P0962 - Elevated proBNP levels are associated with disease severity, cardiac dysfunction, and mortality in congenital diaphragmatic hernia

Purpose: Cardiac dysfunction is emerging as a key culprit in the morbidity and mortality of congenital diaphragmatic hernia (CDH). N-terminal pro b-type natriuretic peptide (proBNP), a hormone released secondary to ventricular stretch, has been used as a prognosticator and biomarker of severity in heart failure and cardiomyopathy. We hypothesized that proBNP levels would be associated with cardiac dysfunction and high-risk disease in CDH.

Methods: All patients in the CDH Study Group (CDHSG) from 2015 to 2019 were included. Mean proBNP was used for patients with multiple values. Cardiac function was determined using echocardiograms from the first 72 hours of life. Univariate and receiver operating characteristics analyses were performed using Stata/IC v16.1.

Results: A total of 2,337 patients were identified. Of those, 212 (9%) had at least one proBNP value, ranging from 2.5 to 142,207.5 pg/mL. Of patients who had a proBNP measurement, 3 (1.5%) had CDHSG stage A defects, 58 (29.6%) B, 111 (56.6%) C, and 24 (12.2%) D. Patients with high-risk defects (Stage C/D) had significantly higher proBNP levels compared to patients with low-risk defects (Stage A/B) (7,776, IQR 2,438–18,802 vs. 4,075, IQR 1,882–7,490, p=0.008). proBNP was higher in patients who died (14,100, IQR 4,377–22,900) versus survivors (4,911, IQR 1,883–9,810) (p<0.001). Patients with any cardiac dysfunction on their initial echocardiogram had higher proBNP than patients with normal cardiac function (8,379, IQR 3,361–20,411 vs. 4x778, IQR 1,917–9,810) (p=0.005), but no proBNP cutoff value was highly sensitive and specific for cardiac dysfunction (AUC=0.61, maximum Youden’s-J statistic=0.21) (Figure).

Conclusion: Among patients with CDH, elevated proBNP was associated with high-risk defects, cardiac dysfunction, and mortality. Although additional study is needed to determine the optimal timing and frequency of measurement, proBNP shows significant promise as a prognostic factor and biomarker in congenital diaphragmatic hernia-associated cardiac dysfunction.