Hepatocyte growth factor predicts failure of Fontan circulation

Aims This study aimed to assess the value of the hepatocyte growth factor (HGF) as an independent predictor of a Fontan circulation failure. Methods and results This retrospective case–control study included 34 consecutive patients (19 men and 15 women) who underwent a post‐operative cardiac catheterization after a Fontan operation at the Saitama Medical University International Medical Center between April 2017 and December 2019. We divided the patients into two groups according to the HGF level: HGF < 0.4 ng/mL ( n  = 20, normal HGF group) and HGF ≥ 0.4 ng/mL ( n  = 14, elevated HGF group). The age at the time of the cardiac catheterization was 59.3 ± 7.9 months. The range of the duration between the Fontan operation and the cardiac catheterization was 37.5 ± 7.9 months. The age ( P  = 0.417), gender ( P  = 0.08), morphology of the functional ventricle ( P  = 0.99), presence or closure of the Fontan fenestration ( P  = 0.704), and rate of medication use (angiotensin‐converting enzyme inhibitors or angiotensin II receptor blockers) ( P  = 0.99) were equivalent between the two groups. Laboratory parameters including the brain natriuretic peptide level ( P  = 0.085), serum creatinine level ( P  = 0.27), and aspartate aminotransferase level ( P  = 0.235) were similar between the two groups. The elevated HGF group had a higher C‐reactive protein level than the normal HGF group (0.42 ± 0.14 and 0.05 ± 0.01 mg/dL, P  = 0.005). The elevated HGF group had a higher central venous pressure (CVP) level than the normal HGF group (13.4 ± 0.7 and 9.7 ± 0.4 mmHg, P  < 0.0001), and the HGF was positively correlated with the CVP ( P  = 0.0004, r 2  = 0.33). The SvO 2 level was significantly lower in the elevated HGF group than in the normal HGF group (61.9 ± 2.3% and 75.0 ± 1.2%, P  < 0.0001), and the HGF was negatively correlated with the SvO 2 ( P  < 0.0001, r 2  = 0.65). Of the 34 patients, six underwent catheter interventions. Patients who underwent catheter interventions had a higher HGF level than those who did not (0.44 ± 0.03 and 0.37 ± 0.01 ng/mL, P  = 0.032). The receiver operating characteristic curve created for the discrimination of a catheter intervention revealed that an HGF value of >0.405 ng/mL could detect the need for a catheter intervention with 75.0% sensitivity and 83.3% specificity. A multivariable regression analysis showed that an elevated HGF was an independent predictor of an elevated CVP ( β ‐coefficient 21.2, SE 5.5, P  = 0.0005) and decreased SvO 2 ( β ‐coefficient −92.9, SE 12.4, P  < 0.0001). Conclusions The HGF is an independent predictor of a failure of a Fontan circulation. The HGF is an indicator for an additional catheter intervention after a Fontan operation.