BackgroundSoluble suppression of tumorogenicity 2 (sST2) has been shown to be of prognostic value in patients with chronic and acute left heart failure. The present study aims to assess the predictive value of sST2 levels in adult patients with complex congenital heart disease (CHD).MethodsIn 169 consecutive patients with complex CHD and a mean age of 28.2 ± 12.0 years, sST2 levels were compared to 32 healthy controls and associated with clinical status as well as the occurrence of major adverse cardiac events (MACE). Mean follow-up time was 35.6 ± 24.9 months.ResultsIn CHD patients, median sST2 levels were 29.7 ng/ml compared to 26.4 ng/ml in healthy controls (p = 0.007) and increased with different types of CHD and the severity of MACE. According to ROC analysis, the most important predictors of acute heart/Fontan failure were NYHA class III/IV (AUC 0.804, p<0.001, CI 0.668–0.941), NT-proBNP levels (AUC 0.794, p<0.001, CI 0.640–0.948), γGT levels (AUC 0.793, p<0.001, CI 0.678–0.909) and sST2 levels (AUC 0.742, p = 0.004, CI 0.626–0.858), with NYHA class III/IV as the strongest independent predictor (p<0.001). All-cause mortality was best predicted by sST2 levels (AUC 0.890, p<0.001, CI 0.741–1.000), NT-proBNP levels (AUC 0.875, p = 0.001, CI 0.766–0.984) and NYHA class III/IV (AUC 0.837, p = 0.003, CI 0.655–1.000) with sST2 as the strongest independent predictor (p<0.001). Moreover, AUC increased to 0.918 combining both biomarkers and net reclassification improved with the addition of sST2.ConclusionIn patients with complex CHD, sST2 may have additive value to natriuretic peptides for the prediction of all-cause mortality.