Enhancing Prediction of Cancer Therapy-Related Cardiomyopathy From Surveillance Echocardiograms

Q: What is the clinical evidence from this study?

Study design: Case-Control. Population: Cancer Therapy-Related Cardiomyopathy. Intervention: Echocardiographic parameters. Primary outcome: Cardiomyopathy (OR 1.3, 95% CI 1.1-1.6).

Kasey J. Leger; Kayla Stratton; Ritu Sachdeva; Saro H. Armenian; Aarti Bhat; Patrick M. Boyle; Lindsay A. Edwards; Lillian R. Meacham; Shanti Narasimhan; Paul C. Nathan; Karim Thomas Sadak; Surbhi Sharma; William L. Border; Wendy M. Leisenring; Eric J. Chow

doi:10.1016/j.jacadv.2025.102363

November 21, 2025JACC AdvancesOpen Access

Enhancing Prediction of Cancer Therapy-Related Cardiomyopathy From Surveillance Echocardiograms

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Key result

Early echocardiographic abnormalities predict ~30% greater cardiomyopathy risk in childhood cancer survivors.

OR 1.3
95% CI 1.1-1.6

Figures

Graphical abstract published by JACC Advances — Graphical abstract · Published by JACC Advances · CC BY-NC-ND

Why the study?

Early echocardiographic indicators of cardiac remodeling may enhance cardiomyopathy risk prediction in childhood cancer survivors, but whether influential measures could be combined into a robust risk prediction model was unknown.

Can early abnormalities in multiple echocardiographic parameters accurately predict the development of cardiomyopathy within 2 years in childhood cancer survivors?

Key Points

To assess whether influential echocardiographic markers can be combined to build a robust 2-year cardiomyopathy risk prediction model in childhood cancer survivors.
Multicenter retrospective study evaluating 281 digitally archived surveillance echocardiograms across 146 childhood cancer survivors (52 cardiomyopathy cases and 94 noncases).
Echocardiograms were centrally quantitated in a blinded fashion across 27 parameters.
Least absolute shrinkage and selection operator (LASSO) and logistic regression were used to identify 2-year predictors and generate area under the receiver operating characteristic curves (AUC) across training and test data sets.
In the basic logistic regression model, 2-year cardiomyopathy was significantly predicted by LV end-systolic dimension (OR: 1.2; 95% CI: 1.1-1.4), septal A' velocity (OR: 1.3; 95% CI: 1.1-1.6), and apical 4-chamber longitudinal strain (OR: 1.2; 95% CI: 1.0-1.3).
Anthracycline dose was also predictive of cardiomyopathy (OR: 1.2 per 100 mg/m2; 95% CI: 1.0-1.5).
LASSO models achieved an AUC of 0.80 (95% CI: 0.71-0.89) to 0.83 (95% CI: 0.76-0.89) in the training set and 0.76 (95% CI: 0.58-0.92) to 0.85 (95% CI: 0.74-0.95) in the test set, with similar discrimination when cancer treatment exposures were included.

Study Design

Type

Case-Control

Blinding

Blinded

Multicenter

Yes

Structured PICO

Can early abnormalities in multiple echocardiographic parameters accurately predict the development of cardiomyopathy within 2 years in childhood cancer survivors?

P

Population

146 childhood cancer survivors (≥1-year post-therapy), median age at cancer diagnosis 6.5 years, 41.8% female, across the United States and Canada. The cohort includes 52 cardiomyopathy cases (left ventricular fractional shortening ≤28% or ejection fraction ≤50% on ≥2 occasions or leading to medication initiation) and 94 noncases (survived ≥5 years, maintaining fractional shortening ≥30% and ejection fraction ≥55%).

I

Intervention

Echocardiographic parameter assessment (using LASSO regression to select from 27 parameters, including LV end-systolic dimension, septal A' velocity, and apical 4-chamber longitudinal strain) to predict the development of cardiomyopathy.

C

Comparator

None (prediction model evaluating patients who developed cardiomyopathy versus those who did not).

O

Outcome

Development of cardiomyopathy (defined as LVFS ≤28% or LVEF ≤50% on ≥2 occasions or requiring initiation of medical therapy) within the subsequent 2 years, assessed by area under the receiver operating characteristic curve (AUC).surrogate

Main Result

Effect estimate: OR 1.3 (95% CI 1.1-1.6)

Limitations

Reliance on older archived echocardiograms with variable image quality
Unmeasurable parameters of interest in many studies, such as LVEF (due to inadequate windows in pediatric patients)
Use of single-plane apical 4-chamber longitudinal strain (A4LS) as a surrogate due to inability to measure global longitudinal strain (GLS) in 90% of echocardiograms

Implication

Early multi-parameter echocardiographic abnormalities (such as LV end-systolic dimension, septal tissue velocities, and longitudinal strain) successfully identify childhood cancer survivors at high risk for cardiomyopathy up to 2 years before standard LVEF or LVFS decline.

Abstract

BACKGROUND: Early echocardiographic indicators of cardiac remodeling may enhance cardiomyopathy risk prediction in childhood cancer survivors (CCS). OBJECTIVES: The objective of the study was to assess whether influential echocardiographic measures can be combined to develop a robust cardiomyopathy risk prediction model in CCS. METHODS: Multicenter retrospective study of ≥1-year CCS with digitally archived surveillance echocardiograms, enrolled cardiomyopathy cases (left ventricular [LV] fractional shortening ≤28% or LV ejection fraction ≤50% on ≥2 occasions) and noncases (≥5-year CCS who maintained fractional shortening ≥ 30% and ejection fraction ≥55% without initiation of cardiac medications). Echocardiograms were centrally quantitated in a blinded fashion. Least absolute shrinkage and selection operator regression identified the most influential 2-year predictors of cardiomyopathy among 27 echocardiographic parameters. Logistic regression was used to generate ORs with 95% CIs. Estimates were applied to the training and test data sets to generate area under the receiver operating characteristic curves (AUC). RESULTS: : 1.3; 95% CI: 1.1-1.6) were strongly predictive of cardiomyopathy. AUCs were similar if cancer treatment exposures were included. CONCLUSIONS: Early abnormalities in echocardiographic parameters of structure and function predict subsequent cardiomyopathy in CCS and can identify high-risk survivors who warrant early intervention.

Discussion

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Cite This Study

Leger et al. (2025) conducted a case-control in Cancer Therapy-Related Cardiomyopathy. Echocardiographic parameters was evaluated on Cardiomyopathy (OR 1.3, 95% CI 1.1-1.6). Early abnormalities in echocardiographic parameters of structure and function strongly predicted subsequent cardiomyopathy in childhood cancer survivors (OR 1.3; 95% CI 1.1-1.6).

synapsesocial.com/papers/6a163d1e7720a05aca78dc51 https://doi.org/10.1016/j.jacadv.2025.102363

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Enhancing Prediction of Cancer Therapy-Related Cardiomyopathy From Surveillance Echocardiograms

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Enhancing Prediction of Cancer Therapy-Related Cardiomyopathy From Surveillance Echocardiograms

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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