Abstract
Introduction: Although many biomarkers are associated with heart failure, limited data is available on their prognostic predictive value in adults with congenital heart disease (ACHD). We investigate the potential of various biomarkers to predict ACHD mortality. Methods and Results: This is a single-center, retrospective cohort study. Blood levels of neurohormones (endothelin-1 [ET1], norepinephrine [NE], aldosterone, and plasma renin activity [PRA]); inflammatory biomarkers (high sensitivity C-reactive protein [hs-CRP], high sensitivity tumor necrosis factor [hs-TNF]-α, 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 115 ACHD (mean age, 30 ± 10 years). NYHA class was I/ II in 86% and III/IV in 14%. The subjects were divided into two groups: patients with single-ventricle (SV group, n = 65) and with two-ventricle physiology (TV group, n = 50). We retrospectively analyzed the relationship between levels of biomarkers and cardiovascular death. During a mean follow-up period of 4.6 years, 17 (14%) cardiovascular deaths occurred, including 7 in the SV group. Univariate cox regression analysis in all subjects showed strong association between elevated levels of ET1, NE, RPA, hs-CRP, sTNF-RI and II, IL-6, and BNP and cardiovascular death (p< 0.05). In the SV group, using multivariate cox regression model, BNP and sTNF-RI were the most powerful predictors in these biomarkers (adjusted hazard ratio [aHR] of BNP: 14.84; 95%CI: 2.21-99.36 per 1 SD increase, p = 0.005) (aHR of sTNF-RI: 2.30; 95%CI: 1.91-4.55 per 1 SD increase, p = 0.017). The optimal cut-off values of BNP and sTNF-RI for mortality were 196 pg/mL and 1.26 ng/mL, respectively. Conversely, in the TV group, only IL-6 was an independent predictor of mortality (aHR: 3.24; 95%CI: 1.57-6.68 per 1 SD increase, p = 0.001), while BNP was not strongly associated with outcomes. The optimal cut-off value of IL-6 for mortality was 2.3 pg/mL. Conclusion: Various biomarkers, including sTNF-R, BNP, and IL-6, are associated with prognosis in overall ACHD. The most prominent mortality predictors might differ, due to differences in SV or TV physiology.
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