Cardiac arrhythmias contribute significantly to cardiovascular morbidity and mortality. Atrial fibrillation is the most common sustained cardiac arrhythmia and one of the major causes of stroke, heart failure, sudden death and cardiovascular morbidity. With a global prevalence of 0.51%, which has increased by 33% in the last 20 years, atrial fibrillation also imposes rising healthcare costs. Epidemiological studies have provided evidence that genetic factors play a key role in the pathogenesis of the disease. Developing a mechanistic classification of atrial fibrillation based on health modifiers like genetic susceptibility is essential to improve personalized prevention and management of atrial fibrillation.
So far, available management strategies have limited efficacy due to an incomplete understanding of the underlying biological mechanisms. Sinus node dysfunction often coexists with atrial fibrillation; however, the underlying molecular mechanisms are not well understood. SHOX2 variants are associated with early-onset and familial atrial fibrillation and sinus node dysfunction demonstrating a genetic link between both conditions.