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Biomarker sST2 in Adults with Transposition of the Great Arteries Palliated by Mustard Procedure: A Five-Year Follow-up

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Abstract

The Mustard procedure was an early cardiac surgery for transposition of the great arteries (TGA). Despite being successful, it has been associated with long-term arrhythmias and heart failure. A key factor complicating management in adults with congenital heart disease (CHD) is the deficiency of biomarkers predicting outcome. Soluble suppression of tumorogenicity-2 (sST2) is secreted by cardiomyocytes in response to mechanical strain and fibrosis. We hypothesized that adults with a Mustard procedure would have higher levels of sST2 than healthy individuals, and this would correlate with clinical outcome. We performed a single-center study in patients managed during childhood with a Mustard procedure versus age-matched controls. Clinical and demographic data were collected and biomarkers (sST2, cTnI, BNP, lipid panel, insulin, and glucose) were obtained. There were 18 patients (12 male) in the Mustard cohort and 18 patients (6 male) in the control group (22–49 years, mean of 35.8 vs. mean 32.6 years, respectively, p = ns). Nine Mustard subjects were NYHA class II, and 9 subjects were class III. The control group was asymptomatic. sST2 in the Mustard group was elevated in 56% vs. 17% in controls (p = 0.035). Of the Mustard subjects with elevated sST2, 60% had elevated cTnI and BNP, and 90% had low HDL. Over five years, the Mustard patients with elevated sST2 values had greater medication use, arrhythmias, hospitalizations, and ablation/pacer implantations than Mustard subjects with normal sST2. Mustard subjects with elevated sST2 had other biomarker abnormalities and clinically worse outcomes. Thus, sST2 may add a predictive value to cardiac-related morbidity and mortality.

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Funding

This project was funded in part with support from the Short-Term Training Program in Biomedical Sciences Grant, T35 HL 110854, from the National Institutes of Health (to HNF), 1P01HL134599 from NHLBI (to RMP), and the Indiana Clinical and Translational Sciences Institute, 5UL1TR002529 from NCATS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Author notes

  1. Haley N. Ferguson and Hugo R. Martinez have contributed equally to this manuscript.

Authors and Affiliations

  1. Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Haley N. Ferguson

  2. Division of Pediatric Cardiology, Le Bonheur Children’s Hospital, University of Tennessee Health Science Center, Memphis, TN, 38105, USA

    Hugo R. Martinez

  3. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    P. Melanie Pride & R. Mark Payne

  4. Clinical Trials Management Organization, The Ohio State University, Columbus, OH, 43210, USA

    Elizabeth A. Swan

  5. Division of Cardiology, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, 1044 West Walnut St, Room R4-302b, Indianapolis, IN, 46202, USA

    Roger A. Hurwitz & R. Mark Payne

Authors
  1. Haley N. Ferguson
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  2. Hugo R. Martinez
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  3. P. Melanie Pride
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  4. Elizabeth A. Swan
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Contributions

HNF, HRM, and RMP wrote the manuscript. HNF and HRM contributed equally to this work. PMP performed the sST2 assays and reviewed the manuscript. HRM and EAS recruited subjects and performed chart review, and EAS reviewed the manuscript. RAH reviewed and edited the manuscript. RMP supervised the project. All authors have reviewed this manuscript.

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Correspondence to R. Mark Payne.

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Ferguson, H.N., Martinez, H.R., Pride, P.M. et al. Biomarker sST2 in Adults with Transposition of the Great Arteries Palliated by Mustard Procedure: A Five-Year Follow-up. Pediatr Cardiol 44, 927–932 (2023). https://doi.org/10.1007/s00246-023-03105-0

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