Does diastolic dysfunction precede systolic dysfunction in trastuzumab-induced cardiotoxicity? Assessment with multigated radionuclide angiography (MUGA)

J Nucl Cardiol. 2016 Aug;23(4):824-32. doi: 10.1007/s12350-015-0164-x. Epub 2015 Jun 6.

Abstract

Background: Trastuzumab is successfully used for the treatment of HER2-positive breast cancer. Because of its association with cardiotoxicity, LVEF is monitored by MUGA, though this is a relatively late measure of cardiac function. Diastolic dysfunction (DD) is believed to be an early predictor of cardiac impairment. We evaluate the merit of MUGA-derived diastolic function parameters in the early detection of trastuzumab-induced cardiotoxicity (TIC).

Methods and results: 77 trastuzumab-treated patients with normal baseline systolic and diastolic function were retrospectively selected (n = 77). All serial MUGA examinations were re-analyzed for systolic and diastolic function parameters. 36 patients (47%) developed SD and 45 patients (58%) DD during treatment. Both systolic and diastolic parameters significantly decreased. Of the patients with SD, 24 (67%) also developed DD. DD developed prior to systolic impairment in 54% of cases, in 42% vice versa, while time to occurrence did not differ significantly (P = .52). This also applied to the subgroup of advanced stage breast cancer patients (P = .1).

Conclusions: Trastzumab-induced SD and DD can be detected by MUGA. An impairment of MUGA-derived diastolic parameters does not occur prior to SD and therefore cannot be used as earlier predictors of TIC.

Keywords: Breast cancer; cardiotoxicity; diastolic function; monoclonal antibodies; radionuclide imaging.

MeSH terms

  • Antineoplastic Agents, Immunological / adverse effects
  • Breast Neoplasms / complications
  • Breast Neoplasms / drug therapy*
  • Cardiotoxins / adverse effects
  • Cardiotoxins / therapeutic use
  • Coronary Angiography / methods*
  • Female
  • Humans
  • Middle Aged
  • Radionuclide Angiography / methods*
  • Reproducibility of Results
  • Retrospective Studies
  • Sensitivity and Specificity
  • Stroke Volume / drug effects*
  • Trastuzumab / adverse effects*
  • Trastuzumab / therapeutic use
  • Treatment Outcome
  • Ventricular Dysfunction, Left / chemically induced*
  • Ventricular Dysfunction, Left / diagnostic imaging*

Substances

  • Antineoplastic Agents, Immunological
  • Cardiotoxins
  • Trastuzumab