Sinus node dysfunction and atrial fibrillation-Relationships, clinical phenotypes, new mechanisms, and treatment approaches

Although the anatomical basis of the pathogenesis of sinus node dysfunction (SND) and atrial fibrillation (AF) is located primarily in the left and right atria, increasing evidence suggests a strong correlation between SND and AF, in terms of both clinical presentation and formation mechanisms. However, the exact mechanisms underlying this association are unclear. The relationship between SND and AF may not be causal, but is likely to involve common factors and mechanisms, including ion channel remodeling, gap junction abnormalities, structural remodeling, genetic mutations, neuromodulation abnormalities, the effects of adenosine on cardiomyocytes, oxidative stress, and viral infections. Ion channel remodeling manifests primarily as alterations in the funny current (I-f) and Ca2+ clock associated with cardiomyocyte autoregulation, and gap junction abnormalities are manifested primarily as decreased expression of connexins (Cxs) mediating electrical impulse propagation in cardiomyocytes. Structural remodeling refers primarily to fibrosis and cardiac amyloidosis (CA). Some genetic mutations can also cause arrhythmias, such as SCN5A, HCN4, EMD, and PITX2. The intrinsic cardiac autonomic nervous system (ICANS), a regulator of the heart's physiological functions, triggers arrhythmias.In addition, we discuss arrhythmias caused by viral infections, notably Coronavirus Disease 2019 (COVID-19). Similarly to upstream treatments for atrial cardiomyopathy such as alleviating CA, ganglionated plexus (GP) ablation acts on the common mechanisms between SND and AF, thus achieving a dual therapeutic effect.

Automated summary

Although the exact mechanisms are unclear, there is evidence supporting a strong correlation between sinus node dysfunction (SND) and atrial fibrillation (AF), both in terms of clinical presentation and formation mechanisms. The association between SND and AF involves factors such as ion channel remodeling, gap junction abnormalities, structural remodeling, genetic mutations, neuromodulation abnormalities, adenosine effects, oxidative stress, and viral infections. Treatments targeting common mechanisms, such as ganglionated plexus (GP) ablation, can have dual therapeutic effects on both SND and AF.