Cardiac Biomarkers in Pediatrics

Bottom Line Up Front (BLUF):

1. Compared to healthy adults, the serum troponin and BNP levels in healthy neonates and infants less than 1 year have normal ranges with 99th percentiles nearly two orders of magnitude greater.
2. Though studies have begun to quantify the normal ranges in pediatric populations, as of January 2022, no diagnostic cutoffs have been validated (or even proposed).
3. Indeed, considering the markedly higher normal ranges, and as argued by Assandro et al in 2013, these cardiac biomarkers may lack the ability to distinguish disease from non-disease in some (or all) pediatric age groups.
4. No one should order a cardiac biomarker in pediatric patients with the intent to rule-in or rule-out disease without:
   • Evidence that the marker can distinguish disease from non-disease (as represented by the AUROC) in the age group in question.
   • Knowing the diagnostic-cutoff for the disease in question, as well as the sensitivity and specificity associated with that cutoff.
5. False-positive interpretation of cardiac biomarkers can lead to unnecessary invasive testing, which is itself a harm, but which also carries a non-negligible risk of additional harm (i.e. procedural complications).
6. If a consultant recommends ordering a troponin or BNP in one of these age groups, the consulting provider should inquire about the cut-off, the sensitivity, and the specificity; if the consultant cannot provide this information, further research and/or additional consultants should be strongly considered prior to ordering these tests. There is very little clinical utility to a test result which no one knows how to interpret, and there is a risk of harm from a test result which is likely to be misinterpreted.

TROPONIN

Biochemistry

Released due to multiple types of myocardial injury (ischemia, necrosis, apoptosis, cytotoxicity, inflammation). Certain levels, in the proper context, constitute the definition of myocardial infarction. However, troponin can undergo non-ischemic release during heart failure, inflammation, and other conditions (such as infiltrative diseases).[REF]

BNP

Biochemistry

Released solely due to myocardial stretch/strain of the left ventricle, which is usually synonymous with heart failure.[REF]

METHODS

Literature searches were performed for the specific test types available at YKDRH:

1. high-sensitivity Troponin T
2. N-Terminal pro-BNP

Broader searches, such as for troponin in general are prone to return results for conventional low sensitivity troponin or for troponin-I; data from these are not applicable to interpretation of high-sensitivity troponin-T. Similarly, data regarding B-type natriuretic peptide (BNP) cannot be applied to the test which we have, which is N-Terminal Pro-BNP.

Troponin-T PubMed Search

(pediatric*[Title] OR neonat*[Title] OR infant*[Title] OR child*[Title] or adolescant*[Title]) AND (troponin T[Title] AND high-sensitivity[Title]) Search

with diagnostic outcomes:

(pediatric*[Title] OR neonat*[Title] OR infant*[Title] OR child*[Title] or adolescant*[Title]) AND (troponin T[Title] AND high-sensitivity[Title]) AND ("area under the receiver operating characteristic curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity*[Title/Abstract])

BNP PubMed Search

(pediatric*[Title] OR neonat*[Title] OR infant*[Title] OR child*[Title] or adolescant*[Title]) AND (BNP[Title] OR "N-Terminal pro-B-Type Natriuretic Peptide"[Title]) Search

with diagnostic outcomes:

(pediatric*[Title] OR neonat*[Title] OR infant*[Title] OR child*[Title] or adolescant*[Title]) AND ("N-Terminal pro-B-Type Natriuretic Peptide"[Title]) AND ("area under the receiver operating characteristic curve"[Title/Abstract] OR AUROC[Title/Abstract] OR specificity[Title/Abstract]) Search

REFERENCES

Keywords

Cardiac Biomarker Troponin BNP Pediatric Neonate Infant Toddler Child Adolescant

Author[s]

Andrew W. Swartz, MD

Reviewer[s]

Leslie Herrmann, MD