title: Longitudinal assessment of concurrent changes in left ventricular ejection fraction and left ventricular myocardial tissue characteristics after administration of cardiotoxic chemotherapies using T1-weighted and T2-weighted cardiovascular magnetic resonance.
abstract: BACKGROUND
  In a murine anthracycline-related cardiotoxicity model, increases in cardiovascular magnetic resonance myocardial contrast-enhanced T1-weighted signal intensity are associated with myocellular injury and decreases with left ventricular ejection fraction. We sought to determine whether T1- and T2-weighted measures of signal intensity associate with decreases in left ventricular ejection fraction in human subjects receiving potentially cardiotoxic chemotherapy.
  
  
  RESULTS
  In 65 individuals with breast cancer (n=51) or a hematologic malignancy (n=14), we measured left ventricular volumes, ejection fraction, and contrast-enhanced T1-weighted and T2-weighted signal intensity before and 3 months after initiating potentially cardiotoxic chemotherapy using blinded, unpaired analysis of cardiovascular magnetic resonance images. Participants were aged 51 ± 12 years, of whom 55% received an anthracycline, 38% received a monoclonal antibody, and 6% received an antimicrotubule agent. Overall, left ventricular ejection fraction decreased from 57 ± 6% to 54 ± 7% (P<0.001) because of an increase in end-systolic volume (P<0.05). T1-weighted signal intensities also increased from 14.1 ± 5.1 to 15.9 ± 6.8 (P<0.05), with baseline values trending higher among individuals who received chemotherapy before study enrollment (P=0.06). Changes in T1-weighted signal intensity did not differ within the 17 LV myocardial segments (P=0.97). Myocardial edema quantified from T2-weighted images did not change significantly after 3 months (P=0.70).
  
  
  CONCLUSIONS
  Concordant with previous animal studies, cardiovascular magnetic resonance measures of contrast-enhanced T1-weighted signal intensity occur commensurate with small but significant left ventricular ejection fraction declines 3 months after the receipt of potentially cardiotoxic chemotherapy. These data indicate that changes in T1-weighted signal intensity may serve as an early marker of subclinical injury related to the administration of potentially cardiotoxic chemotherapy in human subjects.
authors.affiliation: From the Departments of Internal Medicine (Section on Cardiovascular Medicine) (J.H.J., S.V., M.E.H., D.W.K., V.T., W.G.H.), Public Health Sciences (R.B.D., T.L.L.), Biomedical Engineering (C.A.H.), Internal Medicine (Hematology and Oncology Section) (J.A.L., L.R.E.), and Radiology (W.G.H.), Wake Forest University School of Medicine, Winston-Salem, NC.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Jordan
authors.affiliation: From the Departments of Internal Medicine (Section on Cardiovascular Medicine) (J.H.J., S.V., M.E.H., D.W.K., V.T., W.G.H.), Public Health Sciences (R.B.D., T.L.L.), Biomedical Engineering (C.A.H.), Internal Medicine (Hematology and Oncology Section) (J.A.L., L.R.E.), and Radiology (W.G.H.), Wake Forest University School of Medicine, Winston-Salem, NC.
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.affiliation: From the Departments of Internal Medicine (Section on Cardiovascular Medicine) (J.H.J., S.V., M.E.H., D.W.K., V.T., W.G.H.), Public Health Sciences (R.B.D., T.L.L.), Biomedical Engineering (C.A.H.), Internal Medicine (Hematology and Oncology Section) (J.A.L., L.R.E.), and Radiology (W.G.H.), Wake Forest University School of Medicine, Winston-Salem, NC.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Hamilton
authors.affiliation: From the Departments of Internal Medicine (Section on Cardiovascular Medicine) (J.H.J., S.V., M.E.H., D.W.K., V.T., W.G.H.), Public Health Sciences (R.B.D., T.L.L.), Biomedical Engineering (C.A.H.), Internal Medicine (Hematology and Oncology Section) (J.A.L., L.R.E.), and Radiology (W.G.H.), Wake Forest University School of Medicine, Winston-Salem, NC.
authors.forename: Sujethra
authors.initials: S
authors.lastname: Vasu
authors.affiliation: From the Departments of Internal Medicine (Section on Cardiovascular Medicine) (J.H.J., S.V., M.E.H., D.W.K., V.T., W.G.H.), Public Health Sciences (R.B.D., T.L.L.), Biomedical Engineering (C.A.H.), Internal Medicine (Hematology and Oncology Section) (J.A.L., L.R.E.), and Radiology (W.G.H.), Wake Forest University School of Medicine, Winston-Salem, NC.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Hall
authors.affiliation: From the Departments of Internal Medicine (Section on Cardiovascular Medicine) (J.H.J., S.V., M.E.H., D.W.K., V.T., W.G.H.), Public Health Sciences (R.B.D., T.L.L.), Biomedical Engineering (C.A.H.), Internal Medicine (Hematology and Oncology Section) (J.A.L., L.R.E.), and Radiology (W.G.H.), Wake Forest University School of Medicine, Winston-Salem, NC.
authors.forename: Dalane W
authors.initials: DW
authors.lastname: Kitzman
authors.affiliation: From the Departments of Internal Medicine (Section on Cardiovascular Medicine) (J.H.J., S.V., M.E.H., D.W.K., V.T., W.G.H.), Public Health Sciences (R.B.D., T.L.L.), Biomedical Engineering (C.A.H.), Internal Medicine (Hematology and Oncology Section) (J.A.L., L.R.E.), and Radiology (W.G.H.), Wake Forest University School of Medicine, Winston-Salem, NC.
authors.forename: Vinay
authors.initials: V
authors.lastname: Thohan
authors.affiliation: From the Departments of Internal Medicine (Section on Cardiovascular Medicine) (J.H.J., S.V., M.E.H., D.W.K., V.T., W.G.H.), Public Health Sciences (R.B.D., T.L.L.), Biomedical Engineering (C.A.H.), Internal Medicine (Hematology and Oncology Section) (J.A.L., L.R.E.), and Radiology (W.G.H.), Wake Forest University School of Medicine, Winston-Salem, NC.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Lawrence
authors.affiliation: From the Departments of Internal Medicine (Section on Cardiovascular Medicine) (J.H.J., S.V., M.E.H., D.W.K., V.T., W.G.H.), Public Health Sciences (R.B.D., T.L.L.), Biomedical Engineering (C.A.H.), Internal Medicine (Hematology and Oncology Section) (J.A.L., L.R.E.), and Radiology (W.G.H.), Wake Forest University School of Medicine, Winston-Salem, NC.
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Ellis
authors.affiliation: From the Departments of Internal Medicine (Section on Cardiovascular Medicine) (J.H.J., S.V., M.E.H., D.W.K., V.T., W.G.H.), Public Health Sciences (R.B.D., T.L.L.), Biomedical Engineering (C.A.H.), Internal Medicine (Hematology and Oncology Section) (J.A.L., L.R.E.), and Radiology (W.G.H.), Wake Forest University School of Medicine, Winston-Salem, NC.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Lash
authors.affiliation: From the Departments of Internal Medicine (Section on Cardiovascular Medicine) (J.H.J., S.V., M.E.H., D.W.K., V.T., W.G.H.), Public Health Sciences (R.B.D., T.L.L.), Biomedical Engineering (C.A.H.), Internal Medicine (Hematology and Oncology Section) (J.A.L., L.R.E.), and Radiology (W.G.H.), Wake Forest University School of Medicine, Winston-Salem, NC. ghundley@wakehealth.edu.
authors.forename: W Gregory
authors.initials: WG
authors.lastname: Hundley
mesh_terms: D000328:Adult; D018943:Anthracyclines / Q000009:adverse effects*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004489:Edema, Cardiac / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013318:Stroke Volume / Q000187:drug effects*; D013997:Time Factors; D050257:Tubulin Modulators / Q000009:adverse effects*; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D050257:Tubulin Modulators
keywords: anthracyclines; cardiotoxicity; chemotherapy; left ventricular function; magnetic resonance imaging