Paroxysmal Atrial Fibrillation Patients Research Articles

Impact of Colchicine Monotherapy on the Risk of Acute Pericarditis Following Atrial Fibrillation Ablation

BackgroundAcute pericarditis is a known complication of ablation procedures for atrial fibrillation (AF). ObjectivesThis study aimed to evaluate the benefits of colchicine monotherapy in terms of reducing the risk of pericarditis and related hospitalization rate in AF patients undergoing catheter ablation. MethodsConsecutive AF patients undergoing first catheter ablation were classified into 3 groups based on their colchicine use: Group 1: no colchicine; group 2: colchicine from 7 days before to 1 month after ablation; and group 3: colchicine from the day of the procedure to 1 month after. Standard institutional protocol was used to follow all patients for 1 year. ResultsA total of 1,075 patients were classified into groups 1 (n = 607), 2 (n = 213), and 3 (n = 255). Symptoms of acute pericarditis were reported in 129 patients (12%): group 1: n = 106 (17.5%); group 2: n = 4 (1.9%); and group 3: n = 19 (7.5%); P < 0.001. Rate of mild-moderate as well as severe pericarditis were significantly lower in group 2. In the multivariable regression analysis, pre- and post-ablation colchicine use was seen to be associated with significantly lower risk of acute pericarditis and related hospitalization compared with the other 2 groups. In addition, at 1-year follow-up, arrhythmia-free survival rate was significantly higher in paroxysmal AF patients receiving colchicine compared with the no-colchicine population. ConclusionsColchicine therapy starting 7 days before to 1 month after the ablation procedure was associated with significantly lower risk of acute pericarditis and related hospitalization. In addition, paroxysmal AF patients receiving colchicine had a higher arrhythmia-free survival rate compared with those not receiving colchicine.

Comparison of efficacy of pulmonary vein isolation between cryoballoon ablation and high-power short-duration ablation

BackgroundHigh-power short-duration (HPSD) and cryoballoon ablation (CBA) has been used for pulmonary vein isolation (PVI). ObjectiveWe aimed to compare the efficacy of PVI between CBA and HPSD ablation in patients with paroxysmal atrial fibrillation (PAF). MethodsWe retrospectively analyzed 251 consecutive PAF patients from January 2018 to July 2020. Of them, 124 patients (mean age 57.2 ± 10.1 year) received HPSD and 127 patients (mean age 59.6 ± 9.4 year) received CBA. In HPSD group, the radiofrequency energy was set as 50 W/10 s at anterior wall and 40 W/10 s at posterior wall. In CBA group, 28 mm s generation cryoballoon was used for PVI according the guidelines. ResultsThere was no significant difference in baseline characteristics between these 2 groups. The time to achieve PVI was significantly shorter in cryoballoon ablation group than in HPSD group (20.6 ± 1.7 min vs 51.8 ± 36.3, P = 0.001). The 6-month overall recurrence for atrial tachyarrhythmias was not significantly different between the two groups (HPSD:14.50% vs CBA:11.0%, P = 0.40). There were different types of recurrent atrial tachyarrhythmia between these 2 groups. Recurrence as atrial flutter was significantly more common in CBA group compared to HPSD group (57.1% vs 12.5%, P = 0.04). ConclusionIn PAF patients, CBA and HPSD had a favourable and comparable outcome. The recurrence pattern was different between CBA and HPSD groups.

Efficacy, Safety and Feasibility of Superior Vena Cava Isolation in Patients Undergoing Atrial Fibrillation Catheter Ablation: An Up-to-Date Review.

Pulmonary vein isolation (PVI) is the cornerstone in atrial fibrillation (AF) ablation; yet, the role of arrhythmogenic superior vena cava (SVC) is increasingly recognized and different ablation strategies have been employed in this context. SVC can act as a trigger or perpetuator of AF, and its significance might be more pronounced in patients undergoing repeated ablation. Several cohorts have examined efficacy, safety and feasibility of SVC isolation (SVCI) among AF patients. The majority of these studies explored as-needed SVCI during index PVI, and only a minority of them included repeated ablation subjects and non-radiofrequency energy sources. Studies of heterogeneous design and intent have explored both empiric and as-needed SVCI on top of PVI and reported inconclusive results. These studies have largely failed to demonstrate any clinical benefit in terms of arrhythmia recurrence, although safety and feasibility are undisputable. Mixed population demographics, small number of enrollees and short follow-up are the main limitations. Procedural and safety data are comparable between empiric SVCI and as-needed SVCI, and some studies suggested that empiric SVCI might be associated with reduced AF recurrences in paroxysmal AF patients. Currently, no study has compared different ablation energy sources in the setting of SVCI, and no randomized study has addressed as-needed SVCI on top of PVI. Furthermore, data regarding cryoablation are still in their infancy, and regarding SVCI in patients with cardiac devices more safety and feasibility data are needed. PVI non-responders, patients undergoing repeated ablation and patients with long SVC sleeves could be potential candidates for SVCI, especially via an empiric approach. Although many technical aspects remain unsettled, the major question to answer is which clinical phenotype of AF patients might benefit from SVCI?

Porous tip radiofrequency ablation catheter reduced heart failure-related complications and healthcare resource utilization in paroxysmal atrial fibrillation patients.

A 56-hole porous tip radiofrequency catheter was developed to provide more uniform cooling with less fluid delivery than a prior 6-hole irrigated design. This study aimed to evaluate the impact of contact force (CF) ablation with the porous tip on complications (congestive heart failure [CHF] and non-CHF related), healthcare resource utilization, and procedural efficiency in patients undergoing de novo paroxysmal atrial fibrillation (PAF) ablations in a real-world setting. Consecutive de novo PAF ablations were performed between February 2014 and March 2019 by six operators at a single US academic center. The 6-hole design was used through December 2016 with the 56-hole porous tip adopted in October 2016. The outcomes of interest included symptomatic CHF presentation and CHF-related complications. Of 174 patients who were included, mean age was 61.1± 10.8 years, 67.8% were male, and 25.3% had a history of CHF. Ablation with the porous tip catheter significantly decreased fluid delivery (1177 vs. 1912 mL with the 6-hole design; p< .0001). CHF-related complications within 7 days, particularly fluid overload, were substantially reduced with the porous tip (15.2% vs. 5.3% of patients; p =.0281) and the proportion of patients with symptomatic CHF presentation within 30 days postablation was significantly lower (14.7% vs. 32.5%; p =.0058). The 56-hole porous tip led to significantly reduced CHF-related complications and healthcare utilization in PAF patients undergoing CF catheter ablation when compared to the prior 6-hole design. This reduction likely results from the significant decrease in fluid delivery during the procedure.

Efficacy of catheter ablation for atrial fibrillation in patients with significant functional mitral regurgitation.

Catheter ablation has been established to be an effective therapy for paroxysmal atrial fibrillation (AF) and is recommended as the treatment of choice for many patients, including those with clinically significant functional mitral regurgitation (MR). However, there is little information available about the clinical efficacy of catheter ablation for paroxysmal AF in patients with significant functional MR. We performed a retrospective study of 247 patients with paroxysmal AF who underwent AF ablation. The study included 28 (11.3%) patients with significant functional MR and 219 (88.7%) without significant functional MR. AF recurrence was defined as the occurrence of confirmed atrial tachyarrhythmia lasting >30 seconds beyond 3 months after catheter ablation. During a mean follow-up of 20.1 ± 7.4 months (range, 3-36 months), 45 (18.2%) patients developed recurrence of AF. The recurrence rate of AF was higher in patients with significant functional MR than in those without significant functional MR (42.9% vs 15.1%; P < .001). Univariable Cox proportional hazards regression analysis showed that significant functional MR (hazard ratio [HR], 3.46; 95% confidence interval [CI], 1.78-6.72; P < .001), age (HR, 1.04; 95% CI, 1.01-1.08; P = .009), the CHA2DS2-VASc score (HR, 1.28; 95% CI, 1.05-1.56; P = .017), and heart failure (HR, 4.71; 95% CI, 1.85-11.96; P = .001) were associated with the risk of recurrence. Multivariable analysis showed that significant functional MR (HR, 2.48; 95% CI, 1.21-5.05; P = .013), age (HR, 1.04; 95% CI, 1.00-1.07; P = .031), and heart failure (HR, 3.39; 95% CI, 1.27-9.03; P = .015) were independent predictors of AF recurrence. Patients with significant functional MR have an increased risk of AF recurrence after catheter ablation.

Left atrial reservoir strain measurements derived from intracardiac echocardiography in patients with atrial fibrillation: comparison with transthoracic echocardiography

BackgroundIntracardiac echocardiography (ICE) provides accurate left atrial (LA) anatomical information in the procedure of atrial fibrillation (AF) ablation but lacks LA functional assessment. LA reservoir strain (LASr) is an excellent marker of LA reservoir function. This study aimed to assess the agreement between LASr derived from ICE and transthoracic echocardiography (TTE) in AF patients and analyze the reproducibility of LASr assessed by ICE combined with speckle tracking imaging.MethodsThis study prospectively enrolled 110 patients with a clinical diagnosis of AF who were ready for AF ablation, including 71 patients with paroxysmal AF and 39 with persistent AF. TTE and ICE examinations were performed on each individual before AF ablation. LASr measurements derived from ICE and TTE images were using dedicated LA-tracking software. Pearson correlation coefficients (r) and Bland–Altman plots were used to evaluate the agreement of LASr between the two modalities. Intraclass correlation coefficients (ICCs) were used to assess intra- and inter-observer reproducibility.ResultsThe agreement between LASr obtained from ICE and TTE, especially between LASrLPV (LASr derived from LA left pulmonary vein view of ICE) and LASrTTE (LASr derived from TTE) were good in both paroxysmal and persistent AF patients [r = 0.890 (P < 0.001) for overall population; r = 0.815 (P < 0.001) and Bias ± LOA: -0.3 ± 9.9% for paroxysmal AF; r = 0.775 (P < 0.001) and Bias ± LOA: -2.6 ± 3.9% for persistent AF, respectively]. But the values of LASr derived from ICE were slightly lower than those of TTE, especially in patients with persistent AF. The ICCs for LASr derived from ICE were excellent (all ICCs > 0.90).ConclusionsIn patients with AF, LASr derived from ICE demonstrated excellent reproducibility and showed good agreement with LASr obtained from TTE. Obtaining LASr from ICE images may be a supplementary method to evaluate LA reservoir function in AF patients and expands the potential of ICE in the field of cardiac function assessment.Graphical

Phosphodiesterase 8 governs cAMP/PKA-dependent reduction of L-type calcium current in human atrial fibrillation: a novel arrhythmogenic mechanism.

Atrial fibrillation (AF) is associated with altered cAMP/PKA signaling and an AF-promoting reduction of L-type Ca2+-current (ICa,L), the mechanisms of which are poorly understood. Cyclic-nucleotide phosphodiesterases (PDEs) degrade cAMP and regulate PKA-dependent phosphorylation of key calcium-handling proteins, including the ICa,L-carrying Cav1.2α1C subunit. The aim was to assess whether altered function of PDE type-8 (PDE8) isoforms contributes to the reduction of ICa,L in persistent (chronic) AF (cAF) patients. mRNA, protein levels, and localization of PDE8A and PDE8B isoforms were measured by RT-qPCR, western blot, co-immunoprecipitation and immunofluorescence. PDE8 function was assessed by FRET, patch-clamp and sharp-electrode recordings. PDE8A gene and protein levels were higher in paroxysmal AF (pAF) vs. sinus rhythm (SR) patients, whereas PDE8B was upregulated in cAF only. Cytosolic abundance of PDE8A was higher in atrial pAF myocytes, whereas PDE8B tended to be more abundant at the plasmalemma in cAF myocytes. In co-immunoprecipitation, only PDE8B2 showed binding to Cav1.2α1C subunit which was strongly increased in cAF. Accordingly, Cav1.2α1C showed a lower phosphorylation at Ser1928 in association with decreased ICa,L in cAF. Selective PDE8 inhibition increased Ser1928 phosphorylation of Cav1.2α1C, enhanced cAMP at the subsarcolemma and rescued the lower ICa,L in cAF, which was accompanied by a prolongation of action potential duration at 50% of repolarization. Both PDE8A and PDE8B are expressed in human heart. Upregulation of PDE8B isoforms in cAF reduces ICa,L via direct interaction of PDE8B2 with the Cav1.2α1C subunit. Thus, upregulated PDE8B2 might serve as a novel molecular mechanism of the proarrhythmic reduction of ICa,L in cAF.

Acute and long-term results with the 3rd generation visually guided laser balloon ablation system for pv isolation

BackgroundVisually guided laser balloon ablation is known as an effective pulmonary vein (PV) isolation device. The third-generation laser balloon ablation system (X3) equipped with compliant balloon and an automated motor-driven laser output mechanism, namely RAPID mode, has been clinically proven for PV isolation.MethodsPV isolation with X3 was performed in all the patients with paroxysmal and early-stage persistent atrial fibrillation (AF). Acute data for PV isolation and clinical outcomes including supraventricular tachyarrhythmia (SVT: AF, atrial flutter, or atrial tachycardia)-free survival rate beyond 1 year were analyzed.ResultsA total of 110 patients (62 ± 13 years old, 80% of paroxysmal AF) were treated with X3. RAPID mode with was utilized to achieve PV isolation in all cases. In combination with RAPID mode and spot mode laser ablation, 91.1% (380/417) of veins were isolated on the first circumferential lesion set and did not require touch-up ablation and during the index procedure 100% of attempted veins were isolated. The mean procedure time was 77.0 ± 22.7 min and LA dwell time was 61.9 ± 22.0 min. Total duration of laser application was 5.1 ± 2.3 min per vein. At 1 year, SVT-free survival rate was 93.7% in paroxysmal AF patients, and 81.1% in persistent AF patients.ConclusionsA novel continuous automatic laser balloon ablation system was proved to be safe and effective for both paroxysmal and persistent AF patients. The clinical result demonstrated that PV isolation with X3 could achieve a high SVT-free survival rate.

A sudden increase in heart rate during ablation of the right superior pulmonary venous vestibule is correlated with pain-relief in patients undergoing atrial fibrillation ablation

BackgroundA sudden increase in heart rate (HR) during ablation of the right superior pulmonary venous vestibule (RSPVV) is often detected in patients undergoing circumferential pulmonary vein isolation (CPVI). In our clinical practices, we observed that some patients had few complaints of pain during the procedures under conscious sedation.AimWe aimed to investigate whether there is a correlation between a sudden increase in HR during AF ablation of the RSPVV and pain relief under conscious sedation.MethodsWe prospectively enrolled 161 consecutive paroxysmal AF patients who underwent the first ablation from July 1, 2018, to November 30, 2021. Patients were assigned to the R group when they had a sudden increase in HR during the ablation of the RSPVV, and the others were assigned to the NR group. Atrial effective refractory period and HR were measured before and after the procedure. Visual Analogue Scale (VAS) scores, vagal response (VR) during ablation, and the amount of fentanyl used were also documented.ResultsEighty-one patients were assigned to the R group, and the remaining 80 were assigned to the NR group. The post-ablation HR (86.3 ± 8.8 vs. 70.0 ± 9.4 b/min; p ≤ 0.001) was higher in the R group than in pre-ablation. Ten patients in the R group had VRs during CPVI, as well as 52 patients in the NR group. The VAS score [2.3 (1.3–3.4) vs. 6.0 (4.4–6.9); p ≤ 0.001)] and the amount of fentanyl used (107 ± 12 vs. 172 ± 26 ug; p ≤ 0.001) were significantly lower in the R group.ConclusionA sudden increase in HR during the ablation of the RSPVV was correlated with pain relief in patients undergoing AF ablation under conscious sedation.

Clinical phenotypes of older adults with non-valvular atrial fibrillation not treated with oral anticoagulants by hierarchical cluster analysis in the ANAFIE Registry.

Although anticoagulants are indicated for many elderly patients with non-valvular atrial fibrillation (NVAF), some patients do not receive anticoagulant therapy, whose characteristics and outcomes are diverse. In this sub-analysis of the All Nippon AF In the Elderly (ANAFIE) Registry, the phenotypes of patients who were not receiving anticoagulants at baseline were evaluated by cluster analysis using Ward's linkage hierarchical algorithm. Of 32,275 enrolled patients, 2445 (7.6%) were not receiving anticoagulants. Two clusters were identified: (1) elderly paroxysmal AF (PAF) patients with a high proportion of catheter ablation history (57%) and (2) very elderly patients with a high prevalence of previous major bleeding (43%). Respective mean ages were 80.9 and 84.2 years, mean CHA2DS2-VASc scores were 3.8 and 4.9, PAF prevalences were 100.0% and 31.4%, proportions of patients with catheter ablation history were 21.0% and 7.9%, and proportions of patients with a history of major bleeding were 4.0% and 10.8%. Annual incidence rates were 2.72% and 8.81% for all-cause death, 1.66% and 5.85% for major adverse cardiovascular or neurological events, 1.08% and 3.30% for stroke or systemic embolism, and 0.69% and 1.19% for major bleeding, respectively. In this cohort of elderly NVAF patients from the ANAFIE Registry who were not receiving anticoagulants, over half had PAF with a high proportion of catheter ablation history and a low incidence of adverse outcomes; for them, non-prescription of anticoagulants may be partially understandable, but they should be carefully monitored regarding AF burden or atrial cardiomyopathy and be adequately anticoagulated when adverse findings are detected. The remaining were very elderly patients with a high prevalence of previous major bleeding and a high incidence of adverse outcomes; for them, non-prescription of anticoagulants is inappropriate because of the high thromboembolic risk. Registration: http://www.umin.ac.jp/; Unique identifier: UMIN000024006.

The Role of Major Biomarkers of Stress in Atrial Fibrillation: A Literature Review.

Numerous studies have reported that physical or emotional stress can provoke atrial fibrillation (AF) or vice versa, which suggests a potential link between exposure to external stressors and AF. This review article sought to describe in detail the relationship between major stress biomarkers and the pathogenesis of AF and presents up-to-date knowledge on the role of physiological and psychological stress in AF patients. For this purpose, this review article contends that plasma cortisol is linked to a greater risk of AF. A previous study has investigated the association between increased copeptin levels and paroxysmal AF (PAF) in rheumatic mitral stenosis and reported that copeptin concentration was not independently associated with AF duration. Reduced levels of chromogranin were measured in patients with AF. Furthermore, the dynamic activity of antioxidant enzymes, including catalase as well as superoxide dismutase, was examined in PAF patients during a period of <48 h. Malondialdehyde activity, serum high-sensitivity C-reactive protein, and high mobility group box 1 protein concentrations were significantly greater in patients with persistent AF or PAF compared to controls. Pooled data from 13 studies confirmed a significant reduction in the risk of AF related to the administration of vasopressin. Other studies have revealed the mechanism of action of heat shock proteins (HSPs) in preventing AF and also discussed the therapeutic potential of HSP-inducing compounds in clinical AF. More research is required to detect other biomarkers of stress, which have not been reported in the pathogenesis of AF. Further studies are required to identify their mechanism of action and drugs to manage these biomarkers of stress in AF patients, which might help to reduce the prevalence of AF globally.

High-Power, Short-Duration Ablation under the Guidance of Relatively Low Ablation Index Values for Paroxysmal Atrial Fibrillation: Long-Term Outcomes and Characteristics of Recurrent Atrial Arrhythmias.

The purpose of this study was to evaluate the difference in effectiveness and safety of high-power, short-duration (HPSD) radiofrequency catheter ablation (RFA) guided by relatively low ablation index (AI) values and conventional RFA in paroxysmal atrial fibrillation (PAF) patients. The HPSD RFA strategy (40-50 W, AI 350-400 for anterior, 320-350 for posterior wall; n = 547) was compared with the conventional RFA strategy (25-40 W, without AI; n = 396) in PAF patients who underwent their first ablation. Propensity-score matching analyses were used to compare the outcomes of the two groups while controlling for confounders. After using propensity-score matching analysis, the HPSD group showed a higher early recurrence rate (22.727% vs. 13.636%, p = 0.003), similar late recurrence rate, and comparable safety (p = 0.604) compared with the conventional group. For late recurrent atrial arrhythmia types, the rate of regular atrial tachycardia was significantly higher in the HPSD group (p = 0.013). Additionally, the rate of chronic pulmonary vein reconnection and non-pulmonary vein triggers during repeat procedures was similar in both groups. For PAF patients, compared with the conventional RFA strategy, the HPSD RFA strategy at relatively low AI settings had a higher early recurrence rate, similar long-term success rate, and comparable safety.

Abnormal Conduction Zone Detected by Isochronal Late Activation Mapping Accurately Identifies the Potential Atrial Substrate and Predicts the Atrial Fibrillation Ablation Outcome After Pulmonary Vein Isolation.

The presence of abnormal substrate of left atrium is a predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation. We aimed to investigate the isochronal late activation mapping to access the abnormal conduction velocity for predicting AF ablation outcome. Forty-five paroxysmal AF patients (30 males, 57.8±8.7 years old) who underwent pulmonary vein isolation were enrolled. Isochronal late activation mapping was retrospectively constructed with 2 different windows of interest: from onset of P wave to onset of QRS wave on surface electrocardiography (W1) and 74 ms tracking back from the end of P wave (W2). Deceleration zone was defined as regions with 3 isochrones (DZa) or ≥4 isochrones (DZb) within a 1 cm radius on the isochronal late activation mapping, and the estimated conduction velocity (ECV) are 0.27 m/s and <0.20 m/s for DZa and DZb, respectively in W2. The distribution of deceleration zone was compared with the location of low-voltage zone (bipolar voltage ≤0.5 mV). Any recurrence of atrial arrhythmias was defined as the primary end point during follow ups after a 3-month blanking period. Pulmonary vein isolation was performed in all patients, and there were 2 patients (4.4%) received additional extrapulmonary vein ablation. After a mean follow-up of 12.7±4.5 months, recurrence of AF occurred in 14 patients (31.1%). Patients with the presence of DZb in W2 had higher AF recurrence (Kaplan-Meier event rate estimates: HR, 9.41 [95% CI, 2.61-33.90]; log-rank P<0.0001). There were 52.6% of the DZb locations in W2 comparable to the distributions of low-voltage zone and 47.4% DZb were distributed in the area without low-voltage zone. Deceleration zone detected by isochronal late activation mapping represents a critical AF substrate, it accurately predicts the AF recurrence following ablation in patients with paroxysmal AF.

Prevalence of Cardio-Embolic Brain Complications in Permanent and Paroxysmal Atrial Fibrillation Patients.

Background: Atrial fibrillation (AF) is the most frequent of all cardiac arrhythmias, with an increasing prevalence in the last 20 years. Cardio-embolic brain complications (CEBC) related to AF often occur or recur, even following appropriate treatment. Method: We conducted a retrospective study and analyzed the presence of stroke, dementia, and Parkinson’s disease (PD) in both paroxysmal and permanent AF patients. The records of 1111 consecutive admitted patients with primary diagnosis of AF at the Municipal Emergency University Hospital, Timisoara, between 2015 and 2016 were examined. Statistical analysis was performed on the patients included in the study based on the inclusion and exclusion criteria. Results: A significant statistical difference was noted among the permanent AF group for stroke (48.75% vs. 26.74%, p < 0.001) and dementia (10.25% vs. 3.86%, p < 0.001) compared to paroxysmal AF patients. Permanent AF patients presented a higher risk of developing stroke, dementia, and PD compared to patients with paroxysmal AF. Meanwhile, male gender and an increase in age showed an increase in the odds of having cardio-embolic brain complications in patients with paroxysmal AF. Conclusion: Based on the results obtained, it can be concluded that the risk of cardio-cerebral embolic complications is greater in permanent AF patients compared to paroxysmal AF cases. Ischemic stroke and dementia are more frequent in the permanent AF group, but analyzing the data regarding the age of onset paroxysmal AF is critical due to the fact that it involves a younger population. Prompt diagnosis and treatment can help significantly in saving stroke patients.

Interleukin-11 Is Elevated in Patients with Atrial Fibrillation, Correlates with Serum Fibrosis Markers, and Represents a Therapeutic Target for Atrial Fibrosis

Introduction: Inflammatory cytokines are closely associated with developing cardiac fibrosis. This research aimed to explore the significant role of IL-11 in atrial fibrosis progression and potential therapeutic targets. Methods: 207 AF patients and 160 healthy subjects were included in the case-control study. Blood samples were analyzed for the level of IL-11 by enzyme-linked immunosorbent assay (ELISA). Angiotensin II (Ang II)-treated fibrosis mouse models were generated, and expression of IL-11 mRNA and protein was detected by RT-qPCR and Western blot. IL-11 antagonist was used to evaluating atrial fibrosis-related markers. Results: The persistent atrial fibrillation patients (n = 76) had significantly larger left atrial size, higher serum levels of hypertrophic protein BNP, proinflammatory cytokine high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) compared to paroxysmal atrial fibrillation patients (n = 131), and healthy subjects (all p < 0.05). Pearson correlation analysis revealed significant positive correlation between serum IL-11 and cardiac fibrosis markers BNP (r = 0.394, p < 0.001), CTX-I (r = 0.418, p < 0.001), PICP (r = 0.306, p < 0.001), PIIINP (r = 0.335, p < 0.001), and TGF-β1 (r = 0.273, p < 0.001). In the fibrosis mouse model, Ang II infusion significantly upregulated IL-11 mRNA and protein expression in the left atrium of mice (p < 0.05), as well as staining intensity of Masson trichrome, the intensity of α-SMA, and it increased mRNA expression of collagen I and III in atrial tissue. IL-11 antagonist treatment significantly attenuated Masson trichrome, number of α-SMA-positive myofibroblasts in atrial tissue. Also, it significantly reduced the p-ERK1/2 in atrial tissue of mice infused with Ang II (p < 0.05). Conclusions: IL-11 is upregulated in the serum of AF patients, and IL-11 inhibitor significantly inhibited Ang II-induced atrial fibrosis, a key pathological feature of AF. Therefore, IL-11 could be a potential therapeutic target for AF.

Post-Stroke Detection of Subclinical Paroxysmal Atrial Fibrillation in Patients With Embolic Stroke of Undetermined Source in the Real World Practice: The Empoli ESUS Atrial Fibrillation (E 2 AF) Study.

Subclinical paroxysmal atrial fibrillation (AF) is one of the main occult causative mechanisms of embolic stroke of undetermined source (ESUS). Aim of this study was to identify AF predictors, and to develop a score to predict the probability of AF detection in ESUS. We retrospectively analyzed ESUS patients undergoing 2-week external electrocardiographic monitoring. Patients with and without AF detection were compared. On the basis of multivariate analysis, predictors of AF were identified and used to develop a predictive score, which was then compared with other existing literature scores. Eighty-two patients, 48 females, mean age±SD 72±10 years, were included. In 36 patients (43.9%) AF was detected. The frequency of age 75 years or above and arterial hypertension, and the median CHA 2 DS 2 -VASc score were significantly higher in patients with AF compared with those without. National Institutes of Health Stroke Scale (NIHSS) score ≥8 was the only independent variable associated with AF detection. We derived the Empoli ESUS-AF (E 2 AF) score (NIHSS ≥8 5 points, arterial hypertension 3 points, age 75 years or above 2 points, age 65 to 74 years 1 point, history of coronary/peripheral artery disease 1 point, left atrial enlargement 1 point, posterior lesion 1 point, cortical or cortical-subcortical lesion 1 point), whose predictive power in detecting AF was good (area under the curve: 0.746, 95% confidence interval: 0.638-0.836) and higher than that of CHA 2 DS 2 -VASc and other scores. In our study NIHSS score ≥8 was the only independent predictor of post-ESUS-AF detection. The E 2 AF score appears to have a good predictive power for detecting AF. External validations are required.

Personal recording devices for arrhythmia detection.

Persistent cardiac arrhythmias are readily amenable to detection by performing a standard electrocardiogram (ECG), but detection of transient (paroxysmal) arrhythmias has long been a significant cause of frustration to both doctors and patients. Often a significantly symptomatic arrhythmia is experienced by the patient but terminates before an ECG can be recorded to allow diagnosis. Prognostically important treatment is often delayed, and recurrent symptomatic attacks represent a high morbidity in patients' lives and result in a burden on emergency services, who often arrive after the arrhythmia has terminated with no resultant progress in making a diagnosis. Another area of concern has been the presence of asymptomatic, but clinically important, arrhythmias that can go unnoticed by people experiencing them and may result in permanent harm; asymptomatic paroxysmal atrial fibrillation in patients with high CHA 2 DS 2-VASc scores being the most common example. Both these issues are now being importantly addressed by the widespread availability of portable ECG recording devices, which patients can either manually activate themselves or program to automatically detect abnormal arrhythmias. Information on the range of devices available and their strengths and weaknesses is limited. This article aims to provide a helpful overview for patients and doctors advising them.

Irisin attenuates angiotensin II-induced atrial fibrillation and atrial fibrosis via LOXL2 and TGFβ1/Smad2/3 signaling pathways.

Irisin was reported as a cardioprotective and anti-oxidative effector, while the effect on atrial fibrosis is unknown. The current research examined irisin's function in atrial fibrillation (AF); atrial fibrosis brought on by Ang II can be suppressed, thus lessening the risk of developing AF. 246 individuals were enrolled in the present case-control study. Chinese AF patients (n=126), 83 of whom were paroxysmal AF (PAF), 43 patients with persistent AF (PeAF), and 120 healthy controls. Saline or Ang II (2.0 mg/kg/day) was subcutaneously injected into healthy male C57BL/6 mice for four weeks. Once daily for four weeks, intraperitoneal injections of exogenous irisin (500 g/kg/day) were administered. In comparison to PAF patients and healthy controls (all P<0.05), PeAF patients had significantly higher rates of heart failure (HF), large left atrial size (LAD), hypertrophic protein B-type natriuretic peptide (BNP), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-terminal telopeptide of type I collagen (CTX-I), and transforming growth factor beta-1 (TGF-β1), while superoxide dismutase (SOD) level was low. Expression of irisin was decreased in AF patients' serum and Ang II-infused mice. Exogenous irisin dramatically reduced apoptosis, atrial fibrosis, atrial inflammation, and the susceptibility to AF caused by Ang II. In the atrial tissue, irisin inhibited Ang II-induced fibroblast transdifferentiation, LOXL2, TGF-β1, collagen production, and phosphorylation of Smad2/3. The study results speculated that irisin could be a potential AF target, and it inhibited atrial fibrosis and significantly impaired increased AF susceptibility through inactivation of LOXL2 and the TGF-β/Smad pathway.

Left atrial epicardial adipose tissue exacerbates electrical conduction disturbance in normal-weight patients undergoing pulmonary vein isolation for atrial fibrillation.

Epicardial adipose tissue (EAT) exacerbates both electrical and structural remodeling in obese atrial fibrillation (AF) patients, but the impacts of EAT on atrial arrhythmogenicity remain unclear in normal-weight AF patients. Therefore, we sought to investigate this issue using electroanatomic mapping. We enrolled drug-refractory 105 paroxysmal AF patients in the normal body mass index range (18.5-24.9 kg/m2 ), who had undergone electroanatomic mapping after pulmonary vein isolation (PVI). One day before PVI, we assessed P-wave duration in a 12-lead electrocardiogram and left atrial (LA)-EAT volumes using contrast-enhanced computed tomography. The patients were divided into two groups based on the median LA-EAT volume (16.0 ml); the high LA-EAT group (≥16.0 ml, n = 53) and low LA-EAT group (<16.0 ml, n = 52). We compared P-wave duration, LA conduction velocity and bipolar voltage, the presence of low-voltage zone (<0.5 mV), and LA volume index on echocardiography between the two groups. The LA bipolar voltage, low-voltage zone, and LA volume index were not different between the high and low LA-EAT groups. However, P-wave duration was significantly longer in the high group than in the low group (p < .001). Additionally, the LA conduction velocity was significantly more depressed in the high group than in the low group (p < .001). Multivariate linear regression analysis revealed that LA-EAT volume was correlated with P-wave duration (β = .367, p < .001) and conduction velocity (β = -.566, p < .001), respectively. Increased LA-EAT volumes were associated with electrical conduction disturbance after PVI in normal-weight patients with AF. P-wave duration may be a clinically useful predictor of LA-EAT.

Inside the “brain” of an artificial neural network: an interpretable deep learning approach to paroxysmal atrial fibrillation diagnosis from electrocardiogram signals during sinus rhythm

Abstract Background With the ongoing, rapid advances in Deep Learning (DL), such solutions can now detect medical conditions even invisible to the human eye. In this direction, efforts have been made to develop DL algorithms that diagnose paroxysmal atrial fibrillation (PAF) from electrocardiogram (ECG) signals in sinus rhythm (SR). However, many of the available approaches function as “black boxes”, with physicians unable to understand and trust their predictions. Purpose To train a DL model to detect PAF patients while in SR and apply an algorithm that interprets and visualises its decisions. Methods We obtained ECG samples from PAF and non-PAF patients during SR, from the PAF Prediction Challenge Database. After discarding unannotated samples and augmenting the sample size (by dividing each signal into 30-second segments), we split the whole dataset into a train (68%), a validation (16%) and a test (16%) set. No pair of samples belonging to different sets originated from the same patient. We trained the InceptionTime neural network on the train/validation sets and tested on the “unseen” test set after “hiding” the correct answers. Its performance was evaluated with the following metrics: Accuracy, f1-score, precision and recall (sensitivity). After repeating this process 20 times, we obtained a distribution for each score. Finally, we adjusted the Grad-CAM interpretation algorithm to our data and used it to visualise the areas perceived as important by the model. Results After pre-processing, 4,080, 30-second, two-lead ECG signals were allocated to the train set, 960 to the validation and 960 to the test set. Each subset contained an equal number of PAF and non-PAF samples. After repeated training and testing, we obtained a median accuracy of 0.84 (interquartile range, IQR: 0.66–0.88), an f1-score of 0.82 (IQR: 0.68–0.88) and a median precision and recall equal to 0.93 (IQR: 0.67–0.99) and 0.77 (IQR: 0.68–0.93), respectively. The Grad-CAM technique highlighted the ECG areas of interest that led to each decision. We selected and present both PAF-positive and -negative samples, perceived either correctly or falsely. Interestingly, correct model decisions tend to focus on the P-wave, while false ones fixate on other regions. Conclusions Although a pilot study with considerable limitations (small sample size, disregard of possible confounding due to comorbidities or other factors), this work shows how DL can be employed to distinguish between PAF and non-PAF patients from SR ECG samples, and confirms the potential of DL-enabled approaches to offer novel diagnostic capabilities. Most importantly, our effort provides a comprehensible, visual interpretation of the model's decisions. Demystifying DL behaviour can, not only improve such efforts by explaining false decisions, but also cultivate trust among clinicians and, possibly, point out directions for future research, since we can now see through the magnifying lens of a neural network. Funding Acknowledgement Type of funding sources: None.