Author + information
- Received August 26, 2019
- Revision received October 8, 2019
- Accepted October 24, 2019
- Published online December 21, 2019.
- Mustafa A. Altaha, MBBS, MSca,
- Mark Nolan, MBBSa,
- Thomas H. Marwick, MD, PhD, MPHb,
- Emily Somerset, MScc,
- Christian Houbois, MDd,
- Eitan Amir, MD, PhDe,
- Paul Yip, PhDf,
- Kim A. Connelly, MD, PhDg,
- Maria Michalowska, BSca,
- Marshall S. Sussman, PhDd,
- Bernd J. Wintersperger, MDd and
- Paaladinesh Thavendiranathan, MD, MSca,d,∗ ()
- aDivision of Cardiology, Peter Munk Cardiac Centre, Ted Rogers Program in Cardiotoxicity Prevention and Department of Medical Imaging, University Health Network, Toronto, Ontario, Canada
- bBaker Heart & Diabetes Institute, Melbourne, Australia
- cRogers Computational Program, Ted Rogers Centre for Heart Research, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada
- dDepartment of Medical Imaging, University Health Network, University of Toronto, Toronto, Ontario, Canada
- eDivision of Medical Oncology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Ontario, Canada
- fDivision Laboratory Medicine and Pathobiology, University Health Network, University of Toronto, Toronto, Ontario, Canada
- gKeenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada
- ↵∗Address for correspondence:
Dr. Paaladinesh Thavendiranathan, Division of Cardiology, Peter Munk Cardiac Center, Ted Rogers Program in Cardiotoxicity Prevention, Toronto General Hospital, 4N-490, 200 Elizabeth Street Toronto, Ontario M5G 2C4, Canada.
Objectives The purpose of this study was to investigate the effect of the temporal and observer variability of cardiac magnetic resonance (CMR)–measured native T1, T2, and extracellular volume fraction (ECV) and serum biomarkers for the detection of cancer-therapeutics-related cardiac dysfunction (CTRCD).
Background Biomarkers and serial quantitative CMR tissue characterization may help identify early myocardial changes of CTRCD, but these parameters require both accuracy and reliability.
Methods A total of 50 participants (age 48.9 ± 12.1 years) underwent 3 CMR studies (1.5-T) and biomarker measurements (high-sensitivity troponin-I and B-type natriuretic peptide) at 3-month intervals: 20 with HER2-positive breast cancer (10 with and 10 without CTRCD), and 30 prospectively recruited healthy participants. T1 and T2 maps were obtained at 3 left ventricular short-axis locations. Temporal and observer variability were calculated as the coefficient of variation and as the standard error of the measurement (SEM) using repeated measures and 2-way analysis of variance. Minimal detected difference was defined as 2 × SEM.
Results Compared with the patients without CTRCD, those with CTRCD had larger temporal change in native T1 (27.2 ms [95% confidence interval (CI): 20.8 to 39.3 ms] vs. 12.4 ms [95% CI: 9.5 to 17.9 ms]), T2 (2.0 ms [95% CI: 1.5 to 2.9 ms] vs. 1.0 ms [95% CI: 0.74 to 1.4 ms]), and ECV (2.1% [95% CI: 1.5% to 3.1%] vs. 1.0% [95% CI: 0.8% to 1.5%]). However, the temporal changes in biomarkers overlapped. The minimal detected difference for T1 (29 ms), T2 (3.0 ms), and ECV (2.2%) in healthy participants approached the mean temporal changes in patients with CTRCD. For individual patients with CTRCD, there was overlap in the temporal changes of all 3 parameters, and the variability in healthy participants with the least overlap for native T1. The interobserver/intraobserver variabilities for the CMR parameters were low (coefficient of variation 0.5% to 4.3%).
Conclusions The temporal changes in both biomarkers and tissue characterization measures in individual patients overlap with the temporal variability in healthy participants and approach the minimal detectable temporal differences. While the accuracy of the parameters awaits further study, the temporal variability of these methods may pose challenges to routine clinical application in individual patients receiving cancer therapy.
- cancer therapeutics related cardiac dysfunction
- extracellular volume fraction
- observer variability
- T1 mapping
- T2 mapping
- temporal variability
This study was funded by an operating grant from the Canadian Institutes of Health Research (137132 and 142456). Dr. Marwick has received research grant support for the SUCCOUR study from GE Medical Systems. Dr. Amir has provided expert testimony for Genentech/Roche; and has served as a consultant for Sandoz, Apobiologix, Myriad Genetics, Agendia, and AstraZeneca. Dr. Yip has served as a consultant for and received research and travel honorarium from Abbott Diagnostics. Drs. Connelly and Thavendiranathan (147814) are supported by the Canadian Institutes of Health Research New Investigator Award. Drs. Sussman and Wintersperger are inventors of the patient method of T1 mapping with incomplete tissue magnetization recovery (US 10314548B2; not used in this study). Dr. Wintersperger has received research support and speakers honorarium from Siemens Healthineers. University Health Network has a Master Research Agreement with Siemens Healthineers. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Jagat Narula, MD, served as Guest Editor for this paper.
- Received August 26, 2019.
- Revision received October 8, 2019.
- Accepted October 24, 2019.
- 2019 American College of Cardiology Foundation
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