scholarly journals The Importance of Cardiac T2* Magnetic Resonance Imaging for Monitoring Cardiac Siderosis in Thalassemia Major Patients

Tomography ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. 130-138
Author(s):  
Narumol Chaosuwannakit ◽  
Pattarapong Makarawate ◽  
Chinnadol Wanitpongpun
Keyword(s):  
Left Ventricular Ejection Fraction ◽  
Serum Ferritin ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Liver Iron ◽  
Ventricular Ejection Fraction ◽  
Cardiac Siderosis ◽  
T2 Mri

Objective: Cardiac T2* magnetic resonance imaging (MRI) has recently attracted considerable attention as a non-invasive method for detecting iron overload in various organs in thalassemia major patients. This study aimed to identify the prevalence of cardiac siderosis in thalassemia major patients and evaluate cardiac T2* MRI for monitoring cardiac siderosis before and after patients receive iron chelation therapy and its relation to serum ferritin, left ventricular ejection fraction, and liver iron concentration. The information gathered would be used for the direct monitoring, detection, and treatment of complications early on. Methods: A total of 119 thalassemia major patients were recruited in the present study. The cardiac T2* MRI was compared to serum ferritin levels, liver iron concentration (LIC), and left ventricular ejection fraction. All patients were classified into four groups based on their cardiac siderosis as having normal, marginal, mild to moderate, or severe cardiac iron overload. At the follow-up at years one, three, and five, the cardiac T2* MRI, LIC, serum ferritin, and left ventricular ejection fraction (LVEF) were determined. Results: The prevalence of cardiac siderosis with cardiac T2* MRI ≤ 25 ms was 17.6% (n = 21). There was no correlation between cardiac T2* MRI and serum ferritin, liver iron concentration, and LVEF (p = 0.39, 0.54, and 0.09, respectively). During one year to five years’ follow-up periods, cardiac T2* MRI (ms) in patients with severe cardiac siderosis had significantly improved from 8.5 ± 1.49 at baseline to 33.9 ± 1.9 at five years (p < 0.0001). Patients with severe, mild-moderate, marginal, and no cardiac siderosis had median LIC (mg/g dw) of 23.9 ± 6.5, 21.6 ± 13.3, 25.3 ± 7.7, and 19.9 ± 5.5 at baseline, respectively. Conclusions: This study supports the use of cardiac T2* MRI to monitor cardiac iron overload in patients who have had multiple blood transfusions. Early diagnosis and treatment of patients at risk of cardiac siderosis is a reasonable method of reducing the substantial cardiac mortality burden associated with myocardial siderosis. Cardiac T2* MRI is the best test that can identify at-risk patients who can be managed with optimization of their chelation therapy.

The effect of deferasirox on cardiac iron in thalassemia major: impact of total body iron stores

Blood ◽  
2010 ◽  
Vol 116 (4) ◽  
pp. 537-543 ◽  
Author(s):  
John C. Wood ◽  
Barinder P. Kang ◽  
Alexis Thompson ◽  
Patricia Giardina ◽  
Paul Harmatz ◽  
...  
Keyword(s):  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Iron Concentration ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Liver Iron ◽  
Ventricular Ejection Fraction ◽  
Iron Stores ◽  
Cardiac Iron

AbstractWe present results from a prospective, multicenter, open-label, single-arm study evaluating response of cardiac and liver iron to deferasirox therapy for 18 months. Twenty-eight patients with abnormal T2* and normal left ventricular ejection fraction were enrolled from 4 US centers. All patients initially received deferasirox doses of 30 to 40 mg/kg per day. Patients were severely iron overloaded: mean liver iron concentration (LIC) 20.3 mg Fe/g dry weight, serum ferritin 4417 ng/mL, and cardiac T2* 8.6 ms. In the intent-to-treat population, 48% reached the primary endpoint (cardiac T2* improvement at 18 months, P = not significant). There were 2 deaths: 1 from congestive heart failure and 1 from sepsis. In the 22 patients completing the trial, LIC and cardiac T2* improvements were 16% (P = .06) and 14% (P = .07), respectively. Cardiac T2* improvement (13 patients) was predicted by initial LIC, final LIC, and percentage LIC change, but not initial cardiac T2*. Cardiac iron improved 24% in patients having LIC in the lower 2 quartiles and worsened 8.7% in patients having LIC in the upper 2 quartiles. Left ventricular ejection fraction was unchanged at all time points. Monotherapy with deferasirox was effective in patients with mild to moderate iron stores but failed to remove cardiac iron in patients with severe hepatic iron burdens. This study was registered at www.clinicaltrials.gov as #NCT00447694.

Low Incidence of Cardiac Siderosis in Heavily Iron Overloaded Egyptian Thalassemics.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5110-5110
Author(s):  
Amal M. El-Beshlawy ◽  
Mona Mohamed Hamdy ◽  
Mona Elgamrawy ◽  
Khaled Abdel Azim ◽  
Doria Salem ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Serum Ferritin ◽  
Conflicts Of Interest ◽  
Iron Concentration ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Study Group ◽  
Ventricular Ejection Fraction ◽  
Cardiac Iron ◽  
Cardiac Siderosis

Abstract Abstract 5110 Introduction Myocardial siderosis in thalassemia major remains the leading cause of death in developing countries. Once heart failure develops, the outlook is usually poor with precipitous deterioration and death. Cardiovascular magnetic resonance (CMR) technology can measure cardiac iron deposition directly using the magnetic relaxation time T2*. This allows earlier diagnosis and treatment and help to reduce mortality from this cardiac affection. Patients and Methods 89 β thalassemia patients (10 to 43 years, mean age of 20.78±6.36) were recruited in this study. All patients were receiving chelation therapy of subcutaneous desferroxamine. Evaluation of hemosiderosis was based on CMR, liver magnetic resonance R2 and serum ferritin. Results T2* values ranged between 4.3 to 53.8 ms with a mean of 28.50±11.74 ms among our study group. The left ventricular ejection fraction (LVEF) as measured by CMR ranged between 55 and 78%; mean=67.66±4.69%.and liver iron concentration (LIC) ranged between 1.5 to 56 mg/g dry weight with a mean of 26.13±13.37 mg/g. Serum ferritin varied among our study group from 533 to 22363ng/ml; mean=4514.27±2847.58ng/ml with 83.15% above 2500ng/ml. The prevalence of myocardial siderosis (T2*<20ms) among our patients was 22/89 patients (24.7%) aged 20.86±7.54 years with a mean T2* value of 12.718±4.36ms and LVEF of 68.59 ±5.84%. LIC and serum ferritin results were 30.85±13.48 mg/g and 6122.86±4185.67ng/ml respectively. There was no correlation between T2* results and the age, LVEF, LIC and serum ferritin of this group (P=0.651, P=0.085, P=0.999 and P=0.627 respectively). Those patients with severe cardiac siderosis (T2*<10ms) constituted 7/89 (7.9%) with a mean age of 18.43±4.35 years. Although these patients had a mean T2* of 7.8±1.73 ms, the LVEF value was 65.14±6.20 % and only one patient had clinical cardiac disease (T2*=4.3 ms and LVEF =55%). LIC and serum ferritin results were 29.84±16.99mg/g and 7202.14±6953.79ng/ml respectively. In this group of severe cardiac siderosis, T2* was not correlated to age (P=0.5), LVEF (P=0.144), LIC (P=0.969) and serum ferritin (P=0.818). Conclusion Low prevalence of myocardial siderosis in the Egyptian thalassemic patients in spite of the very high serum ferritin. In severely iron overloaded patients the cardiac function was not affected. T2* is the best test that can identify at risk patients who can be treated with optimization of their chelation protocols. The possibility of a genetic component for the susceptibility of cardiac iron loading in our population should be considered. 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.

Exjade® Reduces Cardiac Iron Burden in Chronically Transfused β-Thalassemia Patients: An MRI T2* Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2781-2781 ◽  
Author(s):  
J. Wood ◽  
A.A. Thompson ◽  
C. Paley ◽  
B. Kang ◽  
P. Giardina ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Left Ventricular ◽  
Iron Removal ◽  
Left Ventricular Ejection ◽  
Liver Iron ◽  
Ventricular Ejection Fraction ◽  
Cardiac Iron ◽  
The Mean

Abstract Introduction: Despite the routine use of iron chelation therapy, cardiac iron overload results in cardiomyopathy, congestive heart failure and death in approximately 71% of pts with β-thalassemia. Recent MRI studies suggest that the kinetics of cardiac iron uptake and elimination differ from that of liver. Furthermore, different chelators appear to exhibit unique profiles of relative heart and liver iron removal. Deferasirox (DFX; Exjade®) is a once-daily oral iron chelator with demonstrated efficacy in reducing liver iron. In addition, preclinical and single-institution clinical studies have demonstrated cardiac iron removal. This study is a prospective, single-arm multi-institutional trial designed to evaluate the effect of DFX on cardiac iron in pts with β-thalassemia major. Here, we report preliminary results from the first 15 pts who completed 6 months of treatment. Methods: This ongoing study will enroll 30 pts at 4 US centers. DFX is administered at 30–40 mg/kg/day for 18 months. Entry criteria include MRI evidence of cardiac iron (T2* <20 ms) and normal left ventricular ejection fraction (LVEF ≥56%). Serum ferritin is assessed monthly and MRI assessments for liver iron concentration (LIC), cardiac T2* and LVEF are assessed every 6 months. Labile plasma iron (LPI), serum creatinine, biochemical and hematological status are being monitored. Results: At the time of this analysis, 15 of 17 pts had 6 months of evaluation; all were dosed at 30 mg/kg/day. One of the excluded pts was found ineligible (LVEF <56% at baseline) and the other developed cardiac failure prior to 6 months and was switched to continuous DFO (deferoxamine). This pt had markedly elevated cardiac iron (T2*=1.8 ms) at enrollment. All results are reported as mean±SEM (range) unless otherwise stated. Baseline: All 15 evaluable pts (3 male, 12 female; aged 10–43 years) received ≥150 lifetime transfusions. Ferritin was 4927±987 ng/mL (395–10751; n=12). Cardiac T2* was 9.8±1.13 ms (5.0–16.1), LIC was 16.6±4.27 mg/g dw (3.6–62.3) and ejection fraction was 61.2±1.83%. LPI was 0.72±0.28 μmol/L (n=11) and 33% of pts started with abnormal LPI (≥0.5 μmol/L). 6 Month results: At 6 months, the mean decrease in ferritin was 516 ng/mL; 14 of 15 (93%) pts had decreases in hepatic and cardiac iron. The mean reductions in cardiac and hepatic iron were 17.8% (P=0.0136) and 27.0% (P=0.0027), respectively (Figure). There was no change in LVEF by MRI. All patients had normal LPI at 6 months; for pts with abnormal LPI at baseline, the mean LPI dropped from 1.6±0.3 to 0.26±0.1 μmol/L (P=0.003). No pts developed creatinine >upper limit of normal. Four pts had abnormal transaminases on ≥2 occasions but all 4 were abnormal at baseline. Conclusions: The 30 mg/kg/day dose was well tolerated and led to negative cardiac and liver iron balance in 93% of pts. These results are encouraging given this heavily iron-overloaded and heavily transfused population of β-thalassemia pts. Ongoing assessments over 12 and 18 months will elucidate if DFX continues to improve cardiac iron burden and maintain/improve cardiac function in severely iron-overloaded pts. Figure Figure

Deferasirox (Exjade®) Monotherapy Significantly Reduces Cardiac Iron Burden in Chronically Transfused β-Thalassemia Patients: An MRI T2* Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3882-3882 ◽  
Author(s):  
John C Wood ◽  
Alexis A. Thompson ◽  
Carole Paley ◽  
Barinder Kang ◽  
Patricia Giardina ◽  
...  
Keyword(s):  
Iron Concentration ◽  
Safety Data ◽  
Left Ventricular ◽  
Mean Difference ◽  
Left Ventricular Ejection ◽  
Patient Death ◽  
Liver Iron ◽  
Ventricular Ejection Fraction ◽  
Cardiac Iron ◽  
Long Term Study

Abstract Introduction: Despite the availability of iron chelation therapy, accumulation of excess iron in the heart results in cardiomyopathy, congestive heart failure (CHF) and death in approximately 71% of transfused patients with β-thalassemia (β-thal) major. In preclinical and single-institution clinical studies, Exjade®(deferasirox, DFX) has demonstrated efficacy in decreasing cardiac iron. This ongoing study evaluates the effects of DFX on cardiac iron and left ventricular ejection fraction (LVEF) in patients (pts) with β-thal major in a prospective, single-arm, multi-center trial using cardiac MRI T2*. Here, we report preliminary results from patients who have completed 12 or 18 months of treatment. Methods: Twenty-eight pts were enrolled at four US centers. DFX was administered at 30–40 mg/kg/day for 18 months. Entry criteria included MRI evidence of cardiac iron (T2* <20 ms) and normal LVEF (≥56%). Serum ferritin (SF) was assessed monthly and MRI assessments for liver iron concentration (LIC), cardiac T2* and LVEF were done every 6 months. Serum creatinine (SCr), biochemical and hematological status were also monitored. All results are reported as mean±SE (range) unless otherwise stated. Results: At the time of analysis, 18 pts had 12-month evaluations and 12 pts had 18-month evaluations. Five pts discontinued (one non-compliance, two patient decisions, and two deaths). Both deaths were considered unrelated to DFX treatment; the first patient enrolled with markedly elevated baseline cardiac iron (T2*=1.8 ms) and died secondary to CHF. The second patient death was due to sepsis and multi-organ failure. Baseline: All 18 evaluable pts (three male, 15 female; aged 10–44 years) received ≥150 lifetime transfusions. SF was 4324±912 ng/mL (395–16,249). Cardiac T2* was 9.6±0.97 ms (4.6–16.1), LIC was 18.7±3.8 mg Fe/g dry weight (dw; 3.6–62.3) and LVEF was 61.7±1.0%. 12-Month results: At 12 months, 7/18 pts were on 40 mg/kg/day. 12/18 pts (67%) had an increase in cardiac T2* with a mean difference of 2.2 ms (18%; P=0.025). 13/18 pts (72%) had a decrease in LIC with a mean difference of 2.4 mg Fe/g dw (25%; P=0.032). LVEF remained stable. SF fell by 583 ng/mL (n=18; 22%; P=0.147). 18-Month results: At 18 months, 3/12 pts were on 40 mg/kg/day. 10/12 pts (83%) had an increase in cardiac T2* with a mean difference of 4.1 ms (35%; P=0.001). 11/12 pts (92%) had a decrease in LIC with a mean reduction of 4.7 mg Fe/g dw (50%; P=0.003). Mean LVEF trended upward from 61.5 to 63.3% (n=13; P=0.2). SF fell by 1373 ng/mL (n=11; 46%, P=0.006). Safety data from pts (n=25) treated with 30–40 mg DFX were in line with previous studies. The most common drug-related adverse events (AEs; eight pts; 32%) were gastrointestinal in nature. 1/25 patients experienced a suspected SAE (hospitalization due to abdominal pain and vomiting) but completed the study. One patient developed SCr >upper limit of normal (ULN). Two pts (8%) had abnormal transaminases (≥5×ULN) on ≥2 occasions but both had abnormal values at baseline. Conclusions: DFX monotherapy significantly improved cardiac and liver iron after 12 and 18 months. Overall, doses from 30–40 mg/kg/day were well tolerated. Cardiac T2* improvement rates were 1.5–1.9% per month, which is comparable to other monotherapy trials. A trend towards improved LVEF was seen in patients completing 18 months of therapy; however, a larger, long-term study will be required to confirm whether DFX can significantly improve cardiac function in this population. Figure Figure

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

Blood ◽  
2016 ◽  
Vol 128 (12) ◽  
pp. 1555-1561 ◽  
Author(s):  
Juliano L. Fernandes ◽  
Sandra R. Loggetto ◽  
Monica P. A. Veríssimo ◽  
Kleber Y. Fertrin ◽  
Giorgio R. Baldanzi ◽  
...  
Keyword(s):  
Chelation Therapy ◽  
Combined Treatment ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Cardiac Siderosis ◽  
Key Points ◽  
Effective Reduction

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

scholarly journals Left ventricular dysfunction by strain echocardiography in thalassemia patients: a pilot study

2019 ◽  
Vol 8 (1) ◽  
pp. 135
Author(s):  
Akshay Ashok Bafna ◽  
Hetan C. Shah
Keyword(s):  
Serum Ferritin ◽  
Tertiary Care ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Beta Thalassemia ◽  
Lv Function ◽  
Blood Transfusions ◽  
Ventricular Ejection Fraction ◽  
2D Echocardiography

Background: To evaluate the myocardial function and its correlation with serum ferritin and the number of transfusions in beta-thalassemia major patients by using standard echocardiography and left ventricular strain imaging.Methods: This was a cross-sectional exploration study comprised of 56 beta-thalassemia patients conducted at a tertiary-care center in India between September 2016 and August 2017. Patients with age less than 18 years, diagnosed with thalassemia major, recipients of >20 units of blood transfusions, and normal Left Ventricular (LV) function by 2D-echocardiography were included in the study. Severity of iron overload was determined by using serum ferritin levels and LV strain imaging parameters were evaluated by using strain values of 17 LV segments.Results: A total of 56 beta-thalassemia patients were included in the study. Of these, 29(51.8%) patients were boys and 27(48.2%) patients were girls with a mean age of 7.8±1.84 years. Average serum ferritin level was found to be 4089.83 ng/dl. Strain values of the basal lateral wall of the left ventricle were significantly abnormal in patients who received more (>80) transfusions compared with those who received lesser transfusions (p=0.025 and p=0.045), respectively. Patients with serum ferritin >6000 ng/ml had impaired strain (p=0.03).Conclusions: Conventional echocardiographic parameters and Left Ventricular Ejection Fraction (LVEF) do not provide adequate information about LV dysfunction. Systolic strain index imaging of the LV indicated the presence of early LV systolic dysfunction in patients who received a greater number of blood transfusions and patients with higher serum ferritin levels.

A MRI Prospective Survey on Heart and Liver Iron and Cardiac Function in Thalassemia Major Patients Treated with Deferasirox Versus Deferiprone and Desferrioxamine in Monotherapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3631-3631
Author(s):  
Alessia Pepe ◽  
Laura Pistoia ◽  
Liana Cuccia ◽  
Monica Fortini ◽  
Vincenzo Caruso ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Myocardial Iron ◽  
Liver Iron ◽  
Biventricular Function

Abstract Background: No prospective data are available about the efficacy of deferasirox versus deferiprone and desferrioxamine in monotherapy. Our study aimed to prospectively assess the efficacy of deferasirox versus deferiprone and desferrioxamine in monotherapy in a large cohort of thalassemia major (TM) patients by quantitative Magnetic Resonance (MR). Methods: Among the 2551 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network we selected those with an MR follow up study at 18±3 months who had been received one chelator alone between the 2 MR scans. We identified three groups of patients: 235 treated with DFX, 142 with DFP and 162 with DFO. Iron overload was measured by T2* multiecho technique. Liver T2* values were converted into liver iron concentration (LIC) values. Biventricular function parameters were quantitatively evaluated by cine images. Results: Excellent/good levels of compliance were similar in the DFX (98.7%) vs DFP (96.3%) and DFO (97.5%) groups. Among the patients with myocardial iron overload at baseline, in all three groups there was a significant improvement in the global heart T2* value (DFX: +4.58±5.91ms P<0.0001, DFP: 8.53±6.97ms P<0.0001 and DFO: +3.93±5.21 ms P<0.0001) and a reduction in the number of pathological segments (DFX: -4.49±4.55 P<0.0001, DFP: -8.08±5.5.84 ms P=0.001 and DFO: -3.65±3.81 ms P<0.0001). In DFP and in DFO groups there was a significant improvement in left ventricular ejection function (LVEF) (+4.86±6.99% P=0.044 and +3.87±7.48% P=0.004, respectively). Only in the DFP group there was a significant improvement in right ventricular ejection function (RVEF) (6.69±4.61% P=0.001). The improvement in the global heart T2* was significantly lower in the DFX versus the DFP group , but it was not significantly different in the DFX versus the DFO group (Figure 1). The improvement in the LVEF was significantly higher in both DFP and DFO groups than in the DFX group while the improvement in the RVEF was significantly higher in the DFP than in DFX group (Figure 2). Among the patients with hepatic iron at baseline (LIC≥3mg/g dw) the changes were not significantly different in DFX versus the other groups. Conclusions: Prospectively in a large clinical setting of TM patients, DFX monotherapy was significantly less effective than DFP in improving myocardial siderosis and biventricular function and it was significantly less effective than DFO in improving the LVEF. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pepe: Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc..

Value of sequential monitoring of left ventricular ejection fraction in the management of thalassemia major

Blood ◽  
2004 ◽  
Vol 104 (1) ◽  
pp. 263-269 ◽  
Author(s):  
Bernard A. Davis ◽  
Caoimhe O'Sullivan ◽  
Peter H. Jarritt ◽  
John B. Porter
Keyword(s):  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Cardiac Disease ◽  
Chelation Therapy ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Exercise Stress ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

Abstract Regular monitoring of left ventricular ejection fraction (LVEF) for thalassemia major is widely practiced, but its informativeness for iron chelation treatment is unclear. Eighty-one patients with thalassemia major but no history of cardiac disease underwent quantitative annual LVEF monitoring by radionuclide ventriculography for a median of 6.0 years (interquartile range, 2-12 years). Intraobserver and interobserver reproducibility for LVEF determination were both less than 3%. LVEF values before and after transfusion did not differ, and exercise stress testing did not reliably expose underlying cardiomyopathy. An absolute LVEF of less than 45% or a decrease of more than 10 percentage units was significantly associated with subsequent development of symptomatic cardiac disease (P &lt; .001) and death (P = .001), with a median interval between the first abnormal LVEF findings and the development of symptomatic heart disease of 3.5 years, allowing time for intervention. In 34 patients in whom LVEF was less than 45% or decreased by more than 10 percentage units, intensified chelation therapy was recommended (21 with subcutaneous and 13 with intravenous deferoxamine). All 27 patients who complied with intensification survived, whereas the 7 who did not comply died (P &lt; .0001). The Kaplan-Meier estimate of survival beyond 40 years of age for all 81 patients is 83%. Sequential quantitative monitoring of LVEF is valuable for assessing cardiac risk and for identifying patients with thalassemia major who require intensified chelation therapy.

Combination of Two Orally Active Iron Chelating Agents: Efficacy and Safety In a Clinical Setting

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2064-2064
Author(s):  
Vasilios Berdoukas ◽  
Susan Carson ◽  
Anne Nord ◽  
Thomas Hofstra ◽  
Susan Claster ◽  
...  
Keyword(s):  
Left Ventricular Ejection Fraction ◽  
Research Funding ◽  
Dry Weight ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Efficacy And Safety ◽  
Ventricular Ejection Fraction ◽  
Cardiac Iron ◽  
Cardiac Iron Overload

Abstract Abstract 2064 For patients with transfusion dependent anemias, in particular thalassemia major, as part of a compassionate –use program that was approved by the hospital's IRB, we report the efficacy and safety outcomes of combining therapy with deferasirox (DFX) and deferiprone (DFP). The combination of DFP and deferoxamine (DFO)has been shown to be effective in reducing cardiac iron overload but some patients are unable or unwilling to use DFO. DFP alone has also been reported to be cardioprotective. Based on concerns for their welfare in the presence of excessive cardiac iron load, a reduced left ventricular ejection fraction and either severe allergy or intolerance to DFO, 4 adult patients with thalassemia major have been treated with the combination of DFX and DFP for between 6 and 60 months (mean 18 months). All four patients were initially treated with DFO or DFX but DFP at 75–100 mg/kg/day was initiated because of severe cardiac iron overload. DFX at 15–40 mg/kg/day was added based upon high liver iron concentrations(LIC). Efficacy was evaluated by monthly ferritin levels and semiannual cardiac T2* and LIC estimates (using MRI R2 and R2*). All 4 patients had at least two MRI assessments. Table 1shows the changes in ferritin, cardiac T2*, LVEF and mean LIC. Cardiac T2* improved from 5.8 ±1.5 to 7.0 ± 1.5 ms., (p=0.15). If the T2* is recalculated as cardiac iron concentration then the change was from 4.1± 1.3 to 3.3± 1.1 mg/g dry weight (p=0.09). One patient who has been receiving the treatment for 6 months has shown a 1% per month deterioration in T2*. The patients who have been on the combination for 12, 24 and 60 months, have had reductions of 2.7%, 0.5% and 1.5% per month respectively. LVEF improved overall from the baseline value of 52.8% to 58.9% (p=0.02). Ferritin fell from a mean of 5826 to 5544 ng/L (p=0.86). LIC increased from a mean of 20.7 to 28.1 mg/g dry weight (p=0.36). Table 2 shows the baseline and minimum absolute neutrophil counts and baseline and final ALT (IU/L). No drug-related neutropenia (ANC of <1.5 ×109/L), agranulocytosis or arthralgia were observed. No patients demonstrated significant proteinuria and mean creatinine levels were unchanged. ALT's showed fluctuations that were compatible with the degree of LIC. It is important to note that compliance was extremely variable in that one patient (P3), only took DFX once monthly with many lapses in her DFP treatment as well. The other patients also had significant lapses in their compliance as well as long vacation periods during which they did not receive treatment. These results indicate that the combined use of the two oral chelators (DFP & DFX) prevented further cardiac iron loading with a tendency for its reduction, significant improvement in left ventricular ejection fraction, maintenance of ferritin levels and LIC. It is also possible that the DFP cardioprotective effect may be activated even in the presence of poor compliance with it. The combination was well tolerated and easier to manage. It is more acceptable for life-long chelation and positively influenced patients’ quality of life. It seems likely that maximum doses of both medications need to be prescribed for better outcomes and longer periods of follow up are essential. In particular, a prospective randomized study in patients with excessive cardiac iron will be necessary before this combination could be considered standard therapy. Disclosures: Berdoukas: ApoPharma Inc.: Consultancy. Wood:Novartis Inc.: Research Funding; ApoPharma: Honoraria, Membership on an entity's Board of Directors or advisory committees. Coates:Novartis: Research Funding, Speakers Bureau.

Sign in / Sign up

Export Citation Format

Share Document