Prognostic value of multiple biomarkers for cardiovascular mortality in adult congenital heart disease: comparisons of single-/two-ventricle physiology, and systemic morphologically right/left ventricles

Heart Vessels. 2016 Nov;31(11):1834-1847. doi: 10.1007/s00380-016-0807-0. Epub 2016 Feb 8.


Although there are many biomarkers for heart failure, limited data are available regarding their prognostic value in adult congenital heart disease (ACHD). We investigated the potential of various biomarkers to predict ACHD mortality in a single-center, retrospective cohort study. Blood levels of neurohormones [angiotensin II, endothelin-1 (ET-1), norepinephrine (NE), aldosterone, and plasma renin activity]; inflammatory biomarkers [high-sensitivity C-reactive protein (hs-CRP), high-sensitivity tumor necrosis factor, soluble TNF receptor type I and II (sTNF-RI and sTNF-RII), and interleukin-6 (IL-6)]; and brain natriuretic peptide (BNP) were measured in 103 ACHD patients (median age 28 years). Subjects were divided into patients with single-ventricle physiology (SV group, n = 61) and those with two-ventricle physiology (TV group, n = 42); and into patients with a systemic right ventricle (SRV group, n = 25) and those with a systemic left ventricle (SLV group, n = 78). During a median follow-up period of 6.5 years, 12 patients (11 %) died of acute decompensated heart failure (ADHF). Predictive biomarkers, which are related to the New York Heart Association class and cardiothoracic ratio, were as follows: elevated levels of BNP, ET-1, sTNF-RI, NE, and IL-6 in the overall patient group; IL-6, NE, hs-CRP, BNP, and ET-1 in the TV group; BNP and ET-1 in the SV group; BNP, NE, hs-CRP, sTNF-RI, IL-6, and ET-1 in the SLV group. Elevated levels of ET-1 in SRV groups were slightly although not significantly associated with these. Various clinical biomarkers are associated with ADHF mortality in ACHD patients. The most prominent mortality predictors in biomarker profiles may vary according to differences in ventricular physiology and systemic ventricle morphology.

Keywords: Brain natriuretic peptide; Congenital heart disease; Inflammatory cytokine; Neurohormones; Systemic morphologically right ventricle.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Biomarkers / blood*
  • Female
  • Heart Defects, Congenital / blood*
  • Heart Defects, Congenital / diagnostic imaging
  • Heart Defects, Congenital / mortality
  • Heart Defects, Congenital / physiopathology
  • Heart Ventricles / abnormalities*
  • Heart Ventricles / diagnostic imaging
  • Heart Ventricles / physiopathology
  • Humans
  • Male
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Tokyo
  • Ventricular Function, Left
  • Ventricular Function, Right
  • Young Adult


  • Biomarkers