Myocardial high-energy phosphate metabolism is altered after treatment with anthracycline in childhood

Abstract

AbstractObjectivesWe aimed to investigate whether changes in high-energy phosphate metabolism after treatment of children and young adults with anthracycline can be demonstrated non-invasively by 31P magnetic resonance spectroscopy.BackgroundAbnormal myocardial energy metabolism has been suggested as a mechanism for anthracycline-induced cardiotoxicity. Deterioration in such has been shown in animal studies by resonance spectroscopy.MethodsWe studied 62 patients, with a mean age of 13.5 ±5 years,3.7±4.3 years after a cumulative anthracycline dose of 270±137 mg/m2. Normal echocardiographic findings had been elicited in 54 patients. The control group consisted of 28 healthy subjects aged 20±7 years. Resonance spectrums of the anterior left ventricular myocardium were obtained at 1.5 Tesla using an image-selected in vivo spectroscopy localization technique.ResultsThe ratio of phosphocreatine to adenosine triphosphate after blood correction was 1.09±0.43 for the patients, and 1.36±0.36 (mean±SD)for controls (p = 0.005), with a significantly reducedmean ratio even in the subgroup of patients with normal echocardiographic results ( l.11 ± 0. 44 versus1.36±0.36, p=0.01). The ratio did not correlate with the cumulative dose of anthracycline. The ratio of phosphodiester to adenosine triphosphate was similar in patients and controls (0.90±0.56 versus 0.88±0.62).ConclusionsIn patients treated with anthracyclines in childhood, myocardial high-energy phosphate metabolism may be impaired even in the absence of cardiomyopathy. Our data support the concept that anthracycline-induced cardiotoxicity is not clearly dose dependent.