title: Abnormalities in serum biomarkers correlate with lower cardiac index in the Fontan population.
abstract: BACKGROUND
  Fontan survivors have depressed cardiac index that worsens over time. Serum biomarker measurement is minimally invasive, rapid, widely available, and may be useful for serial monitoring. The purpose of this study was to identify biomarkers that correlate with lower cardiac index in Fontan patients. Methods and results This study was a multi-centre case series assessing the correlations between biomarkers and cardiac magnetic resonance-derived cardiac index in Fontan patients ⩾6 years of age with biochemical and haematopoietic biomarkers obtained ±12 months from cardiac magnetic resonance. Medical history and biomarker values were obtained by chart review. Spearman's Rank correlation assessed associations between biomarker z-scores and cardiac index. Biomarkers with significant correlations had receiver operating characteristic curves and area under the curve estimated. In total, 97 cardiac magnetic resonances in 87 patients met inclusion criteria: median age at cardiac magnetic resonance was 15 (6-33) years. Significant correlations were found between cardiac index and total alkaline phosphatase (-0.26, p=0.04), estimated creatinine clearance (0.26, p=0.02), and mean corpuscular volume (-0.32, p<0.01). Area under the curve for the three individual biomarkers was 0.63-0.69. Area under the curve for the three-biomarker panel was 0.75. Comparison of cardiac index above and below the receiver operating characteristic curve-identified cut-off points revealed significant differences for each biomarker (p<0.01) and for the composite panel [median cardiac index for higher-risk group=2.17 L/minute/m2 versus lower-risk group=2.96 L/minute/m2, (p<0.01)].
  
  
  CONCLUSIONS
  Higher total alkaline phosphatase and mean corpuscular volume as well as lower estimated creatinine clearance identify Fontan patients with lower cardiac index. Using biomarkers to monitor haemodynamics and organ-specific effects warrants prospective investigation.
authors.affiliation: 1Department of Pediatrics,Division of Cardiology,Division of Critical Care Medicine,Heart Institute,Cincinnati Children's Hospital Medical Center,Cincinnati,Ohio,United States of America.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Marino
authors.affiliation: 7Department of Pediatrics,Division of Cardiology,The Children's Hospital of Philadelphia,Philadelphia,PennsylvaniaUnited States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Goldberg
authors.affiliation: 9Department of Pediatrics,Division of Pediatric Cardiology,University of Michigan C.S. Mott Children's Hospital,Ann Arbor,Michigan,United States of America.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Dorfman
authors.affiliation: 2Department of Pediatrics,Division of Biostatistics & Epidemiology,Cincinnati Children's Hospital Medical Center,Cincinnati,Ohio,United States of America.
authors.forename: Eileen
authors.initials: E
authors.lastname: King
authors.affiliation: 3Department of Pediatrics,Division of General and Community Pediatrics,Cincinnati Children's Hospital Medical Center,Cincinnati,Ohio,United States of America.
authors.forename: Heidi
authors.initials: H
authors.lastname: Kalkwarf
authors.affiliation: 8Department of Pediatrics,Division of Gastroenterology, Hepatology and Nutrition,The Children's Hospital of Philadelphia,Philadelphia,Pennsylvania,United States of America.
authors.forename: Babette S
authors.initials: BS
authors.lastname: Zemel
authors.affiliation: 1Department of Pediatrics,Division of Cardiology,Division of Critical Care Medicine,Heart Institute,Cincinnati Children's Hospital Medical Center,Cincinnati,Ohio,United States of America.
authors.forename: Margaret
authors.initials: M
authors.lastname: Smith
authors.affiliation: 2Department of Pediatrics,Division of Biostatistics & Epidemiology,Cincinnati Children's Hospital Medical Center,Cincinnati,Ohio,United States of America.
authors.forename: Jesse
authors.initials: J
authors.lastname: Pratt
authors.affiliation: 7Department of Pediatrics,Division of Cardiology,The Children's Hospital of Philadelphia,Philadelphia,PennsylvaniaUnited States of America.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Fogel
authors.affiliation: 10Department of Pediatrics,Division of Pediatric Cardiology,Children's Hospital of Wisconsin,Milwaukee,Wisconsin,United States of America.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Shillingford
authors.affiliation: 11Department of Pediatrics,Division of Cardiology,Ann & Robert H. Lurie Children's Hospital of Chicago,Chicago,IllinoisUnited States of America.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Deal
authors.affiliation: 12Department of Pediatrics,Division of Cardiology,The Mayo Clinic,Rochester,Minnesota,United States of America.
authors.forename: Anitha S
authors.initials: AS
authors.lastname: John
authors.affiliation: 9Department of Pediatrics,Division of Pediatric Cardiology,University of Michigan C.S. Mott Children's Hospital,Ann Arbor,Michigan,United States of America.
authors.forename: Caren S
authors.initials: CS
authors.lastname: Goldberg
authors.affiliation: 13Department of Pediatrics,Division of Cardiology,Nationwide Children's Hospital,ColumbusOhio,United States of America.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Hoffman
authors.affiliation: 14Department of Pediatric and Congenital Heart Surgery,Cleveland Clinic,Cleveland,Ohio,United States of America.
authors.forename: Marshall L
authors.initials: ML
authors.lastname: Jacobs
authors.affiliation: 1Department of Pediatrics,Division of Cardiology,Division of Critical Care Medicine,Heart Institute,Cincinnati Children's Hospital Medical Center,Cincinnati,Ohio,United States of America.
authors.forename: Asher
authors.initials: A
authors.lastname: Lisec
authors.affiliation: 1Department of Pediatrics,Division of Cardiology,Division of Critical Care Medicine,Heart Institute,Cincinnati Children's Hospital Medical Center,Cincinnati,Ohio,United States of America.
authors.forename: Susan
authors.initials: S
authors.lastname: Finan
authors.affiliation: 15Department of Pediatrics,Division of Pediatric Cardiology,University of Minnesota Amplatz Children's Hospital,Minneapolis,Minnesota,United States of America.
authors.forename: Lazaros K
authors.initials: LK
authors.lastname: Kochilas
authors.affiliation: 7Department of Pediatrics,Division of Cardiology,The Children's Hospital of Philadelphia,Philadelphia,PennsylvaniaUnited States of America.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Pawlowski
authors.affiliation: 4Department of Pediatrics,Division of Gastroenterology, Hepatology and Nutrition,Cincinnati Children's Hospital Medical Center,Cincinnati,Ohio,United States of America.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Campbell
authors.affiliation: 5Department of Pediatrics,Division of Hematology/Oncology,Cincinnati Children's Hospital Medical Center,Cincinnati,Ohio,United States of America.
authors.forename: Clinton
authors.initials: C
authors.lastname: Joiner
authors.affiliation: 6Department of Pediatrics,Division of Nephrology and Hypertension,Cincinnati Children's Hospital Medical Center,Cincinnati,Ohio,United States of America.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Goldstein
authors.affiliation: 7Department of Pediatrics,Division of Cardiology,The Children's Hospital of Philadelphia,Philadelphia,PennsylvaniaUnited States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: Stephens
authors.affiliation: 7Department of Pediatrics,Division of Cardiology,The Children's Hospital of Philadelphia,Philadelphia,PennsylvaniaUnited States of America.
authors.forename: Alvin J
authors.initials: AJ
authors.lastname: Chin
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D002302:Cardiac Output / Q000502:physiology*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D018729:Fontan Procedure / Q000379:methods*; D006330:Heart Defects, Congenital / Q000097:blood* / Q000503:physiopathology / Q000601:surgery; D006801:Humans; D008297:Male; D008991:Monitoring, Physiologic / Q000379:methods*; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: Fontan; biomarkers; cardiac MRI; cardiac index