Persistent Atrial Fibrillation Patients Research Articles

Bilirubin Elevation During Hospitalization Post Radiofrequency Catheter Ablation of Persistent Atrial Fibrillation: Variation Trend, Related Factors, and Relevance to 1-Year Recurrence.

The role of total bilirubin (TBIL) in cardiovascular disease has been increasingly recognized in recent decades. Studies have shown a correlation between total bilirubin levels and the prognosis of patients after heart surgery. This study aimed to investigate the clinical significance of bilirubin elevation in persistent atrial fibrillation (PAF) patients who received radiofrequency catheter ablation (RFCA). A total of 184 patients with PAF who received RFCA were retrospectively studied. Laboratory examinations and demographic data were analyzed to identify independent predictors of TBIL elevation. The relationship between TBIL and prognosis was further investigated. Our results indicated that TBIL increased significantly after RFCA. Multiple linear regression analysis showed that TBIL elevation owned a negative correlation with the percentile of low voltage areas (LVAs) in left atria (β=-0.490, P<0.001). In contrast, a positive correlation was observed with the white blood cell (WBC) ratio (β=0.153, P=0.042) and left atrial diameter (LAD) (β=0.232, P=0.025). It was found that postoperative TBIL levels increased and then gradually decreased to baseline within 5 days without intervention. The bilirubin ratio <1.211 indicated the possibility of 1-year AF recurrence after ablation with a predictive value of 0.743 (specificity = 75.00%, sensitivity = 66.67%). Bilirubin elevation post PAF RFCA was a common phenomenon and was associated with 1-year recurrence of AF in PAF patients after RFCA.

Atrial fibrillation ablation compared to pacemaker therapy in patients with tachycardia-bradycardia syndrome: A systematic review and updated meta-analysis.

Tachycardia-bradycardia syndrome (TBS) is a subtype of sick sinus syndrome characterized by prolonged sinus pause (≥3 s) following termination of tachyarrhythmias, primarily atrial fibrillation (AF). There is controversy regarding whether the long-term prognosis of AF ablation is superior to pacemaker implantation. This study aimed to compare the effects of AF ablation and pacemaker therapy in patients with TBS. We conducted a comprehensive search of electronic databases, including PubMed, Cochrane, EmBase, Web of Science, and Chinese BioMedical, up until December 1, 2023. We included studies that reported the effects of AF ablation vs pacemaker therapy in patients with TBS. From this search, we identified 5 studies comprising 843 participants with TBS who underwent catheter AF ablation or pacemaker therapy. Our meta-analysis revealed that AF ablation and pacemaker therapy had similar effects on cardiovascular death (odds ratio [OR] = 0.62 and 95% confidence interval [CI]: 0.14-2.65), procedural complications (OR = 1.53 and 95% CI: 0.67-3.48), and cardiovascular rehospitalization (OR = 0.57 and 95% CI: 0.26-1.22). However, AF ablation provided greater benefits than pacemaker therapy in terms of all-cause mortality (OR = 0.37 and 95% CI: 0.17-0.82), thromboembolism (OR = 0.25 and 95% CI: 0.12-0.49), stroke (OR = 0.28 and 95% CI: 0.13-0.57), heart failure (OR = 0.27 and 95% CI: 0.13-0.56), freedom from AF (OR = 23.32 and 95% CI: 7.46-72.92), and prevention of progression to persistent AF (OR = 0.12 and 95% CI: 0.06-0.24). Furthermore, AF ablation resulted in a reduced need for antiarrhythmic agents (OR = 0.21 and 95% CI: 0.08-0.59). AF ablation can effectively reduce the risk of all-cause mortality, thromboembolism, stroke, heart failure, and progression to persistent AF in patients with TBS. Additionally, it may eliminate the need for further pacemaker therapy in most cases after ablation. Therefore, AF ablation is considered superior to pacemaker therapy in the management of patients with TBS.

Ablation-induced left atrial mechanical dysfunction recovers in weeks after ablation.

The immediate impact of catheter ablation on left atrial mechanical function and the timeline for its recovery in patients undergoing ablation for atrial fibrillation (AF) remain uncertain. The mechanical function response to catheter ablation in patients with different AF types is poorly understood. A total of 113 AF patients were included in this retrospective study. Each patient had three magnetic resonance imaging (MRI) studies in sinus rhythm: one pre-ablation, one immediate post-ablation (within 2days after ablation), and one post-ablation follow-up MRI (≤ 3months). We used feature tracking in the MRI cine images to determine peak longitudinal atrial strain (PLAS). We evaluated the change in strain from pre-ablation, immediately after ablation to post-ablation follow-up in a short-term study (< 50days) and a 3-month study (3months after ablation). The PLAS exhibited a notable reduction immediately after ablation, compared to both pre-ablation levels and those observed in follow-up studies conducted at short-term (11.1 ± 9.0days) and 3-month (69.6 ± 39.6days) intervals. However, there was no difference between follow-up and pre-ablation PLAS. The PLAS returned to 95% pre-ablation level within 10days. Paroxysmal AF patients had significantly higher pre-ablation PLAS than persistent AF patients in pre-ablation MRIs. Both type AF patients had significantly lower immediate post-ablation PLAS compared with pre-ablation and post-ablation PLAS. The present study suggested a significant drop in PLAS immediately after ablation. Left atrial mechanical function recovered within 10days after ablation. The drop in PLAS did not show a substantial difference between paroxysmal and persistent AF patients.

Pulsed field ablation technology for pulmonary vein and left atrial posterior wall isolation in patients with persistent atrial fibrillation.

Limited data exist on pulsed-field ablation (PFA) in patients with persistent atrial fibrillation (PeAF) undergoing left atrial posterior wall isolation (LAPWI). The Advanced TecHnologies For SuccEssful AblatioN of AF in Clinical Practice (ATHENA) prospective registry included consecutive patients referred for PeAF catheter ablation at 9 Italian centers, treated with the FARAPULSETM-PFA system. The primary efficacy and safety study endpoints were the acute LAPWI rate, freedom from arrhythmic recurrences and the incidence of major periprocedural complications. Patients undergoing pulmonary vein isolation (PVI) alone, PWI + LAPWI and redo procedures were compared. Among 249 patients, 21.7% had long-standing PeAF, 79.5% were male; mean age was 63 ± 9 years. LAPWI was performed in 57.6% of cases, with 15.3% being redo procedures. Median skin-to-skin times (PVI-only 68 [60-90] vs. PVI + LAPWI 70 [59-88] mins) did not differ between groups. 45.8% LAPWI cases were approached with a 3D-mapping system, and 37.3% with intracardiac echocardiography. LAPWI was achieved in all patients by means of PFA alone, in 88.8% cases at first pass. LAPWI was validated either by an Ultrahigh-density mapping system or by recording electrical activity + pacing maneuvers. No major complications occurred, while 2.4% minor complications were detected. During a median follow-up of 273 [191-379] days, 41 patients (16.5%) experienced an arrhythmic recurrence after the 90-day blanking period, with a mean time to recurrence of 223 ± 100 days and no differences among ablation strategies. LAPWI with PFA demonstrates feasibility, rapidity, and safety in real-world practice, offering a viable alternative for PeAF patients. LAPWI is achievable even with a fluoroscopy-only method and does not significantly extend overall procedural times.

Circulating exosome long non-coding RNAs are associated with atrial structural remodeling by increasing systemic inflammation in atrial fibrillation patients.

Atrial fibrillation (AF) is the most common cardiac arrhythmia with severe clinical sequelae, but its genetic characteristic implicated in pathogenesis has not been completely clarified. Accumulating evidence has indicated that circulating exosomes and their carried cargoes, such as long non-coding RNAs (lncRNAs), involve in the progress of multiple cardiovascular diseases. However, their potential role as clinical biomarkers in AF diagnosis and prognosis remains unknown. Herein, we conducted the sequence and bioinformatic analysis of circulating exosomes harvested from AF and sinus rhythm patients. A total of 53 differentially expressed lncRNAs were identified, and a total of 6 significantly changed lncRNAs (fold change > 2.0), including NR0046235, NR003045, NONHSAT167247.1, NONHSAT202361.1, NONHSAT205820.1 and NONHSAT200958.1, were verified by qRT-PCR in 215 participants. Moreover, these circulating exosome lncRNA levels were different between paroxysmal and persistent AF patients, which were dramatically associated with abnormal hemodynamics and atrial diameter. Furthermore, we observed that the area under ROC curve (AUC) of six lncRNAs combination for diagnosis of persistent AF was 80.34%. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment pathway analysis indicated these exosome lncRNAs mainly concerning response to chemokine-chemokine receptor interaction, which induced activated inflammation and structural remodeling. In addition, increased plasma levels of CXCR3 ligands, including CXCL4, CXCL9, CXCL10 and CXCL11, were accumulated in AF patient tissues. Our study provides the transcriptome profile revealing pattern of circulating exosome lncRNAs in atrial structural remodeling, which bring valuable insights into improving prognosis and therapeutic targets for AF.

Amino acid profile alteration in age-related atrial fibrillation

BackgroundAmino acids (AAs) are one of the primary metabolic substrates for cardiac work. The correlation between AAs and both atrial fibrillation (AF) and aging has been documented. However, the relationship between AAs and age-related AF remains unclear.MethodsInitially, the plasma AA levels of persistent AF patients and control subjects were assessed, and the correlations between AA levels, age, and other clinical indicators were explored. Subsequently, the age-related AF mouse model was constructed and the untargeted myocardial metabolomics was conducted to detect the level of AAs and related metabolites. Additionally, the gut microbiota composition associated with age-related AF was detected by a 16S rDNA amplicon sequencing analysis on mouse fecal samples.ResultsHigher circulation levels of lysine (Student’s t-test, P = 0.001), tyrosine (P = 0.002), glutamic acid (P = 0.008), methionine (P = 0.008), and isoleucine (P = 0.014), while a lower level of glycine (P = 0.003) were observed in persistent AF patients. The feature AAs identified by machine learning algorithms were glutamic acid and methionine. The association between AAs and age differs between AF and control subjects. Distinct patterns of AA metabolic profiles were observed in the myocardial metabolites of aged AF mice. Aged AF mice had lower levels of Betaine, L-histidine, L-alanine, L-arginine, L-Pyroglutamic acid, and L-Citrulline compared with adult AF mice. Aged AF mice also presented a different gut microbiota pattern, and its functional prediction analysis showed AA metabolism alteration.ConclusionThis study provided a comprehensive network of AA disturbances in age-related AF from multiple dimensions, including plasma, myocardium, and gut microbiota. Disturbances of AAs may serve as AF biomarkers, and restoring their homeostasis may have potential benefits for the management of age-related AF.

Comparison of Arctic Front Advance Pro and POLARx cryoballoons for ablation therapy of atrial fibrillation: an intraprocedural analysis.

Cryoballoon (CB) ablation has become a popular method for pulmonary vein isolation (PVI) in atrial fibrillation (AF) treatment. This study aimed to compare the intraprocedural ablation characteristics of two cryoballoons, Arctic Front Advance Pro™ (AFA-Pro, Medtronic) and POLARx™ (Boston Scientific). In this retrospective single-center study, 230 symptomatic paroxysmal or persistent AF patients underwent CB ablation with either AFA-Pro or POLARx. Propensity-score matching resulted in two cohorts of 114 patients each. Baseline and procedural characteristics were comparable between both CBs. POLARx achieved lower minimal temperatures (e.g., left superior pulmonary vein, LSPV: AFA-Pro - 49.0°C vs. POLARx - 59.5°C) and lower temperatures at time-to-isolation (TTI). Additionally, POLARx reached lower temperatures faster, as evidenced by lower temperatures after 40 and 60s, and a larger mean temperature change between 20 and 40s. POLARx also had a greater area under the curve below 0°C and a longer thawing phase. Both CBs achieved comparable high rates of final PV-isolation. TTI, minimal esophagus temperature, and first-pass isolation rates were similar between groups. Periprocedural complications, including phrenic nerve injuries, were comparable. Troponin levels in the left atrium were elevated with both systems. Values and change in troponin were numerically higher in the POLARx group (delta troponin: AFA-Pro 36.3 (26.4, 125.4) ng/L vs. POLARx 104.9 (49.5, 122.2) ng/L), p = 0.077). AFA-Pro and POLARx are both highly effective and safe CB systems for PVI. POLARx exhibited significant faster and lower freezing characteristics, and numerically higher troponin levels might indicate greater myocardial injury. However, these differences did not translate into improved performance, procedural efficiency, or safety.

Combination of frequency- and time-domain characteristics of the fibrillatory waves for enhanced prediction of persistent atrial fibrillation recurrence after catheter ablation

Catheter ablation (CA) remains the cornerstone alternative to cardioversion for sinus rhythm (SR) restoration in patients with atrial fibrillation (AF). Unfortunately, despite the last methodological and technological advances, this procedure is not consistently effective in treating persistent AF. Beyond introducing new indices to characterize the fibrillatory waves (f-waves) recorded through the preoperative electrocardiogram (ECG), the aim of this study is to combine frequency- and time-domain features to improve CA outcome prediction and optimize patient selection for the procedure, given the absence of any study that jointly analyzes information from both domains. Precisely, the f-waves of 151 persistent AF patients undergoing their first CA procedure were extracted from standard V1 lead. Novel spectral and amplitude features were derived from these waves and combined through a machine learning algorithm to anticipate the intervention mid-term outcome. The power rate index (φ), which estimates the power of the harmonic content regarding the dominant frequency (DF), yielded the maximum individual discriminant ability of 64% to discern between individuals who experienced a recurrence of AF and those who sustained SR after a 9-month follow-up period. The predictive accuracy was improved up to 78.5% when this parameter φ was merged with the amplitude spectrum area in the DF bandwidth (AMSALF) and the normalized amplitude of the f-waves into a prediction model based on an ensemble classifier, built by random undersampling boosting of decision trees. This outcome suggests that the synthesis of both spectral and temporal features of the f-waves before CA might enrich the prognostic knowledge of this therapy for persistent AF patients.

The effect of an initial catheter ablation with an adjunctive ethanol infusion into the vein of Marshall on persistent atrial fibrillation.

Some previous studies have reported that a first-step ethanol infusion into the vein of Marshall (EIVOM) with touch-up radiofrequency (RF) ablation can facilitate mitral isthmus (MI) block and improves the ablation outcomes in persistent atrial fibrillation (PeAF) patients. However, the effect of an initial RF ablation with an adjunctive EIVOM has not been fully investigated. This study enrolled 233 PeAF patients undergoing pulmonary vein isolation and linear ablation including an MI, roof line, and cavotricuspid isthmus ablation. An EIVOM was performed when endocardial ablation with or without coronary sinus ablation failed to create MI block. Bidirectional MI block was achieved in 224 patients (96.1%). Among them, MI block was obtained by only RF ablation in 174/224 patients (77.7%) (RF group) and an adjunctive EIVOM was needed in 50/224 (22.3%) (EIVOM group). During the follow-up, 113 (64.9%) RF group patients were free from AF/atrial tachycardia compared to 41 (82.0%) EIVOM group patients (log-rank p = .045). In a multivariate Cox regression analysis, an adjunctive EIVOM was associated with a lower recurrence rate (hazard ratio = 0.39, 95% confidence interval = 0.17-0.78, p = .006). An initial RF ablation with an adjunctive EIVOM strategy improved MI ablation's acute success rate and was associated with better clinical outcomes.

Ablation of persistent atrial fibrillation based on atrial electrogram duration map: methodology and clinical outcomes from the AEDUM pilot study.

Catheter ablation of persistent atrial fibrillation (PsAF) represents a challenge for the electrophysiologist and there are still divergences regarding the best ablative approach to adopt. Create a new map of the duration of atrial bipolar electrograms (Atrial Electrogram DUration Map, AEDUM) to recognize a functional substrate during sinus rhythm and guide a patient-tailored ablative strategy for PsAF. Forty PsAF subjects were assigned in a 1:1 ratio to either for PVI alone (Group B1) or PVI+AEDUM areas ablation (Group B2). A cohort of 15 patients without AF history undergoing left-sided accessory pathway ablation was used as a control group (Group A). In all patients, voltage and AEDUM maps were created during sinus rhythm. The minimum follow-up was 12 months, with rhythm monitoring via 48-h ECG Holter or by implantable cardiac device. Electrogram (EGM) duration was higher in Group B than in Group A (49±16.2ms vs 34.2±3.8ms; p-value<0.001). In Group B the mean cumulative AEDUM area was 21.8±8.2cm2; no difference between the two subgroups was observed (22.3±9.1cm2 vs 21.2±7.2cm2; p-value=0.45). The overall bipolar voltage recorded inside the AEDUM areas was lower than in the remaining atrial areas [median: 1.30mV (IQR: 0.71-2.38mV) vs 1.54mV (IQR: 0.79-2.97mV); p-value: <0.001)]. Low voltage areas (<0.5mV) were recorded in three (7.5%) patients in Group B. During the follow-up [median 511 days (376-845days)] patients who underwent PVI-only experienced more AF recurrence than those receiving a tailored approach (65% vs 35%; p-value= 0.04). All PsAF patients exhibited AEDUM areas. An ablation approach targeting these areas resulted in a more effective strategy compared with PVI only.

Artificial intelligence–adjudicated spatiotemporal dispersion: A patient-unique fingerprint of persistent atrial fibrillation

BackgroundSpatiotemporal dispersion-guided ablation is a tailored approach for patients in persistent atrial fibrillation (PsAF). The characterization of dispersion extent and distribution and its association with common clinical descriptors of PsAF patients has not been studied. ObjectivesArtificial intelligence–adjudicated dispersion extent and distribution (AI-DED) was obtained with a machine/deep learning classifier (VX1 Software, Volta Medical) in PsAF patients undergoing ablation. The purpose of this study was to test the hypothesis that AI-DED is unique to each patient and independent of common procedural and clinical parameters. MethodsIn a subanalysis of the Ev-AIFib study (NCT03434964), spatiotemporal dispersion maps were built with VX1 software in 78 consecutive persistent and long-standing PsAF patients. AI-DED was quantified using 2 distinct approaches (visual regional characterization or automated global quantification of AI-DED). ResultsAI-DED paired-subregion Euclidean distance measurements between 78 patients (average distance 5.07 ± 0.60; min 2.23; max 9.75) demonstrate that AI-DED is a patient-unique characteristic of PsAF. Importantly, both AF type and AF history do not correlate with AI-DED levels (R2 = 0.006, P = .53; and R2 = 0.03, P = .25, respectively). The most extensive AI-DED levels are not associated with poorer procedural (83%, 81%, and 83% of AF termination in low, medium, and high dispersion groups, respectively; P = .954) and long-term (88%, 75%, and 91% of freedom from AF/atrial tachycardia after multiple procedures; P = .517) outcomes. ConclusionThe atrial distribution and extent of multipolar electrogram spatiotemporal dispersion follow a nonrandom, albeit patient-unique, distribution in PsAF patients. AI-DED may represent a procedure-implementable fingerprint of the PsAF substrate.

Catheter Ablation of Paroxysmal and Persistent Atrial Fibrillation in Patients with Secondary Atrial Septal Defect. Evaluation of the Results and Impact on the Quality of Life

Introduction. The presence of atrial fibrillation (AF) in patients with secondary atrial septal defect (ASD) has significant impact on their quality of life (QoL) and reduces life expectancy. Current guidelines recommend catheter ablation (CA) for patients with AF in case of medical treatment failure, however, its use in patients with AF and ASD is still poorly studied.&#x0D; The aim. To study the efficacy and safety of CA and its impact on the QoL in patients with AF and secondary ASD.&#x0D; Materials and methods. In 2003-2023, 1408 patients with secondary ASD were treated at the National Amosov Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine. Of these, 54 patients who had AF and underwent the CA procedure were included in group 1 of our study. There were 36 (66.7%) men and 18 (33.3%) women aged 24-76 years (mean age 61.4 ± 9.8 years). Four (9.3%) patients had persistent AF and 50 (90.7%) patients had paroxysmal AF. Fifty-six patients with paroxysmal or persistent AF and with the comparable age, duration of symptoms and associated pathology but without ASD were examined as group 2. The type and results of surgical interventions were analyzed according to surgical reports. The results of the treatment and QoL were assessed using the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire during the follow-up period 1, 2 and 3 months after the procedure.&#x0D; Results. Pulmonary vein isolation was performed in all 54 (100%) patients of the group 1, as well as cavotricuspid isthmus ablation in 26 (48.2%) cases, cavotricuspid isthmus ablation and left atrial linear ablation in 2 (3.6%) cases. Type, length and complication of the procedure were comparable to those in the group 2. Fourty-four (81.5%) patients with ASD were free from AF 3 months after procedure, and their results did not differ from those obtained in the group 2 (p &gt; 0.05). Average QoL indicators according to AFEQT significantly improved in both groups of patients who underwent CA. The differences in post-treatment QoL between patients of both groups were insignificant (p &gt; 0.05).&#x0D; Conclusions. CA was found to be safe and beneficial in patients with AF and secondary ASD. The rate of procedural complications and cure rate in patients with AF and secondary ASD (81.5%) were compatible to those in patients without ASD (80.5%). AF has negative effect on the main indicators of the patient’s life. In patients with secondary AF with ASD who underwent CA, a significant improvement in AF symptoms and QoL according to the AFEQT questionnaire (total score 56.1 ± 2.7 before the procedure vs. 78.7 ± 4.0 at follow-up) was noted.

A novel microRNA differentially expressed in patients with persistent and paroxysmal atrial fibrillation.

A novel microRNA differentially expressed in patients with persistent and paroxysmal atrial fibrillation.

Reliable focal and rotational activations in CARTOFINDER mapping using the OctaRay catheter.

The aim of the current study was to elucidated the reliable atrial fibrillation (AF) drivers identified by CARTOFINDER using OctaRay catheter. The reliability of focal and rotational activations identified by CARTOFINDER using OctaRay catheter was assessed by the sequential recordings in each site of both atrium before and after pulmonary vein isolation (PVI) in 10 persistent AF patients. The outcome measures were the reproducibility rate during the sequential recordings and the stability rate between pre- and post-PVI as reliable focal and rotational activations. The study results were compared with those under use of PentaRay catheter (N = 18). Total 68928 points of 360 sites in OctaRay group and 24 177 points of 311 sites in PentaRay were assessed. More focal activation sites were identified in OctaRay group than PentaRay group (7.9% vs. 5.7%, p < .001), although the reproducibility rate and the stability rate were significantly lower in OctaRay group (45.3% vs. 58.9%, p < .001; 11.2% vs. 28.4%, p < .001). Meanwhile, the prevalence of reproducible focal activation sites among overall points was comparable (3.6% vs. 3.3%, p = .08). Regarding rotational activation, more rotational activation sites were identified in OctaRay group (5.1% vs. 0.2%, p < .001), and the reproducibility rate and the stability rate were significantly higher in OctaRay group (45.2% and 12.5% vs. 0.0%, p < .001). Both reliable focal and rotational activation sites were characterized by significantly shorter AF-cycle length (CL) and higher repetition of focal and rotational activations during the recordings compared with the sites of non or unreliable focal and rotational activations. In CARTOFINDER, OctaRay catheter could identify reliable focal activation with high resolution and reliable rotational activation compared with PentaRay catheter. The repetitive focal and rotational activations with short AF-CL could be the potential target during ablation.

Intravenous Cavutilide for Pharmacological Conversion of Paroxysmal and Persistent Atrial Fibrillation in Patients with Heart Failure.

In this retrospective cohort study, 58 patients with stable HF (aged 69 [61;73] years, 30 males, 78% with persistent AF) and 274 patients without HF (aged 63 [57;70] years, 196 males, 56% with persistent AF) were included. The median AF duration in the group with HF was 35.5 [10.6;124] days, and that in the group without HF was 14.5 [3.6;90] days. All patients received 5-30 µg/kg cavutilide intravenously in one to four (if needed) boluses of 5-5-10-10 µg/kg at 15 min intervals. Subsequent boluses were not administered if the patient's sinus rhythm (SR) was restored or if bradycardia, QT prolongation > 500 ms or evidence of proarrhythmia was observed. Holter electrocardiogram monitoring was started before infusion and was continued for 24 h. The main criterion for an antiarrhythmic effect was sinus rhythm restoration within 24 h of the initial bolus. Cavutilide converted AF to SR in 37.9% of patients with HF after bolus 1 (5 µg/kg), in 58.6% after bolus 2 (cumulative dose = 10 µg/kg), in 74% of cases after bolus 3 (cumulative dose = 20 µg/kg) and in 92.8% of cases after bolus 4 (cumulative dose = 30 µg/kg). Cavutilide was effective in 89% of cases with persistent AF with a median duration of 70.5 [30;159] days and in 92% of cases with paroxysmal AF with a median duration of 36 [24;102] h. In the group of patients without HF, the effectiveness of bolus 1 was 36.9%, that of the bolus 2 was 58%, that of the bolus 3 was 77% and that of the bolus 4 was 90.1%. Cavutilide restored SR in 90% of patients with persistent AF with a median duration of 82.5 [28;180] days and in 90% of cases with paroxysmal AF with a median duration of 50 [24;120] h. No statistically significant difference in the probability of SR restoration or the effectiveness of each bolus of cavutilide was found between patients with and without HF. The median time to restoration of SR in patients with HF was 23 [11;55] min, and that in patients without HF was 22 [10;45] min (p = 0.424). No cases of symptomatic/severe bradycardia were observed in either group. QT prolongation over 500 ms after cavutilide injection was registered in 19% of patients without HF and in 15.5% of those with HF (p = 0.58). Short runs of Torsade de pointes tachycardia occurred in one patient (0.4%) without HF after 10 µg cavutilide administration and were successfully treated with MgSO4. Cavutilide demonstrated a high likelihood of AF conversion to SR in paroxysmal (92%) and persistent (89%) arrhythmia and HF. Concomitant HF and its severity do not affect the efficacy and safety of cavutilide.

Modified Haller Index is inversely associated with asymptomatic status in atrial fibrillation patients undergoing electrical cardioversion: a preliminary observation.

No previous study evaluated the possible influence of chest wall conformation on symptoms perception in atrial fibrillation (AF) patients candidates for electrical cardioversion (ECV). We aimed at evaluating the anthropometric and clinical characteristics of patients with persistent AF undergoing ECV, categorized according to the presence or absence of symptoms. This study retrospectively analyzed a series of persistent AF patients scheduled for early ECV who underwent pre-procedural clinical evaluation, MHI (the ratio of chest transverse diameter over the distance between sternum and spine) assessment, transthoracic and transesophageal echocardiography implemented with strain analysis of both left atrium and left atrial appendage. Thromboembolic risk and burden of comorbidities were assessed by CHA<inf>2</inf>DS<inf>2</inf>-VASc Score and Charlson Comorbidity Index (CCI), respectively. The independent predictors of "asymptomatic AF" were assessed. A total of 25 asymptomatic and 90 symptomatic AF patients were retrospectively examined. Compared to symptomatic AF patients, those asymptomatic were significantly older (78.4±3.8 vs. 71.0±7.7 years, P<0.001), predominantly males (84 vs. 44.4%, P<0.001), with significantly lower MHI (2.0±0.1 vs. 2.4±0.1, P<0.001), higher CHA<inf>2</inf>DS<inf>2</inf>-VASc Score (5.8±1.1 vs. 3.6±1.1, P<0.001) and CCI (6.8±1.4 vs. 2.3±0.9, P<0.001), and greater impairment in biventricular systolic function and atrio-auricolar myocardial strain indices. On multivariate logistic regression analysis, CHA<inf>2</inf>DS<inf>2</inf>-VASc Score (OR=2.65, 95% CI: 1.53-4.60) and CCI (OR=2.36, 95% CI: 1.16-4.66) were linearly associated with the endpoint "asymptomatic AF," whereas MHI (OR 0.76, 95% CI 0.59-0.97) was inversely associated with the asymptomatic status. A MHI <2.2 was the best cut-off for detecting asymptomatic AF patients. MHI is inversely associated with asymptomatic status in persistent AF patients undergoing ECV. MHI assessment might represent an innovative practical approach to AF patients.

The Atrial Natriuretic Peptide-to-brain Natriuretic Peptide Ratio Predicts Left Atrial Reverse Remodeling after Rhythm Control Therapy in Patients with Persistent Atrial Fibrillation.

Objective The association between natriuretic peptide levels in atrial fibrillation (AF) patients with advanced left atrial (LA) remodeling and reverse remodeling after rhythm control therapy has not been clarified. The present study assessed the role of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) measurements to predict LA reverse remodeling after catheter ablation (CA) in persistent AF patients with LA enlargement. Methods This study included 88 persistent AF patients with LA enlargement (volume index >48 mL/m2) who underwent CA. Plasma ANP and BNP levels were analyzed before CA in all patients. The study population was divided into 2 groups according to the extent of decrease in the LA volume index (LAVI) at 6 months after CA: responders were those with a ≥15% reduction in the LAVI, and all others were non-responders. Results At follow-up, 58 patients (66%) were classified as responders. The preprocedural ANP level was significantly higher in the responders than in the non-responders (p=0.03). Furthermore, the ANP-to-BNP ratio (ANP/BNP) was significantly higher in the responders than in the non-responders (p<0.01). The ANP/BNP was correlated with the percentage decrease in the LAVI (r = 0.391, p<0.01). A multivariate linear regression analysis revealed that the ANP/BNP before CA was an independent predictor of LA reverse remodeling (p<0.01). Conclusions The preprocedural ANP/BNP was a robust predictor of reverse remodeling of the enlarged LA after sinus rhythm restoration by rhythm control therapy in persistent AF patients.

Relationship between pre-procedural non-ischemic ST-segment depression and the clinical outcomes after catheter ablation in persistent atrial fibrillation patients

Abstract Background ST-segment depression suggests the presence of coronary artery disease (CAD) during sinus rhythm, but the clinical significance, including the outcomes after catheter ablation (CA), in atrial fibrillation (AF) patients remains unknown. Purpose The aim of this study was to investigate the relationship between non-ischemic ST-segment depression during AF rhythm before CA and late arrhythmia recurrence in persistent AF (PerAF) patients. Methods The present study included PerAF patients from the Osaka Rosai Atrial Fibrillation ablation (ORAF) registry who underwent an initial ablation and had no history of CAD. We assigned the patients based on the presence of ST-segment depression before CA and evaluated the impact of relevant factors on ST-segment depression and the relationship between ST-segment depression, including leads locations (anterior leads, inferior leads, and lateral leads) or depression type (upsloping, horizontal and downsloping) or the degree of ST-segment depression and late recurrence of AF (LRAF). Results This study population included a total of 551 patients of which 189 had ST-segment depression. The median follow-up duration was 397 days and LRAF occurred in 195 patients. By multiple regression analysis, diabetes mellitus, hemoglobin, brain natriuretic peptide, left ventricular ejection fraction and left atrial diameter were significant determinants of ST-segment depression before CA. Kaplan-Meier analysis demonstrated that the patients with ST-segment depression had a significantly greater risk of LRAF than those without (p&amp;lt;0.001). Multivariate Cox proportional hazards analysis showed ST-segment depression was independently and significantly associated with a higher risk of LRAF (p&amp;lt;0.001). The patients with ST-segment depression≥0.15mV had a significantly higher risk of LRAF than those with ST-segment depression≥0.15mV (p&amp;lt;0.001). No significant differences among the ST-segment depression leads locations and ST-segment depression type were observed. Conclusion Non-ischemic ST-segment depression during AF rhythm was significantly associated with LRAF post CA in PerAF patients.

Acute impact of the vein of marshall ethanol infusion on newly-formed lesion and mitral line block in persistent atrial fibrillation ablation

Abstract Catheter ablation in persistent atrial fibrillation (PeAF) has limited success. Strategies beyond pulmonary veins isolation failed to demonstrate improvement of long-term rhythm maintenance. The vein of Marshall (VoM) is a promising therapeutic target because it contains triggers and autonomic parasympathetic and sympathetic activity implicated in arrhythmogenesis of AF. Moreover, as the VoM colocalizes with the trajectory of the "mitral isthmus", alcohol infusion into the vein facilitates bidirectional block across the line eliminating protected epicardial connections (1,2). Purpose We evaluated acute impact on lesion formation post-VOM-ETHO and the mitral line block validation after an approach including VOM-ETHO, pulmonary vein isolation (PVI), roof-line, mitral line (ML) and cavo-tricuspid isthmus line in a population of PeAF patients (Figure 1). We aimed also to report procedural outcomes after a short follow-up period. Methods After a detailed electroanatomical map of the left atrium (LA) (filter at 0.05-0.5 mV if the patient was in sinus rhythm or 0.05-0.3 mV in the case of AF), we thus proceeded with the VoM-ETHO using the technique previously described (3,4). LA map was thus repeated to assess the extension of the newly-formed low voltage area (LVA). According to the newly-formed LVAs, mitral isthmus ablation was completed endocardially. PVI, roof-line and cavo-tricuspid isthmus line were performed to complete the ablation setting. Bidirectional block across line was then validated during pacing from left atrial appendage. In case of persistence of conduction through the mitral line due to epicardial gaps, additional ablations were applied in the "anchored wall" or in the "free-wall" of the great cardiac vein (GCV). Results Twenty-one PeAF patients (67±6 years; 67% male) underwent ablation. The medium value of basal LA-LVAs was 3.1±63.8 cmq and the newly-formed LVAs after the VoM-ETHO procedure was 12.35±67.28 cmq. All patients had bidirectional block validated across the roof-line. Bidirectional block of the ML was achieved in 19/21 patients: in 12/21 patients after endocardial line only and in 9/21 after epicardial gaps ablations into the coronary sinus. The ML procedural time was 11.3±65.9 minutes. No major complications occurred. One patient had mild pericardial effusion due to VoM perforation with a spontaneous resolution. After a short follow-up period (6±63 months), no relapse of AF was observed in 19/21 (90%) patients. 12/21 patients were free from antiarrhythmic drugs (AADs). Interestingly, recurrences happened in patients in whom bidirectional block of the mitral line was not achieved. Conclusions VoM ethanol ablation added to PVI and linear lesions in the context of a methodical and anatomical approach seems to have promising results in PeAF patients. This strategy seems to be safe and reproducible. A favourable outcome depended on the interventional setting completion and the procedural end-points validation is crucial.

High FABP4, associated with low-voltage areas, increases the epicardial fibrosis and its glucose metabolism

Abstract Background High plasma levels of FABP4 were associated with epicardial fat volume on persistent AF patients. FABP4 can be released by differentiated adipocytes and macrophages, which can be involved in fibrosis. Purpose Our main objective was to study the association between FABP4 and epicardial fibrosis, which can explain low-voltage areas (LVA) and atrial fibrillation (AF) recurrence. Material and methods Peripheral levels of FABP4 and Galectin-3 were analysed on AF patients undergoing pulmonary vein isolation (PVI) (n=299) and signed informed consent. During the intervention, LVA was evaluated by invasive electroanatomic voltage mapping (EAM). Epicardial (EAT) (n=6) and subcutaneous adipose tissue (SAT) (n=5) were obtained from undergoing open heart surgery patients. Stromal cells were isolated by collagenase digestion, cultured and treated with and without FABP4 100 ng/mL and/or galectin-3 30 ng/mL for 24 hours. The proliferation and migration rate were measured by wound healing assay; mitochondrial activity was studied by MTT assay; and glucose and lactate consumption were detected by colorimetric and fluorescence enzymatic assays, respectively. Gene expression levels were assessed by real-time PCR. Results Regression analysis determined that the main independent predictors of LVA were age, left atrial area and FABP4 levels. Preclinical "in vitro" studies have shown that FABP4 100 ng/mL induced fibrosis in epicardial stromal cells (p=0.0039) and subcutaneous stromal cells (p=0.0009), evidenced by wound healing assay and by the increment of associated fibroblast genes (COL1A2, VIM, TGF-β1). Moreover, the high FABP4 concentration modulates the protein levels and metabolic genes expression (CPT1, FASN, ATGL, related to transport, synthesis and degradation of fatty acids, respectively) on EAT stromal cells. Glucose metabolism without lactate production was also incremented after FABP4 treatment (p&amp;lt;0.0001). Even, on SAT cells, released lactate was reduced after FABP4 treatment (p=0.0218). Conclusions Plasma FABP4 was a predictor of LVA. Our results suggest that this association might be explained by the fibrotic and metabolic role of FABP4 in epicardial cells. Future studies will shed light on the benefits on atrial remodelling with FABP4 modulators.Figure 1Figure 2