Sinoatrial node dysfunction (SND), formerly known as sick sinus syndrome, is a condition affecting the sinoatrial node, the heart's natural pacemaker. It is often age-related, resulting from progressive degenerative fibrosis of the sinoatrial node tissue and surrounding atrial myocardium. These structural changes impair impulse generation and conduction, leading to various syndromes. Clinically, SND frequently presents as sinus bradycardia, where the heart rate drops below 50 beats per minute. This reduced rate can cause symptoms such as dizziness, syncope (sudden loss of consciousness), or, in rare cases, cardiac arrest. Other characteristic ECG changes include chronotropic incompetence (inability to increase heart rate adequately under stress), sinus pause, sinus arrest, different degrees of sinoatrial exit block, atrial fibrillation, and atrioventricular (AV) block.
The degeneration of the sinoatrial node is often exacerbated by age-related changes in heart tissue but can also occur under other pathological conditions. Besides age-related degeneration, other factors contributing to SND include ischemia, infiltrative diseases such as sarcoidosis or amyloidosis, infections, cardiac surgeries, and certain medications. Systemic conditions like hypothyroidism, autonomic dysfunctions, and abnormally increased vagal tone may also play a role.
SND can be classified into isolated and syndromic forms, as well as those associated with cardiomyopathies such as dilated cardiomyopathy (DCM). Isolated forms typically occur without structural cardiac changes and stem from disruptions in the electrical signal transmission of the sinoatrial node itself. In contrast, syndromic forms of SND are associated with other clinical phenomena, often posing additional diagnostic challenges. Syndromic SND is usually part of a broader disease profile involving other systemic or structural anomalies, such as coronary artery disease (CAD) or neurological phenotypes, where SND represents only one aspect of a more complex disorder. In these syndromes, SND can occur alongside other symptoms and complications, pointing to an underlying multisystem disorder. This wide range of potential causes makes SND a clinically heterogeneous condition.
Genetics plays a critical role, particularly in inherited forms of SND. Although most cases of SND are acquired, here are also familial or idiopathic forms caused by genetic factors. These genetic forms, while less common, are clinically significant as they can manifest earlier in life. The genetic heterogeneity of SND means that a wide variety of genes may contribute to its development, complicating diagnosis. Currently, it is estimated that genetic causes can be definitively identified in fewer than 25% of idiopathic or familial SND cases. Most inherited cases follow an autosomal-dominant inheritance pattern, while other modes of inheritance, such as X-linked or recessive inheritance, as well as complex genetic mechanisms like digenic traits or copy number variations (CNVs), are rare.
References
Wilde et al. 2022, Europace 24:1307 / Kusumoto et al. 2019, Circulation 140:e382
