scholarly journals Analysis of Genes Involved in Persistent Atrial Fibrillation: Comparisons of ‘Trigger’ and ‘Substrate’ Differences

2018 ◽  
Vol 47 (3) ◽  
pp. 1299-1309 ◽  
Author(s):  
Rongjun Zou ◽  
Minglei Yang ◽  
Wanting Shi ◽  
Chengxi Zheng ◽  
Hui Zeng ◽  
...  

Background/Aims: Recent research has improved our understanding of the pulmonary vein and surrounding left atrial (LA-PV) junction and the left atrial appendage (LAA), which are considered the ‘trigger’ and ‘substrate’ in the development of atrial fibrillation (AF), respectively. Herein, with the aim of identifying the underlying potential genetic mechanisms, we compared differences in gene expression between LA-PV junction and LAA specimens via bioinformatic analysis. Methods: Microarray data of AF (GSE41177) were downloaded from the Gene Expression Omnibus database. In addition, linear models for microarray data limma powers differential expression analyses and weighted correlation network analysis (WGCNA) were applied. Results: From the differential expression analyses, 152 differentially expressed genes and hub genes, including LEP, FOS, EDN1, NMU, CALB2, TAC1, and PPBP, were identified. Our analysis revealed that the maps of extracellular matrix (ECM)-receptor interactions, PI3K-Akt and Wnt signaling pathways, and ventricular cardiac muscle tissue morphogenesis were significantly enriched. In addition, the WGCNA results showed high correlations between genes and related genetic clusters to external clinical characteristics. Maps of the ECM-receptor interactions, chemokine signaling pathways, and the cell cycle were significantly enriched in the genes of corresponding modules and closely associated with AF duration, left atrial diameter, and left ventricular ejection function, respectively. Similarly, mapping of the TNF signaling pathway indicated significant association with genetic traits of ischemic heart disease, hypertension, and diabetes comorbidity. Conclusions: The ECM-receptor interaction as a possible central node of comparison between LA-PV and LAA samples reflected the special functional roles of ‘triggers’ and ‘substrates’ and may be closely associated with AF duration. Furthermore, LEP, FOS, EDN1, NMU, CALB2, TAC1, and PPBP genes may be implicated in the occurrence and maintenance of AF through their interactions with each other.

Author(s):  
Satoshi Yanagisawa ◽  
Yasuya Inden ◽  
Shuro Riku ◽  
Kazumasa Suga ◽  
Koichi Furui ◽  
...  

Introduction: The risk of developing left atrial (LA) thrombi after initial catheter ablation for atrial fibrillation (AF) and requirements for imaging evaluation for thrombi screening at repeat ablation is unclear. This study aimed to assess the occurrence of thrombus development and frequency of any imaging study evaluating thrombus formation during repeat ablation for AF. Methods: Of 2,066 patients undergoing initial catheter ablation for AF with uninterrupted oral anticoagulation, 615 patients underwent repeat ablation after 258.0 (105.0-882.0) days. We investigated which factors were associated with safety outcomes and requirements for thrombi screening. Results: All patients underwent at least one imaging examination to screen for thrombi in the first session, but the examination rate decreased to 476 patients (77%) before the repeat procedure. The frequency of imaging evaluations was 5.0%, 11%, 21%, 84%, and 91% for transesophageal echocardiography and 18%, 33%, 49%, 98%, and 99% for any imaging modality at repeat ablation performed ≤60 days, ≤90 days, ≤180 days, >180 days, and >1 year after the initial procedure, respectively. Three patients (0.5%) developed LA thrombi at repeat ablation due to identifiable causes, and no patients had thromboembolic events when no imaging evaluation was performed. Multivariate analysis revealed that repeat ablation >180 days, non-paroxysmal atrial arrhythmias, and lower left ventricular ejection fraction were predictors of the risk of thrombus development. Conclusions: The risk development of thrombus at repeat ablation for AF was low. There needs to be a risk stratification for the requirement of imaging screening for thrombi at repeat ablation for AF.


2018 ◽  
Vol 7 (3) ◽  
pp. 12-23
Author(s):  
A. V. Tregubov ◽  
Yu. V. Shubik

Aim. To evaluate the impact of the atrial ectopic activity and left ventricular diastolic dysfunction on predicting the effectiveness of pulmonary vein isolation (PVI) in patients with paroxysmal and persistent atrial fibrillation (AF).Methods. 54 patients with paroxysmal and persistent AF and the normal left ventricular ejection fraction were included in the study. Patients underwent Holter monitoring and echocardiography prior to the intervention to identify the predictors of successful PVI. The follow-up was 12 months after the indexed procedure. The effectiveness of treatment was assessed from the third month of the postoperative period. The criterion of the successful treatment was the absence of the AF paroxysms lasting more than 30 seconds, confirmed by Holter, diurnal and / or multi-day monitoring. The Student's t-test was used to assess the reliability of the differences between the variables characterizing the treatment results in the study groups. The discriminant analysis was performed to develop an algorithm that allows predicting the PVI result. A p value <0.05 was considered statistically significant.Results. Premature atrial contraction over 70 per hour can be considered as the predictor of the successful PVI in patients with normal left atrial size. The severe LA enlargement should be considered as a predictor of poor ablation efficacy. The obtained discriminant function allows predicting the effectiveness of PVI in patients with paroxysmal and persistent AF depending on Holter monitoring and echocardiography. Its sensitivity is high for both predicting success and failure of the intervention.Conclusion. Holter monitoring and echocardiography allow predicting the effectiveness of PVI. The intervention's efficacy in the groups of patients with severe LA enlargement and the combination of normal left atrial size with over 70 PAC per hour should be addressed in the further studies.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Nagaoka ◽  
Y Mukai ◽  
S Kawai ◽  
S Takase ◽  
K Sakamoto ◽  
...  

Abstract Background Atrial functional mitral regurgitation (AFMR) occurs in patients with atrial fibrillation. However, morphological mechanisms of AFMR are poorly understood. Purpose The purpose of this study was to examine the morphological characteristics in patients with AFMR. Methods Among consecutive 795 patients undergoing initial radiofrequency catheter ablation (RFCA) at our hospital, twenty-five patients with persistent AF accompanied by AFMR (≥ moderate) before RFCA (AFMR group) were studied. Age-matched 25 patients with persistent AF without MR were defined as a control group. Results Left ventricular ejection fraction (LVEF) was lower and left atrium volume index was larger in the AFMR group (Table). Mitral valve annulus diameter and length of anterior mitral leaflet (AML) were similar between groups, whereas length of posterior mitral leaflet (PML) was significantly shorter in the AFMR group. Smaller tethering angle of AML (γ in the figure) and shorter tethering height were significantly associated with the occurrence of AFMR, which were different from morphology of functional mitral regurgitation in patients with dilated LV. Multiple regression analysis revealed that less tenting height (p<0.05) and LA dilatation toward the posterior (p<0.01) were significantly related to AFMR. Echocardiographic parameters AFMR (n=25) Control (n=25) P value Age, y 69±8 66±10 NS Male, n (%) 9 (36) 20 (80) P=0.001 LVEF,% 60±9 67±6 P=0.004 LAD, mm 44±5 41±7 NS LAVI, ml/m2 56±17 41±13 P<0.001 MV diameter, mm 3.9±0.4 3.8±0.5 NS α angle, ° 34±9 35±7 NS β angle, ° 48±9 50±8 NS γ angle, ° 32±5 37±5 P=0.0005 AML length, mm 3.0±0.5 3.0±0.5 NS PML length, mm 2.1±0.1 2.4±0.1 P=0.03 Tenting height, mm 1.5±0.1 1.8±0.1 P=0.02 D, mm 0.8±0.3 0.5±0.3 P=0.001 LVEF: left ventricular ejection fraction; LAD: left atrial diameter; LAVI: left atrial volume index; AML: anterior mitral leaflet; PML: posterior mitral leaftlet. Conclusions AFMR occurs in patients with unique morphological features, such as less tethering height and LA dilatation toward the posterior.


2013 ◽  
Vol 68 (11) ◽  
pp. 26-29
Author(s):  
N. E. Grigoriadi ◽  
L. M. Vasilets ◽  
A. V. Tuev ◽  
E. A. Ratanova ◽  
O. V. Khlynova ◽  
...  

Aim. To study the parameters of the structural and functional state of the myocardium in patients with hypertension, to determine their prognostic value on the risk of atrial fibrillation (AF). Patients and methods: the study involved 72 people: patients with hypertension and AF, with isolated hypertension and apparently healthy individuals. All of them performed echocardiography, blood pressure monitoring and monitoring of cardiogram. Results: the dilatation of left atrial was founded: patients with the atrial fibrillation on the background of hypertension observed the most pronounced changes in the left atrial. In patients with hypertension without arrhythmias and in combination with atrial fibrillation severe left ventricular hypertrophy was observed. Left ventricle systolic function in groups has been stored but in patients with atrial fibrillation on the background of hypertension was significantly lower. The risk of atrial fibrillation in patients with hypertension prognostic value are the only values of the age, the volume index of the left atrial to the body surface area and left ventricular ejection fraction. Conclusions. The risk of AF in hypertension occurs over the age of 55 and each subsequent year increases it in 1,2 times,  it increases with an index value of the left atrial to the body surface over 29 ml/m2 and with a decrease in left ventricular ejection fraction less than 58%. 


2021 ◽  
pp. 306-313
Author(s):  
Sorin Nicolae BLAGA ◽  
Nicolae TODOR ◽  
Dumitru ZDRENGHEA ◽  
Radu ROȘU ◽  
Gabriel CISMARU ◽  
...  

Objectives - Structural cardiac, mainly atrial remodeling in non-valvular atrial fibrillation (NVAF) creates conditions for thromboembolic complications, despite the optimization of oral anticoagulant treatment over the past years. This study aims to provide a comparative analysis of patients with NVAF, with and without atrial thrombotic masses, in an integrated approach using clinical, electrocardiographic, anatomohemodynamic cardiac findings assessed by echocardiography, as well as an evaluation of the inflammatory status based on the usual screening blood markers. Methods – The study was based on the anonymous analysis of the medical records of 50 patients with NVAF monitored in a center of cardiology in Cluj-Napoca between March 2019 – February 2020, who received optimal oral anticoagulant treatment, all undergoing transesophageal ultrasound prior to cardioversion or ablation therapy. The statistical data processing methods were based on the “chi square” test and overall model fit logistic regression. Results – Atrial thrombotic complications were found in 7 (14%) patients with NVAF. These had, compared to patients without thrombotic masses, a mean CHA2DS2-VASc scale of 3 versus 2.76 (p=0.05), more frequently other atrial tachyarrhythmias (p<0.01), a more expressed inflammatory reaction (p=0.02), as well as a reduction of LVEF (p<0.01) and the peak left atrial appendage emptying velocity (p<0.01). Conclusions – In addition to a high CHA2DS2-VASc score, left anatomohemodynamic cardiac alteration, atrial arrhythmic complexity and background inflammatory status create conditions for high thromboembolic risk in patients with NVAF. Keywords: non-valvular atrial fibrillation, cardiac thrombosis, left ventricular ejection fraction, inflammatory status, peak left atrial appendage velocity,


EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
M Manfrin ◽  
G Mugnai ◽  
G B Chierchia ◽  
C Bilato ◽  
W G Rauhe

Abstract Background The clinical role of left atrial hypertension (LAH) in patients with atrial fibrillation (AF) and its role as predictor in those undergoing pulmonary vein (PV) isolation is still unknown. Purpose The aim of the present study was to analyse the prevalence of LAH in patients with nonvalvular AF and preserved left ventricular ejection fraction having undergone PV isolation and its implication for AF catheter ablation. Methods Consecutive patients with drug resistant AF who underwent PV isolation at San Maurizio Regional Hospital of Bolzano (Italy) as index procedure were retrospectively included in this analysis. Left atrial hypertension was defined as the LA mean pressure &gt;15 mm Hg. Results A total of 98 consecutive patients (71 males, 72%; mean age 60.3 ± 8.4 years) with drug resistant, non valvular AF and preserved LV ejection fraction having undergone index PV isolation procedure were included in the analysis. Eleven patients (11%) underwent radiofrequency ablation and 87 (89%) cryoballoon ablation. The mean LA pressure was 10.7 ± 4.5 mmHg; LAH occurred in 24 (24%) patients. At a mean follow up of 14.6 ± 7.1 months (median 14 months), the success rate without antiarrhythmic therapy was 71.4% (70/98; considering the blanking period). On multivariate analysis, LAH remained the only independent predictor of definitive AF recurrence (HR 3.02, 1.36-6.72, p = 0.007). Conclusion Left atrial hypertension was found in 24% of patients undergoing PV isolation and was found to be significantly related to both early and late AF recurrences. Univariate and multivariate Cox regressi Univariate analysis Multivariate analysis Early Recurrence (during BP) HR 95%CI P value HR 95%CI P value Age (years) 1.06 1.02-1.10 0.005 1.05 1.00-1.09 0.03 LA volume (ml/m2) 1.02 1.00-1.05 0.04 1.02 1.00-1.05 0.05 LA hypertension 2.46 1.32-4.57 0.004 1.97 1.03-3.79 0.04 Recurrence after the BP HR 95%CI P value HR 95%CI P value Age (years) 1.05 1.00-1.11 0.04 1.04 0.98-1.09 0.15 LA hypertension 3.51 1.62-7.60 0.001 3.02 1.36-6.72 0.007 BP recurrence 1.83 0.84-3.99 0.13 AF atrial fibrillation. BMI: body mass index. LA: left atrium. CAD: coronary artery disease. BP: blanking period. HR: hazard ratio. CI: confidence intervals.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Mohammadali Habibi ◽  
Joao Lima ◽  
Irfan Khurram ◽  
Stefan L Zimmerman ◽  
Vadim Zipunnikov ◽  
...  

Introduction: Atrial fibrillation (AF) is associated with left atrial (LA) electrical, structural, and contractile remodeling. Cardiac magnetic resonance (CMR), late gadolinium enhancement (LGE) and feature tracking are capable of noninvasive quantification of LA fibrosis and myocardial motion, respectively. Hypothesis: Increased LA fibrosis measured with LGE is associated with worsening of the phasic LA function measured with feature tracking CMR. Methods: The cohort included 90 patients (age 61 ± 10 years, 76% male) with symptomatic drug-resistant AF referred for ablation. Peak global longitudinal LA strain (PLAS), LA systolic strain rate (SR-s), and early (SR-ed) and late diastolic (SR-ld) strain rates were measured using cine-CMR images acquired during sinus rhythm. The degree of LGE was quantified using normalized image intensity. Results: Compared to patients with paroxysmal AF (60% of cohort), those with persistent AF had larger maximum LA volume index (LAVImax, 56 ± 17ml/m2 versus 49 ± 13ml/m2 p=0.036), and increased LGE (27.1± 11.7% versus 36.8 ± 14.8% p<0.001). Aside from LA active emptying fraction, all LA parameters (passive emptying fraction, PLAS, SR-s, SR-ed and SR-ld) were lower in patients with persistent AF (p< 0.05 for all). Increased LA fibrosis was associated with lower LA passive emptying fraction, PLAS, SR-s, SR-ed, and SR-ld after adjusting for age, sex, hypertension, heart failure, left ventricular ejection fraction, type of AF, and LA volume (p<0.05 for all). Conclusions: Increased LA fibrosis is associated with decreased LA reservoir, conduit, and booster pump functions. Phasic measurement of LA function using feature-tracking CMR is feasible and may add important information regarding the physiological importance of LA fibrosis.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Gizatulina ◽  
N Y Khorkova ◽  
A V Belokurova ◽  
V E Kharats ◽  
L U Martyanova

Abstract Background Nonvalvular atrial fibrillation (AF) is the most common sustained cardiac dysrhythmia and the most frequent cause of cardio-embolic stroke. It is well known that left atrial appendage thrombi (LAAT) are the source of most embolic strokes in patients with AF, and can be easily identified by transesophageal echocardiography (TEE). Purpose To determine additional LAAT predictors not included in the CHA2DS2-VASc score in patients with nonvalvular AF. Methods Retrospective study enrolled 636 patients with nonvalvular AF (400 males) aged 24–84 years (mean age 57.8±9.1), admitted to our Research Center in 2014–2017 for catheter ablation or electrical cardioversion. All patients had scheduled transthoracic echocardiography (TTE), as well as TEE performed to exclude LAAT. Four forms of cardiac geometry were revealed with the help of TTE according to Recommendations of ASE and EACI: normal geometry, concentric remodeling, eccentric hypertrophy and concentric hypertrophy. Results According to TEE results, LAAT (6.6%) was detected in 42 patients from 636. Patients with LAAT more often had persistent and permanent AF (assigned as “AF stability”), had bigger sizes and volumes of left and right cardiac chambers, lower left ventricular ejection fraction, more expressed LV hypertrophy and lower blood flow velocity in the LA appendage compared to patients without LAAT. Remodeling types also varied: less LAAT patients had normal cardiac geometry and more LAAT patients had LV eccentric hypertrophy. To analyze factors associated with AF, we used a multivariable logistic regression model, involving the potential independent, clinically relevant variables and echocardiographic parameters. Logistic regression analysis identified the latter three as independent predictors for LAAT (Table 1). According to ROC-analysis the quality of the received model was assessed as good: AUC=0.763 (p<0.01), sensitivity – 75.8%, specificity – 72.2%. Table 1 Predictors B Wald statistics χ2 P OR 95% CI AF stability 0.913 4.143 0.042 2.491 1.034–6.000 LA diameter, mm 0.149 8.684 0.003 1.160 1.051–1.281 Eccentric hypertrophy 1.440 7.411 0.006 4.222 1.497–11.908 Constant −10.613 24.088 0.000 Conclusion From risk factors, not included in the CHA2DS2-VASc score, in addition to such predictable values as AF stability and left atrial diameter, such predictor as eccentric left ventricular hypertrophy was revealed, which in our study was associated with more than a 4-fold increase in the risk of LAAT.


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