title: Does diastolic dysfunction precede systolic dysfunction in trastuzumab-induced cardiotoxicity? Assessment with multigated radionuclide angiography (MUGA).
abstract: 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).
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboudumc, Nijmegen, The Netherlands.
authors.forename: E J
authors.initials: EJ
authors.lastname: Reuvekamp
authors.affiliation: Biomedical Photonic Imaging Group, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands. b.f.bulten@utwente.nl.
authors.forename: B F
authors.initials: BF
authors.lastname: Bulten
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboudumc, Nijmegen, The Netherlands.
authors.forename: A A
authors.initials: AA
authors.lastname: Nieuwenhuis
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboudumc, Nijmegen, The Netherlands.
authors.forename: M R A
authors.initials: MR
authors.lastname: Meekes
authors.affiliation: Department for Health Evidence, Radboudumc, Nijmegen, The Netherlands.
authors.forename: A F J
authors.initials: AF
authors.lastname: de Haan
authors.affiliation: Department of Medical Oncology, Radboudumc, Nijmegen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Tol
authors.affiliation: Department of Cardiology, Radboudumc, Nijmegen, The Netherlands.
authors.forename: A H E M
authors.initials: AH
authors.lastname: Maas
authors.affiliation: Department of Cardiology, Radboudumc, Nijmegen, The Netherlands.
authors.forename: S E
authors.initials: SE
authors.lastname: Elias-Smale
authors.affiliation: Biomedical Photonic Imaging Group, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands.|Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: L F
authors.initials: LF
authors.lastname: de Geus-Oei
mesh_terms: D000074322:Antineoplastic Agents, Immunological / Q000009:adverse effects; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy*; D054715:Cardiotoxins / Q000009:adverse effects / Q000627:therapeutic use; D017023:Coronary Angiography / Q000379:methods*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011875:Radionuclide Angiography / Q000379:methods*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013318:Stroke Volume / Q000187:drug effects*; D000068878:Trastuzumab / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000000981:diagnostic imaging*
chemical_list: D000074322:Antineoplastic Agents, Immunological; D054715:Cardiotoxins; D000068878:Trastuzumab
keywords: Breast cancer; cardiotoxicity; diastolic function; monoclonal antibodies; radionuclide imaging