PhD Conferral Mr. Dragan Opačić
Supervisor: prof.dr. U. Schotten
Co-supervisors: Dr. S. Verheule; dr. S. Zeemering
Keywords: Atrial fibrillation, metabolic modulation, trimetazidine, ranolazine
“Metabolic modulators as a treatment of atrial Fibrillation”
Atrial fibrillation (AF), one of the most common arrhythmias in clinical practice, is characterized by the fast and irregular atrial activation and irregular ventricular rate. This chaotic atrial activation is associated with disturbed blood flow in the atria and consequent clot formation. In many patients AF is asymptomatic, but if not treated properly, it can cause devastating thromboembolic complications, including stroke. AF is a progressive disease that usually starts in short episodes that cause specific changes in atrial cell and tissue structure. These changes enable the stabilisation of the arrhythmia until it becomes permanent. Current treatment strategies for AF are mainly focused on prevention of the complication associated with AF, but few are aiming for the inhibition of the arrhythmia progression.
This research investigated a novel approach for the upstream therapy of AF where we use metabolic modulation to prevent changes in atrial tissue associated with the progression of AF. We show that treatment with metabolic modulator trimetazidine preserves atrial structure and function, most likely by preventing mitochondrial damage associated with increased reactive oxygen species production. We believe that this treatment option would be the most beneficial for the group of patients with an early arrhythmia onset to prevent AF associated changes in atrial structure and hence prevent arrhythmia progression and stabilisation.
UM Bestuursgebouw
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