Diagnosis of anthracycline-induced late cardiomyopathy by exercise-spiroergometry and stress-echocardiography

Anthracyclines are used in the therapy of several of the most common paediatric oncological disorders. The usefulness of these agents is limited by cardiotoxicity, with congestive heart failure developing in up to 20% of patients. To stratify possible risk factors, we investigated 38 children with acute lymphoblastic leukaemia for signs of late cardiomyopathy. Exercise-spiroergometry and stress-echocardiography with measurement of fractional shortening (FS) and ejection fraction (EF) as indicators of left ventricular function were performed. ECG, 24 h Holter monitoring, chest X-ray, virus serology and carnitine were analysed. Control subjects were 38 healthy children matched for age and body surface area. All 38 patients had normal echocardiographic findings at rest (EF: 0.73 +/- 0.06; FS: 0.35 +/- 0.05). ten patients had a significant attenuation of left ventricular function after exercise assessed by stress-echocardiography compared to the remaining 28 patients and 38 healthy control subjects (EF: 0.52 +/- 0.08 versus 0.77 +/- 0.06 and 0.80 +/- 0.08; FS: 0.29 +/- 0.06 versus 0.39 +/- 0.05 and 0.41 +/- 0.02); patients with reduced ventricular function after exercise had significant low anaerobic threshold, subnormal maximal oxygen uptake and decreased carnitine levels. The findings were not related to the dosage of administered doxorubicin. There exists no correlation between ECG, 24 h ECG, chest X-ray, virology and left ventricular dysfunction. The benefit of angiotensin converting enzyme inhibitors and the administration of carnitine remains speculative. Conclusion: exercise-spiroergometry and stress-echocardiography are sensitive investigations for diagnosing subclinical cardiomyopathy late after completion of chemotherapy. Investigative findings of cardiomyopathy are not dose related and may provide information for therapeutic prevention before clinical symptoms of cardiomyopathy appear.