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. 2022 Apr;16(2):338-352.
doi: 10.1007/s11764-021-01028-4. Epub 2021 Mar 27.

Asymptomatic systolic dysfunction on contemporary echocardiography in anthracycline-treated long-term childhood cancer survivors: a systematic review

Remy Merkx  1 , Jan M Leerink #  2 , Esmée C de Baat #  3 , Elizabeth A M Feijen  3 , Wouter E M Kok  2 , Annelies M C Mavinkurve-Groothuis  3 , Jacqueline Loonen  4 , Helena J H van der Pal  3 , Louise Bellersen  5 , Chris L de Korte  6 , Leontien C M Kremer  3 , Elvira C van Dalen  3 , Livia Kapusta  7   8
Affiliations

Asymptomatic systolic dysfunction on contemporary echocardiography in anthracycline-treated long-term childhood cancer survivors: a systematic review

Remy Merkx et al. J Cancer Surviv. 2022 Apr.

Abstract

Purpose: Echocardiographic surveillance for asymptomatic left ventricular systolic dysfunction (ALVSD) is advised in childhood cancer survivors (CCS), because of their risk of heart failure after anthracycline treatment. ALVSD can be assessed with different echocardiographic parameters. We systematically reviewed the prevalence and risk factors of late ALVSD, as defined by contemporary and more traditional echocardiographic parameters.

Methods: We searched databases from 2001 to 2020 for studies on ≥ 100 asymptomatic 5-year CCS treated with anthracyclines, with or without radiotherapy involving the heart region. Outcomes of interest were prevalence of ALVSD-measured with volumetric methods (ejection fraction; LVEF), myocardial strain, or linear methods (fractional shortening; FS)-and its risk factors from multivariable analyses.

Results: Eleven included studies represented 3840 CCS. All studies had methodological limitations. An LVEF < 50% was observed in three studies in 1-6% of CCS, and reduced global longitudinal strain (GLS) was reported in three studies in 9-30% of CCS, both after a median follow-up of 9 to 23 years. GLS was abnormal in 20-28% of subjects with normal LVEF. Abnormal FS was reported in six studies in 0.3-30% of CCS, defined with various cut-off values (< 25 to < 30%), at a median follow-up of 10 to 18 years. Across echocardiographic parameters, reported risk factors were cumulative anthracycline dose and radiotherapy involving the heart region, with no 'safe' dose for ALVSD.

Conclusions: GLS identifies higher prevalence of ALVSD in anthracycline-treated CCS, than LVEF.

Implications for cancer survivors: The diagnostic and prognostic value of GLS should be evaluated within large cohorts.

Protocol registration: PROSPERO CRD42019126588.

Keywords: Anthracyclines; Cardiotoxicity; Childhood cancer survivors; Echocardiography; Systolic dysfunction.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA flowchart of study selection. Flowchart describing the systematic literature search and inclusion of studies. *Multiple reasons can be given per study, references in Online Resource 3. **Although directly eligible, 2 of these 6 authors provided additional data upon request
Fig. 2
Fig. 2
Risk of bias summary per study. The risk of bias per study is indicated for each domain. Assessment criteria are shown in Online Resource 2. Green = low risk; yellow = unknown risk; red = high risk; n.a, is not applicable
Fig. 3
Fig. 3
Prevalence of asymptomatic left ventricular systolic dysfunction in childhood cancer survivors. Prevalence is depicted for different echocardiographic parameters and cut-off points in the included studies. *Mean ± SD. Closed symbols depict the original cut-offs from the studies, open symbols were extracted from additional data provided by authors. Symbol size depicts sample size. Continuous values are median [range]. ANT = anthracycline, CI = confidence interval, FS = fractional shortening, GLS = global longitudinal strain, RT = radiotherapy on the heart region
See this image and copyright information in PMC

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