Sinus node dysfunction: current understanding and future directions

The sinoatrial node (SAN) is the primary pacemaker of the heart. Normal SAN function is crucial in maintaining proper cardiac rhythm and contraction. Sinus node dysfunction (SND) is due to abnormalities within the SAN which can affect the heartbeat frequency, regularity, and the propagation of electrical pulses through the cardiac conduction system. As a result, SND often increases the risk of cardiac arrhythmias. SND is most commonly seen as a disease of the elderly given the role of degenerative fibrosis as well as other age-dependent changes in its pathogenesis. Despite the prevalence of SND, current treatment is limited to pacemaker implantation, which is associated with substantial medical costs and complications. Emerging evidence has identified various genetic abnormalities that can cause SND, shedding light on the molecular underpinnings of SND. Identification of these molecular mechanisms and pathways implicated in the pathogenesis of SND is hoped to identify novel therapeutic targets for the development of more effective therapies for this disease. In this review article, we examine the anatomy of the SAN and the pathophysiology and epidemiology of SND. We then discuss in detail the most common genetic mutations correlated with SND and provide our perspectives on future research and therapeutic opportunities in this field.