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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 TGF?/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 TGF?/Smad3 pathway-mediated fibrosis could represent an interesting target for future therapeutic concepts to improve the success rate of AF catheter ablation in women.

SUBMITTER: Li Z

PROVIDER: S-EPMC5581144 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Li Zhi Z Wang Zengwei Z Yin Zongtao Z Zhang Yuji Y Xue Xiaodong X Han Jinsong J Zhu Yan Y Zhang Jian J Emmert Maximilian Y MY Wang Huishan H

Oncotarget 20170317 32

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 cathete ...[more]

PMID: 28881845

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Project description:BackgroundLeft atrial (LA) function following catheter or surgical ablation of de-novo long-standing persistent atrial fibrillation (AF) and its impact on AF recurrence was studied in patients participating in the CASA-AF trial (Catheter Ablation vs. Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation).MethodsAll patients underwent echocardiography preablation, 3 and 12 months post-ablation. LA structure and function were assessed by 2-dimensional volume and speckle tracking strain measurements of LA reservoir, conduit, and contractile strain. Left ventricular diastolic function was measured using transmitral Doppler filling velocities and myocardial tissue Doppler velocities to derive the e', E/e', and E/A ratios. Continuous rhythm monitoring was achieved using an implantable loop recorder.ResultsEighty-three patients had echocardiographic data suitable for analysis. Their mean age was 63.6±9.7 years, 73.5% were male, had AF for 22.8±11.6 months, and had a mean LA maximum volume of 48.8±13.8 mL/m2. Thirty patients maintained sinus rhythm, and 53 developed AF recurrence. Ablation led to similar reductions in LA volumes at follow-up in both rhythm groups. However, higher LA emptying fraction (36.3±10.6% versus 27.9±9.9%; P<0.001), reservoir strain (22.6±8.5% versus 16.7±5.7%; P=0.001), and contractile strain (9.2±3.4% versus 5.6±2.5%; P<0.001) were noted in the sinus rhythm compared with AF recurrence group following ablation at 3 months. Diastolic function was better in the sinus rhythm compared with the AF recurrence group with an E/A ratio of 1.5±0.5 versus 2.2±1.2 (P<0.001) and left ventricular E/e' ratio of 8.0±2.1 versus 10.3±4.1 (P<0.001), respectively. LA contractile strain at 3 months was the only independent predictor of AF recurrence.ConclusionsFollowing ablation for long-standing persistent AF, improvement in LA function was greater in those who maintained sinus rhythm. LA contractile strain at 3 months was the most important determinant of AF recurrence following ablation.RegistrationURL: https://www.Clinicaltrialsgov; Unique identifier: NCT02755688.

Project description:ObjectivesThe CArdioSurgEry Atrial Fibrillation (CASE-AF) registry is a prospective, multicentre study for collecting and analysing real-world data of surgical atrial fibrillation (AF) treatment. This study aimed to evaluate outcomes of surgery for long-standing persistent AF at 1 year.MethodsIn total, 17 centres consecutively include all eligible patients with continuous AF lasting for ≥1 year. Exclusion criteria are missing informed consent or age <18 years. For patient-reported outcomes measures, the European Heart Rhythm Association score was used. No presence of AF (based on ECG findings including Holter ECG and/or implanted devices), no re-ablation, no further cardioversion and no rehospitalization due to AF after a 3-month blanking period defined no AF recurrence at 1 year.ResultsFrom January 2017 to January 2020, a total of 1115 patients were enrolled in CASE-AF. Of them, 202 patients (mean age 69.7 ± 7.8 years, 27.2% female) underwent surgical ablation of long-standing persistent AF (study cohort), mostly accompanied by left atrial appendage closure (n = 180 [89%], resection n = 75 [42%]) and predominantly performed as concomitant (n = 174 [86%]) and left atrial only procedure (n = 144 [71%]). Early mortality (30 days) was 2.0% and morbidity was low. At follow-up (median 14.4 months, interquartile range, 12.7-17.6 months, 100% complete), 106 patients (56%) had no AF recurrence and 93% of them were asymptomatic. AF recurrence was accompanied by AF-related rehospitalization (n = 12, P = 0.003), direct current shock cardioversion (n = 23, P < 0.001), AF ablation (n = 7, P = 0.003) and stroke (n = 3, P = 0.059). Multivariable analysis identified cryoablation, predominantly performed endocardially including additional left atrial (74%) and biatrial (42%) lesions, as a significant factor for freedom from AF recurrence (odds ratio 2.7, 95% confidence interval 1.07-6.79, P = 0.035).ConclusionsAccording to CASE-AF, surgical ablation of long-standing persistent AF is most effective when concomitantly performed using endocardial cryoablation. Ongoing follow-up allows further elucidation of efficacious treatment strategies.

Project description:Complex fractionated atrial electrograms (CFAEs) may represent a phenomenon associated with sources of atrial fibrillation (AF) and are being used increasingly as targets of catheter ablation. However, current methods have limited efficacy for characterizing CFAEs important to substrate arrhythmogenicity and do not measure electrogram morphology.The purpose of this study was to develop a methodology for quantifying the degree of morphologic heterogeneity in CFAE deflections, and to determine whether there are differences in this measurement between paroxysmal and persistent AF patients.Two successive bipolar CFAEs of length 8.4 seconds each were acquired during AF from two sites each at the ostia of the four pulmonary veins (PVs) and from the anterior and posterior left atrial free wall in patients with paroxysmal AF (N = 10) and long-standing persistent AF (N = 10). Extrinsic and intrinsic features of electrogram shape were used to characterize fractionation in CFAE sequences. The extrinsic parameters were the amplitude, upslope, downslope, and width of each deflection. The intrinsic parameter was the voltage profile as characterized by the sum of absolute values. These measurements were compared to the mean interval between CFAE deflections, a standard fractionation indicator.The variability of intrinsic/extrinsic morphologic parameters was higher in paroxysmal than persistent AF at the left superior PV (P < or =.003), the posterior left atrial free wall, anterior left atrial free wall, left inferior PV, and right superior PV (P <.05 for most parameters), and the right inferior PV (not significant). Mean CFAE deflection intervals were longer at all locations in paroxysmal AF but were significant only at the left superior PV and posterior left atrial free wall (P <.05). Quantitative morphologic parameters were not well correlated with dominant frequency (r(2) <0.32); thus, our new measures are robust to changes in activation rate.A novel method for quantifying CFAEs, independent of activation rate, has been developed. The method demonstrates greater significance in the difference between CFAE morphology in paroxysmal and long-standing AF compared with mean interval between CFAE deflections. The differences identified suggest that CFAE morphology may evolve as AF persists.

Project description:PURPOSE:Atrial fibrillation (AF) is the most common heart rhythm disorder and causes considerable morbidity and mortality, resulting in a large public health burden that is increasing as the population ages. It is associated with atrial fibrosis, the amount and distribution of which can be used to stratify patients and to guide subsequent electrophysiology ablation treatment. Atrial fibrosis may be assessed noninvasively using late gadolinium-enhanced (LGE) magnetic resonance imaging (MRI) where scar tissue is visualized as a region of signal enhancement. However, manual segmentation of the heart chambers and of the atrial scar tissue is time consuming and subject to interoperator variability, particularly as image quality in AF is often poor. In this study, we propose a novel fully automatic pipeline to achieve accurate and objective segmentation of the heart (from MRI Roadmap data) and of scar tissue within the heart (from LGE MRI data) acquired in patients with AF. METHODS:Our fully automatic pipeline uniquely combines: (a) a multiatlas-based whole heart segmentation (MA-WHS) to determine the cardiac anatomy from an MRI Roadmap acquisition which is then mapped to LGE MRI, and (b) a super-pixel and supervised learning based approach to delineate the distribution and extent of atrial scarring in LGE MRI. We compared the accuracy of the automatic analysis to manual ground truth segmentations in 37 patients with persistent long-standing AF. RESULTS:Both our MA-WHS and atrial scarring segmentations showed accurate delineations of cardiac anatomy (mean Dice = 89%) and atrial scarring (mean Dice = 79%), respectively, compared to the established ground truth from manual segmentation. In addition, compared to the ground truth, we obtained 88% segmentation accuracy, with 90% sensitivity and 79% specificity. Receiver operating characteristic analysis achieved an average area under the curve of 0.91. CONCLUSION:Compared with previously studied methods with manual interventions, our innovative pipeline demonstrated comparable results, but was computed fully automatically. The proposed segmentation methods allow LGE MRI to be used as an objective assessment tool for localization, visualization, and quantitation of atrial scarring and to guide ablation treatment.

Project description:Objective The relationship between atrial fibrillation (AF) and heart failure with depressed ejection fraction (EF) is complex. AF-related tachycardia-mediated cardiomyopathy (TMC) can lead to worsening EF and clinical heart failure. We sought to determine whether a hybrid team ablation approach (HA) can be performed safely and restore normal sinus rhythm in patients with TMC and heart failure and to delineate the effect on heart failure. Methods We retrospectively analyzed patients with nonparoxysmal (ie, persistent and long-standing persistent) AF-related TMC with depressed left ventricular EF (LVEF ≤40%) and heart failure (New York Heart Association [NYHA] class ≥2) who underwent HA between 2013 and 2018 and had at least 1 year of follow-up. Pre-HA and post-HA echocardiograms were compared for LVEF and left atrial (LA) size. Rhythm success was defined as <30 seconds in AF/atrial flutter/atrial tachycardia without class I or III antiarrhythmic drugs. Results are expressed as mean ± SD and 95% confidence interval (CI) of the mean. Results Forty patients met the criteria for inclusion in our analysis. The mean patient age was 67 ± 9.4 years. The majority of patients had long-standing persistent AF (26 of 40; 65%), and the remainder had persistent AF (14 of 40; 35%). All patients had NYHA class II or worse heart failure (NYHA class II, 36 of 40 [90%]; NYHA class III, 4 of 40 [10%]). The mean time in AF pre-HA was 5.6 ± 6.7 years. All patients received both HA stages. No deaths or strokes occurred within 30 days. Three new permanent pacemakers (7.5%) were placed. Rhythm success was achieved in >60% of patients during a mean 3.5 ± 1.9 years of follow-up. LVEF improved significantly by 12.0% ± 12.5% (95% CI, 7.85%-16.0%; P < .0001), and mean LA size decreased significantly by 0.40 cm ± 0.85 cm (95% CI, 0.69-0.12 cm; P < .01), with a mean of 3.0 ± 1.5 years between pre-HA and post-HA echocardiography. NYHA class improved significantly after HA (mean pre-HA NYHA class, 2.1 ± 0.3 [95% CI, 2.0-2.2]; mean post-HA NYHA class, 1.5 ± 0.6 [95% CI, 1.3-1.7]; P < .0001). Conclusions Thoracoscopic HA of AF in selected patients with TMC heart failure is safe and can result in rhythm success with structural heart changes, including improvements in LVEF and LA size. Graphical abstract Thoracoscopic and endocardial hybrid ablation (HA) of atrial fibrillation (AF) with depressed left ventricular ejection fraction (LVEF). HA in patients with tachycardia-mediated heart failure is safe and provides freedom from AF in the majority of patients. In our cohort, >60% of patients achieved rhythm success, with an average absolute LVEF improvement of 12% and an absolute left atrial size decrease of 0.4 cm, and no patient experienced stroke or death. Video Abstract

Dataset Information

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

Publications

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

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