Atrial fibrosis and substrate based characterization in atrial fibrillation: Time to move forwards

Abstract

Atrial fibrillation (AF) is the most commonly encountered cardiac arrhythmia in clinical practice. However, current therapeutic interventions for atrial fibrillation have limited clinical efficacy as a consequence of major knowledge gaps in the mechanisms sustaining atrial fibrillation. From a mechanistic perspective, there is increasing evidence that atrial fibrosis plays a central role in the maintenance and perpetuation of atrial fibrillation. Electrophysiologically, atrial fibrosis results in alterations in conduction velocity, cellular refractoriness, and produces conduction block promoting meandering, unstable wavelets and micro‐reentrant circuits. Clinically, atrial fibrosis has also linked to poor clinical outcomes including AF‐related thromboembolic complications and arrhythmia recurrences post catheter ablation. In this article, we review the pathophysiology behind the formation of fibrosis as AF progresses, the role of fibrosis in arrhythmogenesis, surrogate markers for detection of fibrosis using cardiac magnetic resonance imaging, echocardiography and electroanatomic mapping, along with their respective limitations. We then proceed to review the current evidence behind therapeutic interventions targeting atrial fibrosis, including drugs and substrate‐based catheter ablation therapies followed by the potential future use of electro phenotyping for AF characterization to overcome the limitations of contemporary substrate‐based methodologies.

Association Between TCF21 Gene Polymorphism with the Incidence of Paroxysmal Atrial Fibrillation and the Efficacy of Radiofrequency Ablation for Patients with Paroxysmal Atrial Fibrillation

“…As a consequence, excessive extracellular matrix deposition and cardiac fibrosis exacerbated AF and triggered the recurrence of AF after RFA. 32 Emerging evidence demonstrated that TCF21 polymorphism plays an important role in cancer, 22,23 coronary artery diseases 16,17 and ventricular septal defects. 18 For instance, the CG and GG genotypes of rs12190287 predict elevated risk of osteosarcoma 23 and conferred genetic susceptibility to VSDs in a Chinese population.…”

Surface ECG–based complexity parameters for predicting outcomes of catheter ablation for nonparoxysmal atrial fibrillation: efficacy of fibrillatory wave amplitude

“…[38] The structural remodeling of atrial fibrosis theoretically leads to a decrease in muscle fiber activation, which affects the FWA voltage. [39,40] Therefore, lower FWA in lead V 1 implies a reduction in right atrial voltage with increased low voltage areas as a result of advanced structural remodeling with progression of AF.…”

Spatial concentration and distribution of phase singularities in human atrial fibrillation: Insights for the AF mechanism

“…This discrepancy could be reconciled by considering that PS formation most likely occurs as a consequence of tissue micro‐structural heterogeneities in combination with dynamic functional factors 44 . According to this idea, areas of local hotspot concentration could be hypothesized to be occurring via the effect of relatively fixed heterogeneities in the myocardium caused by areas of micro‐fibrosis 45 . On the other hand, many and perhaps, most, PSs occur as a consequence of dynamic alterations in tissue conduction and refractoriness.…”