Gender differences in fibrosis remodeling in patients with long-standing persistent atrial fibrillation

Abstract

The success rate of catheter ablation in atrial fibrillation (AF) is known to be lower in females than in males. However, while the exact mechanism for this phenomenon remains to be elucidated, tissue fibrosis may play an important role in this regard. It has been shown that fibrosis promotes AF and its recurrence, thereby substantially reducing the efficacy of catheter ablation in AF patients. Thus, we hypothesized that fibrosis may contribute to gender differences in the outcomes of AF catheter ablation.Here we systematically assessed pulmonary vein sleeves obtained from 166 patients with and without long-standing persistent-AF (LSP-AF) in order to identify gender-specific mechanistic differences in fibrosis remodeling of AF patients.Histological analysis revealed that the female LSP-AF group, rather than its male counterpart, had a higher degree of fibrosis when compared to the NON-AF group. Further analysis using microarray, immunohistochemistry and Western Blot displayed that gender differences in fibrosis remodeling of LSP-AF were mainly due to the inherent differential expression of fibrosis-related genes (n=32) and proteins (n=6). Especially, those related to the TGFβ/Smad3 pathway appeared to be up-regulated in the female LSP-AF group thus promoting an aggravation of fibrosis remodeling. In summary, our data suggest that the aggravation of fibrosis remodeling in women may be an important reason for the low success rate of AF catheter ablation when compared to men. Therefore, inhibiting the TGFβ/Smad3 pathway-mediated fibrosis could represent an interesting target for future therapeutic concepts to improve the success rate of AF catheter ablation in women.

Left Atrial Phasic Function in Patients with Hypertension and Recurrent Atrial Fibrillation: Gender Differences of the Relationship with Diastolic Dysfunction and Central Aortic Pressure

“…В то же время развитие последней нельзя объяснить только опосредованными АГ увеличением массы и толщины стенок ЛЖ [15]. Поэтому можно полагать, что существуют и гендерные особенности других процессов, способствующих нарушению релаксации ЛЖ, в том числе, его фиброзирования [47].…”

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

“…HFpEF), the finding of ventricular fibrosis doubles the procedural failure rate . Therapeutic futility may be particularly common in patients with longstanding AF (with or without overt HFpEF) . In a cohort with preserved ejection fraction and permanent AF, patients with LV fibrosis had an exceptionally high rate of AF recurrence following catheter ablation; the 1‐year procedural success rate in those with extensive fibrosis and LV hypertrophy was only 7% .…”

“…235 Therapeutic futility may be particularly common in patients with longstanding AF (with or without overt HFpEF). 37,241,242 In a cohort with preserved ejection fraction and permanent AF, patients with LV fibrosis had an exceptionally high rate of AF recurrence following catheter ablation; the 1-year procedural success rate in those with extensive fibrosis and LV hypertrophy was only 7%. 243 Even in patients with paroxysmal AF, the diagnosis of HFpEF or biomarkers of systemic inflammation presages a high rate of AF recurrence.…”

Atrial Fibrillation and Arterial Hypertension: Gender Differences of Ventriculoatrial Remodeling With Preserved Ejection Fraction

“…В этой связи можно предполагать, что более выраженное нарушение как структурной, так и функциональной сохранности ЛП у женщин в совокупности с характерным для них профилем ремоделирования ЛЖ могут обусловливать более неблагоприятное течение ФП в женской популяции. И здесь напрашивается вопрос о значимости вклада в более выраженную морфофункциональную перестройку ЛП у женщин присущих им свойств стенок ЛП в виде их возможной большей, чем у мужчин, восприимчивости к фиброзированию [29] и способствующему ему ремоделированию ЛЖ.…”