Introduction
Atrial fibrillation (AF) is a common arrhythmia in clinical practice [1]. A survey by Zhang Shu et al. [2] on 19,368 natural patients aged 35 years old in different regions of China showed that the age-adjusted prevalence of AF was approximately 0.74%. Globally, the current prevalence of AF in adults is estimated to be between 2% and 4%, and is expected to increase [3-6]. AF represents a significant burden to patients, doctors, and the healthcare system. AF is an important cause of heart failure, ischemic stroke and other diseases, which seriously harm the health of humans. With the continued updating of diagnosis and treatment methods, the success rate of AF treatment is gradually improving, but it still does not reach the expected goal. Currently, the treatment of AF mainly includes drug control of ventricular rate, drug cardioversion and maintenance sinus rhythm, percutaneous radiofrequency catheter ablation, percutaneous cryoballoon ablation, and surgical Mazes. However, drug therapy has disadvantages of a low success rate and many side effects, while surgical Maze procedures cause significant trauma and carry a high risk of perioperative death.
Ablation is more effective than drugs [7-10] and has been recommended for AF in domestic and foreign guidelines [11, 12]. However, the long-term success rate of ablation for paroxysmal AF that has been followed up over 1 year is only 50%–80% [13-15], and is even lower for persistent AF [16]. Moreover, the degree of atrial fibrosis is more severe in patients with persistent AF than in patients with paroxymoron AF. Atrial fibrosis is closely related to the occurrence and maintenance of AF. Treatment of atrial fibrosis can effectively reduce the occurrence and burden of AF, but the current clinical methods are limited and ineffective. Therefore, it is important to further study the mechanism of atrial fibrosis and its relationship with the occurrence and development of AF.
Bromodomain-containing protein 4 (BRD4) plays an important role in the process of fibrosis by regulating cell transcription and the cell cycle. Recent studies have found that BRD4 inhibitors can be used for treating fibrotic diseases via target gene-related pathways including the extracellular matrix (ECM) receptor interaction, adhesion protein, PDGF pathway, JNK/MAPK pathway, and the NF-κB pathway. Therefore, BRD4 is considered a potential target in fibrosis. Studies have shown that the inhibition of BRD4 expression can reduce myocardial cell apoptosis and ventricular myocyte fibrosis [17-19]. In 2019, at the 40th Annual Meeting of the American Heart Association, a wall report study presented by Professor Yigang Li [20] found that BRD4 inhibition could reduce the induction rate of AF and alleviate atrial fibrosis, suggesting that BRD4 is a new target for treating atrial fibrosis and AF. This study was the first to establish a link between BRD4 and atrial fibrosis and AF. However, the correlation between the transforming growth factor-β (TGF-β)/SMAD signaling pathway, which is closely related to AF and atrial fibrosis, with BRD4 has not yet been reported. Furthermore, there has been no clinical study on the expression of BRD4 in patients with AF in combination with non-valvular disease and non-ischemic cardiomyopathy. Additionally, the relationship between BRD4 and AF recurrence after ablation remains unknown.
Based on the above views, we further verified the association between BRD4 and AF and atrial fibrosis through clinical observation and animal experiments. As the pathogenesis of AF in valvular disease is more complex, the atrial fibrosis of nonvalvular atrial fibrillation (NVAF) is most commonly caused by valvular disease itself, and valve replacement is the basic treatment strategy. Valvular AF accounts for approximately 12.9% of patients with AF, and the subjects of the current study have NVAF.