title: Left ventricular end-diastolic volume as early indicator of trastuzumab-related cardiotoxicity in HER2+ breast cancer patients: results from a single-center retrospective study.
abstract: BACKGROUND
  Adjuvant trastuzumab therapy increases survival rates in patients with early HER2-positive breast cancer, although it can be potentially cardiotoxic. The aim of this study was to evaluate the prevalence of left ventricular (LV) systolic dysfunction; and the relationship between the presence of cardiovascular risk factors, cardiac therapy and/or echocardiographic parameters of systolic function at baseline and the development of cardiotoxicity in such patients.
  
  
  METHODS
  A total of 227 patients were retrospectively reviewed. Cardiotoxicity was defined as a decrease in LV ejection fraction (EF) below 50% or an absolute decrease of >10 points below the baseline value or any indication of heart failure. Each patient underwent echocardiography at baseline and at follow-up every three months.
  
  
  RESULTS
  The prevalence of cardiotoxicity was 17.6% (15.4% asymptomatic, 2.2% symptomatic). Patients developing LV dysfunction presented hypertension (P=0.041) and diabetes (P=0.01) and used cardiac therapy at baseline more frequently. Smoke habit, age >50 and use of angiotensin-converting enzyme (ACE)-inhibitors, were independent predictors of cardiac damage. Furthermore, patients with LV dysfunction showed baseline LV end-diastolic volume (EDV) higher than those who did not and baseline EDV (OR=1.02; 95% CI: 1.00-1.04; P=0.027) independently predicted cardiotoxicity with 58 mL/m2 as best cut-off point (AUC=0.65, 95% CI: 0.55-0.75]).
  
  
  CONCLUSIONS
  The prevalence of trastuzumab-related cardiotoxicity in patients with HER2-positive early breast cancer is relatively frequent, although asymptomatic in most cases. Baseline EDV resulted as independent predictor of cardiotoxicity suggesting that EDV may be more reliable than LVEF to identify patients at higher risk of developing cardiac damage.
authors.affiliation: Cardiology Unit, Verona University Hospital, Verona, Italy - corinnabergamini@gmail.com.
authors.forename: Corinna
authors.initials: C
authors.lastname: Bergamini
authors.affiliation: Cardiology Unit, Verona University Hospital, Verona, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Torelli
authors.affiliation: Cardiology Unit, Verona University Hospital, Verona, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Ghiselli
authors.affiliation: Cardiology Unit, Verona University Hospital, Verona, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Cardiology Unit, Verona University Hospital, Verona, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Trevisani
authors.affiliation: Cardiology Unit, Verona University Hospital, Verona, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Vinco
authors.affiliation: Cardiology Unit, Verona University Hospital, Verona, Italy.
authors.forename: Stella
authors.initials: S
authors.lastname: Truong
authors.affiliation: Cardiology Unit, Verona University Hospital, Verona, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Benfari
authors.affiliation: Oncology Unit, Verona University Hospital, Verona, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: LA Russa
authors.affiliation: Cardiology Unit, Verona University Hospital, Verona, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Golia
authors.affiliation: Oncology Unit, Verona University Hospital, Verona, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Molino
authors.affiliation: Cardiology Unit, Verona University Hospital, Verona, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Vassanelli
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D066126:Cardiotoxicity / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology; D004452:Echocardiography / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D015995:Prevalence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D013318:Stroke Volume / Q000187:drug effects*; D000068878:Trastuzumab / Q000008:administration & dosage / Q000009:adverse effects*; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced / Q000453:epidemiology; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human