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

Objectives: We aimed to investigate whether changes in high-energy phosphat e metabolism after treatment of children and young adults with anthracyclin e can be demonstrated non-invasively by P-31 magnetic resonance spectroscop y. Background: Abnormal 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. Methods: We st udied 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/m(2). Normal echocardiogra phic findings had been elicited in 54 patients. The control group consisted of 28 healthy subjects aged 20+/-7 years. Resonance spectrums of the anter ior left ventricular myocardium were obtained at 1.5 Tesla using an image-s elected in vivo spectroscopy localization technique. Results: The 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 reduced mean ratio even in the subgroup of patients with normal echocardiographic results (1.11+/-0.44 versus 1.36+/-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 pati ents and controls (0.90+/-0.56 versus 0.88+/-0.62). Conclusions: In patient s treated with anthracyclines in childhood, myocardial high-energy phosphat e metabolism map be impaired even in the absence of cardiomyopathy. Our dat a support the concept that anthracycline-induced cardiotoxicity is not clea rly dose dependent.