Precision Medicine and Imaging Accuracy of a Novel Handheld Wireless Platform for Detection of Cardiac Dysfunction in Anthracycline-Exposed Survivors of Childhood Cancer Saro H. Armenian 1 , Derek Rinderknecht 2 , Kaylene Au 1 , Lanie Lindenfeld 1 , George Mills 1 , Aida Siyahian 1 , Claudia Herrera 1 , Karla Wilson 1 , Kalyanasundaram Venkataraman 3 , Kristen Mascarenhas 1 , Peyman Tavallali 4 , Marianne Razavi 2 , Niema Pahlevan 4,5 , Jon Detterich 6 , Smita Bhatia 7 , and Morteza Gharib 2 Abstract Purpose: Childhood cancer survivors are at risk for anthracycline-related cardiac dysfunction, often developing at a time when they are least engaged in long-term survivorship care. New paradigms in survivorship care and chronic disease screening are needed in this population. We compared the accuracy of a novel handheld mHealth platform (Vivio) as well as echocardi- ography for assessment of cardiac function [left ventricular ejec- tion fraction (EF)] in childhood cancer survivors with cardiac magnetic resonance (CMR) imaging (reference). Experimental Design: Cross-sectional study design was used. Concurrent evaluation of EF was performed using Vivio, two- dimensional (2D) echocardiography, and CMR. Differences in mean EF (2D echocardiography vs. CMR; Vivio vs. CMR) were compared using Bland–Altman plots. Linear regression was used to evaluate proportional bias. Results: A total of 191 consecutive survivors participated [50.7% female; median time from diagnosis: 15.8 years (2–44); median anthracycline dose: 225 mg/m 2 (25–642)]. Echocardiography overestimated mean EF by 4.9% (P < 0.001); linear regression analysis confirmed a proportional bias, when compared with CMR (t ¼ 3.1, P < 0.001). There was no difference between mean EF derived from Vivio and from CMR (–0.2%, P ¼ 0.68). The detection of cardiac dysfunction via echocardiography was poor when compared with CMR [Echo EF < 45% (sensitivity 14.3%), Echo EF < 50% (sensitivity 28.6%)]. Sensitivity was substantially better for Vivio-based measurements [EF < 45% or EF < 50% (sensitivity 85.7%)]. Conclusions: This accessible technology has the potential to change the day-to-day practice of clinicians caring for the large number of patients diagnosed with cardiac dysfunction and heart failure each year, allowing real-time monitoring and management of their disease without the lag-time between imaging and inter- pretation of results. Clin Cancer Res; 24(13); 3119–25. Ó2018 AACR. Introduction Cardiovascular complications are a leading cause of morbidity and mortality in survivors of childhood cancer (1). These survi- vors have a greater than 4-fold risk of developing heart failure when compared with age-matched controls (1–3), and there is a strong dose-dependent association between anthracycline expo- sure and the risk of heart failure (1–3). Outcome following anthracycline-related heart failure is poor; 5-year overall survival is <50% (4, 5), emphasizing the importance of screening for early detection of cardiac dysfunction [abnormal left ventricular ejec- tion fraction (LV EF)] and initiation of pharmacologic therapy prior to the development of clinically overt heart failure. Current long-term follow-up guidelines (6, 7) recommend periodic screening of childhood cancer survivors using an echocardiogram because it is noninvasive and widely available. However, LV EF measured by echocardiography depends on the quality of the acoustic windows which may not be valid in patients with anthracycline-exposed remodeled ventricles (8). Cardiac magnet- ic resonance (CMR) imaging overcomes these limitations due to its lack of reliance on acoustic windows and the absence of geometric assumption bias (8). However, the applicability of CMR for routine screening is limited, because of significant cost and lack of wide availability. Both these modalities require the patient to be seen in a clinic setting, with the attendant costs and inconvenience due to time away from work/school. Thus, there is 1 Department of Population Sciences, City of Hope, Duarte, California. 2 Graduate Aerospace Laboratories, Division of Engineering and Applied Sciences, Califor- nia Institute of Technology, Pasadena, California. 3 Department of Cardiology, City of Hope, Duarte, California. 4 Department of Aerospace and Mechanical Engineering, University of Southern California, Los Angeles, California. 5 Advanced Imaging and Spectroscopy Center, Huntington Medical Research Institutes, Pasadena, California. 6 Division of Cardiology, Department of Pediat- rics, Children's Hospital of Los Angeles, Los Angeles, California. 7 Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, Alabama. Prior presentation: Presented, in part, at the International Conference on Long Term Complications of Treatment of Children and Adolescents for Cancer (2017). Corresponding Author: Saro H. Armenian, City of Hope, 1500 East Duarte Rd, Duarte, CA 91010. Phone: 626-471-7320; Fax: 626-471-9204; E-mail: sarmenian@coh.org doi: 10.1158/1078-0432.CCR-17-3599 Ó2018 American Association for Cancer Research. Clinical Cancer Research www.aacrjournals.org 3119 Downloaded from http://aacrjournals.org/clincancerres/article-pdf/24/13/3119/2045160/3119.pdf by guest on 19 June 2022