Natriuretic Peptides as Well as Endothelin, and Not Troponin Are of Value in Early Diagnosis of Acute Cardiotoxicity in Children Undergoing Hematopoietic Stem Cell Transplantation

The incidence of cadiotoxicity (CT) has been estimated at 5–10% of adult patients following hematopoietic stem cell transplantation (HSCT), but it is unknown in patients undergoing HSCT in childhood. Recent studies showed several biochemical markers as potentially useful for early detection of CT: Atrial Natriuretic Peptide (ANP) secreted by the atria in response to stretch as a result of an increased left atrial pressure, N-terminal fragment of Brain Natriuretic Peptide (NT-proBNP) produced by ventricles in response to ventricular dilatation and increased wall stress, cardiac Troponin I (TnI) the thin-filament contractile protein released to the circulation after myocardial injury and Endothelin 1 (ET-1) a vasoconstrictor peptide synthesized in the vasculature and by the endothelial cells and ventricular myocytes. The aim of the study was to assess the frequency and significance of elevated NT-proBNP, ANP, ET-1 and TnI plasma levels and their correlation to echocardiographic parameters of left ventricular function: shortening fraction (FS) and ejection fraction (EF) in children in early postransplant period. Patients: A total number of 31 consecutive children (22 boys and 9 girls) with median age of 9.6 years (range 0–18), treated with HSCT were included in the study: 12 autologous (aHSCT), 9 unrelated donor (MUD HSCT) and 10 family donor (MSD HSCT) transplantations were performed. The control group consisted of 14 healthy children, with median age of 10.9 years.

Methods: The plasma levels of NT-proBNP, ANP and ET-1 were measured in transplanted patients on days −7, 0, +7, +14 by the Electrochemiluminescent Immunoassay (Biomedica) and TnI by the Immunoassay (Abbot). SF and EF were assessed by echocardiography prior to HSCT and about day +30 and +100 after transplantation. The same tests were performed in the control group. Results: Baseline echocardiographic parameters were within the normal range in all patients included in the study. In comparison with a control group, a trend to decrease median SF and EF values was observed on day +30 (FS > 28% and EF > 55%). In transplanted patients median ET-1 plasma levels were elevated in all analyzed time points when compared to controls (p< 0.05); median NT pro-BNP plasma concentrations were significantly elevated from days −7 to +7 (p< 0.05) and median ANP plasma concentrations on day +7 (p< 0.05). Median levels of TnI did not differ between analyzed and control groups. No correlation was found between elevated biochemical marker levels and echocardiographic parameters evaluated on days +30 and +100 after HSCT. According to the type of transplant, in aHSCT patients ET-1 plasma level elevation was observed in 4 analyzed time points (p< 0.05), while in MUD transplant recipients on day +7 only and in MSD transplant recipients on day +14 only. NT pro-BNP and ANP plasma levels were elevated in MUD transplant recipients on days 0,+7, +14 (p<0.05), in MSD patients on day +7, while in aHSCT patients no difference was found, when compared to controls. The levels of TnI did not differ between patients and controls in any transplant type. Statistically significant correlation was found between ANP level on day +14 and EF on day +100 in MUD patients and in aHSCT patients (r = −0.9 and r = −0.78 respectively).

Conclusions: Elevation of natriuretic peptides (ANP, NT-proBNP) levels may indicate the risk of cardiotoxicity, especially in unrelated transplant recipients. ET-1 plasma concentration is elevated mainly in children following autologous transplantation. The value of measuring TnI levels in the assessment of CT in children following HSCT is low. Further studies are necessary to confirm the role of natriuretic peptides and ET-1 as markers of acute CT regarding the type of transplant.