Synergistic Effects of Weight Loss and Catheter Ablation: Can microRNAs Serve as Predictive Biomarkers for the Prevention of Atrial Fibrillation Recurrence?

Abstract

In atrial fibrillation (AF), multifactorial pathologic atrial alterations are manifested by structural and electrophysiological changes known as atrial remodeling. AF frequently develops in the context of underlying cardiac abnormalities. A critical mechanistic role played by atrial stretch is played by abnormal substrates in a number of conditions that predispose to AF, including obesity, heart failure, hypertension, and sleep apnea. The significant role of overweight and obesity in the development of AF is known; however, the differential effect of overweight, obesity, cardiovascular comorbidities, lifestyle, and other modifiable risk factors on the occurrence and recurrence of AF remains to be determined. Reverse remodeling of the atrial substrate and subsequent reduction in the AF burden by conversion into a typical sinus rhythm has been associated with weight loss through lifestyle changes or surgery. This makes it an essential pillar in the management of AF in obese patients. According to recently published research, microRNAs (miRs) may function as post-transcriptional regulators of genes involved in atrial remodeling, potentially contributing to the pathophysiology of AF. The focus of this review is on their modulation by both weight loss and catheter ablation interventions to counteract atrial remodeling in AF. Our analysis outlines the experimental and clinical evidence supporting the synergistic effects of weight loss and catheter ablation (CA) in reversing atrial electrical and structural remodeling in AF onset and in recurrent post-ablation AF by attenuating pro-thrombotic, pro-inflammatory, pro-fibrotic, arrhythmogenic, and male-sex-associated hypertrophic remodeling pathways. Furthermore, we discuss the promising role of miRs with prognostic potential as predictive biomarkers in guiding approaches to AF recurrence prevention.

Keywords: ROS; atrial fibrillation; catheter ablation; cytokine; fibrosis; hypertension; inflammaging; microRNA; obesity; recurrent atrial fibrillation; sex differences; weight loss.

Figure 1

Major risk factor-related mechanisms in AF: This figure shows the relationship between atrial remodeling and AF and the mechanistic contributors that have been shown to be caused by different risk factors. It should be noted that risk factors are not independent; rather, they frequently contribute to the development of other risk factors. For example, obesity increases the risk of hypertension, diabetes mellitus, and OSA, and both conditions raise the risk of hypertension. RA stands for right atrium, RV for right ventricle, OSA for obstructive sleep apnea, Cx for connexin, LA for left atrium, and LV for left ventricle.

Figure 2

Diagrammatic representation illustrating the miRs most commonly linked to HTN, OSA, ED, inflammation, fibrosis, adipogenesis, oxidative stress, male gender, and mechanoelectric uncoupling, which may be involved in the development and progression of AF.

Figure 3

Evidence of synergistic effects of weight loss and CA for AF management. Proposed effects of targeting miR identified at the intersection of weight loss (left) and CA (right) in AF (upregulation = arrow up; downregulation = arrow down): Following weight loss and CA, the heart’s structure and electrophysiology undergo reverse remodeling, which is characterized by an increase in conduction velocity, an increase in intercellular communication, and a decrease in fibrosis and coagulation as well as inflammation. (A) Left atrium. (B) Ablation lesions around pulmonary veins.