Serial Measurement of Amino-Terminal Pro-B-Type Natriuretic Peptide Predicts Adverse Cardiovascular Outcome in Children With Primary Myocardial Dysfunction and Acute Decompensated Heart Failure

Abstract

Introduction In children, elevated amino terminal pro B-type naturetic peptide (NT-proBNP) levels are associated with impaired heart function. The predictive value of serial monitoring of NT-proBNP levels in acute decompensated heart failure (ADHF) is unclear. Methods This prospective observational study enrolled patients ≤ 21 years with primary myocardial dysfunction and ADHF. NT-proBNP levels were obtained on enrollment (D0), day 2 (D2) and day 7 (D7). Clinical, laboratory and imaging data were collected on enrollment. CV outcome was defined as Heart Transplant (HTx), Ventricular Assist Device (VAD) placement, Extracorporeal Membrane Oxygenation or death at 1 year after admission. NT-proBNP levels and the percent change from D0 to D2 and D0 to D7 were calculated and compared between those with and without adverse cardiovascular (ACV) outcome. Results Sixteen consecutive patients were enrolled. ACV outcome occurred in 6 (37.5%, 4 HTx and 2 VAD). In patients with an ACV outcome, median NT-ProBNP levels at D7 were significantly higher (7,365 Vs. 1,196 pg/ml; p= 0.02) and the percent decline in NT-proBNP was significantly smaller (28% vs. 73%, p=0.02) compared to those without an ACV outcome. ROC curve analysis revealed that a less than 55% decline in NT-proBNP levels at D7 had a sensitivity and specificity of 83% and 90% respectively in predicting an ACV [AUC 0.86, CI (0.68,1.0), p=0.02]. Conclusions In conclusion, children with primary myocardial dysfunction and ADHF, a persistently elevated NT-proBNP and/or a lesser degree of decline in NT-proBNP during the first week of presentation were strongly associated with ACV outcome. Serial NT-proBNP monitoring may allow the early identification of children at risk for worse outcome.

Pediatric Cardiomyopathies

“…51–53 The use of cardiac biomarkers, including B-type natriuretic peptide in DCM, have been helpful in defining children with DCM at high-risk. 54–56 However, extrapolation of adult data has been difficult given pediatric patients have different normative ranges and there is more heterogeneity in this population. 57 …”

“…49, 54, 104 B-type natriuretic peptide levels at hospital admission may be less important than the level when clinically stable or the change in levels with therapy. 55, 56 More specific biomarkers are needed to distinguish patients at highest risk death from those likely to recover. Potential targets for investigation include genetic variants, circulating or imaging markers of inflammation or stress, neurohormonal abnormalities, microRNA, viral genome on endomyocardial biopsy, and markers of extracardiac impairment.…”

Predicting outcome in children with dilated cardiomyopathy: the use of repeated measurements of risk factors for outcome

“…Also, we demonstrated that follow‐up parameters like NT‐proBNP, 6 min walking distance, and longitudinal strain, all obtained relatively early after presentation in cross‐sections of our national cohort of children with DCM, contained important prognostic information 5–8 . However, changes in these risk factors during the further course of the disease, alone or in concert, might hold valuable prognostic information as well 2,6,9 . This may further pinpoint the group of children at the highest risk for adverse outcome, which is essential as these are the patients who should be monitored closely and, importantly, be listed for HTx at a timely stage.…”

Recent and Upcoming Drug Therapies for Pediatric Heart Failure

“…In the pediatric population, the use of BNP and or NT proBNP has been recommended to stratify the severity, and to monitor the progression of HF. To date there is some evidence in children that BNP or NT-proBNP can act as surrogate markers of the likelihood of admission to hospital, as well, the necessity of mechanical circulatory support, or heart transplant after admission with ADHF (85)(86)(87)(88). Recently, a multi-biomarker approach to risk stratification in heart failure has become popular.…”