NT-proBNP Dynamics during Different Stages of Fontan Palliation

Background: As a biomarker of cardiac wall stress, NT-proBNP is a highly reliable prognostic and diagnostic tool in children with congenital heart diseases (CHD). Due to its pronounced age dynamics, strongly different reference intervals apply at each stage of Fontan palliation, impeding the comparison of absolute NT-proBNP values between different stages. In this study, NT-proBNP levels are evaluated in children with univentricular hearts (UVH) undergoing Fontan palliation and compared over time by means of z-log-proBNP, an age-adjusted Z-score for NT-proBNP.

Method: All children with UVH undergoing staged palliation between 2011 and 2021 with an NT-proBNP measurement 7 days or less before surgery (S1P, S2P, or S3P) were enrolled. Since NT-proBNP reference intervals are highly related to age, especially during the time of staged palliation, corresponding z-log values (abbreviated as z-log-proBNP) as age-independent Z-scores were calculated.

Results: Preoperative NT-proBNP measurements were identified in 230 patients before and 137 after Fontan completion. Median time between blood sampling and surgery preoperatively was 2 days (IQR, 1 to 3 days). Across the three stages, a significant decrease was evident in both absolute NT-proBNP levels (before S1P: median 19,600 ng/L [IQR: 8,510–35,000 ng/L]; before S2P: median 3,160 ng/L [IQR: 1,145–5.550 ng/L]; before S3P: median 496 ng/L [IQR: 140–496 ng/L]; p < 0.001) as well as age-adjusted z-log values (before S1P: median 3.43 [IQR: 2.77–3.95]; before S2P: median 3.02 [IQR: 1.89–3.53]; before S3P median 1.16 [IQR: 0.60–2.02]; p < 0.001). After Fontan completion, most patients revealed normal z-log-proBNP values (median: 1.30, IQR: 0.70–1.88) and, therefore, normal NT-proBNP values regardless of age-dependent reference intervals.

Conclusion: During staged palliation, NT-proBNP values decrease from extremely high to nearly normal levels after Fontan completion. This is not a reflection of physiological age dynamics but rather the consequence of systemic ventricular unloading, as demonstrated by means of the age-adjusted z-log value of NT-proBNP.

Publication History

Article published online:
28 January 2023