Early detection of right ventricular diastolic dysfunction by pulsed tissue Doppler echocardiography in iron loaded beta thalassemia patients.

Early heart iron overload in beta thalassemia major patients can be quantified through T2* cardiovascular magnetic resonance (CMR). To clarify the value of tissue Doppler imaging (TDI) in early detection of myocardial dysfunction in iron loaded thalassemia patients diagnosed by CMR. Two groups were included in the study; Group I: 69 asymptomatic thalassemia patients (28 females, 41 males), mean age 18.1 ± 7.03 years (range 6-39 years); Group II (n = 41) healthy normal controls matched for age and sex. Serum ferritin and CMR were performed to assess the cardiac siderosis (T2* < 20 ms). Group I was subdivided into two subgroups; Group Ia (n = 26) T2* < 20 ms and Group Ib (n = 43) T2* > 20 ms. Conventional and Doppler echocardiography of LV, RV dimensions and functions and pulmonary artery pressure were evaluated. Right ventricular diastolic function assessed by tricuspid annular E'/A' was positively correlated with T2* value; lower tricuspid E'/A' ratios were correlated with lower T2* values (r = 0.366, P = 0.002). Tricuspid annular A' was significantly higher in group Ia compared to group Ib (16.7 ± 5.2 vs 12.1 ± 4.0 cm/s, P < 0.001). Tricuspid E'/A' < 1 was common in group Ia compared to group Ib (19/26 (73.0) vs 3/43 (6.97%), P < 0.001). By multivariate analysis, right ventricular diastolic dysfunction (tricuspid E'/A' < 1) was associated with serum ferritin and T2* level of the thalassemia patients. TDI is a promising tool for quantitative assessment of myocardial function and early detection of right ventricular diastolic dysfunction in iron loaded beta thalassemia major patients.

The 6-min walk test: an independent correlate of elevated tricuspid regurgitant jet velocity in children and young adult sickle cell patients.

Elevation of echocardiography-determined tricuspid regurgitant jet velocity (TRV) predicts high systolic pulmonary artery pressure. The present study tested the hypotheses that elevated tricuspid regurgitant jet velocity is associated with both hemolysis and hypoxia and abnormal 6-min walk test (6MWT) results. This study aims to correlate elevated TRV with different clinical laboratory findings and 6MWT and to find the independent predictors of increased TRV. A prospective study of 80 patients aged 5-25 years old with sickle cell disease (SCD) under basal conditions and 40 matched controls was conducted. Hemolytic analysis was assessed by the levels of lactate dehydrogenase, serum bilirubin, and reticulocyte count. Oxygen saturation determination using pulse oximeter and 6MWT were done. The overall prevalence of elevated TRV (≥2.5 m/s) was 28.75 %. Associated risk factors were older age (r = 0.28, p = 0.01), longer duration of disease (r = 0.25, p = 0.025), higher reticulocytic count (r = 0.344, p = 0.002), lower O2 saturation (r = -0.574, p = 0.0001), and shorter walked distance in 6MWT (r = -0.75, p = 0.0001). By multivariate logistic analysis, only the distance walked during 6MWT was the independent correlate of elevated TRV (odds ratio = 0.85; 95 % CI = 0.74 to 0.98 p = 0.033). The study provides evidence for independent association of TRV with abnormal 6MWT results. The 6-min walk test can be used as noninvasive adjuvant tool for functional capacity assessment of SCD patients with elevated TRV.

Low prevalence of cardiac siderosis in heavily iron loaded Egyptian thalassemia major patients.

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) can measure cardiac iron deposition directly using the magnetic relaxation time T2*. This allows earlier diagnosis and treatment and helps to reduce mortality from this cardiac affection. This study aims to determine the prevalence of cardiac siderosis in Egyptian patients who are heavily iron loaded and its relation to liver iron concentration, serum ferritin, and left ventricular ejection fraction. Eighty-nine ß-thalassemia patients receiving chelation therapy (mean age of 20.8 ± 6.4 years) were recruited in this study. Tissue iron levels were determined by CMR with cardiac T2* and liver R2*. The mean ± standard deviation (range) of cardiac T2* was 28.5 ± 11.7 ms (4.3 to 53.8 ms), the left ventricular ejection fraction (LVEF) was 67.7 ± 4.7 % (55 to 78 %), and the liver iron concentration (LIC) was 26.1 ± 13.4 mg Fe/g dry weight (dw) (1.5 to 56 mg Fe/g dw). The mean serum ferritin was 4,510 ± 2,847 ng/ml (533 to 22,360 ng/ml), and in 83.2 %, the serum ferritin was >2,500 ng/ml. The prevalence of myocardial siderosis (T2* of <20 ms) was 24.7 % (mean age 20.9 ± 7.5 years), with mean T2* of 12.7 ± 4.4 ms, mean LVEF of 68.6 ±5.8 %, mean LIC of 30.9 ± 13 mg Fe/g dw, and median serum ferritin of 4,996 ng/ml. There was no correlation between T2* and age, LVEF, LIC, and serum ferritin (P = 0.65, P = 0.085, P = 0.99, and P = 0.63, respectively). Severe cardiac siderosis (T2* of <10 ms) was present in 7.9 %, with a mean age of 18.4 ± 4.4 years. Although these patients had a mean T2* of 7.8 ± 1.7 ms, the LVEF was 65.1 ± 6.2 %, and only one patient had heart failure (T2* of 4.3 ms and LVEF of 55 %). LIC and serum ferritin results were 29.8 ± 17.0 mg/g and 7,200 ± 6,950 ng/ml, respectively. In this group of severe cardiac siderosis, T2* was also not correlated to age (P = 0.5), LVEF (P = 0.14), LIC (P = 0.97), or serum ferritin (P = 0.82). There was a low prevalence of myocardial siderosis in the Egyptian thalassemia patients in spite of very high serum ferritin and high LIC. T2* is the best test that can identify at-risk patients who can be managed with optimization of their chelation therapy. The possibility of a genetic component for the resistance to cardiac iron loading in our population should be considered.

Polyneuropathy Associated with Severe Iron Overload and Oxidative Stress in ß-Thalassemia Patients.

To investigate the frequency of peripheral neuropathy in patients with ß-thalassemia, and to assess its relation to iron overload and oxidative stress. Sixty ß-thalassemia patients with mean age of 19 ± 4.9 years were recruited. Serum ferritin was quantitatively assessed by enzyme-linked immunoassay and biomarkers of oxidative stress were estimated calorimetrically. Electrophysiological studies using NEMUS 2, Galileu Software were carried out. The patients were separated into two groups: those with abnormal nerve conduction studies (NCS) {Group A; N = 38} and those with normal NCS {Group B; N = 22}. Thirty-eight (63.3%) patients had axonal motor neuropathy as evidenced by abnormal NCS (group A), they showed higher mean serum ferritin (p < 0.01), higher mean malondialdehyde (MDA) (p < 0.01), and lower mean nitrous oxide, total antioxidant capacity, paraoxonase-1 (PON1) (p < 0.01) compared to group B. Bivariate analysis of NCS data demonstrated that abnormal NCS were more frequent in splenectomized patients (p = 0.002), and poorly-chelated patients with serum ferritin ≥ 2000 ng/ml (p = 0.001). Significant variables associated with abnormal motor NCS were entered in stepwise regression analysis and only elevated serum ferritin (p = 0.01) was independently associated with abnormal motor NCS (p = 0.02; 95% CI 1.433-51.791). None of the studied patients had sensory neuropathy or myopathy. Peripheral motor neuropathy may occur in ß-thalassemia patients at a high frequency, regardless of their age and gender. Severe iron overload may contribute to the pathogenesis of neuropathy. Other factors including chelation therapy, splenectomy, and oxidative stress might have an enhancing effect that couldn't be proved in this study.

A multicenter, open-label, phase III study of Abcertin in Gaucher disease.

BACKGROUND: Gaucher disease (GD) is caused by a deficiency in the lysosomal enzyme glucocerebrosidase. Enzyme replacement therapy (ERT) is recommended for clinical improvement. METHODS: The efficacy and safety of a new imiglucerase, Abcertin, were assessed in 7 Egyptian patients with treatment-naïve type 1 GD. Each patient was administered a biweekly 60 U/kg dose of Abcertin for 6 months. The primary endpoint was the change in hemoglobin concentration. The secondary endpoints were changes from baseline in platelet counts, spleen and liver volumes, biomarker levels, skeletal parameters, and bone mineral density. RESULTS: The hemoglobin concentration increased by a mean of 1.96 ±â€Š0.91 g/dL (range 1.11-2.80 g/dL) or 20.6% (P = .001). Statistically significant increases in the platelet count and decreases in the spleen volume and biomarker levels were also observed. There were no severe drug-related adverse events. One patient developed anti-imiglucerase antibodies without neutralizing activity. CONCLUSION: Our study results demonstrate the efficacy and safety of Abcertin in patients with type 1 GD. This suggests that Abcertin can be an alternative ERT option for type 1 GD.

Apolipoprotein E gene polymorphism and the risk of left ventricular dysfunction among Egyptian ß-thalassemia major.

In Egypt, ß-thalassemia is the most common hereditary hemolytic anemia. Cardiac dysfunction, secondary to iron overload with formation of oxygen free radicals, is the most common cause of death in ß-thalassemia patients. This study was designed to determine whether the allelic genotype of apolipoprotein E (Apo E), which exhibits antioxidant properties, could represent a genetic risk factor for the development of left ventricular (LV) dysfunction in ß-thalassemia major. Fifty Egyptian ß-thalassemia major patients were subjected to echocardiography to assess LV function. Apo E genotyping by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was done for all patients in addition to 50 age and sex matched healthy control subjects. Patients were classified into three groups. Group I and II were clinically asymptomatic. Group II subjects had evidence of LV dilatation, while Group III patients had clinical and echocardiographic findings of LV failure. Apo E4 allele was significantly higher among Group II and III than in controls. In conclusion, Apo E4 allele can be considered as a genetic risk factor for LV dysfunctions in ß-thalassemic patients. It could be used as predictive indicator for additional risk of LV failure, particularly in asymptomatic patients with LV dilatation, requiring a closer follow-up, to prevent further disease progression.