Cardiac Surveillance for Early Detection of Late Subclinical Cardiac Dysfunction in Childhood Cancer Survivors After Anthracycline Therapy

Abstract

BackgroundIn childhood cancer survivors (CCSs) anthracycline-related cardiotoxicity is an important cause of morbidity and late mortality, but the optimal modality of cardiac surveillance still remains to be defined. The aim of this study was to assess whether non-invasive echocardiography-based functional cardiac measures can detect early subclinical myocardial changes in long-term pediatric cancer survivors who received anthracycline therapy.MethodsTwenty anthracycline-treated long-term CCSs and 20 age, sex, and body surface area matched healthy controls were enrolled in this study. Among cancer survivors, mean age at diagnosis was 6.5 ± 4.4 years, and the mean cumulative anthracycline dose was 234.5 ± 87.4 mg/m2. All subjects underwent a comprehensive functional echocardiographic protocol study including two-dimensional echocardiography (2D Echo), tissue Doppler imaging (TDI), speckle tracking (STE) and three-dimensional echocardiography (3D Echo). Patients were studied at a mean follow-up time of 6.5 ± 2.8 years from the end of therapy.ResultsNo significant differences in two-dimensional left ventricle ejection fraction (LVEF), diastolic parameters and speckle tracking (STE)-derived myocardial strain were observed between patients treated with anthracyclines and controls. Myocardial performance index was significantly prolonged (p = 0.005) and three-dimensional LVEF was significantly reduced (p = 0.002) in CCSs compared to controls, even though most values were within the normal range. There were no significant correlations between 2D, STE, and 3D echocardiographic parameters and age at diagnosis or duration of follow-up. No significant differences in echocardiographic parameters were found when stratifying cancer patients according to established risk factors for anthracycline cardiomyopathy.ConclusionsThis study found significantly reduced three-dimensional LVEF in CCSs compared with controls, despite no significant differences in two-dimensional LVEF and longitudinal strain values. These findings suggest that long-term CCSs who had received anthracycline therapy may be found to have subclinical features of myocardial dysfunction. However, further studies are needed to demonstrate the validity of new imaging techniques, including STE and 3D Echo, to identify patients at risk for cardiomyopathy in the long-term follow-up of CCSs.

Assessment of late cardiotoxic effects in patients treated for cancer in childhood

“…The impairment of diastolic function is similar as described in the above mentioned study, 11 but the authors also reported lower systolic parameters in subgroups with lower doses of anthracycline therapy in comparison to anthracycline‐naïve subjects. This was not observed in our study, even though the median anthracycline dose in our cohort was higher (200 vs. 120 mg/m 2 ).A recent study by Sofia et al 15 compared 20 CCS and 20 controls and described no differences in biplane LVEF calculated by Simpson's rule and global longitudinal strain (GLS), but using RT‐3D echocardiography demonstrated a significant difference in LVEF.However, the mean values of both CCS and controls were in a normal range and no difference between diastolic velocities was found. The patients in this study received a slightly higher dose of anthracyclines, on the other hand the mean follow‐up period was 6.5 ± years, which was a shorter time than in our patient group.…”

Protection against doxorubicin-induced cardiotoxicity by ergothioneine

“…The supplementation with ET in doxorubicin treated animals significantly lowered this doxorubicin-induced increase in MPI score. However, ET supplementation did not reduce this to levels of the saline controls possibly indicating a subclinical left ventricular cardiotoxicity [65]. Perhaps prolonged ET administration or longer observation period is required to demonstrate the efficacy of ET against late-onset cardiac dysfunction (which can occur decades after completion of anthracycline chemotherapy in humans).…”

The pediatric oncology exercise field speeds up to address important issues regarding chemotherapy-related cardiotoxicity

“…Another challenge is the diagnosis of cardiac dysfunction in childhood cancer survivors. There is no broad consensus on how cardiotoxicity should be measured in childhood cancer survivors, leading to heterogeneity between studies (70)(71)(72)(73)(74). Indeed, cardiotoxicity can be measured by a combination of different parameters, such as reduced resting systolic function, reduced resting diastolic dysfunction, impaired hemodynamics and systolic functional reserve measured during exercise or reduced exercise capacity or cardiopulmonary fitness (VO 2 peak).…”