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Original research
Variability in echocardiography and MRI for detection of cancer therapy cardiotoxicity
  1. James Lambert1,
  2. Mariana Lamacie1,
  3. Babitha Thampinathan1,
  4. Mustafa A Altaha1,
  5. Maryam Esmaeilzadeh1,
  6. Mark Nolan1,
  7. Camila Urzua Fresno1,
  8. Emily Somerset2,
  9. Eitan Amir3,
  10. Thomas H Marwick4,
  11. Bernd J Wintersperger5,
  12. Paaladinesh Thavendiranathan1,5
  1. 1 Ted Rogers Program in Cardiotoxicity Prevention, Peter Munk Cardiac Center, Division of Cardiology, University Health Network, University of Toronto, Toronto, Ontario, Canada
  2. 2 Rogers Computational Program, Peter Munk Cardiac Center, Cardiology, University Health Network, University of Toronto, Toronto, Ontario, Canada
  3. 3 Division of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
  4. 4 Baker Heart Research Institute – BHRI, Melbourne, Victoria, Australia
  5. 5 Department of Medical Imaging, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Dr Paaladinesh Thavendiranathan, Division of Cardiology, Peter Munk Cardiac Center, University Health Network, Toronto, ON M5G 2C4, Canada; dinesh.thavendiranathan{at}


Objectives To compare variability of echocardiographic and cardiovascular magnetic resonance (CMR) measured left ventricular (LV) function parameters and their relationship to cancer therapeutics-related cardiac dysfunction (CTRCD).

Methods We prospectively recruited 60 participants (age: 49.8±11.6 years), 30 women with human epidermal growth factor receptor 2-positive breast cancer (15 with CTRCD and 15 without CTRCD) and 30 healthy volunteers. Patients were treated with anthracyclines and trastuzumab. Participants underwent three serial CMR (1.5T) and echocardiography studies at ~3-month intervals. Cine-CMR for LV ejection fraction (LVEF), myocardial tagging for global longitudinal strain (GLS) and global circumferential strain (GCS), two-dimensional (2D) echocardiography for strain and LVEF and three-dimensional (3D) echocardiography for LVEF measurements were obtained. Temporal, interobserver and intraobserver variability were calculated as the coefficient of variation and as the SE of the measurement (SEM). Minimal detected difference (MDD) was defined as 2xSEM.

Results Patients with CTRCD demonstrated larger mean temporal changes in all parameters compared with those without: 2D-LVEF: 4.6% versus 2.8%; 3D-LVEF: 5.2% vs 2.3%; CMR-LVEF: 6.6% versus 2.7%; 2D-GLS: 1.9% versus 0.7%, 2D-GCS: 2.5% versus 2.2%; CMR-GCS: 2.7% versus 1.6%; and CMR-GLS: 2.1% versus 1.4%, with overlap in 95% CI for 2D-LVEF, 2D-GCS, CMR-GLS and CMR-GCS. The respective mean temporal variability/MDD in healthy volunteers were 3.3%/6.5%, 1.8%/3.7%, 2.2%/4.4%, 0.8%/1.5%, 1.9%/3.7%, 1.8%/3.6% and 1.4%/2.8%. Although the mean temporal variability in healthy volunteers was lower than the mean temporal changes in CTRCD, at the individual level, 2D-GLS, 3D-LVEF and CMR-LVEF had the least overlap. 2D-GLS and CMR-LVEF had the lowest interobserver/intraobserver variabilities.

Conclusion Temporal changes in 3D-LVEF, 2D-GLS and CMR LVEF in patients with CTRCD had the least overlap with the variability in healthy volunteers; however, 2D-GLS appears to be the most suitable for clinical application in individual patients.

  • cardiac imaging and diagnostics
  • echocardiography
  • cardiac magnetic resonance (CMR) imaging

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  • Contributors All authors meet ICMJE recommendation criteria for authorship in this manuscript. JL and ML: data analysis, interpretation, drafting of manuscript and final approval. BT, MAA, ME, MN, CU and EA: data analysis, interpretation and final approval. ES: statistical analysis, interpretation, manuscript drafting, critical revisions and final approval. THM: data interpretation, drafting manuscript and final approval. BJW: study design, data interpretation, drafting manuscript and final approval. PT: conception of work, acquisition of data, analysis and interpretation, drafting manuscript and revising it critically and final approval.

  • Funding This study was funded by an operating grant from the Canadian Institutes of Health Research (137132 and 142456). Dr Thavendiranathan (147814) is supported by the Canadian Institutes of Health Research New Investigator Award.

  • Disclaimer PT has received speaker’s honorarium from Amgen, Takeda and Boehringer Ingelheim. BJW has received research support and speaker’s honorarium from Siemens Healthineers. THM receives research support from GE Healthcare for a trial of strain in the assessment of cardiotoxicity. EM has received fees for expert testimony for Roche/Genentech.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.

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