The utility of cardiac biomarkers and echocardiography for the early detection of bevacizumab- and sunitinib-mediated cardiotoxicity

Kimberly Ann Bordun, Sheena Premecz, Megan daSilva, Soma Mandal, Vineet Goyal, Tamara Glavinovic, Matthew Cheung, David Cheung, Christopher W. White, Rakesh Chaudhary, Darren H. Freed, Hector R. Villarraga, Joerg Herrmann, Manish Kohli, Amir Ravandi, James Thliveris, Marshall Pitz, Pawan K. Singal, Sharon Mulvagh, Davinder S. Jassal

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The recent introduction of novel anticancer therapies, including bevacizumab (BVZ) and sunitinib (SNT), is associated with an increased risk of cardiotoxicity. However, early identification of left ventricular (LV) systolic dysfunction may facilitate dose modification and avoid the development of advanced heart failure. Using a murine model of BVZ- and SNTmediated cardiotoxicity, we investigated whether cardiac biomarkers and/or tissue velocity imaging (TVI) using echocardiography can detect early changes in cardiac function, before a decrease in LV ejection fraction is identified. A total of 75 wild-type C57Bl/6 male mice were treated with either 0.9% saline, BVZ, or SNT. Serial monitoring of blood pressure, high-sensitivity troponin I, and echocardiographic indexes were performed over a 14-day study period, after which the mice were euthanized for histological and biochemical analyses. Mice treated with either BVZ or SNT developed systemic hypertension as early as day 7, which increased by day 14. Cardiac biomarkers, specifically high-sensitivity troponin I, were not predictive of early LV systolic dysfunction. Although conventional LV ejection fraction values decreased at day 13 in mice treated with either BVZ or SNT, TVI confirmed early LV systolic dysfunction at day 8. Histological and biochemical analysis demonstrated loss of cellular integrity, increased oxidative stress, and increased cardiac apoptosis in mice treated with BVZ or SNT therapy at day 14. In a murine model of BVZ- or SNT-mediated cardiomyopathy, noninvasive assessment by TVI detected early LV systolic dysfunction before alterations in conventional echocardiographic indexes.

Original languageEnglish (US)
Pages (from-to)H692-H701
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume309
Issue number4
DOIs
StatePublished - Aug 18 2015

Keywords

  • Apoptosis
  • Bevacizumab
  • Cardiac biomarkers
  • Cardio-oncology
  • Cardiotoxicity
  • Echocardiography
  • Heart failure
  • Hypertension
  • Sunitinib

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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