Effects of blood transfusion on exercise capacity in thalassemia major patients

Anemia has an important role in exercise performance. However, the direct link between rapid changes of hemoglobin and exercise performance is still unknown.To find out more on this topic, we studied 18 beta-thalassemia major patients free of relevant cardiac dysfunction (age 33.5±7.2 years,males = 10). Patients performed a maximal cardiopulmolmonary exercise test (cycloergometer, personalized ramp protocol, breath-by-breath measurements of expired gases) before and the day after blood transfusion (500 cc of red cell concentrates). After blood transfusion, hemoglobin increased from 10.5±0.8 g/dL to 12.1±1.2 (p<0.001), peak VO2 from 1408 to 1546mL/min (p<0.05), and VO2 at anaerobic threshold from 965 to 1024mL/min (p<0.05). No major changes were observed as regards heart and respiratory rates either at peak exercise or at anaerobic threshold. Similarly, no relevant changes were observed in ventilation efficiency, as evaluated by the ventilation vs. carbon dioxide production relationship, or in O2 delivery to the periphery as analyzed by the VO2 vs. workload relationship. The relationship between hemoglobin and VO2 changes showed, for each g/dL of hemoglobin increase, a VO2 increase = 82.5 mL/min and 35 mL/min, at peak exercise and at anaerobic threshold, respectively. In beta-thalassemia major patients, an acute albeit partial anemia correction by blood transfusion determinates a relevant increase of exercise performance, observed both at peak exercise and at anaerobic threshold

Extramedullary hematopoiesis is associated with lower cardiac iron loading in chronically transfused thalassemia patients

The aim of this study was to evaluate, in a large cohort of chronically transfused patients, whether the presence of extramedullary hematopoiesis (EMH) accounts for the typical patterns of cardiac iron distribution and/or cardiac function parameters. We retrospectively selected 1,266 thalassemia major patients who had undergone regular transfusions (611 men and 655 women; mean age: 31.368.9 years, range: 4.2\u201366.6 years) and were consecutively enrolled within the Myocardial Iron Overload in Thalassemia network. The presence of EMH was evaluated based on steady-state free precession sequences; cardiac and liver iron overloads were quantified using a multiecho T2* approach; cardiac function parameters and pulmonary diameter were quantified using the steady-state free precession sequences; and myocardial fibrosis was evaluated using the late gadolinium enhancement technique. EMH was detected in 167 (13.2%) patients. The EMH1 patients had significantly lower cardiac iron overload than that of the EMH2 patients (P50.003). The patterns of cardiac iron distribution were significantly different in the EMH1 and EMH2 patients (P< 0.0001), with a higher prevalence of patients with no myocardial iron overload and heterogeneous myocardial iron overload and no significant global heart iron in the EMH1 group EMH1 patients had a significantly higher left ventricle mass index (P50.001) and a significantly higher pulmonary artery diameter (P50.002). In conclusion, in regularly transfused thalassemia patients, EMH was common and was associated with a thalassemia intermedia-like pattern of cardiac iron deposition despite regular transfusion therapy

Potential myocardial iron content evaluation by magnetic resonance imaging in thalassemia major patients treated with Deferoxamine or Deferiprone during a randomized multicenter prospective clinical study.

The purpose of this study was to evaluate if the variations of heart magnetic resonance imaging in beta-thalassemia major patients treated with Deferoxamine B mesylate (DF) or Deferiprone (L1) chelation therapy is a useful tool of the indirect myocardial iron content determination. For this reason, a prospective study was carried out. Seventy-two consecutive patients with beta-thalassemia major (35 treated with DF and 37 with L1) were studied. The main outcome results were laboratory parameters including determination of the liver iron concentration (LIC) and magnetic resonance imaging (MRI) of the heart and liver. The heart to muscle signal intensity ratios (HSIRs) were significantly increased in both the DF (t = -2.8; p < 0.01) and L1 (t = -3.1; p < 0.01) groups after one year of treatment No statistically significant difference in the values of HSIRs was present between the two groups at the beginning of treatment (p = 0.25; t = 1.13), and after one year of treatment (p = 0.20; t = 1.28). The HSIR were inversely correlated to the LIC (r = -0.52; p < 0.001) but not with ferritin levels (r = 0.10; p = 0.18). A positive correlation was found between the variation of HSIRs and that of the liver signal intensity ratios (r=0.52; p < 0.001), and a mild correlation (r = 0.40; p < 0.001) was found between the gamma glutamyltransferase (gammaGt) levels and the HSIRs values. Our data confirm that heart MRI is sensitive enough to detect significant variations of the mean HSIR during iron chelation with DF or L1

Multiparametric Cardiac Magnetic Resonance Survey in Children With Thalassemia Major: A Multicenter Study

Background\u2014Cardiovascular magnetic resonance (CMR) plays a key role in the management of thalassemia major patients, but few data are available in pediatric population. This study aims at a retrospective multiparametric CMR assessment of myocardial iron overload, function, and fibrosis in a cohort of pediatric thalassemia major patients. Methods and Results\u2014We studied 107 pediatric thalassemia major patients (61 boys, median age 14.4 years). Myocardial and liver iron overload were measured by T2* multiecho technique. Atrial dimensions and biventricular function were quantified by cine images. Late gadolinium enhancement images were acquired to detect myocardial fibrosis. All scans were performed without sedation. The 21.4% of the patients showed a significant myocardial iron overload correlated with lower compliance to chelation therapy (P<0.013). Serum ferritin 652000 ng/mL and liver iron concentration 6514 mg/g/dw were detected as the best threshold for predicting cardiac iron overload (P=0.001 and P<0.0001, respectively). A homogeneous pattern of myocardial iron overload was associated with a negative cardiac remodeling and significant higher liver iron concentration (P<0.0001). Myocardial fibrosis by late gadolinium enhancement was detected in 15.8% of the patients (youngest children 13 years old). It was correlated with significant lower heart T2* values (P=0.022) and negative cardiac remodeling indexes. A pathological magnetic resonance imaging liver iron concentration was found in the 77.6% of the patients. Conclusions\u2014Cardiac damage detectable by a multiparametric CMR approach can occur early in thalassemia major patients. So, the first T2* CMR assessment should be performed as early as feasible without sedation to tailor the chelation treatment. Conversely, late gadolinium enhancement CMR should be postponed in the teenager age

Prediction of cardiac complications for thalassemia major in the widespread cardiac magnetic resonance era: a prospective multicentre study by a multi-parametric approach

Aims Cardiovascular magnetic resonance (CMR) has dramatically changed the clinical practice in thalassemia major (TM), lowering cardiac complications. We prospectively reassessed the predictive value of CMR parameters for heart failure (HF) and arrhythmias in TM. ................................................................................................................................................................................................... Methods and results We considered 481 white TM patients (29.48 \ub1 8.93 years, 263 females) enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network. Myocardial and liver iron overload were measured by T2* multiecho technique. Atrial dimensions and biventricular function were quantified by cine images. Late gadolinium enhancement images were acquired to detect myocardial fibrosis. Mean follow-up was 57.91 \ub1 18.23 months. After the first CMR scan 69.6% of the patients changed chelation regimen. We recorded 18 episodes of HF. In the multivariate analysis the independent predictive factors were myocardial fibrosis (HR = 10.94, 95% CI = 3.28\u201336.43, P < 0.0001), homogeneous MIO (compared with no MIO) (HR = 5.56, 95% CI = 1.37\u201322.51, P = 0.016), ventricular dysfunction (HR = 4.33, 95% CI = 1.39\u201313.43, P = 0.011). Arrhythmias occurred in 16 patients. Among the CMR parameters only the atrial dilation was identified as univariate prognosticator (HR = 4.26 95% CI=1.54-11.75, P = 0.005). ................................................................................................................................................................................................... Conclusions CMR guided the change of chelation therapy in nearly 70% of patients, leading to a lower risk of iron-mediated HF and of arrhythmias than previously reported. Homogeneous MIO remained a risk factor for HF but also myocardial fibrosis and ventricular dysfunction identified patients at high risk. Arrhythmias were independent of MIO but increased with atrial dilatation. CMR by a multi-parametric approach dramatically improves cardiac outcomes and provides prognostic information beyond cardiac iron estimation

Sequential alternating deferiprone and deferoxamine treatment compared to deferiprone monotherapy: main findings and clinical follow-up of a large multicenter randomized clinical trial in thalassemia major patients

In β-thalassemia major (β-TM) patients, iron chelation therapy is mandatory to reduce iron overload secondary to transfusions. Recommended first line treatment is deferoxamine (DFO) from the age of 2 and second line treatment after the age of 6 is deferiprone (L1). A multicenter randomized open-label trial was designed to assess the effectiveness of long-term alternating sequential L1-DFO versus L1 alone iron chelation therapy in β-TM patients. Deferiprone 75 mg/kg 4 days/week and DFO 50 mg/kg/day for 3 days/week was compared with L1 alone 75 mg/kg 7 days/week during 5-year follow-up. A total of 213 thalassemia patients were randomized and underwent intention-to-treat analysis. Statistically, a decrease of serum ferritin levels was significantly higher in alternating sequential L1-DFO patients compared with L1 alone patients (p = 0.005). Kaplan-Meier survival analysis for the two chelation treatments did not show statistically significant differences (log-rank test, p = 0.3145). Adverse events and costs were comparable between the groups. Alternating sequential L1-DFO treatment decreased serum ferritin concentration during a 5-year treatment by comparison to L1 alone, without significant differences of survival, adverse events or costs. These findings were confirmed in a further 21-month follow-up. These data suggest that alternating sequential L1-DFO treatment may be useful for some β-TM patients who may not be able to receive other forms of chelation treatment