Impact of inflammation-mediated myocardial fibrosis on the risk of recurrence after successful ablation of atrial fibrillation – the FIBRO-RISK study

Abstract

Introduction:Interventional ablation has been demonstrated to represent an effective therapy in patients with atrial fibrillation (AF), leading to restoration and maintenance of sinus rhythm in the majority of cases. However, recurrence of AF is encountered in 35% to 40% of cases, and the causes for this frequent complication have not been elucidated so far.Material and methods:Here we present the study protocol of the FIBRO-RISK trial, a prospective, single-center, cohort study which aims to investigate the impact of inflammatory-mediated myocardial fibrosis on the risk of recurrence after successful catheter ablation of atrial fibrillation. The level of systemic inflammation in the pre-ablation and immediate post-ablation period will be assessed on the basis of serum levels of inflammatory biomarkers (hsCRP, matrix metalloproteases, interleukin-6), while the level of cardiac fibrosis will be determined based on cardiac magnetic resonance imaging associated with complex post-processing techniques for mapping myocardial fibrosis at the level of left atrium and left ventricle. At the same time, the amount of epicardial fat will serve as an indirect marker of localized inflammation and will be determined at different levels in the heart (surrounding left atrium, right atrium or the entire heart), while ventricular function will be assessed on the basis of serum levels of NT-proBNP prior to the procedure. All these parameters will be investigated in patients with successful ablation of AF, who will be divided into 2 groups: group 1 – patients who develop AF recurrence at 1-year, and group 2 – patients with no recurrence of AF at 1-year. In all patients, the following biomarkers will be determined: serum levels of inflammatory biomarkers and NT-proBNP at 24 hours and 1-year post procedure, the amount of myocardial fibrosis at the level of left atrium and left ventricle at baseline +/− 7 days, and the amount of epicardial fat surrounding left atrium, right atrium and the entire heart at baseline +/− 7 days.The primary endpoint of the study will be represented by the rate of AF recurrence at 1-year post ablation, documented by either ECG or Holter monitoring. The secondary endpoints of the study will consist in:the rate of re-hospitalization,the rate of survival without relapse, andthe rate of major adverse cardiovascular events (MACE rate, including cardiovascular death or stroke).In conclusion, FIBRO-RISK will be the first CMR-based study that will investigate the impact of inflammation-mediated myocardial fibrosis and ventricular remodeling on the risk of recurrence after successful ablation of AF, aiming to validate inflammatory biomarkers and myocardial fibrosis as predictors for AF recurrence.

Evidence for Inflammation as a Driver of Atrial Fibrillation

“…The systemic inflammatory response after coronary artery bypass grafting is correlated with AF occurrence (35). In the FIBRO-RISK study, biomarkers of inflammation and myocardial fibrosis were validated as predictors for AF recurrence (36). Elevated inflammatory biomarkers levels in serum are correlated with prevalence and prognosis of AF (37,38).…”

Impact of the COVID-19 Pandemic and Public Restrictions on Outcomes After Catheter Ablation of Atrial Fibrillation

“…High-sensitivity C-reactive protein levels were also lower among patients undergoing AFCA in the COVID-19 era than those in the pre-COVID-19 era. Importantly, up-regulation of inflammatory biomarkers has been shown to be a valid predictor for AF recurrence ( 13 , 14 ), and inflammation is known to alter atrial electrophysiology and structure to increase vulnerability to AF ( 15 ). Thus, changes in alcohol habits and systemic inflammation during the period of COVID-19 pandemic and associated social distancing might partly explain the results of this study.…”

Updates on epicardial adipose tissue mechanisms on atrial fibrillation

“…Other biophysical strategies should also be considered during ablation because epicardial fat can interfere with radiofrequency delivery to the underlying myocardial tissue 121 . The Fibro‐Risk study revealed the inflammatory role of epicardial fat in myocardial fibrosis and AF recurrence after ablation 122 . Future modulation of epicardial fat quality might improve the non‐pharmacological therapeutic strategic outcomes; this is because structural and electrical reverse remodeling of the LA was observed 2 months after PV isolation in patients with permanent AF 123 …”