent of their cardiac iron deposition. T2* MRI sequences have been previously addressed as a reliable tool for non invasive evaluation of iron load in the liver, heart and pancreas. Patients with T2* value &gt; 20 ms have normal cardiac function while the prevalence of myocardial dysfunction and arrhythmias increases as a consequence of cardiac iron overload (T2* &lt; 20 ms). A previous study comparing cardiac iron overload in transfusion dependent thal.m and SCD patients matched for age and liver iron content, found abnormally low cardiac T2* values (&lt;20 ms) in nearly 40% of patients with thal.m, while the T2* values were normal in the patients with SCD (1) (Blood:103;1934, 2004). The purpose of the present study was to quantify iron content (T2* values) in the liver, heart and pancreas of multitransfused patients with sickle/β-thal. Patients and Methods: Eleven patients with sickle/β-thal., 3 males and 8 females, mean age 31 years ± 9.5 (SD) were analyzed, 6 of them were splenectomized. Their mean ± SD values for hemoglobin was 9.0 gr/dl, for serum ferritin - 3900 ng/ml ± 3944 and for transferrin saturation - 80% ± 23. All of them were transfused and received a mean of 97 packed cell units ± 88 (SD). Only one patient received iron chelation for 10 months until 6 months prior to entering the study. Seven patients received regularly Hydrea 1–1.5 gr/day for &gt; 10 years. MRI evaluation (1.5T, GE MRI system) included: Left ventricular (LV) function (ejection fraction)- steady-state free procession (SSFP) cine sequence as well as iron load quantification- breath-hold multi echo gradient echo T2*, sampled across regions of interest in the LV septum, liver parenchyma and pancreatic tissue. (Eur. Heart J22:2171, 2001) Results: All patients had normal T2* values in the heart (&gt;20ms) and in the pancreas (&gt;30ms). The left ventricular ejection fraction, left ventricular endsystolic and endiastolic volumes (evaluated both by echo-cardiography and by cine function MRI) were normal in all patients. There was no evidence for pleural or pericardial effusion. The diameter of the pulmonary artery and right ventricle were normal. Seven patients demonstrated evidence of mild to moderate iron deposition in the liver (T2* &lt;6.3 ms). In these patients mean serum ferritin (5656 ng/ml) and transferrin saturation (92.4%) were significantly higher (p=0.001) than in 4 patients with normal T2* levels in the liver (&gt;6.3ms) where mean serum ferritin was 872ng/ml and transferrin saturation 59.5%. Conclusion: The T2* MRI values of 11 patients with sickle/β-thal. showed that whereas 7 patients had a certain degree of iron deposition in the liver, none demonstrated cardiac or pancreatic iron deposition. Therefore, with respect to iron deposition, multitransfused patients with sickle/β-thal. are similar to patients with homozygous SCD and not to patients with thal.m and thal intermedia. The reasons for this observation are still unclear. This similarity could be related in part to the relativly low number of transfusions, starting later in life, of patients with homozygous SCD or sickle/β- thal. compared to patients with thal.m. (1) The liver is the dominant iron storage organ and iron liver concentration correlates closely with the total body iron content. While iron uptake by hepatocytes is predominately mediated via transferrin and correlates with serum ferritin levels, as confirmed in the present study, this is not the case in regulation of cardiac and endocrine iron uptake. These organs might acquire the excess metal differently. It is possible that additional and/or different forms of iron, which have been identified, such as non-transferrin bound iron and labile plasma iron, are involved in determining iron loading in the heart and endocrine glands and/or because regulation of iron entry into the plasma by hepcidin might differ. Additional studies are in progress to address these issues.

P088 Evaluation of cardiac iron overload by cardiac MRI T2 in regularly transfused MDS

2009 ◽  
Vol 33 ◽  
pp. S109
Author(s):  
L. Pascal ◽  
C. Rose ◽  
P. Fenaux ◽  
O. Ernst ◽  
H. Chiavassa ◽  
...  
Keyword(s):  
Iron Overload ◽  
Cardiac Mri ◽  
Cardiac Iron ◽  
Cardiac Iron Overload

The heart and inherited haematological disorders

2020 ◽  
pp. 367-382
Author(s):  
Perry Elliott ◽  
Pier D. Lambiase ◽  
Dhavendra Kumar
Keyword(s):  
At Risk ◽  
Iron Overload ◽  
Cardiac Disease ◽  
Cardiac Iron ◽  
Cardiac Iron Overload ◽  
Patients At Risk ◽  
Haematological Disorders

This chapter covers inherited haematological disorders. It explains the pathophysiology, genetics, and iron overload of thalassaemia; cardiac disease in both β‎ and α‎thalassaemia; the pathophysiology, genetics, and iron overload in haemochromatosis; the evaluation of patients; and finally the management of patients at risk of cardiac iron overload.

scholarly journals Plasma level of matrix metalloproteinase-9 in patients with sickle cell disease and its correlation to myocardial iron overload

2020 ◽  
Author(s):  
Tamer Hassan ◽  
Mohamed Badr ◽  
Mohamed Arafa ◽  
Doaa Abdel Rahman ◽  
Manar Fathy ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Plasma Levels ◽  
Restrictive Cardiomyopathy ◽  
Myocardial Iron ◽  
Cell Disease ◽  
Cardiac Iron ◽  
Cardiac Iron Overload

Abstract Cardiac iron overload is secondary to chronic blood transfusion in patients with sickle cell disease (SCD). Iron overload cardiomyopathy is a restrictive cardiomyopathy associated with systolic and diastolic dysfunction. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for tissue remodeling. Many studies offer strong evidence for the role of MMP-9 in LV remodeling. We aimed to detect plasma levels of MMP-9 in patients with SCD and its correlation to myocardial iron overload. A case control study was carried out on 50 patients with SCD and 50 age and sex matched healthy controls. Assessment of cardiac iron overload in patients by MRI T2* was performed. Plasma MMP-9 levels were measured for patients and controls using ELISA. SCD patients had significantly higher levels of MMP-9 than controls. There was highly significant correlation between plasma levels of MMP-9 and serum ferritin. Patients with vaso-occlusive crises (VOC) > 5/year had significantly higher levels of MMP-9 than those with VOC ≤ 5 /year. No significant correlation was found between MMP-9 and cardiac T2*. MMP-9 seems to be a useful marker in SCD patients. Patients with serum ferritin > 1000 ng/ml, recurrent VOC > 5 /year had significantly higher MMP-9 serum levels than others.

Serum Ferritin Predicts Liver but Not Cardiac Iron Burden by Noninvasive MRI in Sickle Cell Disease (SCD.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1421-1421 ◽  
Author(s):  
Robert I. Liem ◽  
Cynthia Rigsby ◽  
Richard J. Labotka ◽  
Andrew DeFreitas ◽  
Alexis A. Thompson
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Content ◽  
Iron Loading ◽  
Cell Disease ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Liver Iron Content ◽  
The Mean

Abstract BACKGROUND: Assumptions about iron loading as well as the utility of ferritin to predict transfusional iron overload among individuals with sickle cell disease (SCD) are largely based on extrapolation from data generated in patients with thalassemia major (TM). Yet recent studies suggest the natural history of iron overload in patients with SCD differs significantly from chronically transfused patients with TM. We sought to evaluate the extent of myocardial and hepatic siderosis using noninvasive imaging in chronically transfused patients with SCD and examine its clinical associations, including relationship to long-term trends in serum ferritin, transfusion history, chelation status and markers of hemolysis and inflammation. METHODS: We evaluated 17 subjects (mean age 15±3.6 yrs, range 9 to 20). The mean transfusion duration was 7.3±3.6 yrs (range 2 to 15). Thirteen (76%) patients were on chelation with deferasirox at the time of screening; 4 were not on chelation Rx. MRI T2*/R2* of the heart and liver using a multiple gradient echo sequence was performed on a single 1.5T GE scanner. Hepatic iron concentration (HIC) values were predicted from liver R2* values. RESULTS: Mean HIC in subjects was 9.9±6.7 mg/gm liver dry weight (range 2.5 to 20.8) and was ≥15 mg/gm in 6/17 (35%) subjects. The mean long-term serum ferritin (past 5 yrs, or duration of transfusion if &lt; 5yrs) was 2318±1122 ng/mL (range 541 to 4225). Using Pearson’s correlation coefficient, we observed a significant relationship between HIC and ferritin (r=0.765, p=&lt;0.001). We generated a receiver operator characteristic (ROC) curve to assess the utility of ferritin as a predictor of elevated HIC, using a threshold HIC thought to predict serious iron-related complications. A ferritin cut-off value ≥2164 ng/mL correctly identified 80% of cases of HIC ≥15 mg/gm (AUC 0.96, p=0.003) in our subjects with 83% sensitivity and 73% specificity. Despite markedly elevated HIC and ferritin values in some subjects, none had myocardial siderosis. All 17 subjects had cardiac MRI T2* values in the normal range &gt; 25 ms. Cardiac iron load measured by T2* did not correlate with HIC or serum ferritin. We examined C-reactive protein (CRP) and B-type natriuretic peptide (BNP) as markers for inflammation and myocardial strain, respectively, in our subjects but neither demonstrated a significant relationship to ferritin or MRI findings. BNP, however, did correlate modestly with both age (r=−0.574, p=0.013) and left ventricular ejection fraction on cardiac MRI (r=0.510, p=0.036). A subset of subjects (n=8) had histologic iron measurements by percutaneous liver biopsy (LBx) within 6 months of MRI. While liver iron content by LBx correlated significantly with HIC by MRI (r=0.759, p=0.03), liver iron content by LBx did not correlate with ferritin (r=0.312, p=0.452). CONCLUSION: We found that serum ferritin is a good predictor of liver iron by MRI R2*, and that long term ferritin values ≥2164 ng/mL predict significant hepatic iron overload as assessed by this noninvasive method. We did not observe appreciable cardiac iron loading in our subjects with SCD, which otherwise might have been predicted by elevated HIC alone, as in individuals with TM. These data suggest that reliable, long term surveillance of transfusion-induced iron overload in SCD may be achieved using serum ferritin and HIC by MRI R2* as surrogate markers of hepatic siderosis rather than relying on liver iron content measured invasively by LBx. Also, previously determined thresholds for significant cardiac iron loading in TM, based on degree of hepatic siderosis, may not be applicable in SCD. Further investigation into alternative mechanisms of iron loading or distribution in these related but distinct disorders is warranted.

Update in Combined Chelation Therapy with Deferoxamine and Deferiprone in Brazilian Patients with Thalassemia Major: Assessment of Three Years

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5415-5415
Author(s):  
Sandra Regina Loggetto ◽  
Mônica Veríssimo ◽  
Antônio Fabron Júnior ◽  
Giorgio Roberto Baldanzi ◽  
Nelson Hamerschlak ◽  
...  
Keyword(s):  
Adverse Events ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Combined Therapy ◽  
Thalassemia Major ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Cardiac Iron Overload

Abstract Introduction: Cardiac failure is a main cause of morbidity and mortality in patients with thalassemia major (TM) who are receiving regular blood transfusion due to iron overload. So, effective and adequate iron chelation is extremely important. Deferoxamine (DFO), the most widely used iron chelator, has poor compliance. Combined therapy with Deferiprone (DFP) increases chelation efficacy, decreases iron-induced complications, improves compliance increasing survival in thalassemia. Objectives: Assessment of efficacy and safety in combined chelation with DFP and DFO in thalassemic patients with iron overload. Methods and results: We have 50 thalassemia major patients in 4 Brazilian Centers (Boldrini Hospital, Sao Paulo Hematology Center, HEMEPAR and FAMEMA) receiving combined chelation therapy with follow up to three years. DFP (75–100 mg/kg/daily) and DFO (30–60 mg/kg, 4–7 days/week) are being administered during one to three years. Median age of this group is 21,5 y/o (range 8–35), with 48% female. Median age to start regular transfusions was 12 months (range 2–140) and to begin chelation therapy was 57 months (range 17–216). All patients were screened for Hepatitis C and 26% had positive sorology and/or PCR. Statistical analysis were made with Spearman test and Fisher test. All patients, except two, did cardiac and liver MRI in the initial phase of the study, resulting in 60,5% with cardiac iron overload (T2*&lt;20ms), being severe in 31,2%. Assessment of liver iron concentration (LIC) showed 95,7% with liver iron overload (&gt;3ug/g dry weight), being severe in 17,4%. During follow up, only 43 patients (86%) was screened with MRI. From these, 67,4% had cardiac iron overload (severe in 32,5%) and 78,6% had liver iron overload (severe in 11,9%). Mean serum ferritin before and after three years were 3095,7 ±1934,5 ng/ml and 2373,9±1987,6 ng/ml, respectively. Our data showed positive correlation between serum ferritin, LIC and ALT, even in initial data and after combined chelation therapy (p&lt;0,001), but there is no correlation between cardiac T2* and LIC and between cardiac T2* and ferritin. DFP adverse events included 8% agranulocytosis, 22% neutropenia, 20% arthralgia and 38% gastric intolerance. DFO adverse events were 2,6% deafness, 2,0% cataract and 12% growth deficit. Hepatic toxicity was found in 6%, but without necessity to stop treatment. Compliance in this group was excellent in 48%, good in 22% and poor in 30%. Conclusions: This is the first multicenter study to evaluate combined chelation therapy in Brazil based on cardiac MRI and LIC. Most patients had cardiac and hepatic iron overload probably because they began iron chelation lately, due to difficult access to iron chelators in the past. Cardiac iron overload didn’t have correlation with ferritin and LIC and these data need more understanding. Age of initial regular blood transfusion, increased transfusional requirement, inadequate chelation or delayed chelation may play a role in this question. Combined therapy with DFO and DFP is effective to decrease serum ferritin and LIC. Follow up and improving compliance may decrease cardiac iron overload. Adverse events are similar to literature. Combined therapy is safety in TM patients with transfusional iron overload.

Oral Chelator Deferiprone in Adult with Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4615-4615
Author(s):  
Ruben Nzouakou ◽  
Anoosha Habibi ◽  
Ketty Lee ◽  
Alain Luciani ◽  
Jean-François Deux ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Ferritin Level ◽  
Cardiac Iron ◽  
Median Level ◽  
Cardiac Iron Overload ◽  
The Mean

Abstract Abstract 4615 INTRODUCTION Long-term blood transfusion is essential for patients with sickle cell disease (SCD) in case of cerebral vasculopathy, organ dysfunction, leg ulcer, failure or intolerance of hydroxyurea treatment. Secondary iron overload is a factor of morbidity and mortality by organ damage. In practice, three chelators are available: deferoxamine (DFO) which is administrated by subcutaneous infusion and therefore source of poor compliance in SCD. Deferasirox (DFX), the new oral chelator is the first line therapy since 2007. Deferiprone (DFP) is an option when DFX or DFO are contraindicated or inadequate. However, DFP has no approval for SCD. The purpose of this study is to describe the characteristics of SCD patients treated by DFP. METHODOLOGY The patients included in this study arise from the group of the patients with long-term blood transfusion by manual exchange in Henri Mondor's SCD center, and in whom iron overload is treated by DFP. The monitoring of iron overload is obtained by regular serum ferritin level, combined liver and heart MRI. Only one iron measure by MRI is available for each patient throughout the study. RESULTS Nine patients (8 SS and 1 Sβ0thal) are included: 5 men and 4 women. The mean age is 44.2 years (22 to 64 years). The median duration of chronic transfusion is 10 years (4 to 27 years). The average dose of DFP is 68 mg / kg / day (50 to 93 mg / kg / day). The median follow-up under DFP is 30 months (7 to 60 months). The median level of serum ferritin before the initiation of DFP is 5830 μg / l (1800 to 9300 μg / l); and the median level of serum ferritin at the end point is 7940 μg / l (4540 to 11300 μg / l). MRI shows an important hepatic iron overload (up to 320 μmol) in all patients and one cardiac iron overload (T2* = 12 ms). Three patients stopped DFP and switch to deferasirox (DFX) as soon as DFX was available. For the other patients, the reason of prescribing DFP instead of DFX was renal failure in 5 patients and DFX related GI symptoms in one patient. No agranulocytosis is observed. The weekly then monthly monitoring of blood count is insured for all patients. No cytolysis by drug's toxicity is observed, except for one patient with liver transplant and who has an active HCV infection. DISCUSSION Serum ferritin level is the easiest marker of iron overload follow-up, but is subject of important variations due to inflammation, hemolysis, and cytolysis. Indeed, MRI is the only one reliable measure. The evidence of cardiac iron overload is proved in one patient, and confirms the importance of this measure on SCD patients. This motivates the edition of guidelines concerning the prevention and monitoring of iron overload among these patients. The dosage of DFP remains reasonable compared to the mean dosage use in other pathologies. This dosage depends of the degree of iron overload and the individual tolerance. Data are not sufficient at these days to evaluate the efficacy of DFP to reduce or to stabilize the level of iron overload. However, we observe globally a good clinical and biological tolerance, even in patients who have organ transplant and therefore have several concomitant treatments. CONCLUSION DFP in patients with SCD is globally well-tolerated, but its efficiency is not proved yet. Approval of DFP for SCD is needed. As life expectancy improves in SCD, more patients will require long-term transfusion and thus iron chelation therapy. Cardiac Iron overload is possible in patients with SCD. So, it would be systematically looked after. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Increased sympathovagal imbalance evaluated by heart rate variability is associated with decreased T2* MRI and left ventricular function in transfusion-dependent thalassemia patients

2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Sintip Pattanakuhar ◽  
Arintaya Phrommintikul ◽  
Adisak Tantiworawit ◽  
Sasikarn Konginn ◽  
Somdet Srichairattanakool ◽  
...  
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Medical Center ◽  
Screening Method ◽  
Left Ventricular ◽  
Cardiac Iron ◽  
Iron Overload Cardiomyopathy ◽  
Cardiac Iron Overload

Early detection of iron overload cardiomyopathy is an important strategy for decreasing the mortality rate of patients with transfusion-dependent thalassemia (TDT). Although cardiac magnetic resonance (CMR) T2* is effective in detecting cardiac iron deposition, it is costly and not generally available. We investigated whether heart rate variability (HRV) can be used as a screening method of iron overload cardiomyopathy in TDT patients. HRV, evaluated by 24-h Holter monitoring, non-transferrin bound iron (NTBI), serum ferritin, left ventricular (LV) ejection fraction (LVEF), and CMR-T2* were determined. Patients with a cardiac iron overload condition had a significantly higher low frequency/high frequency (LF/HF) ratio than patients without a cardiac iron overload condition. Log-serum ferritin (r = −0.41, P=0.008), serum NTBI (r = −0.313, P=0.029), and LF/HF ratio (r = −0.286, P=0.043) showed a significant correlation with CMR-T2*, however only the LF/HF ratio was significantly correlated with LVEF (r = −0.264, P=0.043). These significant correlations between HRV and CMR-T2* and LVEF in TDT confirmed the beneficial role of HRV as a potential early screening tool of cardiac iron overload in thalassemia patients, especially in a medical center in which CMR T2* is not available. A larger number of TDT patients with cardiac iron overload are needed to confirm this finding.

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