Mustafa A Altaha1, Mark Nolan1, Thomas H Marwick2, Emily Somerset3, Christian Houbois4, Eitan Amir5, Paul Yip6, Kim A Connelly7, Maria Michalowska1, Marshall S Sussman4, Bernd J Wintersperger4, Paaladinesh Thavendiranathan8. 1. Division of Cardiology, Peter Munk Cardiac Centre, Ted Rogers Program in Cardiotoxicity Prevention and Department of Medical Imaging, University Health Network, Toronto, Ontario, Canada. 2. Baker Heart & Diabetes Institute, Melbourne, Australia. 3. Rogers Computational Program, Ted Rogers Centre for Heart Research, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada. 4. Department of Medical Imaging, University Health Network, University of Toronto, Toronto, Ontario, Canada. 5. Division of Medical Oncology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Ontario, Canada. 6. Division Laboratory Medicine and Pathobiology, University Health Network, University of Toronto, Toronto, Ontario, Canada. 7. Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada. 8. Division of Cardiology, Peter Munk Cardiac Centre, Ted Rogers Program in Cardiotoxicity Prevention and Department of Medical Imaging, University Health Network, Toronto, Ontario, Canada; Department of Medical Imaging, University Health Network, University of Toronto, Toronto, Ontario, Canada. Electronic address: dinesh.thavendiranathan@uhn.ca.
Abstract
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.
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.
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