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The impact of two different doses of chelating therapy (deferasirox) on echocardiographic tissue Doppler indices in patients with thalassemia major

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Background:  Chelating therapy in transfusion‐dependent patients with β‐thalassemia major (β‐TM) is mandatory to reduce the toxic effect of iron on the myocardium.

Aim:  To evaluate the impact of low and high dose of oral chelating therapy (deferasirox) on pulsed and tissue echocardiographic indices in patients with β‐TM.

Methods:  This interventional study conducted on patients with transfusion‐dependent β‐TM (n = 38) on deferasirox 20 mg/kg/d medication, group (DFX‐20) for at least 6 months, followed by administration of a higher dose of deferasirox, 40 mg/kg/d, group (DFX‐40) for another 6 months. Pulsed and tissue Doppler echocardiography carried out at the beginning and at the end of treatment interval (6 months) for both groups, with monthly blood analysis of serum ferritin, alanine transaminase, hemoglobin, and creatinine. An age‐matched control group of 38 patients was evaluated for echo Doppler blood analysis.

Results:  Patients of group DXF‐40 compared with group DFX‐20, the tissue Doppler echocardiogram showed lower E/Em ratio (16.01 ± 2.85 vs. 19.68 ± 2.81, P < 0.05), higher systolic wave velocity (Sm) (5.87 ± 1.40 vs. 4.80 ± 1.20, P < 0.05), and higher early diastolic wave (Em) velocity (4.25 ± 1.70 vs. 3.50 ± 1.80, P < 0.05), respectively. Patients in group DFX‐20, compared with control group, had M‐Mode echo with thicker left ventricle (LV) septal wall (P < 0.001) and posterior wall (P < 0.01), higher left ventricle end diastolic diameter index (P < 0.05). The pulsed Doppler echocardiogram showed a higher LV transmitral E wave velocity (P < 0.05), higher E/A ratio (P < 0.01), and the duration of deceleration time was significantly shorter (P < 0.01). There were no significant changes observed in the left ventricle ejection fraction percentage (LVEF%) or fractional shortening between both treatment groups. Serum ferritin was significantly lower in DFX‐40 group compared with DFX‐20 β‐TM group (338). There was a significant positive correlation between the serum ferritin and the E/Em ratio (r = 0.31, P < 0.001). The tricuspid valve velocity was significantly higher in β‐TM patients compared with the control group (P < 0.05).

Conclusion:  The increment of oral deferasirox as chelating therapy in β‐TM patients to 40 mg/kg/d over 6 months duration showed a significant increments of systolic and diastolic tissue Doppler velocities with a significant reduction of E/Em ratio in comparison with 20 mg/kg/d. There were no changes of LVEF. A longer duration of follow‐up may be justified in such group of patients.
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Document Type: Research Article

Affiliations: 1: Cardiac Unit, Salmaniya Medical Complex, Ministry of Health, Manama, Bahrain 2: Royal Colleges of Surgeons in Ireland, Medical University of Bahrain, Manama, Bahrain 3: Department of Family and Community Medicine, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain

Publication date: September 1, 2011

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