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 > 20 ms have normal cardiac function while the prevalence of myocardial dysfunction and arrhythmias increases as a consequence of cardiac iron overload (T2* < 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 (<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 > 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 (>20ms) and in the pancreas (>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* <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 (>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.

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.

scholarly journals The impact of magnetic resonance imaging in the assessment of iron overload in heart and liver in transfusion-dependent thalassemic children: Minia experience

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Ashraf M. El Sherif ◽  
Ahmed S. Ibrahim ◽  
Mohamed A. Elsayed ◽  
Ahmed S. Abdelhakim ◽  
Ahlam M. Ismail
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Deposition ◽  
Hepatic Iron ◽  
Resonance Imaging ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Cardiac Iron Overload

Abstract Background Thalassemia is the most prevalent single-gene disorder. Myocardial and hepatic iron depositions lead to complications and eventually death. We aimed to assess the diagnostic efficacy of magnetic resonance imaging T2* (MRI T2*) in quantifying iron overload in liver and heart in transfusion-dependent B-thalassemia major (TDT) children. Methods Prospective clinical study was carried on sixty children diagnosed with TDT. All of them underwent laboratory investigations, including CBC, serum iron, and ferritin levels. MRI T2* of the heart and liver was carried out to measure the iron overload and estimate the left ventricular ejection fraction (LVEF). Results Thirty-eight males and 22 females with TDT with a mean age of 13.23 years were included. Twenty cases (33.3%) had severe liver iron overload, while 36 (60%) had normal cardiac iron. There was a moderate significant negative association between hepatic and cardiac iron deposition (P = 0.03). All cases with severe cardiac iron overload had impaired LVEF below 56%. A non-significant positive association was noticed between cardiac iron deposition and LVEF in T2* (P = 0.08). A moderate negative significant association was detected between hepatic iron deposition and serum ferritin, while a fair negative significant association was found between serum ferritin and cardiac iron deposition with P values of 0.04 and 0.02, respectively. Conclusion MRI T2* is the gold standard for monitoring and follow-up of iron overload in the heart and liver. It should be routinely performed in all TDT children as liver iron, and serum ferritin do not reflect cardiac iron overload.

Comparing the Value of Serum Ferritin, Transfusion History and Magnetic Resonance Imaging for the Prediction of Iron Overload In MDS and AML Patients Undergoing Allogeneic Stem Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3493-3493
Author(s):  
Martin Wermke ◽  
Jan Moritz Middeke ◽  
Nona Shayegi ◽  
Verena Plodeck ◽  
Michael Laniado ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Content ◽  
Iron Concentration ◽  
Transferrin Saturation ◽  
Resonance Imaging ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Liver Iron Content ◽  
Transfusion History

Abstract Abstract 3493 An increased risk for GvHD, infections and liver toxicity after transplant has been attributed to iron overload (defined by serum ferritin) of MDS and AML patients prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nevertheless, the reason for this observation is not very well defined. Consequently, there is a debate whether to use iron chelators in these patients prior to allo-HSCT. In fact, serum ferritin levels and transfusion history are commonly used to guide iron depletion strategies. Both parameters may inadequately reflect body iron stores in MDS and AML patients prior to allo-HSCT. Recently, quantitative magnetic resonance imaging (MRI) was introduced as a tool for direct measurement of liver iron. We therefore aimed at evaluating the accurateness of different strategies for determining iron overload in MDS and AML patients prior to allo-HSCT. Serologic parameters of iron overload (ferritin, iron, transferrin, transferrin saturation, soluble transferrin receptor) and transfusion history were obtained prospectively in MDS or AML patients prior to allo-SCT. In parallel, liver iron content was measured by MRI according to the method described by Gandon (Lancet 2004) and Rose (Eur J Haematol 2006), respectively. A total of 20 AML and 9 MDS patients (median age 59 years, range: 23–74 years) undergoing allo-HSCT have been evaluated so far. The median ferritin concentration was 2237 μg/l (range 572–6594 μg/l) and patients had received a median of 20 transfusions (range 6–127) before transplantation. Serum ferritin was not significantly correlated with transfusion burden (t = 0.207, p = 0.119) but as expected with the concentration of C-reactive protein (t = 0.385, p = 0.003). Median liver iron concentration measured by MRI was 150 μmol/g (range 40–300 μmol/g, normal: < 36 μmol/g). A weak but significant correlation was found between liver iron concentration and ferritin (t = 0.354; p = 0.008). The strength of the correlation was diminished by the influence of 5 outliers with high ferritin concentrations but rather low liver iron content (Figure 1). The same applied to transfusion history which was also only weakly associated with liver iron content (t = 0.365; p = 0.007). Levels of transferrin, transferrin saturation, total iron and soluble transferrin receptor did not predict for liver iron concentration. Our data suggest that serum ferritin or transfusion history cannot be regarded as robust surrogates for the actual iron overload in MDS or AML patients. Therefore we advocate caution when using one of these parameters as the only trigger for chelation therapy or as a risk-factor to predict outcome after allo-HSCT. Figure 1. Correlation of Liver iron content with Ferritin. Figure 1. Correlation of Liver iron content with Ferritin. Disclosures: No relevant conflicts of interest to declare.

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.

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.

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.

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.

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.

Magnetic Resonance T2* Measurement of Myocardial Iron Deposition in Sickle Cell Disease: Risk Factors and Relationship with Cardiac Function.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4604-4604
Author(s):  
Alexander Ngwube ◽  
Andrew Hardie ◽  
Luis Ramos-Duran ◽  
Joseph Schoepf ◽  
Ibrahim Shatat ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Transfusion ◽  
Cardiac Function ◽  
Iron Overload ◽  
Left Ventricular ◽  
Iron Deposition ◽  
Myocardial Iron ◽  
Cardiac Iron ◽  
Paravertebral Muscles ◽  
Cardiac Iron Overload

Abstract Abstract 4604 BACKGROUND Children with thalassemia major (TM) and sickle cell disease (SCD) receiving chronic blood transfusion are at risk of developing cardiac iron overload. Magnetic resonance imaging (MRI) has emerged as a non invasive tool for the direct measurement of myocardial iron deposition in these patients. Previous studies have shown that patients with TM develop significant myocardial iron deposition that correlates with transfusion burden and cardiac function. However, the prevalence of myocardial iron overload, the risk factors and its relationship with cardiac function in patients with SCD are not well known. OBJECTIVE To review the patterns of cardiac iron overload using cardiac MRI in our cohort of children with SCD. METHODS Cardiac MRI studies performed in children with SCD at a steady state from January 2009 to June 2009 at our institution were reviewed. We abstracted demographic and laboratory data and reviewed their transfusion history. These patients were receiving chronic blood transfusion every 3-4 weeks. All patients had been on chelation therapy desferrioxamine and/or deferasirox. In each patient, MR (1.5T Avanto™, Siemens) T2* measurements were performed in the interventricular septum, as well as in the paravertebral muscles as an internal control. Cardiac T2* value of 25-46 was considered normal as previously published. RESULTS A total of 20 patients with Hb SS (50 % male), with a mean age of 14 years were studied. The mean duration of blood transfusion was 9.5 ± 5.3 years. Seventeen patients (85%) were on chronic transfusion for stroke or abnormal TCD and three (15%) for other reasons such as recurrent pain crises and priapism. Overall, the mean cardiac T2* was 31.2 ± 6.6 ms in our patients. Mean T2* values in the myocardium were significantly lower than T2* values measured in the paravertebral muscles in the same patients (31.2 ± 6.6 versus 48.2 ± 5.1, p<0.05). Two patients (10%) had low cardiac T2* (17 and 22) indicating significant myocardial iron deposition. In addition, borderline low T2* values (26 each) were noted in two additional patients (10%) suggesting high myocardial iron deposition. There was a weak but not significant correlation between cardiac T2* and left ventricular end-diastolic volume (r=0.17), left ventricular ejection fraction (r=0.21) and right ventricular end-diastolic volume (r=0.37). Also, there was no statistically significant correlation between myocardial T2* and transfusional burden (r= -0.26), duration of transfusion (r= -0.35), serum ferritin (r= -0.4) and liver iron concentration by biopsy (r= -0.33) and liver T2* (r=0.04). CONCLUSION Our study shows that patients with SCD develop significant cardiac iron overload (low cardiac T2*) than previously reported. However, there was no significant correlation between cardiac T2* and parameters of ventricular function even in patients with high myocardial iron content. The lack of correlation between cardiac T2* and serum ferritin, liver iron content and transfusion burden in our cohort concurs with previous studies. Thus the risk factors for cardiac iron accumulation and its correlation with cardiac function in this patient population remain unclear. Further prospective studies are needed to understand the pathogenesis and the consequences of cardiac iron overload in patients with SCD. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document