title: Correlation of NT-proBNP levels and cardiac iron concentration in patients with transfusion-dependent thalassemia major.
abstract: 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*](-1.22) 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.
authors.affiliation: First Department of Pediatrics, Athens University Medical School, Athens, Greece.
authors.forename: Polyxeni
authors.initials: P
authors.lastname: Delaporta
authors.forename: Antonios
authors.initials: A
authors.lastname: Kattamis
authors.forename: Filia
authors.initials: F
authors.lastname: Apostolakou
authors.forename: Sorina
authors.initials: S
authors.lastname: Boiu
authors.forename: Anastasia
authors.initials: A
authors.lastname: Bartzeliotou
authors.forename: Evangelos
authors.initials: E
authors.lastname: Tsoukas
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papassotiriou
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D017352:Echo-Planar Imaging; D005260:Female; D006486:Hemosiderosis / Q000097:blood* / Q000209:etiology / Q000473:pathology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011446:Prospective Studies; D013318:Stroke Volume; D065227:Transfusion Reaction; D018487:Ventricular Dysfunction, Left / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D017086:beta-Thalassemia / Q000097:blood* / Q000473:pathology / Q000628:therapy
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D007501:Iron