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 alpha, and soluble tumor necrosis factor receptor II were measured. RESULTS NT-proBNP and hsCRP were significantly elevated with more severe symptoms (P < or = .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 < or = .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 alpha was negatively associated with LVSF and LVSFz (P < or = .03) and positively associated with LVSDz and NT-proBNP (P < or = .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 HF. Blood levels of these biomarkers could be used to better assess the severity of HF in children.

[1]  N. Reichek,et al.  Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. , 1989, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[2]  E John Orav,et al.  The incidence of pediatric cardiomyopathy in two regions of the United States. , 2003, The New England journal of medicine.

[3]  M. Schluchter,et al.  Left ventricular structure and function in children infected with human immunodeficiency virus: the prospective P2C2 HIV Multicenter Study. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2 HIV) Study Group. , 1998, Circulation.

[4]  A. Wessel,et al.  Endogenous nitric oxide and soluble tumor necrosis factor receptor levels are enhanced in infants with congenital heart disease , 2001, Critical care medicine.

[5]  W. Pinsky,et al.  Grading the severity of congestive heart failure in infants , 1992, Pediatric Cardiology.

[6]  S. Lipshultz,et al.  Ventricular dysfunction clinical research in infants, children and adolescents. , 2000, Progress in pediatric cardiology.

[7]  G. Manoharan,et al.  Head to head comparison of N-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in patients with/without left ventricular systolic dysfunction. , 2006, Clinical biochemistry.

[8]  H. Miller,et al.  Role of cytokines in heart failure. , 1998, American heart journal.

[9]  S. T. Buckland,et al.  An Introduction to the Bootstrap. , 1994 .

[10]  M. Konstam.  Natriuretic peptides and cardiovascular events: more than a stretch. , 2007, JAMA.

[11]  K. Watterson,et al.  Release of proinflammatory cytokines during pediatric cardiopulmonary bypass: heparin-bonded versus nonbonded oxygenators. , 1997, The Annals of thoracic surgery.

[12]  Stephan von Haehling,et al.  Inflammatory mediators in chronic heart failure: an overview , 2004, Heart.

[13]  J. Towbin,et al.  B-Type Natriuretic Peptide Predicts Adverse Cardiovascular Events in Pediatric Outpatients With Chronic Left Ventricular Systolic Dysfunction , 2006, Circulation.

[14]  A. Olshan,et al.  Multiple comparisons and related issues in the interpretation of epidemiologic data. , 1995, American journal of epidemiology.

[15]  S. Colan,et al.  Cardiovascular trials in long-term survivors of childhood cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  R. Rodeheffer.  Measuring plasma B-type natriuretic peptide in heart failure: good to go in 2004? , 2004, Journal of the American College of Cardiology.

[17]  K. Trinkaus,et al.  Relation of age, severity of illness, and hemodynamics with brain natriuretic peptide levels in patients <20 years of age with heart disease. , 2005, The American journal of cardiology.

[18]  J. Cohn,et al.  C-Reactive Protein in Heart Failure: Prognostic Value and the Effect of Valsartan , 2005, Circulation.

[19]  W. Yin,et al.  Independent prognostic value of elevated high-sensitivity C-reactive protein in chronic heart failure. , 2004, American heart journal.

[20]  S. Colan,et al.  Factors Associated With Establishing a Causal Diagnosis for Children With Cardiomyopathy , 2006, Pediatrics.

[21]  C. Yiannoutsos,et al.  Ordered multiple‐class ROC analysis with continuous measurements , 2004, Statistics in medicine.

[22]  S. Colan,et al.  Incidence, causes, and outcomes of dilated cardiomyopathy in children. , 2006, JAMA.

[23]  K. Dickstein,et al.  Plasma levels of soluble tumor necrosis factor receptor type I during the acute phase following complicated myocardial infarction predicts survival in high-risk patients. , 2005, Journal of the American College of Cardiology.

[24]  T. Mir,et al.  N-Terminal pro-brain natriuretic peptide: normal ranges in the pediatric population including method comparison and interlaboratory variability , 2006, Clinical chemistry and laboratory medicine.

[25]  C. Carlson,et al.  Association of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events. , 2006, JAMA.

[26]  D. Mann,et al.  Cytokines and Cytokine Receptors in Advanced Heart Failure: An Analysis of the Cytokine Database from the Vesnarinone Trial (VEST) , 2001, Circulation.