title: Longitudinal assessment of right ventricular structure and function by cardiovascular magnetic resonance in breast cancer patients treated with trastuzumab: a prospective observational study.
abstract: BACKGROUND
  There are limited data on the effects of trastuzumab on the right ventricle (RV). Therefore, we sought to evaluate the temporal changes in right ventricular (RV) structure and function as measured by cardiovascular magnetic resonance (CMR), and their relationship with left ventricular (LV) structure and function in breast cancer patients treated with trastuzumab.
  
  
  METHODS
  Prospective, longitudinal, observational study involving 41 women with HER2+ breast cancer who underwent serial CMR at baseline, 6, 12, and 18 months after initiation of trastuzumab. A single blinded observer measured RV parameters on de-identified CMRs in a random order. Linear mixed models were used to investigate temporal changes in RV parameters.
  
  
  RESULTS
  Of the 41 women (age 52 ± 11 years), only one patient experienced trastuzumab-induced cardiotoxicity. Compared to baseline, there were small but significant increases in the RV end-diastolic volume at 6 months (p = 0.002) and RV end-systolic volume at 6 and 12 months (p < 0.001 for both), but not at 18 months (p = 0.82 and 0.13 respectively). RV ejection fraction (RVEF), when compared to baseline (58.3%, 95% CI 57.1-59.5%), showed corresponding decreases at 6 months (53.9%, 95% CI 52.5-55.4%, p < 0.001) and 12 months (55%, 95% CI 53.8-56.2%, p < 0.001) that recovered at 18 months (56.6%, 95% CI 55.1-58.0%, p = 0.08). Although the temporal pattern of changes in LVEF and RVEF were similar, there was no significant correlation between RVEF and LVEF at baseline (r = 0.29, p = 0.07) or between their changes at 6 months (r = 0.24, p = 0.17).
  
  
  CONCLUSIONS
  In patients receiving trastuzumab without overt cardiotoxicity, there is a subtle but significant deleterious effect on RV structure and function that recover at 18 months, which can be detected by CMR. Furthermore, monitoring of LVEF alone may not be sufficient in detecting early RV injury. These novel findings provide further support for CMR in monitoring early cardiotoxicity.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT01022086 . Date of registration: November 27, 2009.
authors.affiliation: Department of Medical Imaging, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Ashita
authors.initials: A
authors.lastname: Barthur
authors.affiliation: Division of Hematology/Oncology, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.|Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Brezden-Masley
authors.affiliation: Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.|Terrence Donnelly Heart Centre, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.|Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Connelly
authors.affiliation: Division of Hematology/Oncology, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Vinita
authors.initials: V
authors.lastname: Dhir
authors.affiliation: Sunnybrook Health Sciences Centre, University of Toronto, Cancer Care Ontario, Canadian Center for Applied Research in Cancer Control, Toronto, ON, Canada.
authors.forename: Kelvin K W
authors.initials: KK
authors.lastname: Chan
authors.affiliation: Division of Hematology/Oncology, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Rashida
authors.initials: R
authors.lastname: Haq
authors.affiliation: Department of Medical Imaging, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.|Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Anish
authors.initials: A
authors.lastname: Kirpalani
authors.affiliation: Department of Medical Imaging, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.|Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Barfett
authors.affiliation: Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Jimenez-Juan
authors.affiliation: Department of Medical Imaging, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Gauri R
authors.initials: GR
authors.lastname: Karur
authors.affiliation: Department of Medical Imaging, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada. devad@smh.ca.|Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada. devad@smh.ca.
authors.forename: Djeven P
authors.initials: DP
authors.lastname: Deva
authors.affiliation: Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada. yana@smh.ca.|Terrence Donnelly Heart Centre, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada. yana@smh.ca.|Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada. yana@smh.ca.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Yan
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000074322:Antineoplastic Agents, Immunological / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D066126:Cardiotoxicity; D042241:Early Diagnosis; D005260:Female; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D019028:Magnetic Resonance Imaging, Cine; D008875:Middle Aged; D009864:Ontario; D011237:Predictive Value of Tests; D011446:Prospective Studies; D020127:Recovery of Function; D016037:Single-Blind Method; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D000068878:Trastuzumab / Q000009:adverse effects*; D016896:Treatment Outcome; D018497:Ventricular Dysfunction, Right / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects; D016278:Ventricular Function, Right / Q000187:drug effects*
chemical_list: D000074322:Antineoplastic Agents, Immunological; D000068878:Trastuzumab
keywords: Cardiotoxicity; Cardiovascular magnetic resonance; Right ventricle; Trastuzumab