Multimodality Imaging for Cardiac Surveillance of Cancer Treatment in Children

Publication Date: November 30, 2023
Last Updated: December 6, 2023

Introduction

  • During cancer treatment inclusive of cardiotoxic medications, echocardiographic screening for early detection of subclinical cardiac dysfunction is recommended. The frequency of screening will depend on doses used and other coexisting risk factors.
  • Current criteria for defining early cardiac dysfunction are based on decreased FS or EF that have been poorly validated in prospective studies. Withholding cancer treatment requires multidisciplinary decision-making and must be made cautiously.
  • After completion of treatment, cardiac surveillance is recommended at least every 2 years for high-risk and every 5 years for moderate-risk patients. The cost-benefit for low-risk patients is questionable, and evidence-based recommendations for cardiac surveillance after novel treatments have not been established.

Echocardiographic Evaluation of Children With Cancer

Assessing LV Size and Function

Assessing LV Dimensions, Volumes, and Mass

  • Serial assessment of LV chamber size and wall thickness must be included when evaluating children with cancer before, during, and after treatment.
  • Linear dimensions of the LV cavity, interventricular septum, and posterior wall can be measured either by M-mode echocardiography or by 2D echocardiography. Consistency in the method used for measuring linear dimensions is crucial for interpreting serial changes. The measurements should be corrected for body size, and Z scores should be included in the reports.
  • Left ventricle volume and mass measured by 2D echocardiography using the method of disks or the area-length method can provide additional and more detailed information on LV size.
  • Three-dimensional echocardiography is an emerging technique in pediatrics for assessing LV volume and mass without geometric assumptions.

Assessing LV Systolic Function

  • We recommend the use of EF and not FS for monitoring LV function in children with cancer.
  • For measuring EF by 2D echocardiography, we recommend using the biplane method of disks for serial follow-up. If apical 2-chamber views are limited, the area-length method is a reasonable alternative, especially in young children. When available, 3D echocardiography-based EF calculations are preferable in adolescents and young adults.
  • Each laboratory should consistently utilize a single method for serial assessment of LV function. The method used should be identified in the report.
  • Normal EF is ≥55%. An EF value between 50% and 54% is borderline function and should be confirmed by a second echocardiogram acquired within 1 to 2 weeks (during treatment) or within 6 months (after treatment). In case of borderline LV function, assessment of LV function by other imaging modalities, such as cardiac MRI, can be considered. When EF is <50% a cardio-oncology consultation is recommended.

Use of Tissue Doppler and Myocardial Deformation Imaging

  • Measurement of GLS by STE is a reproducible measurement of LV function that should be included in the assessment of LV function.
  • Given intervendor variability, the use of either a single-vendor or a vendor-neutral strain analysis software is recommended for serial follow-up.
  • Values of GLS equal to or more negative than −18% are considered normal, of −16% to −17% are considered borderline normal, and less negative than −16% are considered abnormal. The predictive value of an early decrease in GLS during treatment and in long-term survivors is uncertain in the presence of preserved EF.
  • If LVEF is >55% but GLS is > –18%, more frequent follow-up could be considered.

Assessing LV Diastolic Function

  • Despite their limitations, assessment of LV diastolic parameters should be considered an essential part of LV functional assessment.
  • We recommend serial assessment of mitral inflow velocities, tissue Doppler velocities at the septal and lateral mitral annulus, LA volume by the biplane method, and peak tricuspid regurgitation velocity.
  • Serial assessment of these parameters can help to identify development of diastolic abnormalities. Diastolic dysfunction remains poorly defined in children, as no specific guidelines have been developed.
  • Left atrial volume assessment is a more stable parameter of LV diastolic function in children. Progressive LA dilatation without obvious explanation could indicate increased LV stiffness and LV filling pressures.
  • Left atrial strain is a promising measure of LA function that requires further validation in children exposed to cancer treatment.

Assessing RV Function

  • Comprehensive echocardiographic surveillance of pediatric cancer patients should include serial assessment of RV size, RV function, and RV systolic pressure.
  • Assessment of RV size should include qualitative assessment of RV size and at least 1 measurement such as RV basal diameter.
  • Quantification of RV function in children includes FAC and TAPSE.
  • Right ventricular free-wall strain and 3D echocardiographic measurements of RV EF are emerging techniques for evaluating RV systolic function, but their utility in monitoring cardiac effects of cancer treatment requires further validation.

Role of Stress Echocardiography

  • The clinical utility of stress echocardiography for monitoring childhood cancer survivors has not been defined. Currently there is no clinical indication to monitor function in pediatric cancer patients based on stress echocardiography.

Use of CMR in Evaluating Children With Cancer

  • Cardiac magnetic resonance imaging is considered a valuable adjunct to echocardiography (1) when echocardiographic imaging windows are limited and do not allow reliable functional assessment; (2) when borderline cardiac dysfunction is detected by echocardiography, defined as EF between 50% and 55%; (3) when myocarditis is suspected and tissue characterization could help with identifying myocardial edema; (4) when constrictive pericarditis is suspected; or (5) when tumor is involving the heart.
  • Every CMR assessment in a pediatric cancer patients must include assessment of LV and RV volumes and EF as well as LV mass. Left atrial and RA volumes can be included in the assessment.
  • If CMR is performed on children with cancer during early or late follow-up to assess LV volumes and function, it is reasonable to include myocardial deformation imaging and tissue characterization (T1 and T2 mapping) to assess diffuse myocardial fibrosis, edema, and iron load (when indicated). Our recommendation is to only use contrast agents when indicated and, if they are used, at the lowest possible dose in patients without evidence of impaired kidney function.
  • Cardiac magnetic resonance imaging can provide additional information about valve function and pericardial disease, including pericardial effusion, and thickening and inflammation of the pericardium if echocardiography is not diagnostic.148
  • Quality assurance and development of dedicated imaging protocols is recommended to standardize image acquisition and analysis.

Use of Cardiac CT in Evaluating Children With Cancer

  • When echo and CMR are not adequate or feasible, CCT can be used to assess cardiac volumes and EF.
  • Other possible indications include cardiac tumors, mediastinal tumors close to the heart, and pericardial thickness as an alternative modality for CMR.
  • In asymptomatic adult survivors who have been exposed to high-risk radiation, surveillance for atherosclerotic coronary artery disease with CAC scans at 5- to 10-year intervals after RT can be considered.
  • Coronary CT angiography is appropriate in symptomatic survivors older than 18 years with a history of RT to assess for RT-related atherosclerotic cardiovascular disease.

Knowledge Gaps and Opportunities or Future Research

Important knowledge gaps were identified when developing the current recommendations.
  1. One of the main limitations for the use of imaging markers in decision-making during cancer treatment is the lack of data on their prognostic value. While fluctuations in cardiac function are common in patients undergoing cancer treatments, the current recommendations for what is considered a clinically relevant change in EF and GLS are mainly based on expert consensus without strong data regarding their clinical prognostic value. Even a reduction below normal values during treatment may be temporary. Recommendations for changes in cancer treatment based on imaging findings alone should therefore be made cautiously and require a multidisciplinary approach, carefully weighing risks and benefits. Further longitudinal data are needed to understand how imaging findings should be used to guide cancer treatment decisions. Additionally, there are very few data informing how imaging data could be used for decision-making regarding initiation of cardioprotective drugs and early cardiac treatment.
  2. For long-term survivors, echocardiographic values of EF and strain are often reported to be lower than in healthy controls but remain in the normal range for the majority of children. Further longitudinal data, requiring follow-up through adult life, are needed to demonstrate whether these differences have prognostic significance.
  3. Current recommendations on the frequency of repeat imaging studies in this population are primarily based on limited prognostic data and expert consensus, mainly taking cancer treatment history into consideration. More research is required on how these follow-up recommendations need to be individualized, taking into consideration overall individual cardiovascular risk profiling. A personalized risk and preventative strategy for individual patients should be developed based on generating more information on the long-term outcomes of these patient cohorts.
  4. Individualized risk profiling will require integration of imaging information with clinical information, as well as biochemical and genetic markers. These models are currently being developed, but given the relatively low incidence of clinical events during childhood, long-term follow-up data will be needed to fully inform these models.
Current available data informing cardiotoxicity surveillance in childhood cancer patients and survivors are largely based on anthracycline-treated children. Furthermore, long-term outcome data are currently based on survivors treated under older pediatric oncology treatment protocols and don’t account for more recent adaptations to anthracycline and radiotherapy dose limitations or cardioprotective therapies. With the development of novel cancer therapies and modern anthracycline dosing strategies, more recently treated cohorts may demonstrate different long-term cardiovascular prognosis.

Recommendation Grading

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Multimodality Imaging for Cardiac Surveillance of Cancer Treatment in Children

Authoring Organization

American Society of Echocardiography

Publication Month/Year

November 30, 2023

Last Updated Month/Year

April 1, 2024

Document Type

Guideline

Country of Publication

US

Document Objectives

Guidelines for using noninvasive imaging techniques to monitor cardiac function in adults undergoing cancer treatment are available. Children with cancer, however, require a different imaging approach. Screening and detection strategies in younger children have largely relied on longitudinal monitoring of echocardiographic measures of left ventricle (LV) systolic function, mainly fractional shortening (FS) and ejection fraction (EF). Despite the important role of echocardiography in the follow-up of this patient group, a recent multicenter study indicated that the overall quality of routine pediatric echocardiograms for childhood cancer survivors was not sufficient to reliably assess LV function. This finding highlights the need to develop recommendations for the standardization of echocardiographic functional assessment as applied to pediatric oncology patients.

Inclusion Criteria

Male, Female, Adolescent, Child, Infant

Health Care Settings

Ambulatory, Hospital, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening, Management

Diseases/Conditions (MeSH)

D054849 - Cardiac Electrophysiology

Keywords

echocardiography, pediatric cancer, cardiac surveillance

Source Citation

Mertens L, Singh G, Armenian S, Chen MH, Dorfman AL, Garg R, Husain N, Joshi V, Leger KJ, Lipshultz SE, Lopez-Mattei J, Narayan HK, Parthiban A, Pignatelli RH, Toro-Salazar O, Wasserman M, Wheatley J. Multimodality Imaging for Cardiac Surveillance of Cancer Treatment in Children: Recommendations From the American Society of Echocardiography. J Am Soc Echocardiogr. 2023 Dec;36(12):1227-1253. doi: 10.1016/j.echo.2023.09.009. PMID: 38043984.