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 (If) 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.

Genetic and non-genetic risk factors associated with atrial fibrillation.

Atrial fibrillation (AF) is the most common arrhythmic disorder and its prevalence in the United States is projected to increase to more than twelve million cases in 2030. AF increases the risk of other forms of cardiovascular disease, including stroke. As the incidence of atrial fibrillation increases dramatically with age, it is paramount to elucidate risk factors underlying AF pathogenesis. Here, we review tissue and cellular pathways underlying AF, as well as critical components that impact AF susceptibility including genetic and environmental risk factors. Finally, we provide the latest information on potential links between SARS-CoV-2 and human AF. Improved understanding of mechanistic pathways holds promise in preventative care and early diagnostics, and also introduces novel targeted forms of therapy that might attenuate AF progression and maintenance.

Causal associations between COVID-19 and atrial fibrillation: A bidirectional Mendelian randomization study.

BACKGROUND AND AIMS: Observational studies showed that coronavirus disease (2019) (COVID-19) attacks universally and its most menacing progression uniquely endangers the elderly with cardiovascular disease (CVD). The causal association between COVID-19 infection or its severity and susceptibility of atrial fibrillation (AF) remains unknown. METHODS AND RESULTS: The bidirectional causal relationship between COVID-19 (including COVID-19, hospitalized COVID-19 compared with not hospitalized COVID-19, hospitalized COVID-19 compared with the general population, and severe COVID-19) and AF are determined by using two-sample Mendelian randomization (MR) analysis. Genetically predicted severe COVID-19 was not significantly associated with the risk of AF [odds ratio (OR), 1.037; 95% confidence interval (CI), 1.005-1.071; P = 0.023, q = 0.115]. In addition, genetically predicted AF was also not causally associated with severe COVID-19 (OR, 0.993; 95% CI, 0.888-1.111; P = 0.905, q = 0.905). There was no evidence to support the association between genetically determined COVID-19 and the risk of AF (OR, 1.111; 95% CI, 0.971-1.272; P = 0.127, q = 0.318), and vice versa (OR, 1.016; 95% CI, 0.976-1.058; P = 0.430, q = 0.851). Besides, no significant association was observed for hospitalized COVID-19 with AF. MR-Egger analysis indicated no evidence of directional pleiotropy. CONCLUSION: Overall, this MR study provides no clear evidence that COVID-19 is causally associated with the risk of AF.

MicroRNAs and Calcium Signaling in Heart Disease.

In hearts, calcium (Ca2+) signaling is a crucial regulatory mechanism of muscle contraction and electrical signals that determine heart rhythm and control cell growth. Ca2+ signals must be tightly controlled for a healthy heart, and the impairment of Ca2+ handling proteins is a key hallmark of heart disease. The discovery of microRNA (miRNAs) as a new class of gene regulators has greatly expanded our understanding of the controlling module of cardiac Ca2+ cycling. Furthermore, many studies have explored the involvement of miRNAs in heart diseases. In this review, we aim to summarize cardiac Ca2+ signaling and Ca2+-related miRNAs in pathological conditions, including cardiac hypertrophy, heart failure, myocardial infarction, and atrial fibrillation. We also discuss the therapeutic potential of Ca2+-related miRNAs as a new target for the treatment of heart diseases.