Langzeituntersuchung zur anthracyclininduzierten Kardiomyopathie bei Kindern und Jugendlichen

Abstract

In order to detect changes in cardiac function, electrocardiographic, echocardiographic and radiologic studies were performed in 71 patients (age 1-26 yrs) who had been treated at the University Children's Hospital Berlin because of malignant diseases according to protocols of the DAL/GPO and had received anthracyclines (doxorubicin or daunorubicin) at cumulative doses up to 480 mg/m2 (median 280 mg/m2). Clinically overt cardiomyopathy was observed in one girl and required transient administration of digoxin. In 2 patients echocardiographic changes led to a reduction of the scheduled anthracycline doses. No patient died from congestive heart failure. During treatment, an increase in the cardiothoracic index was observed in 14 children, and in 16 the ECG showed pathological findings. A decrease in contractility to 25% or less as detected by ultrasound was seen in 15 patients. More than 50% of patients developed echocardiographical signs indicating an impairment of myocardial function. However, persistent changes were only found in 1 patient after discontinuation of treatment. Long-term echocardiographic follow-up studies for 4-48 months (median 14 months) after completion of anthracycline therapy were performed in 18 patients and the findings compared to matched-pair controls. The observed M-mode parameters were completely normal, and the ejection fractions calculated from the two-dimensional ultrasound investigations were in the normal range but slightly diminished compared to controls. Cardiac ultrasound is a non-invasive, reproducible and tolerable procedure for early detection of an anthracycline cardiomyopathy. In our patients, time of occurrence and the extent of pathological changes were not associated with the cumulative applied anthracycline doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Physical performance in long-term survivors of acute leukaemia in childhood

“…While some studies support the ®ndings of Lipshultz et al [20] and Steinherz et al [28] [e.g. 1,9], others arrive at much lower rates of subnormal measurements [11,17,19,25]. In the present study, in which only relatively low ADR doses are encountered, only one patient has a reduced shortening fraction.…”

“…Several recent studies have documented high rates of cardiac dysfunction in long-term survivors of paediatric malignancies treated with anthracyclines [1,9,17,19,20,27,28]. Lipshultz et al [20], for example, found abnormal contractility and/or afterload in 57% of 110 ALL patients 1±15 years after treatment.…”

“…Recent studies indicate that a large proportion of long-term survivors after treatment involving anthracyclines develop overt or subclinical signs of cardiac dysfunction. Potential risk factors for anthracycline-induced cardiotoxicity include high cumulative anthracycline dose [11,21,25,28], previous mediastinal irradiation [10,19,28], young age at diagnosis [20,23], gender [21,22,26,27] and a long interval between treatment and investigation [9,17,20,28].…”

Early detection of doxorubicin and daunorubicin cardiotoxicity by echocardiography: Diastolic versus systolic parameters

“…Whether these alterations are reversible after therapy, as reported for the shortening fraction [13], is unknown. Longterm studies are needed to answer the predictive value of these findings.…”

“…Early diagnosis of anthracycline-induced Cardiotoxicity below a maximum dose is desirable, because the appearance of side-effects is not always correlated with the cumulative dose [5,13]. Even when the anthracycline dose is limited to less than 450 mg/m 2 cardiomyopathy must be expected in 4% of treated patients [5].…”