First Department of Pediatrics, Athens University Medical School, Athens, Greece.
Blood Cells Mol Dis. 2013 Jan;50(1):20-4. doi: 10.1016/j.bcmd.2012.09.002. Epub 2012 Sep 25.
Iron-induced cardiotoxicity remains the leading cause of morbidity and mortality in patients with transfusion-dependent β-thalassemia major. Heart failure in these patients, which may be reversible but has a poor prognosis, is characterized by myocardial iron deposition-related early diastolic dysfunction. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive biomarker for the detection of asymptomatic left ventricular dysfunction. In this study, we prospectively evaluated plasma NT-proBNP levels in 187 adult patients aged 19-54 years with β-TM. Possible correlations with the proposed recently cardiac iron concentration based on an equation derived from heart T2* assessment by MRI: [Fe] = 45.0 × T2* with [Fe] in milligrams per gram dry weight and T2* in milliseconds were explored. We found that: 143 patients had no cardiac hemosiderosis, defined as [Fe] < 1.1 mg/g dry weight, corresponding to T2* > 20 ms and 44 patients had cardiac hemosiderosis, defined as [Fe] > 1.2mg/g dry weight. The main results of the study showed that: a) NT-proBNP levels were markedly increased in thalassemic patients (152.2 ± 190.1 pg/mL, ranged from 6.0 to 1336.0 pg/mL compared to normal control levels 40.1 ± 19.7 pg/mL, p < 0.001, b) NT-proBNP levels were significantly higher in patients with cardiac hemosiderosis compared to patients without cardiac hemosiderosis (185.1 ± 78.0 vs 128.9 ± 20.2 pg/mL, p < 0.05), c) NT-proBNP levels correlated with [Fe] values (r = 0.387, p < 0.001). This correlation was significant in patients with cardiac hemosiderosis (r = 0.520, p < 0.001), but not in patients without cardiac hemosiderosis (p > 0.1), and d) no significant correlation was found between NT-proBNP levels and left ventricular ejection fraction values, (p > 0.3). Our study demonstrated for first time the significant association of NT-proBNP levels and cardiac iron concentration in patients with β-thalassemia major linking blood chemistry and imaging techniques. Multicenter studies of these parameters during iron chelation therapies are needed to validate their association and further exploit its clinical use.
铁诱导的心脏毒性仍然是依赖输血的β-地中海贫血主要患者发病率和死亡率的主要原因。这些患者的心力衰竭可能是可逆的，但预后不良，其特征是心肌铁沉积相关的早期舒张功能障碍。氨基末端脑利钠肽前体（NT-proBNP）是检测无症状左心室功能障碍的敏感生物标志物。在这项研究中，我们前瞻性评估了 187 名 19-54 岁的β-TM 成年患者的血浆 NT-proBNP 水平。并探讨了与最近提出的基于心脏 T2评估的基于方程的心脏铁浓度的可能相关性：[Fe] = 45.0 × T2*，其中[Fe]以毫克/克干重表示，T2以毫秒表示。我们发现：143 名患者没有心脏血色素沉着症，定义为[Fe] < 1.1mg/g 干重，对应 T2* > 20ms，44 名患者有心脏血色素沉着症，定义为[Fe] > 1.2mg/g 干重。该研究的主要结果表明：a）地中海贫血患者的 NT-proBNP 水平明显升高（152.2 ± 190.1pg/ml，范围为 6.0 至 1336.0pg/ml，与正常对照组的 40.1 ± 19.7pg/ml 相比，p < 0.001），b）有心脏血色素沉着症的患者的 NT-proBNP 水平明显高于没有心脏血色素沉着症的患者（185.1 ± 78.0 与 128.9 ± 20.2pg/ml，p < 0.05），c）NT-proBNP 水平与[Fe]值相关（r = 0.387，p < 0.001）。这种相关性在有心脏血色素沉着症的患者中是显著的（r = 0.520，p < 0.001），但在没有心脏血色素沉着症的患者中不显著（p > 0.1），d）NT-proBNP 水平与左心室射血分数值之间无显著相关性（p > 0.3）。我们的研究首次证明了 NT-proBNP 水平与β-地中海贫血主要患者的心脏铁浓度之间的显著相关性，将血液化学和成像技术联系起来。需要进行这些参数的多中心铁螯合治疗研究，以验证它们的相关性，并进一步利用其临床应用。
