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.

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.

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.

Efficacy of deferasirox in reducing and preventing cardiac iron overload in β-thalassemia

Blood ◽  
2010 ◽  
Vol 115 (12) ◽  
pp. 2364-2371 ◽  
Author(s):  
Dudley J. Pennell ◽  
John B. Porter ◽  
Maria Domenica Cappellini ◽  
Amal El-Beshlawy ◽  
Lee Lee Chan ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Reduction ◽  
Geometric Mean ◽  
Iron Concentration ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Liver Iron ◽  
Ventricular Ejection Fraction ◽  
Cardiac Iron ◽  
Cardiac Iron Overload

Cardiac iron overload causes most deaths in β-thalassemia major. The efficacy of deferasirox in reducing or preventing cardiac iron overload was assessed in 192 patients with β-thalassemia in a 1-year prospective, multicenter study. The cardiac iron reduction arm (n = 114) included patients with magnetic resonance myocardial T2* from 5 to 20 ms (indicating cardiac siderosis), left ventricular ejection fraction (LVEF) of 56% or more, serum ferritin more than 2500 ng/mL, liver iron concentration more than 10 mg Fe/g dry weight, and more than 50 transfused blood units. The prevention arm (n = 78) included otherwise eligible patients whose myocardial T2* was 20 ms or more. The primary end point was the change in myocardial T2* at 1 year. In the cardiac iron reduction arm, the mean deferasirox dose was 32.6 mg/kg per day. Myocardial T2* (geometric mean ± coefficient of variation) improved from a baseline of 11.2 ms (± 40.5%) to 12.9 ms (± 49.5%) (+16%; P < .001). LVEF (mean ± SD) was unchanged: 67.4 (± 5.7%) to 67.0 (± 6.0%) (−0.3%; P = .53). In the prevention arm, baseline myocardial T2* was unchanged from baseline of 32.0 ms (± 25.6%) to 32.5 ms (± 25.1%) (+2%; P = .57) and LVEF increased from baseline 67.7 (± 4.7%) to 69.6 (± 4.5%) (+1.8%; P < .001). This prospective study shows that deferasirox is effective in removing and preventing myocardial iron accumulation. This study is registered at http://clinicaltrials.gov as NCT00171821.

Left Ventricular Dysfunction in Chronically Transused Patients with Sickle Cell Anemia and Thalassemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3745-3745
Author(s):  
Lynne Neumayr ◽  
Ellen Fung ◽  
Paul Harmatz ◽  
Ellen Butensky ◽  
John Wood ◽  
...  
Keyword(s):  
Iron Overload ◽  
Sickle Cell ◽  
Cardiac Mri ◽  
Left Ventricular ◽  
Iron Toxicity ◽  
Iron Deposition ◽  
Liver Iron ◽  
Transfusion Therapy ◽  
Cardiac Iron ◽  
Lv Dysfunction

Abstract BACKGROUND: Iron-induced cardiomyopathy has been extensively described in thalassemia (THAL) patients. Left ventricular (LV) dysfunction is the leading cause of death in THAL, with prevalence estimates ranging from 6% to 23%. Recent MRI techniques confirmed that T2* measurements consistent with elevated cardiac iron are associated with LV dysfunction and early mortality. Transfusion therapy is being increasingly used for the treatment and prevention of complications in sickle cell disease (SCD). By adulthood, the majority of SCD patients will have received multiple transfusions and nearly 1/3 will be iron-overloaded. However, cardiomyopathy, its prevalence, and the role of iron toxicity have not been studied in SCD. The Multicenter Study of Iron Overload, a 5-year prospective natural history study, enrolled 152 transfusion dependent THAL, 204 chronically transfused SCD (txSCD) and 64 control SCD in order to compare the effects of iron toxicity in these two diseases. We compared the prevalence of LV dysfunction and its relationship to iron-toxicity in THAL, txSCD and control SCD. METHODS AND RESULTS: Baseline or year 1 echocardiograms (ECHOs) were available in 45% of the patients (80 THAL, 94 txSCD and 16 SCD controls) and reviewed for evidence of LV dysfunction, defined as an ejection fraction ≤ 55% or shortening fraction ≤ 28%. Pulmonary hypertension (PHT) was defined as a tricuspid regurgitant jet velocity (TRV) ≥ 2.5 m/s or pulmonary artery pressure (PAP) ≥ 35 mmHg. ECHOs reported as normal, even without TRV or PAP recorded, were assumed to be negative for PHT. At study entry, THAL and txSCD patients were severely iron over-loaded and their average ferritin and liver iron concentrations were not significantly different: 3506 g/dl and 20 mg/g dry weight. (Serum ferritin in the control SCD was 120 g/dl.) The average age of the patients was 30.3 ± 12 yrs, and did not differ across the three groups. LV dysfunction was found in 22% THAL; THAL patients with LV dysfunction had been transfused longer than those with normal ECHOs (26.5 vs. 21.1 yrs, p=. 03). A subgroup of THAL was screened with cardiac MRI: 11/21 (52%) had evidence of cardiac iron deposition, 4 of these patients (36%) had LV dysfunction. In THAL screened with MRI, all patients with LV dysfunction had cardiac iron deposition. LV dysfunction was seen in 14% of txSCD but in 0% of the control SCD. txSCD patients with LV dysfunction were older (43.7 vs. 28.5, p <. 0001) and more likely to have PHT (75% vs. 22%, p < .001). PHT was more common in txSCD than THAL (29% vs. 15%, p=. 03) and found in 13% of the control SCD group. No txSCD patients were screened with MRI. CONCLUSIONS: LV dysfunction is common in transfusion dependent THAL and associated with duration of transfusion and iron deposition. In SCD, patients with cardiomyopathy were chronically transfused, older, and more likely to have PHT. SCD patients are developing iron overload similar to THAL; cardiac MRI studies are essential for the evaluation of iron deposition and its relationship to cardiomyopathy.

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

Myocardial iron overload

2018 ◽  
pp. 364-374
Author(s):  
John P Carpenter ◽  
John C Wood ◽  
Dudley J Pennell
Keyword(s):  
Heart Failure ◽  
Iron Overload ◽  
Iron Concentration ◽  
Left Ventricular ◽  
Breath Hold ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Single Breath ◽  
Developing Heart ◽  
Cost Efficient

The heart is the target lethal organ in thalassaemia major. Cardiovascular magnetic resonance (CMR) measures iron using the magnetic relaxation time T2*. This allows comparison with the left ventricular function and conventional iron measurements such as liver iron and serum ferritin. The single breath-hold cardiac-gated CMR acquisition takes only 15 seconds, making it cost-efficient and relevant to developing countries. Myocardial T2* of <20 ms (increased iron) correlates with reduced left ventricular ejection fraction, but poor correlation exists with ferritin and liver iron, indicating poor capability to assess future risk. Myocardial T2* of <10 ms is present in >90% of thalassaemia patients developing heart failure, and approximately 50% of patients with T2* of <6 ms will develop heart failure within 1 year without intensified treatment. The technique is validated and calibrated against human heart iron concentration. The treatment for iron overload is iron chelation, and three major trials have been performed for the heart. The first trial showed deferiprone was superior to deferoxamine in removing cardiac iron. The second trial showed a combination therapy of deferiprone with deferoxamine was more effective than deferoxamine monotherapy. The third trial showed that deferasirox was non-inferior to deferoxamine in removing cardiac iron. Each drug in suitable doses can be used to remove cardiac iron, but their use depends on clinical circumstances. Other combination regimes are also being evaluated. Use of T2*, intensification of chelation treatment, and use of deferiprone are associated with reduced mortality (a reduction in deaths by 71% has been shown in the United Kingdom). The use of T2* and iron chelators in the heart has been summarized in recent American Heart Association guidelines.

Cardiac MRI (T2,T2*) Predicts Cardiac Iron in the Gerbil Model of Iron Cardiomyopathy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 376-376 ◽  
Author(s):  
John C. Wood ◽  
Maya Otto-Duessel ◽  
Michelle Aguilar ◽  
Hanspeter Nick ◽  
Marvin D. Nelson ◽  
...  
Keyword(s):  
Cardiac Mri ◽  
Iron Content ◽  
Interstitial Fibrosis ◽  
Iron Concentration ◽  
Dry Weight ◽  
Weight Basis ◽  
Iron Deposition ◽  
Liver Iron ◽  
High Iron ◽  
Cardiac Iron

Abstract Introduction: Transfusional therapy for thalassemia major and sickle cell disease can lead to iron deposition and damage to the heart, liver, and endocrine organs. Iron causes the MRI parameters T1, T2, and T2* to shorten in these organs, creating a potential mechanism for iron quantitation. Validation of liver MRI has been achieved by studying patients undergoing clinically indicated liver biopsy. However, because of the danger and variability of cardiac biopsy, cardiac MRI studies have relied upon “clinical” validation, i.e., the association between low cardiac T2* and cardiac function. In this study, we demonstrate that iron produces similar T1, T2, and T2* changes in the heart and liver, using a gerbil iron overload model. Methods: Twelve gerbils underwent iron dextran loading (200 mg/kg/week) from 2–14 weeks; 5 age-matched controls were studied as well. Animals had in-vivo assessment of cardiac T2* as well as hepatic T2 and T2* using a General Electric 1.5 T CVi system with custom isofluorane anesthesia delivery system, imaging enclosure, coil and pulse sequences. Liver and heart were harvested following imaging, weighed, and portions collected for histology and quantitative iron (Mayo Metals Laboratory, Rochester, MN). Ex-vivo cardiac and liver T1 and T2 measurements were performed on fresh specimens (< 30 minutes post-sacrifice) using a Bruker minispectrometer. Results: Control animals had minimal detectable iron at baseline and did not accumulate iron in the liver or the heart over the 14-week study interval. Chemically-assayed heart iron concentration increased 0.078 mg/g(wet wt)/wk (r2=0.98) and iron content 0.022 mg/wk (r2=0.92) by linear regression analysis. Similarly, assayed liver iron concentration increased 1.15 mg/g(wet wt)/week (r2=0.93) over a 10 week interval and liver iron content increased 3.82 mg/wk (r2=0.96). Liver iron deposition was prominent in both sinusoidal cells and hepatocytes. Interstitial fibrosis was mild and there was no necrosis. Cardiac iron deposition was predominantly endomysial, generally sparing the myocytes themselves. Interstitial fibrosis was prominent, originating from areas of high iron concentration. No myocyte necrosis was observed, however myocyte hypertrophy was evident at high iron concentrations. Cardiac and liver R2* (1/T2*), R2 (1/T2), and R1 (1/T1) rose linearly with tissue iron concentration (r2 averaged 0.94 [0.74 to 0.98]. The slope of these parameter with respect to iron was15–29% steeper in heart than in liver, although these differences reached statistical significance only for R2. Systematic differences in wet-to-dry weight ratio between heart and liver (5.07 vs 3.82) antagonized this effect, however, such that calibrations were similar on a dry-weight basis. Conclusion: Cardiac iron is the primary determinant of cardiac MRI relaxivity. Calibration curves were similar between heart and liver on a dry weight basis. Extrapolation of liver calibration curves to heart may be a rationale approximation in humans where direct tissue validation is difficult and dangerous. Regardless of systematic differences in absolute calibration, these data support prior claims that cardiac R2 and R2* measurements reflect cardiac iron concentration

Gender Differences in Iron Overload and Left Ventricular Function in a Cohort of Thalassemia Major Patients: A Prospective Study of a Single Italian Center Using Cardiovascular Magnetic Resonance.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3819-3819
Author(s):  
Elisabetta Volpato ◽  
Elena Cassinerio ◽  
Maria Rosaria Fasulo ◽  
Paola Pedrotti ◽  
Stefano Pedretti ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gender Differences ◽  
Cardiovascular Magnetic Resonance ◽  
Iron Overload ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Myocardial Iron ◽  
Iron Intake ◽  
Cardiac Iron ◽  
Cardiac Iron Overload

Abstract Introduction: cardiac failure due to secondary iron overload remains the main cause of death in patients with b-Thalassemia Major (TM). Cardiovascular Magnetic Resonance Imaging (CMR) T2* technique is a new tool to assess myocardial iron concentration that allows to tailor the optimal iron chelation treatment for each patient. Aim of the study: to assess left ventricular function and myocardial iron overload in a cohort of TM patients, cared at Hereditary Anemia Center in Milan, Italy. Methods and Results: In 91 TM patients (33 males/58 females, mean age 32 ± 6 yrs) myocardial iron loading was assessed with the use of CMR T2* measurements (CMR Tools, Cardiovascular Imaging Solutions, London, UK). Left ventricular ejection fraction (LVEF) was also assessed with CMR. In the overall group hemoglobin levels were 9.0 ± 1.0 g/dl; the mean serum ferritin levels and iron intake during the six months before CMR evaluation were 1507 ± 1884 ng/ml and 0.34 ± 0.08 mg/kg/die respectively. T2* was significantly different between females and males (24 ± 11 and 32 ± 12 ms, respectively; p &lt; 0.0001), with significant differences in diabetes mellitus prevalence (17% vs 8%, p&lt;0.01) but not in age, serum ferritin, iron intake and hemoglobin levels (Table 1). Seven (7.6%) asymptomatic females showed a severe cardiac iron overload (T2* ≤ 10 ms), 9 patients (9.9%) moderate (T2* between 10.1 and 14 ms), 15 patients (16.4%) mild cardiac iron overload (T2* between 14.1 and 20 ms) and 60 patients (65.9%) had normal T2* (&gt; 20 ms). LVEF was significantly different between females and males (35% vs 57%, p&lt;0.001) with evidence of a significant relationship between iron overload severity and LVEF impairment (r=0.92). Conclusions: CMR cardiac function and T2* assessment allow to detect pre-symptomatic cardiac iron overload. Females are more at risk for severe iron overload and left ventricular impairment. The prevalence of diabetes mellitus and compliance to chelation therapy could be relevant in explaining the gender differences. Clinical parameters and T2* values in men and women with thalassemia major Men p Women SD: standard deviation Number of patients (n. of pts) 33 - 58 Age ± SD (years) 33 ± 6 ns 32 ± 6 Hemoglobin levels ± SD (g/dl) 9.0 ± 1.7 ns 9.0 ± 0.8 Ferritin levels ± SD (ng/ml) 964 ± 891 ns 1821 ± 2216 Iron intake ± SD (mg/Kg/die) 0.30 ± 0.07 ns 0.36 ± 0.09 Mean T2* value ± SD (ms) 32 ± 12 &lt;0.0001 24 ± 11 T2*&lt; 10 ms (n. of pts) 0 - 7 T2* between 10.1 and 14 ms (n. of pts) 1 - 8 T2* between 14.1 and 20 ms (n. of pts) 7 - 8 T2* &gt; 20 ms (n. of pts) 25 - 35 T2*&lt; 10 ms (n. of pts) plus LVEF≤ 57 % 0/0 (0%) - 6/7 (85.7%) T2* between 10.1 and 14 ms (n. of pts) plus LVEF≤ 57 % 1/1 (100%) - 3/8 (37.5%) T2* between 14.1 and 20 ms (n. of pts) plus LVEF≤ 57 % 3/7 (42.8%) - 1/8 (12.5%) T2* &gt; 20 ms (n. of pts) plus LVEF≤ 57 % 7/25 (28%) - 5/35 (14.3%)

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.

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