Late effects of anthracycline therapy in childhood in relation to the function of the heart at rest and under physical stress

Abstract

To evaluate the long-term effects of anthracyclines on the myocardium of the young child we examined 34 patients who had been treated with anthracyclines in childhood. In addition to anthracycline, the patients were treated with other potentially cardiotoxic substances within the framework of different protocols. The mean cumulative anthracycline dose was 128.6 mg/m² the average age at onset of chemotherapy 4.2 years, and the time interval after discontinuation of treatment 9.0 years. The cardiological examination consisted of a physical examination, electrocardiography and echocardiography, including Doppler and bio-impedance cardiography. The patients were studied at rest and after physical exercise with a cycle ergometer test in a supine position. The results of the physical examination, the electrocardiogram at rest and the 24 h Holter monitoring were normal. The left ventricular enddiastolic diameter, shortening fraction, velocity of fibre shortening (VCF), the diastolic flow profile at the mitral valve level and the cardiac stroke volume at rest were also normal. However, the shortening fraction (SF) was below the margin of 2 standard deviations in two patients and the VCF in three patients. There was a significant reduction in septal thickness, (−1.4 SD,P<0.0004), in the width of left ventricular posterior wall (−1.5 SD,P>0.0002) and in the left ventricular myocardial mass (−0.76 SD,P=0.0042). Physical working capacity was normal. Immediately after physical stress the expected rise of SF and VCF did not occur and the SF fell below the values at rest. In comparison to a healthy control group the SF and the VCF were markedly decreased (P>0.0001). The stroke volume decreased by 14% compared to the pre-exercise value.

Conclusion

Chemotherapy with anthracyclines even in low dosages, results in myocardial damage, which does not however, effect physical capacity over a long penod but which is revealed by reduced left ventricular wall thickness and myocardial mass. Functional effects include insufficient increase of SF, VCF and stroke volume during physical exercise.