Role In Atrial Fibrillation Research Articles

Embolism to the main limb arteries in patients with atrial fibrillation

Introduction. Acute limb ischemia due to embolism in patients with atrial fibrillation remains poorly studied. Objective – to study the clinical significance and role of atrial fibrillation (AF) in the development of embolism to the bifurcation of the aorta and the main arteries of the limbs. Materials and methods. Treatment results of 1816 patients with acute ischemia of the extremities due to embolism treated at a specialized vascular surgical department for the past 30 years were analyzed. 1611 (88.7 %) of them had AF. The distribution into studied groups was according to the period time factor. Group 1 (n = 744) consisted of patients admitted in the period from 1991 to 2000; in group 2 (n = 568) – admitted in the period from 2001 to 2010, in group 3 (n = 299) – from 2011 to 2020. Methods included clinical examination, electrocardiography, Doppler-ultrasound, echocardiography. Results. The role of rheumatic heart disease as a cause of AF has decreased over the past decades by almost 10 times (from 19.5 % in group 1 to 2.0 % in group 3). Currently, the main background diseases for the development of AF are arterial hypertension and various forms of coronary artery disease. Embolism in patients with AF may develop in the arteries of all vascular areas of the systemic circulation, but in the practice of a vascular surgeon more often in the main arteries of minor caliber – the brachial (24.5 %) and popliteal (13.0 %). Multiple embolisms to various vascular areas were found in 2.8 % of patients. Urgent surgical revascularization of the limb by open embolectomy was performed in 1481 (91.9 %) patients that allowed 1348 (83.7 %) to be discharged with limb-sparing. Conclusion. In patients with acute limb ischemia of embologenic ethiology, comorbid AF has 88.7 % of them. Urgent embolectomy allows 83.7 % of patients to be discharged without limb amputation. Hospital mortality in the period 1991–2000 was 15.6 %, the last decade has been reduced to 7.4 %.

Role of Interatrial Conduction in Atrial Fibrillation. Mechanistic Insights From Renewal Theory-Based Fibrillatory Dynamic Analysis

Inter-atrial conduction has been postulated to play an important role in atrial fibrillation (AF). The pathways involved in inter-atrial conduction during AF remain incompletely defined. We recently showed physiological assessment of fibrillatory dynamics could be performed using renewal theory, which determines rates of phase singularity formation (λf) and destruction (λd). Using the renewal approach, we aimed to understand the role of the inter-atrial septum and other electrically coupled regions during AF.

Collagen Remodeling and Fatty Acid Regulation Biomarkers in Understanding the Molecular Pathogenesis of Atrial Fibrillation.

Atrial Fibrillation (AF) is the most common cardiac arrythmia in the world. Structural remodeling and fatty acid metabolism dysregulation are believed to play a role in the development of AF. This study explored different biomarkers in the blood of AF patients and a control population to determine if there was a significant difference between the two groups. Plasma samples were collected from 73 patients with confirmed diagnosis of AF from Loyola University Clinic. Control group represented commercially available plasma (n = 50). Sandwich ELISA kits were used to quantify the collagen remodeling proteins and liver type fatty acid binding protein (L-FABP) in the AF population and the control population. Non-esterified fatty acids (NEFAs) were measured using an enzymatic colorimetric kit from Wako Diagnostics. Statistical analyses were performed using GraphPad Prism. All the collagen remodeling biomarkers were significantly higher in AF patients compared to the control group. The fatty acid dysregulation biomarkers were elevated in the AF patients. Spearman correlation analyses yielded significant correlations between L-FABP and TIMP-1 (r = 0.47, P < 0.001), NEFA and TIMP-2 (r = 0.41, P = 0.002), NEFA and ICTP (r = 0.41, P =0 .002), and NEFA and PIIINP (r = 0.61, P < 0.0001). The elevation of collagen remodeling biomarkers suggests an upregulation of these biomarkers and their potential role in AF, which may contribute to atrial fibrosis. L-FABP and NEFAs were elevated in AF patients. The correlations between the collagen remodeling and fatty acid dysregulation biomarkers may be due to their involvement in structural remodeling of the atria.

Role of Atrial Fibrillation, Obstructive Sleep Apnea and Heart Failure in Left Atrial Structural Remodeling

Role of Atrial Fibrillation, Obstructive Sleep Apnea and Heart Failure in Left Atrial Structural Remodeling

Role of atrial fibrillation in patients with acute ischemic stroke

Role of atrial fibrillation in patients with acute ischemic stroke

Activation of PKG-CREB-KLF15 by melatonin attenuates Angiotensin II-induced vulnerability to atrial fibrillation via enhancing branched-chain amino acids catabolism

Mitochondrial reactive oxygen species (ROS) damage and atrial remodeling serve as the crucial substrates for the genesis of atrial fibrillation (AF). Branched-chain amino acids (BCAAs) catabolic defect plays critical roles in multiple cardiovascular diseases. However, the alteration of atrial BCAA catabolism and its role in AF remain largely unknown. This study aimed to explore the role of BCAA catabolism in the pathogenesis of AF and to further evaluate the therapeutic effect of melatonin with a focus on protein kinase G (PKG)-cAMP response element binding protein (CREB)-Krüppel-like factor 15 (KLF15) signaling. We found that angiotensin II-treated atria exhibited significantly elevated BCAA level, reduced BCAA catabolic enzyme activity, increased AF vulnerability, aggravated atrial electrical and structural remodeling, and enhanced mitochondrial ROS damage. These deleterious effects were attenuated by melatonin co-administration while exacerbated by BCAA oral supplementation. Melatonin treatment ameliorated BCAA-induced atrial damage and reversed BCAA-induced down-regulation of atrial PKGIα expression, CREB phosphorylation as well as KLF15 expression. However, inhibition of PKG partly abolished melatonin-induced beneficial actions. In summary, these data demonstrated that atrial BCAA catabolic defect contributed to the pathogenesis of AF by aggravating tissue fibrosis and mitochondrial ROS damage. Melatonin treatment ameliorated Ang II-induced atrial structural as well as electrical remodeling by activating PKG-CREB-KLF15. The present study reveals additional mechanisms contributing to AF genesis and highlights the opportunity of a novel therapy for AF by targeting BCAA catabolism. Melatonin may serve as a potential therapeutic agent for AF intervention.

Diversity among differentially expressed genes in atrial appendages of atrial fibrillation: The role and mechanism of SPP1 in atrial fibrosis.

Structural remodeling plays an important role in the occurrence and maintenance of atrial fibrillation (AF), but the mechanism is currently unclear. This study was designed to investigate the transcriptomic mechanism of structural remodeling of AF through bioinformatic analysis and in vivo and vitro experiments. Transcriptomic datasets were retrieved from the Gene Expression Omnibus (GEO) database, and bioinformatics analysis was performed to screen mRNAs associated with AF. Cell and animal models were constructed to verify the bioinformatic findings using RT-qPCR and western blot analysis. Then, SPP1 was screened as the target gene, and the mechanism by which it promotes fibrosis was further studied in human cardiac fibroblasts (HCFs) using western blot analysis. After retrieval, the GSE14975, GSE31821, GSE79768, GSE115574 and GSE128188 datasets were used in this study. In total, 147 differentially expressed genes (DEGs) were identified in left atrial appendix tissue and 85 in right atrial appendix tissue. According to the enrichment analysis results, the calcium signaling pathway was found to play an important role in AF, in which EGFR, AGTR1, HTR2B, CD38 and BDKRB1 might be the key genes. Moreover, SPP1 was identified as a key driver through PPI analysis and experimentally proved to reduce the expression of p27 by regulating the PI3K/Akt signaling pathway, sequentially promoting HCF fibrosis. Bioinformatics analysis showed that the calcium signaling pathway might play an important role in AF, while SPP1 could promote myocardial fibrosis through the PI3K/Akt/p27 signaling axis.

Atrial Fibrillation and Peri-Atrial Inflammation Measured through Adipose Tissue Attenuation on Cardiac Computed Tomography

Background: Inflammation plays a key role in atrial fibrillation (AF). Epicardial adipose tissue around the atrial wall can influence atrial morpho-functional properties. The aim of this study was to assess whether an increased quantity and/or density of adipose tissue located around the left atrium (Fat-LA) are related to AF, independently from atrial size. Methods: eighty patients who underwent AF ablation and 80 patients without history of AF were selected. The Fat-LA mass was quantified as tissue within −190 to −30 Hounsfield Units (HU) on cardiac computed tomography angiograms (CCTA), and the mean adipose tissue attenuation was assessed. Results: Adipose tissue mass was higher in patients with AF (5.42 ± 2.94 mL) versus non-AF (4.16 ± 2.55 mL, p = 0.007), but relative fat quantity did not differ after adjusting for atrial size. Mean fat density was significantly higher in AF (−69.15 HU) versus non-AF (−76.82 HU, p < 0.0001) participants. In the logistic regression models, only the addition of mean Fat-LA attenuation led to a significant improvement of the model’s chi-square (from 22.89 of the clinical model to 31.69 of the clinical and adipose tissue attenuation model, p < 0.01) and discrimination (AUC from 0.775 to 0.829). Conclusions: Fat-LA volume is significantly greater only in absolute terms in patients with AF, but this difference does not hold after adjusting for the larger LA of AF subjects. On the contrary, a higher Fat-LA density was associated with AF, independently from LA size, providing incremental value over other variables that are associated with AF.

Pan-Cancer Analysis of Atrial-Fibrillation-Related Innate Immunity Gene ANXA4.

Background: Atrial fibrillation (AF) is the most common tachyarrhythmia around the world. Cancer is one of the main causes of death worldwide. A recent study demonstrated that cancer was associated with an increased incidence of AF. In the present study, we aimed to explore possible mechanisms and potential common therapeutic targets between AF and cancer.Methods: Differentially expressed proteins between AF and sinus rhythm were identified utilizing proteomics analysis. Weighted gene correlation network analysis was applied to cluster proteins into different modules and investigate associations between modules and AF. Hub immune-related genes were selected via InnateDB database and verified using qRT-PCR. RNA sequencing and clinical data of 33 different cancer types were achieved from The Cancer Genome Atlas (TCGA). The correlations between ANXA4 expression and the prognosis were calculated utilizing Cox regression analysis and Kaplan-Meier survival analysis. Spearman's rank correlation test was used to assess associations between ANXA4 and immune infiltration and DNA methylation. Enrichment analysis was performed through gene ontology and gene set enrichment analysis (GSEA).Results:ANXA4 was identified as hub immune-related gene between AF and sinus rhythm. Expression levels of ANXA4 increased in diverse cancer types. Survival analysis suggested prognostic significance of ANXA4 expression levels in various cancer types. Immune correlation analysis indicated that ANXA4 expression levels were associated with tumor immune infiltration in most cancer types. ANXA4 might influence the efficacy of immunotherapy via tumor burden and microsatellite instability. GSEA results indicated that high ANXA4 expression groups were mainly enriched in peroxisome, bile acid biosynthesis, and p53 pathway.Conclusion:ANXA4 was identified as a hub immune-related gene in AF, which has never been reported. Pan-cancer analysis indicated its potential as a novel clinical prognostic marker and therapeutic target in diverse cancer types. ANXA4 might play crucial roles in AF and cancer, and targeted therapy for ANXA4 might reduce the incidence of AF in cancer patients.

Serum Beta-2 Microglobulin: A Possible Biomarker for Atrial Fibrillation.

BackgroundAtrial fibrillation (AF) is the most common persistent arrhythmia that can cause complications (including stroke). Therefore, its diagnosis and treatment require increased attention. Although beta-2 microglobulin (β2-MG) is a novel marker of cardiovascular disease, its role in AF has not been evaluated.Material/MethodsWe conducted a case-control study with 61 patients who had normal heart rhythm (control group) and 60 patients with AF (research group). We analyzed the serum β2-MG levels in both groups and performed multivariate analysis to assess the correlation between β2-MG and left atrial remodeling. In addition, β2-MG levels were compared between the left atrial blood and peripheral venous blood of another set of 57 patients with AF, who underwent cryoballoon ablation.ResultsThere were no statistically significant differences in the baseline characteristics (age, sex, history of hypertension, diabetes mellitus, previous stroke, coronary heart disease, and estimated glomerular filtration rate) of the control and research groups. The left atrial anteroposterior diameters (LAD) and left ventricular end-systolic diameters in the AF group were significantly larger compared to the control group (P<0.01). Serum β2-MG levels in patients with AF were significantly higher (P<0.01) and positively correlated with the LAD (B-coefficient 25.482, 95% CI 14.410~36.554, P<0.01), serum β2-MG levels in the left atrial blood were significantly higher than those in peripheral venous blood (P<0.01), and serum β2-MG levels were an independent predictor of AF.ConclusionsWith the development of atrial fibrillation, the serum β2-MG levels increase and are closely related to the left atrial remodeling due to AF. Therefore, β2-MG can be an effective biomarker for predicting AF.

MiR‑101a‑3p overexpression prevents acetylcholine‑CaCl2‑induced atrial fibrillation in rats via reduction of atrial tissue fibrosis, involving inhibition of EZH2.

Atrial fibrillation (AF), a clinically common heart arrhythmia, can result in left ventricular hypofunction, embolism and infarction. MicroRNA (miR)-101a-3p is lowly expressed in atrial tissues of patients with AF, but its role in AF remains unknown. In the present study, an AF model in rats was established via intravenous injection of acetylcholine (Ach)-CaCl2. The downregulation of miR-101a-3p and upregulation of enhancer of zeste 2 homolog 2 (EZH2) were observed in AF model rats, indicating the involvement of miR-101a-3p and EZH2 in AF development. To study the effect of miR-101a-3p on AF in vivo, AF model rats were intramyocardially injected with lentivirus expressing miR-101a-3p. Electrocardiogram analysis identified that miR-101a-3p overexpression restored disappeared P wave and R-R interphase changes in Ach-CaCl2-induced rats. Overexpression of miR-101a-3p also increased the atrial effective refractory period, reduced AF incidence and shortened duration of AF. Histological changes in atrial tissues were observed after H&E and Masson staining, which demonstrated that miR-101a-3p reduced atrial remodeling and fibrosis in AF model rats. Moreover, EZH2 expression was downregulated in atrial tissues by miR-101a-3p induction. Immunohistochemistry for collagen I and collagen III revealed a reduction in atrial collagen synthesis following miR-101a-3p overexpression in AF model rats. Additionally, miR-101a-3p lowered the expression of pro-fibrotic biomarkers, including TGF-β1, connective tissue growth factor, fibronectin and α-smooth muscle actin. The luciferase reporter assay results also indicated that EZH2 was a target gene of miR-101a-3p. Taken together, it was found that miR-101a-3p prevented AF in rats possibly via inhibition of collagen synthesis and atrial fibrosis by targeting EZH2, which provided a potential target for preventing AF.

Activated Factor X Signaling Pathway via Protease-Activated Receptor 2 Is a Novel Therapeutic Target for Preventing Atrial Fibrillation.

Activated factor X (FXa), which contributes to chronic inflammation via protease-activated receptor 2 (PAR2), might play an important role in atrial fibrillation (AF) arrhythmogenesis. This study aimed to assess whether PAR2 signaling contributes to AF arrhythmogenesis and whether rivaroxaban ameliorates atrial inflammation and prevents AF. In Study 1, PAR2 deficient (PAR2-/-) and wild-type mice were infused with angiotensin II (Ang II) or a vehicle via an osmotic minipump for 2 weeks. In Study 2, spontaneously hypertensive rats (SHRs) were treated with rivaroxaban, warfarin, or vehicle for 2 weeks after 8 h of right atrial rapid pacing. The AF inducibility and atrial remodeling in both studies were examined. Ang II-treated PAR2-/- mice had a lower incidence of AF and less mRNA expression of collagen1 and collagen3 in the atrium compared to wild-type mice treated with Ang II. Rivaroxaban significantly reduced AF inducibility compared with warfarin or vehicle. In SHRs treated with a vehicle, rapid atrial pacing promoted gene expression of inflammatory and fibrosis-related biomarkers in the atrium. Rivaroxaban, but not warfarin, significantly reduced expression levels of these genes. The FXa-PAR2 signaling pathway might contribute to AF arrhythmogenesis associated with atrial inflammation. A direct FXa inhibitor, rivaroxaban, could prevent atrial inflammation and reduce AF inducibility, probably by inhibiting the pro-inflammatory activation.

Necroptosis is required for atrial fibrillation and involved in aerobic exercise-conferred cardioprotection.

Necroptosis, a novel programmed cell death, plays a critical role in the development of fibrosis, yet its role in atrial fibrillation (AF) remains elusive. Mounting evidence demonstrates that aerobic exercise improves AF‐related symptoms and quality of life. Therefore, we explored the role of necroptosis in AF pathogenesis and exercise‐conferred cardioprotection. A mouse AF model was established either by calcium chloride and acetylcholine (CaCl2‐Ach) administration for 3 weeks or high‐fat diet (HFD) feeding for 12 weeks, whereas swim training was conducted 60 min/day, for 3‐week duration. AF susceptibility, heart morphology and function and atrial fibrosis were assessed by electrophysiological examinations, echocardiography and Masson's trichrome staining, respectively. Both CaCl2‐Ach administration and HFD feeding significantly enhanced AF susceptibility (including frequency and duration of episodes), left atrial enlargement and fibrosis. Moreover, protein levels of necroptotic signaling (receptor‐interacting protein kinase 1, receptor‐interacting protein kinase 3, mixed lineage kinase domain‐like protein and calcium/calmodulin‐dependent protein kinase II or their phosphorylated forms) were markedly elevated in the atria of AF mice. However, inhibiting necroptosis with necrostatin‐1 partly attenuated CaCl2‐Ach (or HFD)‐induced fibrosis and AF susceptibility, implicating necroptosis as contributing to AF pathogenesis. Finally, we found 3‐week swim training inhibited necroptotic signaling, consequently decreasing CaCl2‐Ach‐induced AF susceptibility and atrial structural remodeling. Our findings identify necroptosis as a novel mechanism in AF pathogenesis and highlight that aerobic exercise may confer benefits on AF via inhibiting cardiac necroptosis.

Small-Molecule Integrated Stress Response Inhibitor Reduces Susceptibility to Postinfarct Atrial Fibrillation in Rats via the Inhibition of Integrated Stress Responses.

Phosphorylation of the eukaryotic translation initiation factor 2 α-subunit, which subsequently upregulates activating transcription factor 4 (ATF4), is the core event in the integrated stress response (ISR) pathway. Previous studies indicate phosphorylation of eukaryotic translation initiation factor 2 ɑ-subunit in atrial tissue in response to atrial fibrillation (AF). This study investigated the role of ISR pathway in experimental AF by using a small-molecule ISR inhibitor (ISRIB). Accordingly, rats were subjected to coronary artery occlusion to induce myocardial infarction (MI), or sham operation, and received either trans-ISRIB (2 mg/kg/d, i.p.) or vehicle for seven days. Thereafter, animals were subjected to the AF inducibility test by transesophageal rapid burst pacing followed by procurement of left atrium (LA) for assessment of atrial fibrosis, inflammatory indices, autophagy-related proteins, ISR activation, ion channel, and connexin 43 expression. Results showed a significant increase in the AF vulnerability and the activation of ISR in LA as evidenced by enhanced eukaryotic translation initiation factor 2 ɑ-subunit phosphorylation. ISRIB treatment suppressed upregulation of ATF4, fibrosis as indexed by determination of α-smooth muscle actin and collagen levels, inflammatory macrophage infiltration (i.e., CD68 and inducible nitric oxide synthase/CD68-positive macrophage), and autophagy as determined by expression of light chain 3. Further, ISRIB treatment reversed the expression of relevant ion channel (i.e., the voltage-gated sodium channel 1.5 , L-type voltage-dependent calcium channel 1.2, and voltage-activated A-type potassium ion channel 4.3) and connexin 43 remodeling. Collectively, the results suggest that the ISR is a key pathway in pathogenesis of AF, post-MI, and represents a novel target for treatment of AF. SIGNIFICANCE STATEMENT: The activation of integrated stress response (ISR) pathway as evidenced by enhanced eukaryotic translation initiation factor 2 ɑ-subunit phosphorylation in left atrium plays a key role in atrial fibrillation (AF). ISR inhibitor (ISRIB) reduces AF occurrence and atrial proarrhythmogenic substrate. The beneficial action of ISRIB may be mediated by suppressing ISR pathway-related cardiac fibrosis, inflammatory macrophage infiltration, autophagy, and restoring the expression of ion channel and connexin 43. This study suggests a key dysfunctional role for ISR in pathogenesis of AF with implications for novel treatment.

Galectin-3 in patients with atrial fibrillation and restored sinus rhythm

Cardiac fibrosis is the hallmark of atrial remodeling in atrial fibrillation. Galectin-3 (Gal-3) is a biomarker of fibrosis. It is well studied in heart failure, but the data about its role in atrial fibrillation are sparse. The aim of the study was to evaluate the levels of Gal-3 in patients with atrial fibrillation after sinus rhythm restoration, to examine the association between this biomarker and other factors for developing atrial fibrillation and to assess its prognostic role. We included 67 patients (35 male) at the mean age of 67.36±7.25 years, with Gal-3 test after sinus rhythm restoration, a subgroup of participants in placebo-controlled randomized clinical trial of treatment with spironolactone. They were followed up for atrial fibrillation recurrence and hospitalizations. The effect of demographic parameters and other factors on Gal-3 levels were evaluated before and one year after treatment. Mean Gal-3 at baseline was 16.9±6.8 ng/ml. Higher levels of Gal-3 were associated with female gender (р=0.008), increasing age (р=0.005), renal dysfunction (p<0.0001) and gout (р=0.002). Higher thromboembolic risk as assessed by CHA2DS2-VASc score was significantly related to Gal-3. The levels of biomarker did not affect the number of atrial fibrillation recurrences (p=0.9) and hospitalizations. No correlation was found with treatment with spironolactone, antiarrhythmic and antihypertensive drugs. Higher Gal-3 in atrial fibrillation was associated with female sex, renal dysfunction, and history of gout. The levels of Gal-3 were not related to rhythm control. Treatment with spironolactone did not affect the biomarker of fibrosis Gal-3 in AF patients. Higher Gal-3 was related to high embolic risk.

Clinical and electrophysiological characteristics of extra-pulmonary vein triggers in patients who underwent catheter ablation for atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background Extra-pulmonary vein (PV) triggers play significant roles in atrial fibrillation (AF) recurrence after AF catheter ablation (AFCA). Purpose We explore the clinical and electrophysiological characteristics of extra-PV triggers in de novo and repeat-AFCA procedure. Methods We included 2,151 patients who had de novo AFCA and 319 repeat AFCA (female 28.0%, 59.1 ± 10.8 years old, paroxysmal AF 65.1%) those underwent post-procedural isoproterenol (ISO) provocation tests. We analysed the clinical, electrophysiological, and procedure-related factors associated with extra-PV triggers. Results Extra-PV triggers were documented in 11.9% (1.19 ± 0.42 foci) after de novo-AFCA and 27.0% (1.37 ± 0.65 foci) after repeat-AFCA (p = 0.004). LA volume index (OR 1.02 [1.01-1.03], p = 0.004), history of vascular disease (OR 0.55[0.31-0.91], p = 0.028) and Lead I amplitude of electrocardiogram (OR &amp;lt;0.01 [&amp;lt;0.01-0.62], p = 0.032) were independently associated with the existence of extra-PV triggers in de-novo procedure. Women (OR 1.84 [1.03-3.25], p = 0.037) and LA appendage volume (OR 1.04 [1.01-1.07] p = 0.027) were independently associated with extra-PV triggers during the redo-mapping procedure. Septum (28.4%), coronary sinus (24.0%), and superior vena cava (19.6%) were common extra-PV foci, and septal foci were more commonly found in repeat mapping (38.4% vs. 25.0%, p = 0.025). Among 65 patients who showed extra-PV at the repeat procedures, 19 (29.2%) matched with previous focal or empirical extra-PV ablation sites and 9 (13.8%) were multiple or unmappable sites. AF recurrence rates were significantly higher in both patients with extra-PV triggers after de novo procedures (Log-rank P &amp;lt;0.001; HR 1.93 [1.58-2.36], p= &amp;lt;0.001) and repeat procedures (Log-rank P &amp;lt;0.001, HR 1.87 [1.29-2.70], p= &amp;lt;0.001). Conclusion ISO provoked extra-PV triggers commonly found in AF patients with significant remodelling and previous empirical or focal extra-PV ablations. Existence of extra-PV triggers were independently associated with poorer rhythm outcome after both de novo and repeat AFCA. Denovo AF ablation outcome OverallExtra-PV triggers (-)Extra-PV triggers (+)p-value(n = 2151)(n = 1895)(n = 256)Age, yrs58.98 ± 10.9558.73 ± 11.0360.76 ± 10.200.006Male, (%)1550 ( 72.1)1389 ( 73.3)161 ( 62.9)0.001Follow up duration, month50.30 (37.71)51.65 (37.95)40.71 (34.58)&amp;lt;0.001Early recurrence (%)579 ( 27.8)455 ( 24.9)124 ( 48.4)&amp;lt;0.001Clinical recurrence (%)699 ( 33.6)584 ( 32.0)115 ( 44.9)&amp;lt;0.001Abstract Figure. AF free survival according to Extra PVT

Long-term results of tricuspid annuloplasty with 3-dimensional-shaped rings: effective and durable!

3-Dimensional (3D)-shaped rings are largely adopted for tricuspid annuloplasty, but evidence about their long-term results is scanty. The goal of this study was to analyse the long-term results of tricuspid annuloplasty with 3D-shaped rings. A retrospective review of our prospectively maintained database was carried out to identify all patients who underwent tricuspid valve repair with 3D-shaped rings between January 2011 and December 2014. Kaplan-Meier methods were used to analyse long-term survival. Cumulative incidence function using death as the competitive outcome was used to estimate cardiac death. A total of 168 patients were identified. The median age was 66 years. Eighty-two patients (49%) were in advanced New York Heart Association functional class III-IV. Atrial fibrillation (AF) was present in 101 (60%); the median ejection fraction was 60%. In 82 (49%) patients, a Medtronic 3D Contour annuloplasty ring was employed; in the remaining 86 (51%) patients, an Edwards MC3 ring was used. Cumulative incidence function of cardiac death, with non-cardiac death as a competing risk, was 1.9 ± 1.1%, 95% confidence interval (CI) (0.51-4.95) at 7 years. The cumulative incidence function of recurrence of tricuspid regurgitation (TR) ≥2+ at 7 years was 14 ± 3.17%, 95% CI (8.49-20.82). Recurrence of TR ≥2+ at 7 years was not significantly different between the Medtronic 3D Contour and the Edwards MC3 rings (P = 0.3). AF was identified as the only independent predictor of recurrence of TR ≥2+. 3D-shaped rings are effective and durable. TR recurrence was relatively low at 7 years and usually moderate (2+/4+) without a significant difference between the 2 types of rings. The role of AF as a predictor of TR recurrence was confirmed.

Bioinformatic analysis for the identification of potential gene interactions and therapeutic targets in atrial fibrillation.

Atrial fibrillation (AF) is the most common type of tachycardia. The major injury caused by AF is a systemic embolism. Although AF therapies have evolved substantially, the success rate of sinus rhythm maintenance is relatively low. The reason is the incomplete understanding of the AF mechanisms. A Gene Expression Omnibus (GEO) dataset (GSE79768) was downloaded. Differentially expressed genes (DEGs) were identified by bioinformatic analysis. Enriched terms and pathways were identified by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was constructed to determine regulatory genes. CytoHubba and the Molecular Complex Detection (MCODE) algorithm were used to identify potential hub genes and important modules. The Predicting Associated Transcription Factors From Annotated Affinities (PASTAA) method was used to predict transcription factors (TFs). Two hundred thirty-five upregulated DEGs and seventy-seven downregulated DEGs were identified. In the GO biological process, cellular component, and molecular function analyses, positive regulation of cell migration, anchoring junctions, and cell adhesion molecule binding were enriched significantly. The Hippo signalling pathway was the most significantly enriched pathway. In the PPI network analysis, we found that Class A/1 (rhodopsin-like receptors) may be the critical module. Ten hub genes were extracted, including 6 upregulated genes and 4 downregulated genes. CXCR2, TLR4, and CXCR4 may play critical roles in AF. In the TF prediction, we found that Irf-1 may be implicated in AF. We found that the CXCR4, TLR4, CXCR2 genes, the Hippo signalling pathway and the class A/1 (rhodopsin-like receptors) module may play critical roles in AF occurrence and maintenance, which may provide novel targets for AF treatment.

The effects of cardiac stretch on atrial fibroblasts: analysis of the evidence and potential role in atrial fibrillation.

Atrial fibrillation (AF) is an important clinical problem. Chronic pressure/volume overload of the atria promotes AF, particularly via enhanced extracellular matrix (ECM) accumulation manifested as tissue fibrosis. Loading of cardiac cells causes cell stretch that is generally considered to promote fibrosis by directly activating fibroblasts, the key cell type responsible for ECM production. The primary purpose of this article is to review the evidence regarding direct effects of stretch on cardiac fibroblasts, specifically: (i) the similarities and differences among studies in observed effects of stretch on cardiac fibroblast function; (ii) the signalling pathways implicated; and (iii) the factors that affect stretch-related phenotypes. Our review summarizes the most important findings and limitations in this area and gives an overview of clinical data and animal models related to cardiac stretch, with particular emphasis on the atria. We suggest that the evidence regarding direct fibroblast activation by stretch is weak and inconsistent, in part because of variability among studies in key experimental conditions that govern the results. Further work is needed to clarify whether, in fact, stretch induces direct activation of cardiac fibroblasts and if so, to elucidate the determining factors to ensure reproducible results. If mechanical load on fibroblasts proves not to be clearly profibrotic by direct actions, other mechanisms like paracrine influences, the effects of systemic mediators and/or the direct consequences of myocardial injury or death, might account for the link between cardiac stretch and fibrosis. Clarity in this area is needed to improve our understanding of AF pathophysiology and assist in therapeutic development.

Clinical Applications of Laser Technology: Laser Balloon Ablation in the Management of Atrial Fibrillation.

Catheter-based ablation techniques have a well-established role in atrial fibrillation (AF) management. The prevalence and impact of AF is increasing globally, thus mandating an emphasis on improving ablation techniques through innovation. One key area of ongoing evolution in this field is the use of laser energy to perform pulmonary vein isolation during AF catheter ablation. While laser use is not as widespread as other ablation techniques, such as radiofrequency ablation and cryoballoon ablation, advancements in product design and procedural protocols have demonstrated laser balloon ablation to be equally safe and effective compared to these other modalities. Additionally, strategies to improve procedural efficiency and decrease radiation exposure through low fluoroscopy protocols make this technology an increasingly promising and exciting option.