Blood Test for BNP Flags Dangerous Heart Shunts in Infants

A simple blood test measuring B-type natriuretic peptide (BNP) may help doctors judge how serious a congenital heart shunt is in infants without resorting to invasive procedures, according to a new cross-sectional study published in the Egyptian Pediatric Association Gazette. Researchers found that plasma BNP levels rose with the size and type of left-to-right shunt, correlated strongly with pulmonary artery pressure, and showed excellent diagnostic accuracy for detecting these defects, with an area under the ROC curve of 0.939 and a cutoff above 23.5 pg/ml that achieved 85.5 percent sensitivity and 100 percent specificity.

Congenital heart disease is the leading congenital malformation worldwide, affecting roughly one percent of live births and carrying a considerable burden of childhood morbidity and mortality. Left-to-right shunt lesions, including ventricular septal defect (VSD), atrial septal defect (ASD), and patent ductus arteriosus (PDA), are among the most common and clinically important subtypes. These shunts allow systemic blood to pass into the pulmonary circulation, causing volume overload, chamber dilatation, and increased pulmonary pressures, which can progress to heart failure, pulmonary hypertension, and Eisenmenger’s syndrome depending on shunt magnitude. Accurate assessment of shunt significance is therefore essential to guide timely intervention and prevent complications.

Although echocardiography and cardiac catheterization remain the diagnostic standards, echocardiography may be suboptimal in some infants, while catheterization is invasive, costly, and carries procedural risks. BNP, released mainly from the ventricles in response to wall stress and volume overload, is a promising biomarker of cardiac dysfunction. In adult populations, BNP levels have been validated as diagnostic and prognostic markers in heart failure and other cardiovascular conditions, but evidence in pediatrics remains less established. Previous studies have suggested that BNP concentrations correlate with shunt volume and clinical severity in children with cyanotic congenital heart disease, and BNP has been investigated as a surrogate marker for hemodynamic burden in specific conditions such as large PDA with pulmonary hypertension in premature infants. Nonetheless, the utility of BNP for routine evaluation of shunt significance in infants with congenital heart disease remains a matter of ongoing investigation.

The study was carried out at two tertiary care hospitals between October 2024 and April 2025 and enrolled 61 infants diagnosed with left-to-right shunt lesions confirmed by echocardiography: 26 with ASD, 25 with VSD, and 10 with PDA. A control group of 30 age- and sex-matched healthy infants admitted to the same hospitals was also included. All participants underwent detailed clinical history, physical examination, and echocardiographic and hemodynamic evaluation. Plasma BNP levels were measured using a commercially available chemiluminescent microparticle immunoassay. Shunt severity was classified as non-significant when the pulmonary-to-systemic flow ratio (Qp/Qs) was below 1.5, mild between 1.5 and 2.0, and marked above 2.0. Mean pulmonary artery pressure (mPAP) was estimated using the tricuspid regurgitation pressure gradient in all included patients.

Clinical manifestations such as exertional dyspnea, dyspnea during feeding, failure to thrive, crepitation, and heart failure on treatment were notably more common in infants with VSD and PDA compared with those with ASD. Echocardiography revealed markedly higher mPAP in VSD (43.1 ± 13.7 mmHg) and PDA (46.5 ± 16 mmHg) compared with ASD (22.2 ± 5.1 mmHg, P < 0.001). Pressure gradient across the defect was present only in VSD. Left ventricular dilation was observed in 96 percent of VSD and 90 percent of PDA patients versus none in ASD, while preserved ejection fraction was seen in all ASD patients but only 60 percent of VSD and 30 percent of PDA patients. Tricuspid regurgitation severity also differed significantly, with moderate regurgitation predominating in VSD. The Qp/Qs ratio indicated a significantly higher proportion of marked shunts in VSD (56 percent) and PDA (60 percent) compared with ASD (19.2 percent).

Plasma BNP levels differed significantly between the studied groups. Median levels were highest in PDA at 125 pg/ml, compared with 40 pg/ml in VSD, 30 pg/ml in ASD, and 14.5 pg/ml in healthy controls. BNP also differed according to shunt significance by Qp/Qs ratio, with markedly higher levels in infants with significant shunts (median 80 pg/ml) compared with those with mild shunts (31 pg/ml) and non-significant shunts (15 pg/ml). Spearman correlation analysis demonstrated a statistically significant positive relationship between plasma BNP levels and mPAP across all cases (rs = 0.676, P < 0.001), with significant positive correlations within each lesion type: ASD (rs = 0.830), VSD (rs = 0.798), and PDA (rs = 0.703). The strongest correlation was observed in the ASD group.

ROC curve analysis for plasma BNP to predict the presence of a left-to-right shunt revealed excellent diagnostic performance with an AUC of 0.939 (95 percent CI: 0.884–0.979). The best cutoff point was above 23.5 pg/ml, at which sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were 85.5 percent, 100 percent, 100 percent, 76.9 percent, and 90 percent, respectively. Subgroup analysis showed more modest diagnostic ability for ASD (AUC 0.58) and good performance for VSD (AUC 0.70), while BNP demonstrated strong diagnostic performance for PDA (AUC 0.896), where a cutoff above 77.5 pg/ml yielded 80 percent sensitivity and 90 percent specificity. For predicting shunt significance by Qp/Qs ratio, BNP showed excellent performance for mild significance (AUC 0.91) and equally good performance for marked significance (AUC 0.87).

In a multivariable model adjusted for age and sex, age was not significantly associated with log-transformed BNP levels, indicating that BNP levels were more closely related to hemodynamic burden than to demographic factors. Hemodynamically significant shunts remained strong independent predictors of BNP elevation compared with healthy controls, with the highest relative fold-increase observed in PDA, followed by VSD and ASD. This is physiologically consistent with greater volume overload and myocardial stretch in larger left-to-right shunts. The modest BNP elevation in ASD likely reflects the fact that BNP is more closely associated with ventricular wall stress than with isolated atrial volume loading, as ASD is characterized by volume and pressure overloading of the right chambers of the heart.

The authors acknowledge several limitations. The small number of PDA cases (n = 10) introduces wide 95 percent confidence intervals, particularly for sensitivity estimates, and diagnostic performance metrics can appear unstable in small samples. The study also had a single-center design and used convenience sampling, which may limit generalizability. The lack of invasive hemodynamic validation as cardiac catheterization was not routinely performed due to the non-invasive study design, and the single time-point BNP measurement prevents assessment of longitudinal changes after intervention. Larger multicenter studies with serial BNP measurements are needed to confirm these findings and define BNP’s prognostic value.

Despite these limitations, the clinical implications are important, especially in low- and middle-income regions where access to echocardiography or catheterization is limited. BNP measurement is simple, reproducible, and minimally invasive, and its ability to distinguish hemodynamically significant from non-significant shunts may guide early intervention and improve outcomes. Taken together, these data position BNP as a robust adjunct to conventional imaging in assessing the hemodynamic significance of acyanotic congenital heart disease, with the consistently higher BNP observed in PDA highlighting the particular burden this lesion imposes on ventricular stress and pulmonary circulation.

Subject of Research: Plasma BNP as a non-invasive biomarker for assessing shunt significance in infants with left-to-right congenital heart disease

Article Title: Correlation of plasma B-type natriuretic peptide with shunt significance in infants with left-to-right congenital heart disease

Article References: Elbayaa, D. A., Handouka, N. M., Eita, A. A. E., Elafifi, A., & Gobarah, A. A. (2026). Correlation of plasma B-type natriuretic peptide with shunt significance in infants with left-to-right congenital heart disease. Egyptian Pediatric Association Gazette, 74(1), Article 113. https://doi.org/10.1186/s43054-026-00608-2

Image Credits: AI Generated

DOI: 10.1186/s43054-026-00608-2

Keywords: BNP, congenital heart disease, left-to-right shunt, ASD, VSD, PDA, pulmonary artery pressure, Qp/Qs ratio, diagnostic accuracy, ROC curve, infants, echocardiography