Atlas-based measures of left ventricular shape may improve characterization of adverse remodeling in anthracycline-exposed childhood cancer survivors: a cross-sectional imaging study.

Background: Adverse cardiac remodeling is an important precursor to anthracycline-related cardiac dysfunction, however conventional remodeling indices are limited. We sought to examine the utility of statistical atlas-derived measures of ventricular shape to improve the identification of adverse anthracycline-related remodeling in childhood cancer survivors.
Methods: We analyzed cardiac magnetic resonance imaging from a cross-sectional cohort of 20 childhood cancer survivors who were treated with low (< 250 mg/m ² [ N  = 10]) or high (≥250 mg/m ² [ N  = 10]) dose anthracyclines, matched 1:1 by sex and age between dose groups. We reconstructed 3D computational models of left ventricular end-diastolic shape for each subject and assessed the ability of conventional remodeling indices (volume, mass, and mass to volume ratio) vs. shape modes derived from a statistical shape atlas of an asymptomatic reference population to stratify anthracycline-related remodeling. We compared conventional parameters and five atlas-based shape modes: 1) between survivors and the reference population ( N  = 1991) using multivariable linear regression, and 2) within survivors by anthracycline dose (low versus high) using two-sided T-tests, multivariable logistic regression, and receiver operating characteristic curves.
Results: Compared with the reference population, survivors had differences in conventional measures (lower volume and mass) and shape modes (corresponding to lower overall size and lower sphericity; all p  < 0.001). Among survivors, differences in a shape mode corresponding to increased basal cavity size and altered mitral annular orientation in the high-dose group were observed ( p  = 0.039). Collectively, atlas-based shape modes in conjunction with conventional measures discriminated survivors who received low vs. high anthracycline dosage (area under the curve [AUC] 0.930, 95% confidence interval 0.816, 1.00) significantly better than conventional measures alone (AUC 0.710, 95% confidence interval 0.473, 0.947; AUC comparison p  = 0.0498).
Conclusions: Compared with a reference population, heart size is smaller in anthracycline-exposed childhood cancer survivors. Atlas-based measures of left ventricular shape may improve the detection of anthracycline dose-related remodeling differences.
Competing Interests: Competing interestsA.D.M. and J.H.O. are co-founders of and have an equity interest in Insilicomed, and A.D.M. has an equity interest in Vektor Medical. A.D.M. and J.H.O. serve on the scientific advisory board of Insilicomed, and A.D.M. as scientific advisor to both companies. Some of their research grants have been identified for conflict of interest management based on the overall scope of the project and its potential benefit to these companies. The authors are required to disclose this relationship in publications acknowledging the grant support; however, the research subjects and findings reported in this study did not involve the companies in any way and have no specific relationship with the business activities or scientific interests of either company. The terms of this arrangement have been reviewed and approved by the University of California San Diego in accordance with its conflict of interest policies. HKN, RX, NF, SG, DI, LL, EA, SH, AT, BK, SA: These authors declare they have no competing interests.
(© The Author(s) 2020.)