Blood biomarkers in patients with repaired Tetralogy of Fallot (rTOF); A systematic review and meta-analysis

Background: The clinical use and prognostic value of plasma brain natriuretic peptide (NT-proBNP) and soluble suppression of tumourigenicity-2 (sST2) levels are not known in patients with repaired Tetralogy of Fallot (rTOF).Objectives: We evaluated blood biomarkers in rTOF patients by combining the available evidence, focussing on prognosis, adverse echocardiographic findings and exercise intolerance.Methods: This systematic review and meta-analysis were carried out in accordance with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. For the primary prognostic outcomes, a meta-analysis was performed. For hemodynamic outcomes, a pooled meta-analysis of correlation coefficients (r) was performed. The study protocol was registered with PROSPERO(CRD42020211897).Results: We analysed 1479 patients with repaired TOF in 23 studies. Mean age was 22.7 +/- 8.3 years. The mean value of NT-proBNP was 174.4.1 +/- 56.4 pg/ml while ST2 drawn from two investigations was 26.95 ng/ml. There was no difference in mean NT-proBNP between older and younger subjects (160.4 +/- 37.7 vs190.6 +/- 72.9, pg/ml, respectively; p > .05). NT-proBNP levels were higher in TAP studies than others with other RVOT intervention (191.6 +/- 57 vs 151 +/- 46, pg/ml, p < .05). Elevated NT-proBNP levels were associated with an increased risk of adverse cardiovascular outcomes including death, arrhythmias and acute heart failure with a hazard ratio (HR) of 1.18 (95% CI 1.07-1.31, p.001). We noted a moderate correlation between NT-proBNP levels and exercise intolerance, RV structural and volumetric changes (r = -.52, r = 0.41, P < .001).Conclusions: NT-proBNP levels are elevated in patients with surgically repaired TOF and are associated with an increased risk of cardiovascular adverse outcomes and exercise intolerance.