Usefulness of N-Terminal-Pro-B-Type Natriuretic Peptide as a Screening Tool for Identifying Pediatric Patients with Congenital Heart Disease

Emmanuel Jairaj Moses, BSc(Hons), MSc; Sharifah A.I. Mokhtar, MBBCh (Hons), MMed; Amir Hamzah, MD, MMed; Basir Selvam Abdullah, BSc; Narazah Mohd Yusoff, MBBS, MMed, PhD

Disclosures

Lab Med. 2011;42(2):75-80. 

In This Article

Results

Congenital heart disease patients who were symptomatic and asymptomatic had significantly higher values of NT-proBNP (mean=1361 pg/mL, P<0.001 and mean=238 pg/mL, P=0.005), respectively, compared to healthy patients (mean=120 pg/mL). N-terminal-pro-B-type natriuretic peptide levels were much higher in CHD patients with dilated left heart chambers (mean=676 pg/mL, P<0.001) or dilated right heart chambers (mean=660 pg/mL, P<0.001). Congenital heart disease patients with non-dilated heart chambers had lower NT-proBNP values (mean=251 pg/mL). However, this level was still significantly higher (P=0.039) than the value obtained for healthy patients. Patients with acyanotic heart diseases had high NT-proBNP levels (mean=372 pg/mL, P<0.001) compared to normal patients. The levels in patients with cyanotic heart disease were higher still (mean=1023 pg/mL, P<0.001). There was a non-significant increase of NT-proBNP levels in patients with mild CHD (mean=151 pg/mL; P=0.567). However, this changed drastically as the disease progressed to moderate (mean=512 pg/mL, P<0.001) and severe (mean=2512 pg/mL).There was no significant difference of NT-proBNP levels between healthy male and female subjects (P=0.392). A similar observation was made between male CHD patients and female CHD patients (P=0.085).

Multiple linear regression analysis was carried out to determine the strongest predictors of NT-proBNP levels. A good regression model was obtained (adjusted R2=0.780, F5,146=107.93, P<0.001). Based on this model, the strongest factors that influenced NT-proBNP levels are the severity of the CHD (standardized β coefficient=0.788, P<0.001) and presence of CHD in general (standardized β coefficient=0.372, P<0.001).

Receiver operating characteristic (ROC) curves were constructed (Figure 2A-2D) to evaluate the diagnostic performance of this test in differentiating the various types of CHD. Based on the curves, a suitable cut-off value for NT-proBNP levels was chosen to select for pediatric patients with various types of CHD. An NT-proBNP cut-off value of 91 pg/mL could differentiate an Acyanotic Heart Disease (ACNHD) patient (n=101) from a healthy sample population (n=33) with a sensitivity of 84% and specificity of 42% (Figure 2A). On the other hand, congenital nonspherocytic hemolytic disease (CNHD) patients (n=18) could be differentiated from a healthy sample population (n=33) at an NT-proBNP cut-off value of 318 pg/mL with 94% sensitivity and 97% specificity (Figure 2B). Likewise, an NT-proBNP value of 408 pg/mL was 83% sensitive and 57% specific in differentiating patients with ACNHD (n=101) from patients with CNHD (n=18) (Figure 2C). Generally, a patient with CHD (n=119) could be differentiated from a healthy sample population (n=33) at a NT-proBNP cut-off value of 98 pg/mL with 82% sensitivity and 46% specificity (Figure 2D).

Figure 2.

(2A) Receiver operating characteristic curve showing the ability of NT-proBNP to identify patients with ACNHD (AUC [95%CI]: 0.75[0.67–0.83]). (2B) Receiver operating characteristic curve showing the ability of NT-proBNP to identify patients with CNHD (AUC [95%CI]: 0.98[0.94–1.01]). (2C) Receiver operating characteristic curve showing the ability of NT-proBNP to differentiate patients with ACNHD and CNHD (AUC [95%CI]: 0.74[0.63–0.84]). (2D) Receiver operating characteristic curve showing the ability of NT-proBNP to identify patients with CHD in general. (AUC [95%CI]: 0.79[0.72–0.86]).

Similarly, another set of ROC curves was constructed (Figure 3) to analyze the diagnostic performance of NT-proBNP in predicting the severity of the heart lesions. An NT-proBNP cut-off value of 64 pg/mL could differentiate patients with mild CHD (n=54) from the control patients (n=33) with a sensitivity of 83% and specificity of 30% (Figure 3A). Patients with moderate CHD (n=33) could be differentiated from the control patients (n=33) at an NT-proBNP cut-off value of 178 pg/mL with 92% sensitivity and 70% specificity (Figure 3B). This test can perfectly (sensitivity 100%, specificity 100%) discriminate between patients with severe CHD (n=29) from the healthy sample population (n=33) at an NT-proBNP level of 440 pg/mL.

Figure 3.

(3A) Receiver operating characteristic curve showing the ability of NT-proBNP to identify patients with mild CHD (AUC [95%CI]: 0.57[0.45–0.70]). (3B) Receiver operating characteristic curve showing the ability of NT-proBNP to identify patients with moderate CHD (AUC [95%CI]: 0.94 [0.88–0.99]). (3C) Receiver operating characteristic curve showing the ability of NT-proBNP to identify patients with severe CHD (AUC: 1.00).

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