N-terminal fragment of proBNP is a marker of high cardiac output cardiomyopathy evaluated by CMR in thalassemia syndromes

In thalassemia patients heart failure remains the main cause of mortality. High cardiac output state due to chronic anaemia is a significant determinant of cardiomyopathy, in particular in thalassemia intermedia (TI) patients (a moderate form, not transfusion dependent). Hypoxia and volume overload are known stimuli for plasma N-terminal fragment of proBNP (NT-proBNP) raise. Nevertheless, NT-proBNP role in clinical management of thalassemia patients has not been fully investigated.

Aim of our study was to assess the role of NT-proBNP assay in a large prospective cohort of thalassemia patients, evaluated by cardiovascular magnetic resonance (CMR).

215 thalassemia patients (39 TI, age 38 ± 12 years, 51% females) and 176 thalassemia major patients (TM, age 30 ± 9 years, 54% females) underwent consecutively CMR (1.5 T) and blood sampling for plasma assay of NT-proBNP. Myocardial iron overload was assessed using a multislice multiecho T2* approach able to provide the global T2* value in the left ventricle. Cine sequences were obtained to quantify biventricular morphological and functional parameters. RV and LV volumes and ejection fraction (EF) were evaluated by a semi-automatic software (Mass Plus, Leiden, NL).

NT-proBNP levels were comparable in TI and TM patients (139 ± 146 ng/L versus 108 ± 122 ng/L; P = NS). Mean haemoglobin levels (P < 0.0001) and myocardial iron overload (P = 0.001) were significantly lower in TI than in TM patients. Left end-diastolic volume (P < 0.0001) and mass indexes (P = 0.002), right ejection fraction (P < 0.0001) and biatrial area indexes (P = 0.006) were significantly higher in TI vs. TM patients. In TI patients NT-proBNP was negatively associated with mean haemoglobin levels (r = -0.6, P = 0.008) and positively with left and right atrial area indexes (r = 0.6, P = 0.001 and r = 0.4, P = 0.007, respectively), left and right end diastolic volume indexes (r = 0.5, P = 0.003 and r = 0.3, P = 0.04, respectively) and left ventricular mass index (r = 0.4, P = 0.007). In TM patients no significant correlation was found between NT-proBNP levels and morphological biventricular parameters. In both groups no significant correlation was found between NT-proBNP levels and myocardial iron overload.

Hypoxia and volume overload due to chronic anaemia, more pronounced in TI patients, justify the correlation between NT-proBNP and high cardiac output-related findings in TI patients. These data suggest a) a potential routinary use of NT-proBNP as marker of high cardiac output cardiomyopathy in the anaemic thalassemia population; b) to reconsider the current haematological/transfusional management in TI patients.