Associations between neurohormonal and inflammatory activation and heart failure in children

Background Adult heart failure (HF) has been shown to be associated with neuroendocrine and inflammatory activation. We hypothesize that neuroendocrine and inflammatory activation also associate with symptom severity and echocardiographic measurements in pediatric HF. Methods Nineteen children with HF were divided into 3 symptom severity groups. Measurements were made of left ventricular (LV) ejection fraction, LV shortening fraction (LVSF), LV shortening fraction Z score (LVSFz), and LV end-systolic (LVSDz) and diastolic diameter Z scores. Blood levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor a, and soluble tumor necrosis factor receptor II were measured. Results NT-proBNP and hsCRP were significantly elevated with more severe symptoms (P <= .003) and discriminated between clinical severity groups (volume under the receiver operating characteristic surface = 0.58 and 0.62, P = .007 and P = .002, respectively). NT-proBNP was negatively associated with LV ejection fraction, LVSF, and LVSFz (P <= .05) and positively associated with LVSDz (P < .001). High-sensitivity C-reactive protein was negatively associated with LVSF (P = .02) and positively associated with NT-proBNP (P = .03). Tumor necrosis factor a was negatively associated with LVSF and LVSFz (P = .03) and positively associated with LVSDz and NT-proBNP (P <= .02). Soluble tumor necrosis factor receptor II was negatively associated with LVSFz (P = .03). Conclusions Neuroendocrine and inflammatory activation are associated with more severe symptoms and worse cardiac characteristics in pediatric HE Blood levels of these biomarkers could be used to better assess the severity of HF in children.