title: Body Surface Area and Baseline Blood Pressure Predict Subclinical Anthracycline Cardiotoxicity in Women Treated for Early Breast Cancer.
abstract: OBJECTIVE
  Anthracyclines are highly effective chemotherapeutic agents which may cause long-term cardiac damage (chronic anthracycline cardiotoxicity) and heart failure. The pathogenesis of anthracycline cardiotoxicity remains incompletely understood and individual susceptibility difficult to predict. We sought clinical features which might contribute to improved risk assessment.
  
  
  METHODS
  Subjects were women with early breast cancer, free of pre-existing cardiac disease. Left ventricular ejection fraction was measured using cardiovascular magnetic resonance before and >12 months after anthracycline-based chemotherapy (>3 months post-Trastuzumab). Variables associated with subclinical cardiotoxicity (defined as a fall in left ventricular ejection fraction of ≥5%) were identified by logistic regression.
  
  
  RESULTS
  One hundred and sixty-five women (mean age 48.3 years at enrollment) completed the study 21.7 months [IQR 18.0-26.8] after starting chemotherapy. All received anthracyclines (98.8% epirubicin, cumulative dose 400 [300-450] mg/m2); 18% Trastuzumab. Baseline blood pressure was elevated (≥140/90mmHg, mean 147.3/86.1mmHg) in 18 subjects. Thirty-four subjects (20.7%) were identified with subclinical cardiotoxicity, independent predictors of which were the number of anthracycline cycles (odds ratio, OR 1.64 [1.17-2.30] per cycle), blood pressure ≥140/90mmHg (OR 5.36 [1.73-17.61]), body surface area (OR 2.08 [1.36-3.20] per standard deviation (0.16m2) increase), and Trastuzumab therapy (OR 3.35 [1.18-9.51]). The resultant predictive-model had an area under the receiver operating characteristics curve of 0.78 [0.70-0.86].
  
  
  CONCLUSIONS
  We found subclinical cardiotoxicity to be common even within this low risk cohort. Risk of cardiotoxicity was associated with modestly elevated baseline blood pressure-indicating that close attention should be paid to blood pressure in patients considered for anthracycline based chemotherapy. The association with higher body surface area suggests that indexing of anthracycline doses to surface area may not be appropriate for all, and points to the need for additional research in this area.
authors.affiliation: Department of Cardiology, North and East Hertfordshire NHS Trust, Stevenage, United Kingdom.|Institute for Human Health and Performance, University College London, London, United Kingdom.|NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital and Imperial College, London, United Kingdom.
authors.forename: Paul
authors.identifier: http://orcid.org/0000-0002-3215-9695
authors.initials: P
authors.lastname: Kotwinski
authors.affiliation: NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital and Imperial College, London, United Kingdom.
authors.forename: Gillian
authors.initials: G
authors.lastname: Smith
authors.affiliation: Centre for Cardiovascular Genetics, University College London, London, United Kingdom.
authors.forename: Jackie
authors.initials: J
authors.lastname: Cooper
authors.affiliation: Institute for Human Health and Performance, University College London, London, United Kingdom.|Barts Heart Centre, St Bartholemew's Hospital, Barts Health NHS Trust, London, United Kingdom.
authors.forename: Julie
authors.initials: J
authors.lastname: Sanders
authors.affiliation: Institute for Human Health and Performance, University College London, London, United Kingdom.
authors.forename: Louise
authors.initials: L
authors.lastname: Ma
authors.affiliation: NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital and Imperial College, London, United Kingdom.|Cardiovascular Imaging Unit, Cardiology Department, Germans Trias i Pujol University Hospital, Badalona. Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Teis
authors.affiliation: Institute for Human Health and Performance, University College London, London, United Kingdom.|The Anaesthetic Department, Derriford Hospital, Plymouth, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Kotwinski
authors.affiliation: Department of Anaesthesia and Critical Care, University College London Hospital, London, United Kingdom.|UCL Institute of Cardiovascular Science and NIHR University College London Hospitals Biomedical Research Centre, London, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Mythen
authors.affiliation: NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital and Imperial College, London, United Kingdom.
authors.forename: Dudley J
authors.initials: DJ
authors.lastname: Pennell
authors.affiliation: LOC, London, United Kingdom.
authors.forename: Alison
authors.initials: A
authors.lastname: Jones
authors.affiliation: Institute for Human Health and Performance, University College London, London, United Kingdom.|UCL Institute of Cardiovascular Science and NIHR University College London Hospitals Biomedical Research Centre, London, United Kingdom.
authors.forename: Hugh
authors.initials: H
authors.lastname: Montgomery
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects*; D001830:Body Surface Area; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology; D054715:Cardiotoxins / Q000008:administration & dosage / Q000009:adverse effects; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D018570:Risk Assessment; D000068878:Trastuzumab / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D054715:Cardiotoxins; D015251:Epirubicin; D000068878:Trastuzumab