Abstract
Current clinical risk assessment strategies have poor accuracy for identifying patients who will suffer adverse perioperative events. There is an ongoing need to integrate clinical variables with novel technology and biomarkers to accurately predict outcome after pediatric heart surgery. We tested the hypothesis that miRNAs-208a, -208b, and -499 can serve as noninvasive biomarkers for the extent of myocardial damage and the postoperative clinical course of pediatric patients with congenital heart defects (CHDs) at an early time point following surgery. Serum samples were obtained from 79 pediatric patients before and 6, 12, and 24 h after surgery. MiRNAs-208a, -208b, and -499 were quantified by RQ-PCR. Correlations between the patient’s clinical variables and miRNA levels were tested. Our results show that the levels of the three miRNAs were elevated at 6 h after surgery, remained high at 12 h and declined at 24 h after the operation. The amount of all three miRNAs at 6 h after surgery correlated with surgical and laboratory parameters. Their amount at 12 h after surgery correlated with the length of stay at the hospital. Expression levels of miRNA-208a at 6 h were related to the appearance of cardiac complications, and could predict whether a patient will sustain complications or will be ventilated for more than 48 h after surgery. Circulating miRNA-208a is a predictor for the risk of developing cardiac complications during the postoperative course as early as 6 h after heart surgery for CHD in pediatric patients.
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References
Jenkins KJ (2004) Risk adjustment for congenital heart surgery: the RACHS-1 method. Semin Thorac Cardiovasc Surg Pediatr Card Surg Ann 7:180–184
Jenkins KJ, Gauvreau K (2002) Center-specific differences in mortality: preliminary analyses using the Risk Adjustment in Congenital Heart Surgery (RACHS-1) method. J Thorac Cardiovasc Surg 124:97–104
Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355
Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T (2010) Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 285:17442–17452
Corsten MF, Dennert R, Jochems S, Kuznetsova T, Devaux Y, Hofstra L, Wagner DR, Staessen JA, Heymans S, Schroen B (2010) Circulating microRNA-208b and microRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genetics 3:499–506
Wang GK, Zhu JQ, Zhang JT, Li Q, Li Y, He J, Qin YW, Jing Q (2010) Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J 31:659–666
Wang E, Nie Y, Zhao Q, Wang W, Huang J, Liao Z, Zhang H, Hu S, Zheng Z (2013) Circulating miRNAs reflect early myocardial injury and recovery after heart transplantation. J Cardiothorac Surg 8:165
Yao Y, Du J, Cao X, Wang Y, Huang Y, Hu S, Zheng Z (2014) Plasma levels of microRNA-499 provide an early indication of perioperative myocardial infarction in coronary artery bypass graft patients. PLoS ONE 9:e104618
Zhou X, Mao A, Wang X, Duan X, Yao Y, Zhang C (2013) Urine and serum microRNA-1 as novel biomarkers for myocardial injury in open-heart surgeries with cardiopulmonary bypass. PLoS ONE 8:e62245
Bolkier Y, Nevo-Caspi Y, Salem Y, Vardi A, Mishali D, Paret G (2016) Micro-RNA-208a, -208b, and -499 as biomarkers for myocardial damage after cardiac surgery in children. Pediatr Crit Care Med 17:e193–e197
Tanindi A, Cemri M (2011) Troponin elevation in conditions other than acute coronary syndromes. Vasc Health Risk Manag 7:597–603
Momeni M, Poncelet A, Rubay J, Matta A, Veevaete L, Detaille T, Houtekie L, Clement de Clety S, Derycke E, Moniotte S, Sluysmans T, Veyckemans F (2017) Does postoperative cardiac troponin-I have any prognostic value in predicting midterm mortality after congenital cardiac surgery? J Cardiothorac Vasc Anesth 31:122–127
Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18:997–1006
Fernandes BA, Maher KO, Deshpande SR (2016) Cardiac biomarkers in pediatric heart disease: a state of art review. World J Cardiol 8:719–727
Lowenthal A, Camacho BV, Lowenthal S, Natal-Hernandez L, Liszewski W, Hills NK, Fineman JR, Bernstein HS (2012) Usefulness of B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide as biomarkers for heart failure in young children with single ventricle congenital heart disease. Am J Cardiol 109:866–872
Gidlof O, Smith JG, Miyazu K, Gilje P, Spencer A, Blomquist S, Erlinge D (2013) Circulating cardio-enriched microRNAs are associated with long-term prognosis following myocardial infarction. BMC Cardiovasc Disord 13:12
Cheng C, Wang Q, You W, Chen M, Xia J (2014) MiRNAs as biomarkers of myocardial infarction: a meta-analysis. PLoS ONE 9:e88566
Hammer S, Loeff M, Reichenspurner H, Daebritz S, Tiete A, Kozlik-Feldmann R, Reichart B, Netz H (2001) Effect of cardiopulmonary bypass on myocardial function, damage and inflammation after cardiac surgery in newborns and children. Thorac Cardiovasc Surg 49:349–354
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We thank Amisragas for their continuous support of the Department of Intensive Care. Esther Eshkol is thanked for editorial assistance.
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All procedures were performed in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from the legal representatives of all individual participants included in the study.
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Keren Zloto and Tal Tirosh-Wagner have contributed equally to this work.
Yael Nevo-Caspi and Gidi Paret have contributed equally to this work.
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Zloto, K., Tirosh-Wagner, T., Bolkier, Y. et al. MiRNA-208a as a Sensitive Early Biomarker for the Postoperative Course Following Congenital Heart Defect Surgery. Pediatr Cardiol 39, 1565–1571 (2018). https://doi.org/10.1007/s00246-018-1931-7
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DOI: https://doi.org/10.1007/s00246-018-1931-7