title: Assessment of left ventricular diastolic function during trastuzumab treatment in patients with HER2-positive breast cancer.
abstract: BACKGROUND
  The ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (e', E/e' ratio) as estimated by tissue Doppler imaging is a noninvasive surrogate for the left ventricular diastolic function. Because diastolic dysfunction usually precedes systolic dysfunction in cardiovascular diseases, we investigated whether monitoring the E/e' ratio can help to predict the risk of trastuzumab-induced cardiotoxicity.
  
  
  METHODS
  E/e' ratio on tissue Doppler imaging was retrospectively reviewed to assess its value for early detection of the left ventricular ejection fraction (LVEF) decline in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who received trastuzumab with or without cytotoxic chemotherapy. Echocardiography was performed at baseline and every 3 months after treatment began.
  
  
  RESULTS
  Among 129 patients, LVEF declined in 25 (19 %) during trastuzumab treatment; the decline was grade 2 in 23 patients and grade 3 in 2. Elevation of the E/e' ratio to more than 15 was detected in 17 patients (13 %), 7 of whom (5.4 % of total) concurrently had LVEF decline. A weak negative correlation was observed between E/e' elevation and the worst LVEF decline (P = 0.0077), which was confirmed by multiple regression analysis (P = 0.023). E/e' ratio at baseline or 3 months after beginning trastuzumab treatment was not significantly associated with the subsequent LVEF decline.
  
  
  CONCLUSIONS
  Monitoring of the left ventricular diastolic function on the basis of the E/e' ratio at baseline or 3 months after is unlikely to predict LVEF decline in patients who receive trastuzumab. However, there is a potential chronological relation between E/e' elevation and LVEF decline, implying that the degree of E/e' elevation could have a role as a surrogate marker for predicting the LVEF decline characteristic of trastuzumab-induced cardiotoxicity.
authors.affiliation: Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya, 466-8560, Japan. kh99081@med.nagoya-u.ac.jp.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Honda
authors.affiliation: Department of Clinical Laboratory, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Takeshita
authors.affiliation: Division of Biostatistics, Clinical Research Center, Aichi Medical University, Nagakute, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Murotani
authors.affiliation: Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya, 466-8560, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Mitsuma
authors.affiliation: Department of Breast and Endocrine Surgery, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Breast and Endocrine Surgery, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tsunoda
authors.affiliation: Department of Breast and Endocrine Surgery, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Toyone
authors.initials: T
authors.lastname: Kikumori
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.affiliation: Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya, 466-8560, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ando
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D066126:Cardiotoxicity / Q000209:etiology; D015150:Echocardiography, Doppler; D005260:Female; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D000068878:Trastuzumab / Q000009:adverse effects* / Q000627:therapeutic use; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Breast cancer; Cardiotoxicity; E/e′; Trastuzumab