Cardiac Events in Childhood Cancer Survivors Treated with Anthracyclines: The Value of Previous Myocardial Strain Measurement

Abstract

In echocardiographic surveillance of anthracycline-treated childhood cancer survivors (CCS), left ventricular ejection fraction (LVEF) has insufficient prognostic value for future cardiac events, whereas longitudinal strain may be more sensitive. We describe the long-term incidence of cardiac events in CCS after previous measurement of LVEF and myocardial strain. Echocardiography, including four-chamber view longitudinal strain (4CH-LS), of 116 anthracycline-treated CCS was obtained between 2005–2009 (index echocardiography). Follow-up was obtained at the late-effects clinic. Primary outcome was occurrence of cardiac events, defined as either symptomatic heart failure, life-threatening arrhythmias, LVEF < 40% or cardiac death, in CCS with normal versus abnormal index 4CH-LS. LVEF from subsequent echocardiograms was obtained to evaluate its natural course as a secondary outcome. After index echocardiography (median 13.1 years since childhood cancer diagnosis), our study added a median follow-up of 11.3 years (median last clinical contact 23.6 years since diagnosis). Only three CCS developed a cardiac event (6.2, 6.4 and 6.7 years after index echocardiography), resulting in a ten-year cumulative incidence of 2.7% (95%CI 0.9–8.2). All three CCS had a clearly reduced index 4CH-LS and relevant cardiovascular risk factors, whereas their index LVEFs were around the lower limit of normal. Index LVEF correlated with index 4CH-LS but mean long-term natural course of LVEF was comparable for CCS with abnormal versus normal index 4CH-LS. Absolute 10-year cumulative incidence of cardiac events in anthracycline-treated CCS during long-term follow-up was low. Sensitive echocardiographic measurements, such as 4CH-LS may be useful to tailor surveillance frequency in a selected group of CCS without cardiovascular disease.

Longitudinal strain analysis for assessment of early cardiotoxicity during anthracycline treatment in childhood sarcoma: A single center experience

“…Longitudinal strain was the most frequently affected parameter of systolic function (impaired in 42%, as compared to impaired FS in 5% and vLVEF in 12%). This finding, together with results from previous studies of childhood cancer survivors, indicates a superior sensitivity of LS compared to LVEF and FS 27,28 . Median values for vLVEF and FS remained above the cut‐off values for defining ventricular dysfunction (vLVEF <53% and FS <0.28 respectively) during and after treatment.…”

“…Including analysis of LS has therefore T A B L E 2 Re-analysis of FS and LVEF in echocardiograms eligible for LS-analysis. been suggested as an option when GLS is not feasible, 27,28 since LSanalysis only requires a standard apical four-chamber view of the left ventricle of adequate image quality and frame rate. 41,42 The feasibility, as well as the reproducibility, sensitivity and specificity, of an echocardiographic method are of relevance both in research and in clinical practice.…”

“…LS, and preferably GLS, may be particularly useful to further scrutinize the significance of borderline FS or LVEF values and aid in decision-making regarding surveillance intensity, both during and after anthracycline treatment. 10,27,28,41 To improve the understanding of the variable course of individual patients and to provide outcome measures for further research on early detection of cardiovascular toxicity, adherence to detailed standardized echocardiographic protocols including left ventricular systolic strain analysis 46 (preferably GLS, alternatively LS) should be implemented in clinical practice. We are now preparing a prospective study to validate LS and GLS in echocardiographic surveillance during and after anthracycline treatment in children to confirm and expand the retrospective results presented here.…”

“…27,28 Median values for vLVEF and FS remained above the cut-off values for defining ventricular dys-…”

“…Impairment in GLS of >15% from baseline or deformation measured by GLS less than 17% is defined as significant deterioration 9,23,26 . Previous studies indicate that deterioration in GLS, as well as in LS, during and early after anthracycline treatment may identify individuals at higher risk of subsequent cardiac dysfunction 14,27,28 . In children, the prognostic importance of GLS and LS warrants further clarification and these methods are not included in standard pediatric cancer surveillance protocols 8,29 .…”