title: Relation of Pre-anthracycline Serum Bilirubin Levels to Left Ventricular Ejection Fraction After Chemotherapy.
abstract: Myocardial injury because of oxidative stress manifesting through reductions in left ventricular ejection fraction (LVEF) may occur after the administration of anthracycline-based chemotherapy (A-bC). We hypothesized that bilirubin, an effective endogenous antioxidant, may attenuate the reduction in LVEF that sometimes occurs after receipt of A-bC. We identified 751 consecutively treated patients with cancer who underwent a pre-A-bC LVEF measurement, exhibited a serum total bilirubin level <2 mg/dl, and then received a post-A-bC LVEF assessment because of symptomatology associated with heart failure. Analysis of variance, Tukey's Studentized range test, and chi-square tests were used to evaluate an association between bilirubin and LVEF changes. The LVEF decreased by 10.7 ± 13.7%, 8.9 ± 11.8%, and 7.7 ± 11.5% in group 1 (bilirubin at baseline ≤0.5 mg/dl), group 2 (bilirubin 0.6 to 0.8 mg/dl), and group 3 (bilirubin 0.9 to 1.9 mg/dl), respectively. More group 1 patients experienced >15% decrease in LVEF compared with those in group 3 (p = 0.039). After adjusting for age, coronary artery disease/myocardial infarction, diabetes mellitus, hematocrit, and the use of cardioactive medications, higher precancer treatment bilirubin levels and lesser total anthracycline doses were associated with LVEF preservation (p = 0.047 and 0.011, respectively). In patients treated with anthracyclines who subsequently develop symptoms associated with heart failure, pre-anthracycline treatment serum bilirubin levels inversely correlate with subsequent deterioration in post-cancer treatment LVEF. In conclusion, these results suggest that increased levels of circulating serum total bilirubin, an intrinsic antioxidant, may facilitate preservation of LVEF in patients receiving A-bC for cancer.
authors.affiliation: Cardiovascular Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Trinity
authors.initials: T
authors.lastname: Vera
authors.affiliation: Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.affiliation: Cardiovascular Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Jordan
authors.affiliation: Cardiovascular Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Whitlock
authors.affiliation: Cardiovascular Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina; Comparative Medicine, Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Giselle C
authors.initials: GC
authors.lastname: Meléndez
authors.affiliation: Hematology and Oncology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Zanetta S
authors.initials: ZS
authors.lastname: Lamar
authors.affiliation: Hematology and Oncology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Porosnicu
authors.affiliation: Gastroenterology and Hepatology and Molecular Medicine Translational Science, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
authors.affiliation: Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina; Center for Structural Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Poole
authors.affiliation: Cardiovascular Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina; Division of Radiologic Sciences, Department of Radiology, Wake Forest School of Medicine, Winston-Salem, North Carolina. Electronic address: ghundley@wakehealth.edu.
authors.forename: W Gregory
authors.initials: WG
authors.lastname: Hundley
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001663:Bilirubin / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy; D003630:Daunorubicin / Q000494:pharmacology / Q000627:therapeutic use; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D019337:Hematologic Neoplasms / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D015255:Idarubicin / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012189:Retrospective Studies; D013318:Stroke Volume / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D004317:Doxorubicin; D001663:Bilirubin; D015255:Idarubicin; D003630:Daunorubicin