Exercise performance is decreased in patients with Thalassemia major (TM), but the relative impact of anemia and iron overload on exercise capacity is unknown. We assessed the cardiopulmonary function of 71, well-transfused TM patients via graded treadmill exercise stress test. All patients underwent MRI of the heart, pancreas, and liver and diagnostic phlebotomy. Patients ranged in age from 13 to 46 years of age. Fifteen patients were excluded from analysis due to submaximal effort. Mean Vo 2 max was 83.0% of predicted and was limited by abnormal cardiovascular mechanisms, consisting of a decreased O 2 pulse (86.6% of predicted) in men and decreased maximum heart rate (HR) response (85% of predicted) in women. Patients with hemoglobin less than 12 g/dL had lower O 2 pulse and Vo 2 max, regardless of sex. Cardiac iron was negatively associated with maximum HR response and Vo 2 max (r 2 5 0.10 and 0.08, respectively, P < 0.05). Vo 2 max was correlated with cardiac R2*, hs-CRP, sex and hemoglobin in decreasing strength of association. In thalassemia, exercise performance is limited by impaired stroke-volume reserve in men and blunted HR response in women. Iron toxicity may be mediated through vascular inflammation and direct modulation of HR response to exercise. Am. J.
Summary This study compared pulmonary function tests (PFTs) with cardiac, pancreatic and liver iron in 76 thalassemia major (TM) patients. Restrictive lung disease was observed in 16%, hyperinflation in 32%, and abnormal diffusing capacity in 3%. While no patients met Global Initiative for Chronic Lung Disease criteria for airways obstruction, there were indicators of small airways disease and air trapping. PFTs did not correlate with somatic iron burden, blood counts or haemolysis. Restrictive lung disease was associated with inflammation. We conclude that TM patients have pulmonary abnormalities consistent with small airways obstruction. Restrictive disease and impaired diffusion are less common.
Previous research showed decreased exercise performance in patients with Thalassemia major (TM). It is assumed that cardiac iron overload causes this limitation, but cardiac and liver iron levels have not been correlated with exercise performance in TM. We assessed the cardiopulmonary function of 61 TM patients via graded treadmill exercise stress test and compared this to liver and cardiac iron levels determined by MRI. Patient age was 26.0±9.2y (range 11−48y). Patients were heavily iron loaded with hepatic iron concentration (HIC) of 10.2±9.5mg/g dry weight liver (abnormal>2mg/g) and cardiac R2* of 92±87Hz (abnormal >50Hz). 12 patients did not reach maximal exercise based on RQ≥1.15 and were excluded from analysis. 54% of patients had decreased aerobic capacity (based on Vo2 max < 85% of predicted; mean Vo2 max 30.9±7.9ml/min/kg). Exercise was limited by abnormal cardiovascular mechanisms in 27% of patients (based on O2 pulse ≤80% of predicted). 2 patients were limited by respiratory mechanics (breathing reserve <15%). Increased cardiac iron was associated with decreased Vo2max (R2 0.090, p=0.036) and the percent of predicted maximum heart rate achieved (R2 0.120, p=0.015). Low hemoglobin was associated with low Vo2 max (R2 0.154, p=0.006) and low percent of predicted O2 pulse (R2 0.090, p= 0.038). High liver iron correlated with low percent of predicted O2 pulse (R2 0.097, p=0.031). Advanced age was correlated with greater proportion of maximal heart rate achieved (R2 0.083, p=0.044). We conclude that exercise limitation is common in TM patients. Although cardiac and liver iron correlated with exercise limitation, the strongest predictor was anemia. We speculate that measurement of cardiac and liver iron does not predict exercise limitation in these patients. This abstract is funded by: NIH.
4053 Poster Board III-988 Introduction Hemoglobinopathies are among the most common genetic diseases in the work. Many hemoglobinopathy patients require lifeline transfusion, iron chelation, and careful monitoring of iron stores. Liver iron concentration (LIC) is an excellent metric of transfusional iron balance and total body iron stores(1). Noninvasive LIC estimation by MRI is gradually replacing liver biopsy but remains limited by cost and availability, particularly in regions where thalassemia is prevalent(2). Quantitative computed tomography (QCT) was proposed as a means to estimate LIC 30 years ago, but there has been surprisingly limited validation(3-5). QCT is cheaper and more available than MRI. Steady improvements in CT instrumentation and standardization warrant a re-evaluation of QCT for iron quantitation. In this study, we determined liver attenuation as a function of MRI-predicted liver iron concentration in 45 patients over a 6 year period. Methods This study represents a convenience sample of all iron-overloaded patients who had undergone both QCT for bone density and LIC measurement by MRI at Children's Hospital Los Angeles. 64 usable observations were obtained in 45 patients; 14 patients had multiple exams(range 2-6). MRI and QCT examinations were considered “paired” if the scans were less than 120 days apart (59 studies). MRI liver R2 and R2* examinations were performed and analyzed as previously described(2). Quantitative CT was performed on a General Electric Hilite Advantage. A single axial 10 mm thick slice was collected at the L1 level using a KVp of 80 at 70 mA for 1 second. Three hydroxyappetite phantoms, calibrated to 0, 125, and 250 Hounsfield units, were placed in scanning platform (CT-T bone densitometry package; GE Medical Systems), approximately 7 cm from mid-vertebral body. Calibration curve was obtained from regions of interest drawn within the three phantoms, using linear regression calculated by custom MATLAB routines. Regions of interest in the liver were drawn in ∼ 9 cm2 regions of the right and left lobe of the liver, as well as a region encompassing the entire cross-sectional area of the liver. Results Most patients had thalassemia major and moderate to severe iron overload, with a LIC of 14.1 ± 14 mg/g dry weight and a cardiac R2* of 70.5 ± 95.0 Hz (median T2* of 30.9 ms). Patients who were receiving regular transfusions were well transfused, with a pre-transfusion hemoglobin of 9-9.5 g/dl. All chronically transfused patients were using deferoxamine until approximately 2005, with most switching to deferasirox in 1/2005. Figure 1 demonstrates MRI-predicted LIC as a function of liver attenuation. There is a strong linear relationship having a slope of 0.591 mg/g dry weight of liver per HU. Normal liver attenuation ranges in non iron overload children and young adults is 57-76 HU. Upper limit of normal corresponds to a predicted LIC of 6 m/g, indicating an intrinsic lack of sensitivity for qCT at low iron concentrations. Time-courses of CT-iron relationship from 14 patients whom had serial evaluations paralleled the regression line and were well constrained by the 95% confidence intervals, suggesting the calibration is suitable for serial analysis (not shown). Whole liver attenuation values were unbiased with respect to values from the right and left lobe; coefficient of variation was 2.2-4.9%. Conclusion The present work represents the largest human validation of QCT for liver iron quantitation. QCT techniques have inadequate sensitivity to discriminate LIC values less than 6 mg/g but are not limited by high iron concentrations. High reproducibility makes them suitable for tracking serial LIC changes. QCT may be an acceptable surrogate for LIC in hospitals lacking the software, personnel, or financial resources to support MRI or SQUID LIC measurements. Acknowledgments: This work supported by NIH HL075592, CDC (U27/CCU922106) and GCRC (NIH #RR00043-43). Disclosures: No relevant conflicts of interest to declare.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.