Assessment of Early-Onset Chronic Progressive Anthracycline Cardiotoxicity in Children: Different Response Patterns of Right and Left Ventricles

Abstract

We aimed to assess early-onset chronic progressive cardiotoxicity in the left and right ventricles with increasing cumulative anthracycline doses. We evaluated 72 patients within the first year after doxorubicin and/or daunorubicin treatment (median 1.3 months; range 0.3-11.5) and 31 healthy controls. Pretreatment and posttreatment QT interval analyzes were performed in 27 newly diagnosed patients. The echocardiographic data of all examinations of 72 patients were classified into three groups according to instant cumulative anthracycline doses: treatment group (TG)-I (≤120 mg/m(2); n = 26), TG-II (120-240 mg/m(2); n = 39), and TG-III (≥240 mg/m(2); n = 40). Diastolic and systolic parameters were analyzed by conventional echocardiography and tissue Doppler imaging (TDI) and compared with those of healthy controls. The mean age for patients and controls was 8.2 ± 4.5 and 9.6 ± 4.2 years, respectively (p > 0.05). QTc dispersion significantly increased after anthracycline treatment (p = 0.02). TDI showed decreased E' velocity (p < 0.001) and E'/A' ratio (p < 0.001) at lateral tricuspid annulus segment in TG-I, and these findings continued in TG-II and -III. In addition, S' velocity decreased in TG-I, -II, and -III at lateral mitral annulus (10.5 ± 2.6 cm/s, p < 0.05; 9.9 ± 2.2 cm/s, p < 0.001; and 10.1 ± 2.3 cm/s, p < 0.01, respectively). However, decrease in left-ventricular ejection fraction was statistically significant in TG-II and -III (p < 0.001). Although myocardial performance index was significantly increased in all treatment groups in both segments, it was primarily due to significant increases in isovolumic relaxation time at the lateral tricuspid annulus and isovolumic contraction time at the lateral mitral annulus. Abnormalities in diastolic function in right ventricle and systolic function in the left ventricle were observed even with a cumulative anthracycline dose <120 mg/m(2) by TDI. In addition, anthracycline treatment led to an increase in QTc dispersion.

Relevance of Tricuspid Annular Peak Systolic Velocity (S′) to Detect Systolic Right-Ventricular Impairment After Anthracycline Cancer Treatment in Childhood

“…They also found that the tricuspid annular peak systolic velocity (S 0 ) was significantly lower in a patient group receiving anthracycline at doses[240 mg/m 2 than those observed in a control group. In accordance with the findings of Kocabas et al [2], the impairment of RV and LV function after anthracycline treatment using cardiac magnetic resonance imaging has also been described in long-term survivors of childhood cancer [4]. For the convenience of the readership of Pediatric Cardiology, we add that recently our group published normal S 0 values with z-scores for healthy pediatric patients [3].…”

“…This comparison probably would have improved the statistical power of their analysis, although we must state that the normal values for this age group are close to adult normal values. The remarkable study from Kocabas et al [2] clearly supports the notion that the right ventricle is susceptible to anthracycline in pediatric cancer patients. We thank the investigators for addressing the need for careful and systematic evaluation of both RV and LV function in the context of the need of cancer treatment with anthracycline in children and look forward for more interesting studies from this group.…”

“…We read with interest the article ''Assessment of EarlyOnset Chronic Progressive Anthracycline Cardiotoxicity in Children: Different Response Patterns of Right and Left Ventricles'' from Kocabas et al [2]. In our opinion, this is an excellent article describing the effect of cumulative dose on left-ventricular (LV) and right-ventricular (RV) function in pediatric patients receiving cancer treatment using tissue Doppler imaging (TDI) parameters.…”

“…The importance of TDI measurements of LV and RV function in the process of dose evaluation of anthracycline treatment has also been described to be a clinically useful technique for the assessment of LV and RV function [1]. Kocabas et al [2] clearly state that abnormalities of RV and the LV function were observed even with a cumulative anthracycline dose \120 mg/m 2 . They also found that the tricuspid annular peak systolic velocity (S 0 ) was significantly lower in a patient group receiving anthracycline at doses[240 mg/m 2 than those observed in a control group.…”

Right ventricular function in long-term adult survivors of childhood lymphoma and acute lymphoblastic leukaemia

“…16 The other study included 72 survivors and documented lower RV s ′ in the group treated with .240 mg/m 2 , but also lower RV myocardial performance index in survivors treated with lower anthracycline doses. 17 In addition, one study of 56 survivors of childhood cancer treated with anthracycline doses ,300 mg/m 2 found lower peak systolic strain values in the basal RV free wall, but not in the mid or apical free wall, and TAPSE was equal in patients and controls. 18 All the mentioned studies were on paediatric patients.…”