Early surveillance of anthracycline induced cardiotoxicity in children using echocardiography and biomarkers: A prospective study
Authors: Henry M , Esmaeilzadeh M , Christie A , Lam E , Wheately J , Fackoury C , Slorach C , Hui W , Somerset E , Fan S , Nathan P , Mertens L 
Published: February 2021

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): CIHR

Background
Anthracyclines, which are commonly used in cancer treatment can induce myocardial damage, result in heart failure during treatment and have cardiac effects even decades after treatment. Monitoring of cardiotoxicity during treatment is largely based on the use of echocardiographic functional markers like ejection fraction and more recently myocardial strain imaging. Some studies have also looked at the utility of biomarkers like troponin and BNP. The utility of this surveillance strategy remains controversial as larger prospective studies are lacking.

Purpose
The aim of this study was to prospectively describe the impact of anthracycline treatment on echocardiographic functional parameters and cardiac biomarkers (high sensitivity troponin T and NT-Pro BNP) during the treatment period and twelve months after completion of treatment. In the current study we wanted to look at whether monitoring parameters during treatment were predictive of left ventricular function 12 months after treatment.

Methods
This was a prospective multi-centre nested case-control study of 256 children diagnosed with cancer requiring anthracycline therapy. Baseline functional echocardiographic parameters and cardiac biomarkers were obtained prior to starting anthracycline therapy, during the treatment protocol, and 12 months after treatment completion. Patients were assigned to one of two comparison groups based on the fractional shortening at the12-month echocardiogram: patients in group 1 had normal fractional shortening, (FS ³ 28%) while patients in group 2 had reduced fractional shortening (FS &lt; 28%).

Results
A total of 917 echoes were performed, 376 of these occurred during the treatment period. FS was reduced in 27 (7%) of echoes obtained during the treatment period with 22 patients developing new onset dysfunction. Twelve months after treatment completion 232 patients had normal FS (Group 1), while 24 patients showed reduced FS (Group 2). Both groups had normal systolic function and cardiac biomarkers at baseline, however patients in group 2 were older at diagnosis (13.2 years (11.8-16) vs 6.5 years (3.4-13.2), p = 0.003) and received a higher cumulative anthracycline dose (200 mg/m2 (143-318) vs 125 mg/m2 (75-200), p= 0.005). One third (8/24) of patients in group 2 had at least 1 abnormal echo during the treatment period compared to 7% (16/232) in the normal group P &lt; 0.001. The proportion of patients with at least one abnormal biomarker during this period however, was similar between groups.
Conclusion(s)
Patients receiving higher accumulative anthracycline doses and those with abnormal FS during the treatment period are at higher risk of having reduced cardiac function 12 months after treatment. High sensitivity troponin and NT-Pro BNP levels during the treatment period fail to discriminate patients at risk of developing early reduced systolic function. The relationship of these early results to long term cardiac function remains to be demonstrated.