Noninvasive Measures of Ventricular-Arterial Coupling and Circumferential Strain Predict Cancer Therapeutics–Related Cardiac Dysfunction

Hari K. Narayan, Benjamin French, Abigail M. Khan, Theodore Plappert, David Hyman, Akinyemi Bajulaiye, Susan Domchek, Angela DeMichele, Amy Clark, Jennifer Matro, Angela Bradbury, Kevin Fox, Joseph R. Carver, Bonnie Ky

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Objectives This study sought to determine the relationships between echocardiography-derived measures of myocardial mechanics and cancer therapeutics–related cardiac dysfunction (CTRCD). Background Doxorubicin and trastuzumab are highly effective breast cancer therapies, but have a substantial risk of CTRCD. There is a critical need for the early detection of patients at increased risk of toxicity. Methods We performed a prospective, longitudinal cohort study of breast cancer participants undergoing doxorubicin and/or trastuzumab therapy. Echocardiography was performed prior to therapy initiation (baseline) and at standardized follow-up intervals during and after completion of therapy. Ejection fraction (EF), strain, strain rate, and ventricular-arterial coupling (effective arterial elastance [Ea]/end-systolic elastance [Eessb]) were quantitated. CTRCD was defined as a ≥10% reduction in EF from baseline to <50%. Multivariable logistic regression models were used to determine the associations between baseline levels and changes from baseline in echocardiographic measures and CTRCD. Receiver-operating characteristic curves were used to evaluate the predictive ability of these measures. Results In total, 135 participants contributed 517 echocardiograms to the analysis. Over a median follow-up time of 1.9 years (interquartile range: 0.9 to 2.4 years), 21 participants (15%) developed CTRCD. In adjusted models, baseline levels and changes in Ea/Eessb, circumferential strain, and circumferential strain rate were associated with 21% to 38% increased odds of CTRCD (p < 0.001). Changes in longitudinal strain (p = 0.037), radial strain (p = 0.015), and radial strain rate (p = 0.006) were also associated with CTRCD. Ea/Eessb (area under the curve: 0.703; 95% confidence interval: 0.583 to 0.807) and circumferential strain (area under the curve: 0.655; 95% confidence interval: 0.517 to 0.767) demonstrated the greatest predictive utility. Sensitivity analyses using an alternative CTRCD definition did not impact our results. Conclusions Over an extended follow-up time, ventricular-arterial coupling and circumferential strain were strongly predictive of CTRCD. Our findings suggest a noninvasive strategy to identify high-risk patients prior to, during, and after cardiotoxic cancer therapy.

Original languageEnglish (US)
Pages (from-to)1131-1141
Number of pages11
JournalJACC: Cardiovascular Imaging
Issue number10
StatePublished - Oct 1 2016
Externally publishedYes


  • cardio-oncology
  • cardiotoxicity
  • echocardiography
  • mechanics

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine


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