Echocardiographic Assessment of Cardiac Function in Pediatric Survivors of Anthracycline-Treated Childhood Cancer

Abstract

Background: Anthracycline-induced cardiotoxicity is a major cause of morbidity and mortality in childhood cancer survivors (CCSs). Echocardiographic myocardial strain imaging is recommended in adult patients with cancer, but its role in pediatric CCSs has not been well established. Aims of this study were to determine the prevalence of abnormalities in left ventricular strain in pediatric CCSs, to compare strain with other echocardiographic measurements and blood biomarkers, and to explore risk factors for reduced strain. Methods: CCSs ≥3 years from their last anthracycline treatment were enrolled in this multicenter study and underwent a standardized functional echocardiogram and biomarker collection. Regression analysis was used to identify factors associated with longitudinal strain (LS). Results: Five hundred forty-six pediatric CCSs were compared with 134 healthy controls. Abnormal left ventricular ejection fraction (<50%) and mean LS ( Z score, <−2) was found in 0.8% and 7.7% of the CCSs, respectively. LS was significantly lower in CCSs than in controls, but the absolute difference was small (0.7%). Lower LS in CCSs was associated with older current age and higher body surface area. Sex, cumulative anthracycline dose, radiotherapy, and biomarkers were not independently associated with LS. Circumferential strain, diastolic parameters, and biomarkers were not significantly different in pediatric CCSs. Conclusions: Global systolic function and LS are only mildly reduced in pediatric CCSs, and most LS values are within normal range. This makes single LS measurements of limited added value in identifying CCSs at risk for cardiac dysfunction. The utility of strain imaging in the long-term follow-up of CCS remains to be demonstrated.

Cardiac Function After Cardiotoxic Treatments for Childhood Cancer—Left Ventricular Longitudinal Strain in Screening

“…However, the role of myocardial strain imaging among children is less well-established. In agreement with our results, several studies have found that the global systolic function and LV longitudinal strain are reduced among CCSs ( 2 , 28 – 31 ), though these factors have yet to be proven to be more sensitive than LV EF in the early follow-up.…”

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

“…Our current study demonstrated significantly decreased LVSF in CCSs compared to healthy controls (p = 0.027), but no significant difference in LVEF, with all CCSs having LVSF and LVEF values within the normal range. Our findings are similar to those found in a recent multicenter cohort study by Slieker et al (35), demonstrating lower measures of global systolic function in CCSs when compared with healthy controls; however, these differences were small and parameters of LV function were largely within the normal range. In contrast, another recent study by Border et al (36) found a measurable longitudinal decline in many standard echocardiographic parameters of cardiac function, including FS and EF, in CCSs compared to controls, supporting the utility of conventional measures of global systolic function to detect myocardial dysfunction in cancer population.…”

“…However, a more recent multicenter study of cardiac strain in a large cohort of pediatric CCSs found only mild differences in parameters of longitudinal strain between patients and healthy controls, with most CCSs (92.3%) having longitudinal strain values within the normal range. Thus, this report concluded that the utility of strain imaging in the long-term follow-up of CCSs remains to be demonstrated (35). Our study found normal values of global strain in both groups, and there was no significant difference in peak mean systolic longitudinal strain in any apical view.…”

“…Recent reports from international Cardiological Societies recommend measurements of LV function by STE and 3D Echo in the long-term follow-up of adult cancer survivors (29,44), but their role in pediatric CCSs has not been well established (33). Therefore, these advanced echocardiographic techniques require further validation with longitudinal follow-up studies, prior to be recommended in clinical practice, dependent also on availability and adequate operator experience (33,35,45).…”

Diagnosis, Prevention, Treatment and Surveillance of Anthracycline-Induced Cardiovascular Toxicity in Pediatric Cancer Survivors

“…Abnormal NT-proBNP levels have been detected in 20-30% of asymptomatic survivors [69,71]. While other studies have not found significantly abnormal levels of NT-proBNP in isolation [60,72], there is a significant correlation of cumulative anthracycline dose with increased BNP levels and CMR ECV [60] and of NT-proBNP with GLS alone [44], as well as CMR ECV and GLS [60]. This suggests that, while serum biomarkers may not serve as an independent predictor of cardiac toxicity, they can be helpful when assessed in correlation with imaging markers.…”