Observational Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Dec 26, 2017; 9(12): 822-829
Published online Dec 26, 2017. doi: 10.4330/wjc.v9.i12.822
Endothelin-1 activation in pediatric patients undergoing surgical coarctation of the aorta repair
Benjamin Steven Frank, Tracy T Urban, Suhong Tong, Courtney Cassidy, Max B Mitchell, Christopher S Nichols, Jesse A Davidson
Benjamin Steven Frank, Jesse A Davidson, Division of Cardiology, Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, United States
Tracy T Urban, Children’s Hospital Colorado Research Institute, Aurora, CO 80045, United States
Suhong Tong, Department of Biostatistics, University of Colorado Denver, Aurora, CO 80045, United States
Courtney Cassidy, Department of Pediatric Cardiology, Children’s Hospital Colorado, Aurora, CO 80045, United States
Max B Mitchell, Department of Surgery, University of Colorado Denver, Aurora, CO 80045, United States
Christopher S Nichols, Department of Anesthesiology, University of Colorado Denver, Aurora, CO 80045, United States
Author contributions: Frank BS and Davidson JA primarily designed the research; Urban TT, Tong S, Cassidy C, Mitchell MB and Nichols CS contributed to study conception and design; Frank BS and Urban TT collected the clinical data; Cassidy C collected and analyzed the echocardiographic data; Tong S performed the statistical analysis; Frank BS and Davidson JA primarily wrote the article; Urban TT, Tong S, Cassidy C, Mitchell MB and Nichols CS contributed to editing, reviewing, and final approval of the article.
Supported by NIH/NCATS Colorado CTSA, No. UL1 TR00 1082-04. Contents are the authors’ sole responsibility and do not necessarily represent official NIH views. The study sponsor had no input into the study design, collection, analysis, and interpretation of data, the writing of the report, and the decision to submit the paper for publication.
Institutional review board statement: This study was reviewed and approved by the Colorado Multiple Institution Review Board.
Informed consent statement: Written informed consent was obtained from the study subjects’ parents in all cases. Written assent was obtained from all subjects aged between seven years and eighteen years.
Conflict-of-interest statement: The authors have no conflicts of interest to disclose. Dr. Davidson is supported by NIH/NHLBI 1K23HL123634. This funding source was not used to generate the data presented in this manuscript.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Benjamin Steven Frank, MD, Academic Fellow, Division of Cardiology, Department of Pediatrics, University of Colorado Denver, 13123 E. 16th Ave, Box B100, Aurora, CO 80045, United States. benjamin.frank@childrenscolorado.org
Telephone: +1-720-7771954 Fax: +1-720-7777290
Received: August 24, 2017
Peer-review started: August 25, 2017
First decision: September 25, 2017
Revised: October 21, 2017
Accepted: November 10, 2017
Article in press: November 10, 2017
Published online: December 26, 2017
Abstract
AIM

To determine endothelin-1 (ET-1) concentration before and after surgical coarctectomy and evaluate its association with left ventricular geometric change.

METHODS

A prospective, cohort study of 24 patients aged 2 d to 10 years with coarctation of the aorta undergoing surgical repair. A sub-cohort of patients with age < 1 mo was classified as “neonates”. Echocardiograms were performed just prior to surgery and in the immediate post-op period to assess left ventricle mass index and relative wall thickness (RWT). Plasma ET-1 levels were assessed at both time points. Association between ET-1 levels and ventricular remodeling was assessed.

RESULTS

Patients < 1 year demonstrated higher pre-op ET-1 than post-op (2.8 pg/mL vs 1.9 pg/mL, P = 0.02). Conversely, patients > 1 year had no change in ET-1 concentration before and after surgery (1.1 vs 1.4, NS). Pre-op, patients < 1 year demonstrated significantly higher ET-1 than older children (2.8 vs 1.1, P = 0.001). Post-op there was no difference between the age groups (1.9 vs 1.4, NS). Neither RWT nor left ventricle mass index (LVMI) varied from pre-op to post-op. The subset of neonates showed a strong positive correlation between pre-op ET-1 and RWT (r = 0.92, P = 0.001). Patients with ET-1 > 2 pg/mL pre-op demonstrated higher LVMI (65.7 g/m2.7vs 38.5 g/m2.7, P = 0.004) and a trend towards higher RWT (45% vs 39%, P = 0.07) prior to repair than those with lower ET-1 concentration.

CONCLUSION

ET-1 concentration is significantly variable in the peri-operative period surrounding coarctectomy. Older children and infants have different responses to surgical repair suggesting different mechanisms of activation.

Keywords: Biomarkers, Cardiac remodeling, Pediatric, Neonate, Left ventricular hypertrophy

Core tip: Patients with coarctation of the aorta are at risk for a variety of short- and long-term complications after surgical repair. Endothelin-1 (ET-1) is a peptide hormone known to cause both cardiac myocyte hypertrophy and vasoconstriction that has been linked to late ventricular hypertrophy in this population. Peri-operative endothelin concentration in this population has not been previously defined. We demonstrate that neonates with coarctation of the aorta have high pre-operative ET-1 levels that decrease post-operatively. Older coarctation patients have more modest ET-1 activation that is unchanged post-operatively. These findings suggest two distinct patterns of ET-1 activation within this population.