MicroRNAs as potential biomarkers in congenital heart surgery

J Thorac Cardiovasc Surg. 2020 Apr;159(4):1532-1540.e7. doi: 10.1016/j.jtcvs.2019.03.062. Epub 2019 Apr 4.

Abstract

Objective: Pediatric congenital heart surgery (CHS) involves intracardiac, valvular, and vascular repairs. Accurate tools to aid short-term outcome prediction in pediatric CHS are lacking. Clinical scores, such as the vasoactive-inotrope score and ventilation index, are used to define outcome in clinical studies. MicroRNA-1-3p (miR-1) is expressed by both cardiomyocytes and vascular cells and is regulated by hypoxia. In adult patients, miR-1 increases in the circulation after open-heart cardiac surgery, suggesting its potential as a clinical biomarker. Thus, we investigated whether perioperative circulating miR-1 measurements can help predict post-CHS short-term outcomes in pediatric patients.

Methods: Plasma miR-1 was retrospectively measured in a cohort of 199 consecutive pediatric CHS patients (median age 1.2 years). Samples were taken before surgery and at the end of the operation. Plasma miR-1 concentration was measured by reverse transcription-quantitative polymerase chain reaction and expressed as miR-1 copies/μL and as relative expression to spiked-in exogenous cel-miR-39.

Results: Baseline plasma miR-1 did not vary across different diagnoses, increased during surgery (204-fold median relative increase, P < .001), and was associated with aortic crossclamp duration postoperatively (P < .001). Importantly, miR-1 levels at the end of the operation positively correlated with intensive care stay (P < .001), early severe cardiovascular events (P = .01), and with high vasoactive-inotrope score (P = .001) and ventilation index (P < .001), suggesting that miR-1 could accelerate the identification of patients with cardiopulmonary bypass-related ischemic complications, requiring more intensive support.

Conclusions: Our study suggests miR-1 as a novel potential circulating biomarker to predict early postoperative outcome and inform clinical management in pediatric heart surgery.

Keywords: biomarkers; congenital heart disease; microRNAs; outcome prediction; pediatric cardiac surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Cardiac Surgical Procedures / adverse effects*
  • Child, Preschool
  • Cohort Studies
  • Female
  • Heart Defects, Congenital / metabolism*
  • Heart Defects, Congenital / surgery*
  • Humans
  • Infant
  • Length of Stay
  • Male
  • MicroRNAs / blood*
  • Postoperative Complications / blood*
  • Postoperative Complications / etiology*
  • Predictive Value of Tests

Substances

  • Biomarkers
  • MIRN1 microRNA, human
  • MicroRNAs