Quantification of ventricular stress in univentricular hearts during early childhood using age-independent zlog-NT-proBNP.

BACKGROUND: Children with univentricular hearts (UVH) undergo up to three palliative surgical procedures to achieve complete circulatory separation (Fontan circulation). As a marker of cardiac wall stress, NT-proBNP is a promising tool to assess systemic ventricular load in these patients. However, different reference intervals (RI) apply to each stage, as NT-proBNP is highly age-dependent. METHODS: Children undergoing systemic-to-pulmonary (SP) shunt placement (stage 1), bidirectional cavopulmonary shunt (BCPS, stage 2) or total cavopulmonary connection (TCPC, stage 3) between 2011 and 2021 with NT-proBNP measurement within 7 days before surgery were included. Furthermore, outpatients after TCPC with NT-proBNP measurement were enrolled. Biomarker levels were evaluated using its age-adjusted z-score ("zlog-NT-proBNP"; age-independent RI, -1.96 to +1.96), allowing comparison between different stages and revealing changes in systemic ventricular load independent of the marked physiological decline in RI with age. RESULTS: Overall, 289 children (227 before, 62 after TCPC) met the eligibility criteria. Median time between blood sampling and surgery (SP shunt/BCPS/TCPC) was 2 [1-3] days and 3.2 [2.0-4.5] years after TCPC. Age-adjusted zlog-NT-proBNP levels were 3.47 [2.79-3.93] in children with native UVH (before SP shunt), 3.10 [1.89-3.58] at stage 1 (before BCPS), 1.08 [0.51-1.88] at stage 2 (before TCPC), and 1.09 [0.72-1.75] at stage 3 (after TCPC/Fontan completion). Consequently, BCPS revealed the strongest decrease (median - 2.02 logarithmized standard deviations, p < 0.001). CONCLUSIONS: In children with UVH undergoing staged Fontan palliation, zlog-NT-proBNP is a highly promising tool for course assessment of systemic ventricular load, independent of the age-related decline in physiological NT-proBNP concentration.

Development of Weight and Height Age z-Score after Total Cavopulmonary Connection.

OBJECTIVE: We aimed to analyze somatic growth of patients after total cavopulmonary connection (TCPC) as well as to identify factors influencing postoperative catch-up growth. METHODS: A total of 309 patients undergoing TCPC at 4 years old or less between 1994 and 2021 were included. Weight for age z-score (WAZ) and height for age-z-score (HAZ) at TCPC and at postoperative time between 1 and 3 years were calculated. Factors influencing somatic growth were analyzed. RESULTS: Most frequent diagnosis and initial palliation were hypoplastic left heart syndrome (HLHS) (34%) and the Norwood procedure (51%), respectively. Median age and weight at TCPC were 2.0 (IQR: 1.7-2.5) years and 11.3 (10.5-12.7) kg, respectively. Median 519 days after TCPC, a significant increase in WAZ (-0.4 to -0.2, p < 0.001) was observed, but not in HAZ (-0.6 to -0.6, p = 0.38). Older age at TCPC (p < 0.001, odds ratio [OR]: 2.6) and HLHS (p = 0.007, OR: 2.2) were risks for low WAZ after TCPC. Older age at TCPC (p = 0.009, OR: 1.9) and previous Norwood procedure (p = 0.021, OR: 2.0) were risks for low HAZ after TCPC. Previous bidirectional cavopulmonary shunt (BCPS) was a protective factor for both WAZ (p = 0.012, OR: 0.06) and HAZ (p = 0.028, OR: 0.30) at TCPC. CONCLUSION: In patients undergoing TCPC at the age of 4 years or less, a significant catch-up growth was observed in WAZ after TCPC, but not in HAZ. Previous BCPS resulted to be a protective factor for a better somatic development at TCPC. HLHSs undergoing Norwood were considered as risks for somatic development after TCPC.