Serum B-Type Natriuretic Peptide as a Biomarker for Clinical Severity of Heart Failure in Pediatric Heart Disease

Congestive heart failure is a chronic disease. One of the challenges in managing patients with heart failure is developing methods of assessing the severity of each patient’s illness and tailoring treatment to match it. At present, there are numerous modalities used to describe patients in heart failure. The clinical history, examination, laboratory tests, radiographs, functional, and invasive testing all provide glimpses into the natural history of the disease, but only reveal unrelated facets of the disease. A great challenge is learning to connect this diverse stream of data. Several biochemical markers have been identified that are elevated in patients with heart failure and which react dynamically to changes in cardiac physiology. If they can reliably determine the progress of cardiac disease and guide therapy they would be a useful addition to the cardiologist’s armamentarium. The purpose of this study is to determine if one of these markers, B-type natriuretic peptide (BNP) can reliably demonstrate the severity of illness in patients as determined by clinical history and other forms of testing. BNP is a thirty-two amino acid peptide produced by ventricular myocytes, which has been shown to have vasodilatory, diuretic, and natriuretic properties. Additionally, there is evidence that suppresses both the sympathetic nervous system and renin-angiotensin axis, the neurohormonal axis linked to structural remodeling and ventricular dysfunction in chronic heart failure. Studies have demonstrated that levels of serum BNP are dramatically higher in patients with both acute and chronic heart failure. This was first demonstrated in patients presenting to emergency departments with a chief complaint of dyspnea. In these studies, a serum BNP, quantified by radioimmunoassay (RIA), over 100 pg/mol differentiated between cardiogenic and non-cardiogenic dyspnea with a sensitivity of 90% and specificity of 73-76%, rates superior to all other markers [1, 2] In other settings BNP has had mixed results as a screening test for cardiac disease. The use of BNP in a primary care setting as an initial screen for cardiac disease was not able to demonstrate improvements in screening for early heart failure [3]. However, in an ICU setting, BNP has been shown to be a sensitive screen for previously unidentified cardiac dysfunction [4]. This suggests that for populations with higher prevalence of cardiac failure, BNP can effectively screen for ventricular dysfunction. Prospective trials comparing serum BNP to other diagnostic modalities, such as impedance cardiography and tissue Doppler, have confirmed BNP’s efficacy as a screen for ventricular dysfunction, establishing serum BNP thresholds (98-150 pg/mol on RIA) for the detection of CHF with high sensitivity (65-92%) and specificity (85-88%) [4-6]. Several studies have demonstrated that serum BNP levels in children with ventricular stress are elevated, in a similar fashion to adults. A retrospective study demonstrated that ventricular dysfunction can be correlated with elevated BNP (mean: 623 + 146 pg/mol) and that a cut-off of 40 pg/mol identified ventricular dysfunction with a sensitivity of 85% and specificity of 81% [7]. A prospective study in pediatric patients with ventricular septal defect corroborated this, noting that BNP could be used to identify increased ventricular pressure loads; BNP > 20 pg/mol screened for elevated pulmonary artery pressures (>20 mmHg) with a sensitivity of 82% and specificity of 89% [8]. This suggests that in both adult and pediatric populations BNP is grossly elevated in populations with increased ventricular stress. However, it is not clear whether adult normative data can be applied to children, as the hemodynamic profiles of children undergo radical changes through normal development. One small study in preterm infants demonstrated that BNP levels are transiently elevated in the first week of life, but that in patients with normal anatomy, BNP levels rapidly normalize to adult levels [9]. However, it is unclear 1) whether BNP levels remain at this level in normal children throughout their development and 2) whether serum BNP in a diseased state varies consistently in ill patients of different ages.