# Pharmacogenetics and Personalized Medicine after Cardiac Surgery in Children

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $638,941

## Abstract

Project Summary
Congenital heart disease (CHD) is the most common human congenital malformation, and represents a
leading cause of infant mortality. Roughly half of children with CHD will require surgical repairs/palliations, and
are at risk for postoperative complications. Arrhythmias are common after CHD surgery, contribute
substantially to morbidity and mortality, and are important long-term concerns for the more than 1 million US
adults living with CHD. An individual patient's risk for arrhythmias is variable and not predicted by clinical
factors alone, thus we hypothesize that genetic variants predispose patients to these serious complications.
Dexmedetomidine is a widely used sedative after CHD surgery but is associated with marked inter-patient
variability in efficacy, and potential adverse effects including bradyarrhythmias. Previous studies in adults have
demonstrated genetic variants that alter dexmedetomidine pharmacodynamics, but studies in children have not
been performed. The long term goal of this research program is to identify genetic variants that affect adverse
outcomes after CHD surgery, along with actionable pharmacogenetic (drug-gene) interactions, in order to
perform pre-operative genotyping and incorporation of genetic and clinical risk factors into individualized
treatment plans, ultimately improving the care and reducing mortality and morbidity for patients with CHD. In
order to achieve these goals, we established an ongoing cohort of over 1,600 children undergoing more than
2,200 CHD surgical procedures with detailed phenotypic information, coupled with DNA samples. Further, we
have developed methods using mass spectrometry to accurately determine drug concentrations using small
sample volumes (100µL plasma) enabling the use of leftover plasma from blood samples obtained for clinical
purposes to probe disposition of drugs such as dexmedetomidine. In Specific Aim 1, we will test the hypothesis
that genetic variants are associated with atrial arrhythmias after CHD surgery in children under 1 year of age.
In Specific Aim 2 we will test the hypothesis that genetic variants alter pharmacokinetics and
pharmacodynamics of dexmedetomidine after CHD surgery in children. Accomplishing these aims will
ultimately lead to a personalized approach to care and improve clinical outcomes for patients with CHD.

## Key facts

- **NIH application ID:** 9925823
- **Project number:** 5R01HD084461-06
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Todd L Edwards
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $638,941
- **Award type:** 5
- **Project period:** 2016-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925823

## Citation

> US National Institutes of Health, RePORTER application 9925823, Pharmacogenetics and Personalized Medicine after Cardiac Surgery in Children (5R01HD084461-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9925823. Licensed CC0.

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