Abnormalities in serum biomarkers correlate with lower cardiac index in the Fontan population

Bradley S. Marino, David J. Goldberg, Adam L. Dorfman, Eileen King, Heidi Kalkwarf, Babette S. Zemel, Margaret Smith, Jesse Pratt, Mark A. Fogel, Amanda J. Shillingford, Barbara J. Deal, Anitha S. John, Caren S. Goldberg, Timothy M. Hoffman, Marshall L. Jacobs, Asher Lisec, Susan Finan, Lazaros K. Kochilas, Thomas W. Pawlowski, Kathleen Campbell & 4 others Clinton Joiner, Stuart L. Goldstein, Paul Stephens, Alvin J. Chin

Research output: Research - peer-reviewArticle

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.

LanguageEnglish (US)
Pages59-68
Number of pages10
JournalCardiology in the Young
Volume27
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Biomarkers
Serum
Population
Magnetic Resonance Spectroscopy
Area Under Curve
Erythrocyte Indices
ROC Curve
Alkaline Phosphatase
Creatinine
Survivors
Hemodynamics

Keywords

  • biomarkers
  • cardiac index
  • cardiac MRI
  • Fontan

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Cardiology and Cardiovascular Medicine

Cite this

Marino, B. S., Goldberg, D. J., Dorfman, A. L., King, E., Kalkwarf, H., Zemel, B. S., ... Chin, A. J. (2017). Abnormalities in serum biomarkers correlate with lower cardiac index in the Fontan population. Cardiology in the Young, 27(1), 59-68. DOI: 10.1017/S1047951116000093

Abnormalities in serum biomarkers correlate with lower cardiac index in the Fontan population. / Marino, Bradley S.; Goldberg, David J.; Dorfman, Adam L.; King, Eileen; Kalkwarf, Heidi; Zemel, Babette S.; Smith, Margaret; Pratt, Jesse; Fogel, Mark A.; Shillingford, Amanda J.; Deal, Barbara J.; John, Anitha S.; Goldberg, Caren S.; Hoffman, Timothy M.; Jacobs, Marshall L.; Lisec, Asher; Finan, Susan; Kochilas, Lazaros K.; Pawlowski, Thomas W.; Campbell, Kathleen; Joiner, Clinton; Goldstein, Stuart L.; Stephens, Paul; Chin, Alvin J.

In: Cardiology in the Young, Vol. 27, No. 1, 01.01.2017, p. 59-68.

Research output: Research - peer-reviewArticle

Marino, BS, Goldberg, DJ, Dorfman, AL, King, E, Kalkwarf, H, Zemel, BS, Smith, M, Pratt, J, Fogel, MA, Shillingford, AJ, Deal, BJ, John, AS, Goldberg, CS, Hoffman, TM, Jacobs, ML, Lisec, A, Finan, S, Kochilas, LK, Pawlowski, TW, Campbell, K, Joiner, C, Goldstein, SL, Stephens, P & Chin, AJ 2017, 'Abnormalities in serum biomarkers correlate with lower cardiac index in the Fontan population' Cardiology in the Young, vol 27, no. 1, pp. 59-68. DOI: 10.1017/S1047951116000093
Marino BS, Goldberg DJ, Dorfman AL, King E, Kalkwarf H, Zemel BS et al. Abnormalities in serum biomarkers correlate with lower cardiac index in the Fontan population. Cardiology in the Young. 2017 Jan 1;27(1):59-68. Available from, DOI: 10.1017/S1047951116000093
Marino, Bradley S. ; Goldberg, David J. ; Dorfman, Adam L. ; King, Eileen ; Kalkwarf, Heidi ; Zemel, Babette S. ; Smith, Margaret ; Pratt, Jesse ; Fogel, Mark A. ; Shillingford, Amanda J. ; Deal, Barbara J. ; John, Anitha S. ; Goldberg, Caren S. ; Hoffman, Timothy M. ; Jacobs, Marshall L. ; Lisec, Asher ; Finan, Susan ; Kochilas, Lazaros K. ; Pawlowski, Thomas W. ; Campbell, Kathleen ; Joiner, Clinton ; Goldstein, Stuart L. ; Stephens, Paul ; Chin, Alvin J./ Abnormalities in serum biomarkers correlate with lower cardiac index in the Fontan population. In: Cardiology in the Young. 2017 ; Vol. 27, No. 1. pp. 59-68
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AU - Marino,Bradley S.

AU - Goldberg,David J.

AU - Dorfman,Adam L.

AU - King,Eileen

AU - Kalkwarf,Heidi

AU - Zemel,Babette S.

AU - Smith,Margaret

AU - Pratt,Jesse

AU - Fogel,Mark A.

AU - Shillingford,Amanda J.

AU - Deal,Barbara J.

AU - John,Anitha S.

AU - Goldberg,Caren S.

AU - Hoffman,Timothy M.

AU - Jacobs,Marshall L.

AU - Lisec,Asher

AU - Finan,Susan

AU - Kochilas,Lazaros K.

AU - Pawlowski,Thomas W.

AU - Campbell,Kathleen

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N2 - 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.

AB - 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.

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