# Genomics of Post-Operative Atrial Fibrillation After Cardiac Surgery

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $746,205

## Abstract

PROJECT SUMMARY / ABSTRACT
To improve outcomes for patients undergoing cardiac surgery, the genetic propensities for developing
post-operative atrial fibrillation (poAF) will be assessed utilizing atrial tissue acquired during the
surgical procedure. Roughly 30% of patients who present for cardiac surgery in normal sinus rhythm
will experience poAF, making it the most common complication after cardiac surgery. Patients that
experience poAF are more likely to suffer a number of adverse outcomes, including additional time in
the ICU, increased risk of stroke, and increased all-cause 30-day and 6-month mortality. Thus,
evidence suggests that poAF itself contributes to poor patient outcomes following cardiac surgery.
A number of labs have identified genetic variants associated with both ambulatory AF and poAF, but
despite these genetic insights, the biological mechanisms underlying its development have not been
established. This is largely because human left atrial tissue has not been comprehensively
characterized in this context. Previous work has demonstrated that gene transcription in atrial tissue
is altered in patients with poAF, relative to those without, and that genetic variants markedly influence
transcriptional responses in this tissue. Proposed experiments build upon this work, examining both
genetic and epigenetic mechanisms of poAF using left atrial samples collected from a carefully
selected cohort of 200 patients primarily of European origin who are in normal sinus rhythm as they
undergo cardiac surgery. Molecular comparisons of tissue-specific RNA expression and DNA
methylation (Aim 1), analysis of quantitative trait loci of poAF (Aim 2), and functional validation in
cardiomyocytes (Aim 3) will then be made between patients who subsequently do and do not develop
poAF, testing the global hypothesis that DNA, RNA, and methylation changes in the human left atrium
contribute to the development of poAF. By characterizing the transcriptome and methylome of left
atrial tissue from cardiac surgery patients and using whole-genome genotyping, we will be able to
identify both the gene expression differences that predispose individuals to poAF, and the genetic
variants that underlie this predisposition.
Successful completion of this study will advance biological knowledge of poAF by validating existing
targets, identifying novel predictors and novel pathways, describing the tissue-specific expression and
methylation pattern in the human left atrium and its association with poAF, and identifying new
pharmacological targets for the prevention and treatment of poAF. Resulting insights could potentially
benefit both surgery and non-surgery AF patients, thereby improving the lives of millions of patients.

## Key facts

- **NIH application ID:** 10985437
- **Project number:** 7R01HL149998-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** JOCHEN DANIEL MUEHLSCHLEGEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $746,205
- **Award type:** 7
- **Project period:** 2021-03-15 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10985437

## Citation

> US National Institutes of Health, RePORTER application 10985437, Genomics of Post-Operative Atrial Fibrillation After Cardiac Surgery (7R01HL149998-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10985437. Licensed CC0.

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