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Review
. 2023 Mar 1;324(3):H259-H278.
doi: 10.1152/ajpheart.00618.2022. Epub 2022 Dec 23.

Sinus node dysfunction: current understanding and future directions

Pavan Manoj  1 , Jitae A Kim  2 , Stephanie Kim  3 , Tingting Li  4 , Maham Sewani  3 , Mihail G Chelu  5 , Na Li  4
Affiliations
Review

Sinus node dysfunction: current understanding and future directions

Pavan Manoj et al. Am J Physiol Heart Circ Physiol. .

Abstract

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.

Keywords: automaticity; pacemaker; sinus node dysfunction.

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Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

Figure 1.
Figure 1.
Gross anatomy of human and mouse sinoatrial node (SAN). A: lateral view of a human heart specimen showing location of the SAN. Reproduced from Hayes et al. (5). B: posterior view of a X-Gal-stained mouse heart showing the SA nodal area. Reproduced from Lee et al. (6). C: dissected human heart showing SAN area (dotted circle). Reproduced from Mitrofanova et al. (7). D: dissected SAN tissue from a mouse. Approximate sizes are shown. Ao, aorta; CCV, common carotid vein; CT, crista terminalis; IAS, interatrial septum; IVC, inferior vena cava; LA, left atrium; RCV, right carotid vein; RA, right atrium; RAA, right atrial appendage; SVC, superior vena cava. Reproduced images, as indicated, are used with permission.
Figure 2.
Figure 2.
Electrophysiology of pacemaker cells. A: ionic current in each phase of an action potential in a pacemaker cell. B: interplay between membrane clock and Ca2+ clock. Casq2, calsequestrin-2; PLB, phospholamban; RyR2, ryanodine receptor type 2; SERCA, sarco(endo)plasmic reticulum Ca2+-ATPase; SR, sarcoplasmic reticulum. B was created with BioRender.com and published with permission.
Figure 3.
Figure 3.
Classifications of sinus node dysfunction. SAN, sinoatrial node.
Figure 4.
Figure 4.
Dual-chamber pacemaker. Standard dual-chamber pacemaker consisting of a pulse generator in the upper chest and leads implanted into the right atrium and right ventricle.
See this image and copyright information in PMC

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