Biomarkers of Myocardial Injury in Congenital Heart Disease: More Questions than Answers
Journal
Pediatrics and Neonatology
Journal Volume
57
Journal Issue
6
Pages
451-452
Date Issued
2016
Author(s)
Abstract
Since the first study of a biochemical marker in myocardial injury was published in Science in 1954,1Ladue J.S. Wroblewski F. Karmen A. Serum glutamic oxaloacetic transaminase activity in human acute transmural myocardial infarction.Science. 1954; 120: 497-499Crossref PubMed Scopus (212) Google Scholar numerous circulating marker proteins have been identified as valuable biomarkers of acute myocardial injury. Currently, creatine kinase (CK)-MB mass (heart type), myoglobin, and troponin I are widely used in the diagnosis and risk stratification of myocardial ischemia in adults. Although this type of myocardial insult rarely occurs in patients with congenital heart disease (CHD), several studies have indicated that hemodynamic overload in CHD results in elevated levels of cardiac injury biomarkers, suggesting that myocardial damage also could be attributed to nonischemic etiologies.2Boucek Jr., R.J. Kasselberg A.G. Boerth R.C. Parrish M.D. Graham Jr., T.P. Myocardial injury in infants with congenital heart disease: evaluation by creatine kinase MB isoenzyme analysis.Am J Cardiol. 1982; 50: 129-135Abstract Full Text PDF PubMed Scopus (29) Google Scholar, 3Sugimoto M. Ota K. Kajihama A. Nakau K. Manabe H. Kajino H. Volume overload and pressure overload due to left-to-right shunt-induced myocardial injury. Evaluation using a highly sensitive cardiac troponin-I assay in children with congenital heart disease.Circ J. 2011; 75: 2213-2219Crossref PubMed Scopus (44) Google Scholar In this issue of Pediatrics and Neonatology, Neves et al4Neves A.L. Cabral M. Leite-Moreira A. Monterroso J. Ramalho C. Guimarães H. et al.Myocardial injury biomarkers in newborns with congenital heart disease.Pediatr Neonatol. 2016; 57: 488-495PubMed Scopus (8) Google Scholar measured the levels of CK-MB, myoglobin, and troponin I from either cord blood or peripheral blood in newborns with various types of CHD. Although the overall levels of these biomarkers were not statistically different from those in healthy controls, they found that the plasma level of CK-MB, mostly from cord blood, was predictive of the need for subsequent neonatal cardiac surgery. A cut-off value of 4.6 ng/mL was identified as having the best discriminative power to predict neonatal cardiac surgery. Furthermore, the authors demonstrated that the CK-MB level was related to tissue Doppler-derived left ventricular diastolic function, suggesting a pathophysiological etiology of elevated CK-MB in this cohort of newborns with CHD. It is generally believed that fetus with CHD, even with critical form of CHD, may have minimal hemodynamic stress under fetal circulation (except for those with severe right-sided valvular regurgitation). It is the transition from fetal to postnatal circulation that unmasks the hemodynamic impact in some cases of CHD. The results of Neves et al4Neves A.L. Cabral M. Leite-Moreira A. Monterroso J. Ramalho C. Guimarães H. et al.Myocardial injury biomarkers in newborns with congenital heart disease.Pediatr Neonatol. 2016; 57: 488-495PubMed Scopus (8) Google Scholar challenge this concept. Their data imply that myocardial injury is already present at the fetal stage (or at least at the perinatal stage). Previously, inflammatory, fibrotic, and angiogenic factors in cord blood have been investigated in fetuses with cardiac neonatal lupus and CHD.5Saxena A. Izmirly P.M. Han S.W. Briassouli P. Rivera T.L. Zhong H. et al.Serum biomarkers of inflammation, fibrosis, and cardiac function in facilitating diagnosis, prognosis, and treatment of anti-SSA/Ro-associated cardiac neonatal lupus.J Am Coll Cardiol. 2015; 66: 930-939Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 6Llurba E. Sánchez O. Ferrer Q. Nicolaides K.H. Ruíz A. Domínguez C. et al.Maternal and foetal angiogenic imbalance in congenital heart defects.Eur Heart J. 2014; 35: 701-707Crossref PubMed Scopus (84) Google Scholar The results from the Neves et al study4Neves A.L. Cabral M. Leite-Moreira A. Monterroso J. Ramalho C. Guimarães H. et al.Myocardial injury biomarkers in newborns with congenital heart disease.Pediatr Neonatol. 2016; 57: 488-495PubMed Scopus (8) Google Scholar provide novel insights into the process of myocardial damage related to CHD by measuring cardiac injury biomarkers in the cord blood. Nonetheless, several limitations must be addressed. The authors pooled cord blood and peripheral blood in their analyses. As mentioned in their study results, these cardiac injury biomarkers were significantly higher in peripheral blood samples than in cord blood. Therefore, providing a single cut-off value of CK-MB from a mixture of cord blood and peripheral blood for assessing the risk of neonatal cardiac surgery was unreasonable. In addition, since dramatic hemodynamic changes may occur after birth, correlation analysis between circulating biomarkers and echocardiographic parameters should be performed using both types of data acquired simultaneously. Furthermore, the study group consisted of a mixed, heterogeneous population of CHD cases, and the sample size of each type of CHD was quite limited. Therefore, it remains unknown whether the CK-MB level differs among different types of CHD. Finally, there was no data regarding the potential differences in CK-MB level in newborns with the same type of CHD but different clinical severity. As a result, it is far from clear whether measuring CK-MB level can guide therapy in newborns with CHD. The author has no conflicts of interest to declare.
SDGs
Other Subjects
biological marker; creatine kinase; myoglobin; troponin I; biological marker; blood level; congenital heart disease; Editorial; fetus circulation; heart muscle injury; hemodynamic stress; human; umbilical cord blood; congenital heart malformation; heart injury; Biomarkers; Heart Defects, Congenital; Heart Injuries; Humans
Publisher
Elsevier (Singapore) Pte Ltd
Type
editorial