Longitudinal changes of right ventricular deformation mechanics during trastuzumab therapy in breast cancer patients

Eur J Heart Fail. 2019 Apr;21(4):529-535. doi: 10.1002/ejhf.1385. Epub 2019 Feb 27.

Abstract

Background: Trastuzumab improves dramatically the prognosis of HER2-positive breast cancer patients, but it may lead to cardiotoxicity with left ventricular (LV) systolic dysfunction. Its effects on right ventricular (RV) function have not however been elucidated. We sought to assess LV and RV deformation mechanics during treatment with trastuzumab in breast cancer patients.

Methods and results: We studied 101 consecutive women (mean age 54.3 ± 11.4 years) receiving trastuzumab for 12 months; 62 of them (61.4%) had previously received anthracyclines and 26 (25.7%) were receiving taxanes concurrently with trastuzumab. Comprehensive two-dimensional echocardiography with speckle tracking imaging of LV and RV global longitudinal strain (GLS) and RV free wall longitudinal strain (FWLS) analyses were performed at baseline and every 3 months up to treatment completion. Cardiotoxicity was defined as a decrease of baseline LV ejection fraction > 10 percentage units to a value < 50%. At 3 months, only LV GLS was significantly reduced (-19.5 ± 2.7 to -18.7 ± 2.8, P = 0.0410), while at 6 months, LV GLS, RV GLS and RV FWLS had significantly declined reaching their lowest values (-17.9 ± 6.1, P = 0.002, -19.6 ± 5.2, P = 0.003 and -19.7 ± 5.6, P = 0.004, respectively). Ten women (9.9%) developed cardiotoxicity. A RV GLS percent change of -14.8% predicted cardiotoxicity with 66.7% sensitivity and 70.8% specificity (area under the curve 0.68, 95% confidence interval 0.54-0.81), classifying correctly 90% of women with cardiotoxicity. This cut-off is quite similar to the 15% change of LV GLS previously suggested as predictive of cardiotoxicity.

Conclusions: Deformation mechanics of both the left and right ventricle follow similar temporal pattern and degree of impairment during trastuzumab therapy, confirming the global and uniform effect of trastuzumab on myocardial function.

Keywords: Cardio-oncology; Cardiotoxicity; Myocardial deformation; Myocardial strain; Right ventricle; Speckle tracking; Trastuzumab.

MeSH terms

  • Adult
  • Anthracyclines
  • Antineoplastic Agents, Immunological / adverse effects*
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use
  • Biomechanical Phenomena
  • Breast Neoplasms / drug therapy*
  • Cardiotoxicity / diagnostic imaging
  • Cardiotoxicity / etiology
  • Cardiotoxicity / physiopathology*
  • Echocardiography
  • Female
  • Heart Failure / chemically induced
  • Heart Failure / diagnostic imaging
  • Heart Failure / physiopathology*
  • Heart Ventricles / diagnostic imaging
  • Heart Ventricles / drug effects
  • Heart Ventricles / physiopathology
  • Humans
  • Middle Aged
  • Retrospective Studies
  • Taxoids
  • Trastuzumab / adverse effects*
  • Trastuzumab / pharmacology
  • Trastuzumab / therapeutic use
  • Ventricular Dysfunction, Left
  • Ventricular Dysfunction, Right / chemically induced
  • Ventricular Dysfunction, Right / diagnostic imaging
  • Ventricular Dysfunction, Right / physiopathology
  • Ventricular Function, Left
  • Ventricular Function, Right / drug effects

Substances

  • Anthracyclines
  • Antineoplastic Agents, Immunological
  • Taxoids
  • Trastuzumab