Diagnostic and Prognostic Value of Myocardial Work Indices for Identification of Cancer Therapy-Related Cardiotoxicity.

Background: Echocardiographic global longitudinal strain (GLS) is a useful measure for detection of cancer treatment-related cardiac dysfunction (CTRCD) but is influenced by blood pressure changes. This limitation may be overcome by assessment of myocardial work (MW), which incorporates blood pressure into the calculation.
Objectives: This work aims to determine whether myocardial work indices (MWIs) can help diagnose or prognosticate CTRCD.
Methods: In this prospective cohort study, 136 women undergoing anthracycline and trastuzumab treatment for HER2+ breast cancer, underwent serial echocardiograms and cardiac magnetic resonance pre- and post-anthracycline and every 3 months during trastuzumab. GLS, global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency were measured. CTRCD was defined with cardiac magnetic resonance. Generalized estimating equations quantified the association between changes in GLS and MWIs and CTRCD at the current (diagnosis) and subsequent visit (prognosis). Regression tree analysis was used to explore the combined use of GLS and MW for the diagnostic/prognostic assessment of CTRCD.
Results: Baseline left ventricular ejection fraction (LVEF) was 63.2 ± 4.0%. Thirty-seven (27.2%) patients developed CTRCD. An absolute change in GLS (standardized odds ratio [sOR]: 1.97 [95% CI: 1.07-3.66]; P = 0.031) and GWI (sOR: 1.73 [95% CI: 1.04-2.85]; P = 0.033) were associated with concurrent CTRCD. An absolute change in GLS (sOR: 1.79 [95% CI: 1.22-2.62]; P = 0.003), GWI (sOR: 1.67 [95% CI: 1.20-2.32]; P = 0.003), and GCW (sOR: 1.65 [95% CI: 1.17-2.34]; P = 0.005) were associated with subsequent CTRCD. Change in GWI and GCW demonstrated incremental value over GLS and clinical factors for the diagnosis of concurrent CTRCD. In a small group with a GLS change <3.3% (absolute), and a >21 mm Hg reduction in systolic blood pressure, worsening of GWI identified patients with higher probability of concurrent CTRCD (24.0% vs 5.2%). MWIs did not improve identification of subsequent CTRCD beyond knowledge of GLS change.
Conclusions: GLS can be used to diagnose and prognosticate cardiac magnetic resonance (CMR) defined CTRCD, with additional value from MWIs in selected cases. (Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538).
Competing Interests: Funding Support and Author Disclosures This study was funded by an operating grant from the Canadian Institutes of Health Research (137132 and 142456) and the Ontario Early Research Award to Dr Thavendiranathan. University Health Network has a Master Research Agreement with Siemens Healthineers. Dr Amir has received fees for expert testimony from Genentech/Roche; and has received honoraria from Amgen. Dr Abdel-Qadir has received support from a National New Investigator Award from the Heart and Stroke Foundation of Canada. Dr Marwick has been supported in part by a Project Grant (1119955) from the National Health and Medical Research Council, Canberra, Australia; and has received an unrestricted grant from General Electric Healthcare, Horten, Norway, for the support of the SUCCOUR trial. Dr Thavendiranathan (147814) has been supported by the Canadian Institutes of Health Research New Investigator Award and a Canada Research Chair in Cardio-oncology; and has received speaker honorarium from Amgen, Boehringer Ingelheim, and Takeda. Dr Wintersperger has received research support and speaker honorarium from Siemens Healthineers; and provides consultation to Bayer AG.
(Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)