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March 17, 2017Oncotarget92 citationsOpen Access

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

ZLZhi LiZWZengwei WangZYZongtao Yin

Key Result

Female patients with long-standing persistent atrial fibrillation exhibited a significantly higher degree of fibrosis remodeling (collagen volume fraction 29.83% vs 20.82%, P=0.0019) compared to non-AF females, whereas no significant difference was observed in males.

Study Design

Type

Observational (n=166)

Multicenter

No

Structured PICO

P
Population
166 patients with dilated left atria and concomitant mitral valve disease, divided into female NON-AF (n=30), female LSP-AF (n=55), male NON-AF (n=35), and male LSP-AF (n=46). Key exclusions: diabetes, smoking or alcohol consumption within 10 years.
O
Outcome
Collagen volume fraction (CVF) and expression of fibrosis-related genes and proteins in pulmonary vein sleevessurrogate

Female patients with long-standing persistent atrial fibrillation exhibit significantly greater atrial fibrosis and upregulation of the TGFβ/Smad3 pathway compared to males, which may explain their lower success rates with catheter ablation.

Main Result

Absolute Event Rate: 29.83% vs 20.82%

p-value: p=0.0019

Limitations

  • As all patients in our study had LSP-AF, the conclusions drawn from this study cannot be applied to a population with other types of AF such as lonely AF and paroxysmal AF.

Abstract

// Zhi Li 1 , Zengwei Wang 1 , Zongtao Yin 1 , Yuji Zhang 1 , Xiaodong Xue 1 , Jinsong Han 1 , Yan Zhu 1 , Jian Zhang 1 , Maximilian Y. Emmert 2 and Huishan Wang 1 1 Department of Cardiovascular Surgery, Shenyang Northern Hospital, Shenyang, China 2 Clinic for Cardiovascular Surgery, University Hospital Zurich, Rämistrasse, Zürich, Switzerland Correspondence to: Huishan Wang, email: // Maximilian Y. Emmert, email: // Keywords : gender differences; atrial fibrillation; remodeling; mitral valve; pulmonary vein Received : November 07, 2016 Accepted : February 06, 2017 Published : March 17, 2017 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.

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Cite This Study

Li et al. (2017) conducted an observational in Long-standing persistent atrial fibrillation (n=166). Long-standing persistent atrial fibrillation (Female) vs. Non-atrial fibrillation (Female) was evaluated on Collagen volume fraction (CVF) (p=0.0019). Female patients with long-standing persistent atrial fibrillation exhibited a significantly higher degree of fibrosis remodeling (collagen volume fraction 29.83% vs 20.82%, P=0.0019) compared to non-AF females, whereas no significant difference was observed in males.

synapsesocial.com/papers/6a12c08b06ed52b5c2c07a5ehttps://doi.org/10.18632/oncotarget.16342
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