UCLA researchers at the Geffen School of Medicine have identified a novel biomarker and therapeutic target for early diagnosis and treatment of post-operative atrial fibrillation.
BACKGROUND: Post-operative atrial fibrillation (POAF) is a common complication following cardiac surgery, affecting 30-50% of patients. Patients who develop POAF have an increased risk of stroke, thromboembolism, and cardiac arrest. In addition, patients experiencing POAF also have an increased risk of atrial fibrillation (AF) recurrence later in life, suggesting that POAF serves as a “stress test” that reveals underlying AF susceptibility. Patients who develop POAF also face a heavier financial burden as well, due to both the increased hospitalization stay and the high likelihood of developing additional cardiovascular complications. Despite its prevalence, little is known about molecular mechanisms promoting POAF. Treatments for POAF typically includes the antiarrhythmic amiodarone, which targets many ion channels non-specifically and has significant side effects. Thus, a reliable molecular biomarker for POAF would allow for improved diagnostic screening of underlying AF susceptibility that extends far beyond the perioperative period. In addition, atrial cardiomyocyte administration of FGF13 through viral or plasmid vectors would replenish FGF13 activity and prevent AF.
INNOVATION: Researchers at UCLA led by Dr. Thomas Vondriska have identified the fibroblast growth factor 13 (FGF13) protein as an informative biomarker and potential therapeutic target for POAF.
Using RNA sequencing methods to monitor gene expression changes in patient samples from cardiac surgery biopsies, the inventors have demonstrated that low FGF13 levels correlated with the development of POAF. Abnormally low FGF13 levels could also be detected in patient samples prior to the onset of AF, making FGF13 a potent early diagnostic marker and therapeutic target for AF both within and outside of the perioperative setting. These findings also provide novel insight into the mechanism of the development of new onset AF after cardiac surgery.
POTENTIAL APPLICATIONS:
- Viral or plasmid directed atrial myocyte FGF13 expression to reduce AF risk/treat AF
- Novel biomarker for diagnosis of etiology of AF susceptibility in patients developing POAF
- Drug target for therapeutic development to treat both POAF and AF outside of the perioperative setting
- Insight into molecular mechanism responsible for atrial arrythmias post cardiac surgery
ADVANTAGES:
- Novel molecular target for the treatment of AF susceptibility
- Reduced post-operative surgery hospitalization financial burden on patients
- Early detection and accurate prognosis of future AF susceptibility
DEVELOPMENT-TO-DATE: In addition to initial transcriptomic studies in human myocytes, the inventors have demonstrated that a knockdown of FGF13 gene expression using an in vivo mouse model resulted in prolonged cardiac action potential duration (APD). Prolonged APD has been implicated in AF pathogenesis and these results support the inventors’ model of decreased FGF13 causing POAF vulnerability post cardiac surgery.
Related Papers (from the inventors only):
Fischer MA et al. Decreased Left Atrial Cardiomyocyte Fibroblast Growth Factor 13 Expression Increases Vulnerability to Postoperative Atrial Fibrillation in Humans. J Am Heart Assoc. 13(12): e034896 (2024)
KEYWORDS: Atrial fibrillation (AF), Post-operative atrial fibrillation (POAF), Cardiac surgery, cardiac electrophysiology, inflammation, arrhythmia, fibroblast growth factor, myocytes, transcriptomics