Perpetuation Of Atrial Fibrillation Research Articles

Association Between Sleep Apnea Treatment and Health Care Resource Use in Patients With Atrial Fibrillation.

Obstructive sleep apnea (OSA) contributes to the generation, recurrence, and perpetuation of atrial fibrillation, and it is associated with worse outcomes. Little is known about the economic impact of OSA therapy in atrial fibrillation. This retrospective cohort study assessed the impact of positive airway pressure (PAP) therapy adherence on health care resource use and costs in patients with OSA and atrial fibrillation. Insurance claims data for ≥1 year before sleep testing and 2 years after device setup were linked with objective PAP therapy use data. PAP adherence was defined from an extension of the US Medicare 90-day definition. Inverse probability of treatment weighting was used to create covariate-balanced PAP adherence groups to mitigate confounding. Of 5867 patients (32% women; mean age, 62.7 years), 41% were adherent, 38% were intermediate, and 21% were nonadherent. Mean±SD number of all-cause emergency department visits (0.61±1.21 versus 0.77±1.55 [P=0.023] versus 0.95±1.90 [P<0.001]), all-cause hospitalizations (0.19±0.69 versus 0.24±0.72 [P=0.002] versus 0.34±1.16 [P<0.001]), and cardiac-related hospitalizations (0.06±0.26 versus 0.09±0.41 [P=0.023] versus 0.10±0.44 [P=0.004]) were significantly lower in adherent versus intermediate and nonadherent patients, as were all-cause inpatient costs ($2200±$8054 versus $3274±$12 065 [P=0.002] versus $4483±$16 499 [P<0.001]). All-cause emergency department costs were significantly lower in adherent and intermediate versus nonadherent patients ($499±$1229 and $563±$1292 versus $691±$1652 [P<0.001 and P=0.002], respectively). These data suggest clinical and economic benefits of PAP therapy in patients with concomitant OSA and atrial fibrillation. This supports the value of diagnosing and managing OSA and highlights the need for strategies to enhance PAP adherence in this population.

Vein of Marshall Ethanol Infusion for AF Ablation; A Review.

The outcomes of persistent atrial fibrillation (AF) ablation are modest with various adjunctive strategies beyond pulmonary vein isolation (PVI) yielding largely disappointing results in randomised controlled trials. Linear ablation is a commonly employed adjunct strategy but is limited by difficulty in achieving durable bidirectional block, particularly at the mitral isthmus. Epicardial connections play a role in AF initiation and perpetuation. The ligament of Marshall has been implicated as a source of AF triggers and is known to harbour sympathetic and parasympathetic nerve fibres that contribute to AF perpetuation. Ethanol infusion into the Vein of Marshall, a remnant of the superior vena cava and key component of the ligament of Marshall, may eliminate these AF triggers and can facilitate the ease of obtaining durable mitral isthmus block. While early trials have demonstrated the potential of Vein of Marshall 'ethanolisation' to reduce arrhythmia recurrence after persistent AF ablation, further randomised trials are needed to fully determine the potential long-term outcome benefits afforded by this technique.

Exploring the Intricate Interplay Between Obesity and Atrial Fibrillation: Mechanisms, Management, and Clinical Implications.

Atrial fibrillation (AF) stands as a prevalent and escalating cardiac arrhythmia in the United States, with obesity emerging as a prominent modifiable risk factor. This article explores the intricate relationship between obesity and AF, delving into the multifaceted pathophysiological mechanisms linking the 2 conditions. Various factors, such as autonomic dysfunction, left atrial stretch, inflammation, and hormonal imbalances, contribute to the initiation and perpetuation of AF in obese individuals. The Atrial Fibrillation Better Care pathway, emphasizing lifestyle modifications and weight loss strategies, emerges as a practical guideline for managing AF in obesity. This comprehensive review underscores the critical role of obesity as a significant modifiable risk factor for AF, urging a proactive approach to its management. Implementing the Atrial Fibrillation Better Care approach, focusing on encouraging physical activity, promoting healthy dietary habits, and raising awareness about the risks associated with obesity prove essential in preventing and mitigating the burden of AF in the obese population.

Developing Pharmacological Therapies for Atrial Fibrillation Targeting Mitochondrial Dysfunction and Oxidative Stress: A Scoping Review.

Atrial fibrillation (AF) is a cardiac arrhythmia caused by electrophysiological anomalies in the atrial tissue, tissue degradation, structural abnormalities, and comorbidities. A direct relationship exists between AF and altered mitochondrial activity resulting from membrane potential loss, contractile dysfunction, or decreased ATP levels. This review aimed to elucidate the role of mitochondrial oxidative mechanisms in AF pathophysiology, the impact of mitochondrial oxidative stress on AF initiation and perpetuation, and current therapies. This review followed the Preferred Reporting Items for Systematic Reviews and the Meta-Analysis Extension for Scoping Reviews. PubMed, Excerpta Medica Database, and Scopus were explored until June 2023 using "MESH terms". Bibliographic references to relevant papers were also included. Oxidative stress is an imbalance that causes cellular damage from excessive oxidation, resulting in conditions such as AF. An imbalance in reactive oxygen species production and elimination can cause mitochondrial damage, cellular apoptosis, and cardiovascular diseases. Oxidative stress and inflammation are intrinsically linked, and inflammatory pathways are highly correlated with the occurrence of AF. AF is an intricate cardiac condition that requires innovative therapeutic approaches. The involvement of mitochondrial oxidative stress in the pathophysiology of AF introduces novel strategies for clinical treatment.

Ubiquitin-specific protease 38 promotes inflammatory atrial fibrillation induced by pressure overload.

Atrial structural and electrical remodelling is a major reason for the initiation and perpetuation of atrial fibrillation (AF). Ubiquitin-specific protease 38 (USP38) is a deubiquitinating enzyme, but its function in the heart remains unknown. The aim of this study was to investigate the effect of USP38 in pressure overload-induced AF. Cardiac-specific knockout USP38 and cardiac-specific transgenic USP38 mice and their corresponding control mice were used in this study. After 4 weeks with or without aortic banding (AB) surgery, atrial echocardiography, atrial histology, electrophysiological study, and molecular analysis were assessed. Ubiquitin-specific protease 38 knockout mice showed a remarkable improvement in vulnerability to AF, atrial weight and diameter, atrial fibrosis, and calcium-handling protein expression after AB surgery. Conversely, USP38 overexpression further increased susceptibility to AF by exacerbating atrial structural and electrical remodelling. Mechanistically, USP38 interacted with and deubiquitinated nuclear factor-kappa B (NF-κB), and USP38 overexpression increased the level of p-NF-κB in vivo and in vitro, accompanied by the upregulation of NOD-like receptor protein 3 (NLRP3) and inflammatory cytokines, suggesting that USP38 contributes to adverse effects by driving NF-κB/NLRP3-mediated inflammatory responses. Overall, our study indicates that USP38 promotes pressure overload-induced AF through targeting NF-κB/NLRP3-mediated inflammatory responses.

Left Atrial Low-Voltage Areas Predict the Risk of Atrial Fibrillation Recurrence after Radiofrequency Ablation.

Atrial fibrillation (AF), the most frequently encountered arrhythmia worldwide, is associated with increased cardiovascular morbidity and mortality. Left atrial (LA) and antral region of the pulmonary veins (PVs) remodeling are risk factors for AF perpetuation. Among the methods of LA fibrosis quantification, bipolar voltage mapping during three-dimensional electro-anatomical mapping is less studied. The main aim of this study was to analyze the relationship between the degree of LA fibrosis quantified in low-voltage areas and the efficacy of AF radiofrequency catheter ablation. All consecutive patients with AF ablation were included, and the degree of LA fibrosis was measured based on the low-voltage areas in the LA and the antral region of PVs (<0.5 mV for patients in sinus rhythm and <0.25 mV for patients in AF at the time of the ablation procedure). The efficacy of AF ablation was determined by the rate of recurrence after a blanking period of three months. A total of 106 patients were included; from these, 38 (35.8%) had AF recurrence after RF ablation, while 68 (64.2%) were free of events. The area and percentage of LA fibrosis were significantly higher in the patients with AF recurrence (p = 0.018 and p = 0.019, respectively). However, no significant differences were found between the patients with and without AF recurrence in terms of the area and percentage of PVs fibrosis (p = 0.896 and p = 0.888, respectively). Moreover, LA fibrosis parameters proved to be excellent predictors for AF recurrence (areas under the curve of 0.834 and 0.832, respectively, p < 0.001) even after adjustment for LA indexed volume and CHA2DS2-VASc score. In conclusion, LA fibrosis measured on bipolar voltage maps increases the risk of AF recurrence after the RF catheter ablation procedure.

Conduction velocity mapping in atrial fibrillation using omnipolar technology.

Recent studies have shown that atrial slow conduction velocity (CV) is associated with the perpetuation of atrial fibrillation (AF). However, the criteria of CV measurement have not been standardized. The aim of this study was to evaluate the relationship between the slow CV area (SCVA) measured by novel omnipolar technology (OT) and AF recurrence. This study included 90 patients with AF who underwent initial pulmonary vein isolation (PVI). The segmented surface area of the SCVA was measured by left atrial (LA) electrophysiological mapping using OT before the PVI. The proportion of the SCVA at each cutoff value of CV (from<0.6to<0.9m/s) was compared between the patients with and without AF recurrence. During a mean follow-up period of 516±197 days, the recurrence of AF after the initial PVI was observed in 23 (25.5%) patients. In patients with AF recurrence, the proportion of the SCVA in the LA posterior, LA appendage (LAA), and LA anterior were significantly higher than those without AF recurrence. The multivariate analysis indicated that the proportion of the low voltage area and the SCVA in the LA anterior (local CV<0.7m/s) were independent predictors of AF recurrence (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.01-1.14; p=0.03; HR, 1.40; 95% CI, 1.07-1.83; p=0.01, respectively). By evaluating the local CV using OT, it was indicated that SCVA with CV<0.7m/s in the LA anterior is strongly associated with AF recurrence after PVI.

Characterization of unipolar electrogram morphology: a novel tool for quantifying conduction inhomogeneity.

Areas of conduction inhomogeneity (CI) during sinus rhythm may facilitate the initiation and perpetuation of atrial fibrillation (AF). Currently, no tool is available to quantify the severity of CI. Our aim is to develop and validate a novel tool using unipolar electrograms (EGMs) only to quantify the severity of CI in the atria. Epicardial mapping of the right atrium (RA) and left atrium, including Bachmann's bundle, was performed in 235 patients undergoing coronary artery bypass grafting surgery. Conduction inhomogeneity was defined as the amount of conduction block. Electrograms were classified as single, short, long double (LDP), and fractionated potentials (FPs), and the fractionation duration of non-single potentials was measured. The proportion of low-voltage areas (LVAs, <1 mV) was calculated. Increased CI was associated with decreased potential voltages and increased LVAs, LDPs, and FPs. The Electrical Fingerprint Score consisting of RA EGM features, including LVAs and LDPs, was most accurate in predicting CI severity. The RA Electrical Fingerprint Score demonstrated the highest correlation with the amount of CI in both atria (r = 0.70, P < 0.001). The Electrical Fingerprint Score is a novel tool to quantify the severity of CI using only unipolar EGM characteristics recorded. This tool can be used to stage the degree of conduction abnormalities without constructing spatial activation patterns, potentially enabling early identification of patients at high risk of post-operative AF or selection of the appropriate ablation approach in addition to pulmonary vein isolation at the electrophysiology laboratory.

Box Lesion Isolation of the Left Atrial Posterior Wall with Radiofrequency Ablation Restricted in Predetermined Lines for the Treatment of Persistent Atrial Fibrillation: The Prognostic Role of Acute Interventional Outcome and Trigger Identification.

The left atrial posterior wall (PW) is known to be a critical substrate for the initiation and perpetuation of atrial fibrillation (AF) and has been explored as a target for catheter ablation, particularly in persistent AF (PerAF). In this retrospective study, we investigate the clinical outcome of patients with PerAF who underwent PW isolation (PWI) restricted in predetermined lines in addition to pulmonary vein isolation (PVI). One hundred consecutive patients (64 ± 9.1 years, 66% male, 20% with previous PVI ablation) underwent PWI in a box lesion setting for PerAF lasting >3 months (34% long-standing PerAF). PW triggers were defined as either foci from the PW that repeatedly induced AF or as isolated AF or atrial tachycardia (AT) within the PW. After a mean follow-up period of 25.6 ± 6.7 months, 61% of the patients remained in sinus rhythm after the last procedure. In 79 patients, the PW was successfully isolated, while, in 21 patients, complete isolation was not possible due to failure in completion of the roof line (n = 16), the floor line (n = 7), or both (n = 2). Patients with incomplete isolation had similar AF/AT recurrence rates compared to those with complete PWI. In 12 patients, PW triggers were identified, and PWI in these patients was shown to have a significantly better prognosis in terms of sinus rhythm maintenance (P = .031). Failure of complete PWI does not predispose a patient to an inferior outcome nor is it responsible for iatrogenic ATs. The presence of AF triggers within the PW leads to a particularly favorable result after box lesion isolation.

NADPH Oxidases and Oxidative Stress in the Pathogenesis of Atrial Fibrillation.

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and its prevalence increases with age. The irregular and rapid contraction of the atria can lead to ineffective blood pumping, local blood stasis, blood clots, ischemic stroke, and heart failure. NADPH oxidases (NOX) and mitochondria are the main sources of reactive oxygen species in the heart, and dysregulated activation of NOX and mitochondrial dysfunction are associated with AF pathogenesis. NOX- and mitochondria-derived oxidative stress contribute to the onset of paroxysmal AF by inducing electrophysiological changes in atrial myocytes and structural remodeling in the atria. Because high atrial activity causes cardiac myocytes to expend extremely high energy to maintain excitation-contraction coupling during persistent AF, mitochondria, the primary energy source, undergo metabolic stress, affecting their morphology, Ca2+ handling, and ATP generation. In this review, we discuss the role of oxidative stress in activating AF-triggered activities, regulating intracellular Ca2+ handling, and functional and anatomical reentry mechanisms, all of which are associated with AF initiation, perpetuation, and progression. Changes in the extracellular matrix, inflammation, ion channel expression and function, myofibril structure, and mitochondrial function occur during the early transitional stages of AF, opening a window of opportunity to target NOX and mitochondria-derived oxidative stress using isoform-specific NOX inhibitors and mitochondrial ROS scavengers, as well as drugs that improve mitochondrial dynamics and metabolism to treat persistent AF and its transition to permanent AF.

Catheter ablation using pulmonary vein isolation with versus without left atrial posterior wall isolation for persistent atrial fibrillation: an updated systematic review and meta-analysis.

Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation of atrial fibrillation (AF); however, the results are suboptimal for persistent AF. The left atrial posterior wall (LAPW) is thought to be a major additional area in initiation and perpetuation of persistent AF. Therefore, adjunctive ablation of the posterior wall may reduce AF recurrence in patients with persistent AF. The objective of this study was to compare outcomes of catheter ablation in patients with persistent AF using PVI alone versus a combination of PVI and LAPW isolation. Literature search was conducted in PubMed, PubMed Central, Scopus, and Embase since inception to February 2023. Screening of studies was done via Covidence software. Risk of bias assessment was done using appropriate tools. Data extraction and a narrative synthesis were carried out accordingly. Ten studies were included, of which five were randomized controlled trials. PVI with LAPW ablation group had significantly lower recurrence of overall atrial tachyarrhythmia (OR 0.47, CI 0.32-0.70) and AF (OR 0.39, CI 0.23-0.69). In sensitivity analysis, freedom from atrial arrhythmias was noted to be significantly higher in the PVI with LAPW ablation group (OR 2.22, CI 1.36-3.64). However, there was no significant difference in occurrence of atrial flutter (OR 1.36, CI 0.86-2.14) or with periprocedural adverse events (OR 1.10, CI 0.60-1.99). LAPW ablation, in addition to PVI, significantly improves the rates of arrhythmia freedom and reduces the recurrence of overall atrial tachyarrhythmia. There was no significant difference in atrial flutter or periprocedural adverse events.

Discovery of TBX20 as a Novel Gene Underlying Atrial Fibrillation.

Atrial fibrillation (AF), the most prevalent type of sustained cardiac dysrhythmia globally, confers strikingly enhanced risks for cognitive dysfunction, stroke, chronic cardiac failure, and sudden cardiovascular demise. Aggregating studies underscore the crucial roles of inherited determinants in the occurrence and perpetuation of AF. However, due to conspicuous genetic heterogeneity, the inherited defects accounting for AF remain largely indefinite. Here, via whole-genome genotyping with genetic markers and a linkage assay in a family suffering from AF, a new AF-causative locus was located at human chromosome 7p14.2-p14.3, a ~4.89 cM (~4.43-Mb) interval between the markers D7S526 and D7S2250. An exome-wide sequencing assay unveiled that, at the defined locus, the mutation in the TBX20 gene, NM_001077653.2: c.695A>G; p.(His232Arg), was solely co-segregated with AF in the family. Additionally, a Sanger sequencing assay of TBX20 in another family suffering from AF uncovered a novel mutation, NM_001077653.2: c.862G>C; p.(Asp288His). Neither of the two mutations were observed in 600 unrelated control individuals. Functional investigations demonstrated that the two mutations both significantly reduced the transactivation of the target gene KCNH2 (a well-established AF-causing gene) and the ability to bind the promoter of KCNH2, while they had no effect on the nuclear distribution of TBX20. Conclusively, these findings reveal a new AF-causative locus at human chromosome 7p14.2-p14.3 and strongly indicate TBX20 as a novel AF-predisposing gene, shedding light on the mechanism underlying AF and suggesting clinical significance for the allele-specific treatment of AF patients.

Mechanisms of Atrial Fibrillation: How Our Knowledge Affects Clinical Practice.

Atrial fibrillation (AF) is a very common arrhythmia that mainly affects older individuals. The mechanism of atrial fibrillation is complex and is related to the pathogenesis of trigger activation and the perpetuation of arrhythmia. The pulmonary veins in the left atrium arei confirm that onfirm the most common triggers due to their distinct anatomical and electrophysiological properties. As a result, their electrical isolation by ablation is the cornerstone of invasive AF treatment. Multiple factors and comorbidities affect the atrial tissue and lead to myocardial stretch. Several neurohormonal and structural changes occur, leading to inflammation and oxidative stress and, consequently, a fibrotic substrate created by myofibroblasts, which encourages AF perpetuation. Several mechanisms are implemented into daily clinical practice in both interventions in and the medical treatment of atrial fibrillation.

Unraveling direction- and rate-dependent unipolar electrogram morphology using spontaneous atrial extraystoles

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial extrasystoles (AES) are notorious for triggering episodes of atrial fibrillation (AF). AES provoke conduction disorders due to (dispersion in) refractoriness and enhanced non-uniform anisotropy of atrial tissue, which are related to initiation and perpetuation of AF. However, the direction- and rate-dependency of electrophysiological tissue properties on epicardial unipolar electrogram (EGM) morphology is unknown. Purpose To examine the impact of spontaneous AES on potential amplitude, -type (single-, double-, fractionated), -duration and low-voltage areas (LVA), and to correlate these differences with various degrees of prematurity and aberrancy. Methods Intra-operative high-resolution epicardial mapping of the right and left atrium (RA, LA), Bachmann’s Bundle (BB) and pulmonary vein area (PVA) was performed during SR in 298 patients. EGM characteristics were quantified during SR and AES, and subsequently compared. AES were categorized according their prematurity index (&amp;gt; 25% shortening) and degree of aberrancy (none, mild, moderate and severe). LVA were defined as the amount of unipolar voltages &amp;lt;1 mV. Results During 917 unique AES (495 premature; 364 mild-, 186 moderate- and 167 severe aberrant), average voltage decreased (-1.1 [-1.2, -0.9] mV, P&amp;lt;0.001) at all atrial regions, whereas the amount of LVA and fractionation increased (respectively +3.6 [2.9, 4.3]% and +3.2 [2.7, 3.7]%, P&amp;lt;0.001). Although potential voltages were mainly decreased during AES, in 910 (99.2%) AES, at least 0.8% (median 33.3 [19.0–52.1] %) of the recorded voltages was locally larger during AES compared to SR. Only weak or moderate correlations were found between each of the parameters and prematurity indices (R2&amp;lt;0.592, P&amp;lt;0.001). On the other hand, voltages decreased and the amount of fractionation increased with increasing degree of aberrancy. The effect of AES with opposite propagation direction was frequently similar as compared to severely aberrant AES. All parameters were most severely affected by either opposite or severely aberrant AES, without clear relation with degree of prematurity. Conclusions Unipolar EGM characteristics during spontaneous AES are mainly directional-dependent and not rate-dependent. This indicates enhanced non-uniform anisotropy that is induced by spontaneous AES.

Effect of right and left-sided programmed atrial extrasystoles on conduction across Bachmanns Bundle and initiation of atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial extrasystoles (AES) originating from the pulmonary veins are notorious for triggering episodes of atrial fibrillation (AF). However, non-pulmonary vein triggers, emerging from e.g. the superior vena cava, left atrial posterior free wall, left atrial appendage (LAA), terminal crest and interatrial septum, play also an important role in a significant part of AF patients. AES provoke conduction disorders due to (dispersion in) refractoriness and enhanced non-uniform anisotropy of atrial tissue, which are related to initiation and perpetuation of AF. Bachmann’s bundle (BB) is the main route for interatrial conduction and plays a key role in AF development. However, the exact mechanistic effects of AES on BB in AF initiation are still unknown. Purpose To examine the impact of programmed electrical stimulation (PES) from the left and right atrium on activation and electrophysiological features of BB. Methods Intra-operative high-resolution epicardial mapping of BB was performed during sinus rhythm (SR) in 30 patients (27 male, 64±10 years). PES included a S1 sequence of 400 ms followed by a S2 of 300, 250 and 200 ms provided from the left and right atrial appendage (LAA/RAA). Electrophysiological features included unipolar voltage, conduction velocity, potential type (single, short/long double and fractionated) and conduction delay/block (CDCB). Features of the shortest captured S2 were compared to the S1 sequence. Results The average cycle length during SR was 962 [869–1085] ms. Compared to SR, during S1 pacing from both the RAA and LAA, voltage (RAA: -0.49 [-1.25–0.06] mV; LAA: -0.17 [-0.97–0.42] mV, P&amp;lt;0.001) and conduction velocity (RAA: -2.72 [-6.85–0.36] cm/s; LAA: -1.28 [-12.37–0.85] cm/s, P&amp;lt;0.001) decreased, and the amount of fractionation increased. In addition, CDCB increased specifically during RAA S1 pacing (+1.8 [0.1–3.2]%, P&amp;lt;0.001), while total activation time increased during LAA pacing (+16 [-1–29] ms, P&amp;lt;0.001). Applying the maximal captured S2, 12 patients had a refractory period of 250 ms, 13 patients of 200 ms and 3 patients &amp;lt;200 ms. In 4 patients, AF was induced by a S2 of 250 or 200 ms from either RAA or LAA. During both RAA and LAA S2 pacing, voltage (RAA: -1.33 [-2.51–-0.64] mV; LAA: -0.91 [-1.64–-0.46] mV, P&amp;lt;0.001) and conduction velocity (RAA: -16.34 [-24.49–-6.70] cm/s; LAA: -8.63 [-19.95–-1.25] cm/s, P&amp;lt;0.001) decreased, while total activation time (RAA: +26 [11–59] ms; LAA: +21 [2–46] ms, P&amp;lt;0.001) and CDCB (RAA: +5.7 [3.5–11.7] %; LAA: +4.1 [0.4–6.5] %, P&amp;lt;0.001) increased. Specifically, the average length of CDCB lines increased remarkably during LAA S2 pacing (+22 [8–39] mm, P&amp;lt;0.001) and even more during RAA S2 pacing (+36 [19–80] mm, P&amp;lt;0.001). Conclusions Premature AES affect interatrial conduction via BB by enhancing conduction disorders. This indicates that BB is involved in AF initiation by ectopic beats, independently of their origin from the right or left atrium.

Impact of the individual relationship between focal or rotational regions of interest and atrial cardiomyopathy in patients with chronic forms of atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background The mechanisms for the initiation and perpetuation of atrial fibrillation (AF) are still not completely understood. The CARTOFINDER module represents a novel approach for the visualisation of repetitive focal and rotational activations in patients with AF. Purpose The aim of this prospective observational study was to evaluate the potential relationship between findings from CARTOFINDER mapping and individual atrial arrhythmia substrates. Beyond that, the impact of atrial fibrosis on patients’ outcome was analysed. Methods A total of 20 consecutive patients (69 ± 9 years, 55 % male) underwent ablation for persistent AF (PERS) applying a 3D-mapping system with the integrated CARTOFINDER module. Regions of interest (ROIs) were identified before ablation. The individual amount and distribution of atrial fibrosis in the left atrium (LA) based on anatomical segments was determined by LGE CMR prior to the ablation procedure. 3, 6 and 12 month-follow-up data were assessed. Results In all patients, ablation procedures were performed successfully (n=20, 100%). LA mapping time was 09.30 ± 03.53 min, mean ablation duration was 26.40 ± 07.51 mi, mean fluoroscopy time amounted to 6.66 ± 1.85 min. Consistent with Utah classes II-III, LGE-CMR revealed an intermediate degree of 21.41 ± 6.16% LA fibrosis. Focal and rotational ROIs were identified in all patients (mean no ROIs per Patient n = 416.45 ± 204.57). Univariate logistic regression calculation documented no consistent correlation between the percentage of LA fibrosis and the probability for the occurrence of ROIs (posterior: regression coefficient (b) =0.36, p-value (p) =0.24; anterior: b=-0.08, p=0.54; lateral: b=0.31, p=0,39; septal:b=-0.12; p=0.66; right PVs: b=0.34, p=0.27; left PVs: b=0.07, p=0.79; LAA: -0.91, p=0.11). Between the degree of atrial cardiomyopathy and the number of ROIs no association was observed (b=10.86, p=0.15). 12 months AF-free survival amounted to 70% (n=14). The degree of LA fibrosis showed no significant correlation with AF-free survival (logistic regression: posterior: b=0.33, p=0.12; anterior: b=-0.03, p=0.83; lateral: b=0.31, p=0,35; septal:b=-0.07; p=0.79; right PVs: b=0.81, p=0.15; left PVs: b=0.37, p=0.25; LAA: -0.16, p=0.54). Conclusions This study reports on initial observations concerning the relationship between focal and rotational activations and atrial fibrosis in PERS AF. No evidence for a consistent correlation between the occurrence or number of ROIs and the degree of atrial arrhythmia substrates was revealed. Beyond that, the amount of LA fibrosis did not correlate with the 12 months AF-free survival rate. Larger studies are warranted to verify our first results.

Construction and integrated analysis of the ceRNA network hsa_circ_0000672/miR-516a-5p/TRAF6 and its potential function in atrial fibrillation

Atrial fibrosis is a crucial contributor to initiation and perpetuation of atrial fibrillation (AF). This study aimed to identify a circRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) regulatory network related to atrial fibrosis in AF, especially to validate hsa_circ_0000672/hsa_miR-516a-5p/TRAF6 ceRNA axis in AF preliminarily. The circRNA-miRNA-mRNA ceRNA network associated with AF fibrosis was constructed using bioinformatic tools and literature reviews. Left atrium (LA) low voltage was used to represent LA fibrosis by using LA voltage matrix mapping. Ten controls with sinus rhythm (SR), and 20 patients with persistent AF including 12 patients with LA low voltage and 8 patients with LA normal voltage were enrolled in this study. The ceRNA regulatory network associated with atrial fibrosis was successfully constructed, which included up-regulated hsa_circ_0000672 and hsa_circ_0003916, down-regulated miR-516a-5p and five up-regulated hub genes (KRAS, SMAD2, TRAF6, MAPK11 and SMURF1). In addition, according to the results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, these hub genes were clustered in TGF-beta and MAPK signaling pathway. In the patients with persistent AF, hsa_circ_0000672 expression in peripheral blood monocytes was significantly higher than those in controls with SR by quantitative real-time polymerase chain reaction (p-value < 0.001). Furthermore, hsa_circ_0000672 expression was higher in peripheral blood monocytes of persistent AF patients with LA low voltage than those with LA normal voltage (p-value = 0.002). The dual-luciferase activity assay confirmed that hsa_circ_0000672 exerted biological functions as a sponge of miR-516a-5p to regulate expression of its target gene TRAF6. Hsa_circ_0000672 expression in peripheral blood monocytes may be associated with atrial fibrosis. The hsa_circ_0000672 may be involved in atrial fibrosis by indirectly regulating TRAF6 as a ceRNA by sponging miR-516a-5p.

The complex interplay between right ventricular dysfunction and atrial fibrillation - a narrative review.

Atrial fibrillation (AF) is one of the most common sustained arrhythmias in clinical practice, associated with multiple comorbidities and complication. The potential predictors of AF onset and perpetuation or specific drivers of complications need future investigation. Right ventricular (RV) dysfunction plays an important role in the development of new-onset AF warranting in-depth analysis in relation to AF. RV may play a significant role in a better characterization of the cardiac substrate of AF patients. The relation between RV dysfunction and AF is bidirectional as AF may be one of the causes of RV dysfunction and their coexistence worsens the overall patient prognosis. Our aim is to present in a narrative review the most relevant data regarding the complex relationship between AF and RV dysfunction.

Conduction velocity is reduced in the posterior wall of hypertrophic cardiomyopathy patients with normal bipolar voltage undergoing ablation for paroxysmal atrial fibrillation.

We investigated characteristics of left atrial conduction in patients with HCM, paroxysmal AF and normal bipolar voltage. Patients with hypertrophic cardiomyopathy (HCM) exhibit abnormal cardiac tissue arrangement. The incidence of atrial fibrillation (AF) is increased fourfold in patients with HCM and confers a fourfold increased risk of death. Catheter ablation is less effective in HCM, with twofold increased risk of AF recurrence. The mechanisms of AF perpetuation in HCM are poorly understood. We analyzed 20 patients with HCM and 20 controls presenting for radiofrequency ablation of paroxysmal AF normal left atrial voltage(> 0.5mV). Intracardiac electrograms were extracted from the CARTO mapping system and analyzed using Matlab/Python code interfacing with Core OpenEP software. Conduction velocity maps were calculated using local activation time gradients. There were no differences in baseline demographics, atrial size, or valvular disease between HCM and control patients. Patients with HCM had significantly reduced atrial conduction velocity compared to controls (0.44 ± 0.17 vs 0.56 ± 0.10m/s, p = 0.01), despite no significant differences in bipolar voltage amplitude (1.23 ± 0.38 vs 1.20 ± 0.41mV, p = 0.76). There was a statistically significant reduction in conduction velocity in the posterior left atrium in HCM patients relative to controls (0.43 ± 0.18 vs 0.58 ± 0.10m/s, p = 0.003), but not in the anterior left atrium (0.46 ± 0.17 vs 0.55 ± 0.10m/s, p = 0.05). There was a significant association between conduction velocity and interventricular septal thickness (slope = -0.013, R2 = 0.13, p = 0.03). Atrial conduction velocity is significantly reduced in patients with HCM and paroxysmal AF, possibly contributing to arrhythmia persistence after catheter ablation.

Characteristics of immune clusters and cell abundance in patients with different subtypes of nonparoxysmal atrial fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. Inflammation plays an important role in the initiation and perpetuation of AF. The present study was conducted to characterize immune clusters in nonparoxysmal AF and to distinguish immune subtypes of nonparoxysmal AF. Immune-related algorithms (CIBERSORT, ESTIMATE, and ssGSEA) were used to evaluate the immune cluster characterization and cell abundance, and multivariable logistics analysis was performed to determine the most relevant immune cells. We identified differentially expressed genes (DEGs) and used consensus clustering analysis to identify nonparoxysmal AF subtypes. Weighted gene coexpression network analysis (WGCNA) was used for finding highly correlated gene sets and attach to external sample traits. And it was conducted twice to identify the immune- and subtype- related modules. Finally, Metascape was used to compare the biological functions of the two nonparoxysmal AF subtypes we obtained. CytoHubba was used to identify the hub genes of these two subtypes. Based on the results of bioinformatics analysis, regulatory T cells, resting NK cells, active mast cells and neutrophils were considered to be closely related to nonparoxysmal AF. The brown module was identified as the most relevant module to the above immune cells by WGCNA. We identified two major nonparoxysmal AF subtypes by consensus clustering analysis and their enriched biological functions by Metascape. The hub genes are TYROBP, PTPRC, ITGB2, SPI1, PLEK, and CSF1R in permanent AF and JAM3, S100P, ARPC5, TRIM34, and GREB1L in persistent AF. This study revealed two major nonparoxysmal AF subtypes and eleven hub genes, which provide potential therapeutic targets for anti-inflammatory treatments of nonparoxysmal AF.