Atrial Pacing Improves Mitochondrial Function in Peripheral Blood Mononuclear Cells in Patients with Cardiac Implantable Electronic Devices.

Mitochondrial dysfunction contributes significantly to the development of atrial fibrillation (AF). Conflicting data regarding the atrial pacing and the risk of AF existed and the impact of atrial pacing on mitochondrial function remains unknown. Therefore, we sought to examine the association between atrial pacing percentage and mitochondrial function in patients with cardiovascular implantable electronic devices (CIED) with atrial pacing capability. This is a cross-sectional study involving 183 patients with CIED with atrial pacing capability. The oxidative stress and mitochondrial function were determined in peripheral blood mononuclear cells (PBMCs). Among 183 patients, 55.7% had permanent pacemakers, 7.7% had defibrillators and 36.6% had cardiac resynchronization therapy. Mean age was 67.5±14.7 years with 51% being male. Mean left ventricular ejection fraction (LVEF) was 53.9 ± 16.8%. We demonstrated that the presence of atrial pacing above 50% correlated with higher levels of mitochondrial spared respiratory capacity (P=0.043) and coupling efficiency (P=0.045). After adjusting with multiple linear regression for age, sex, LVEF, history of AF, sick sinus syndrome, co-morbidities, eGFR, CRT, and percentage of ventricular pacing, our findings revealed a statistically significant association between a higher percentage of atrial pacing and increased spared respiratory capacity (ß 0.217, P=0.046), lower non-mitochondrial respiration (ß -0.230, P=0.023) and proton leak (ß -0.247, P=0.022). We demonstrated that atrial pacing enhances mitochondrial performance in PBMCs and left ventricular contractile performance in patients with CIED. This observation may serve as additional support for the preventive effect of atrial pacing in the prevention of atrial arrhythmia.

Characterization of atrial arrhythmias following mitral valve repair: Incidence and risk factors.

OBJECTIVES: This study aims to investigate the occurrence, type and correlation of early and late atrial arrhythmias following mitral valve repair in patients with no preoperative history of atrial arrhythmias. METHODS: Patients undergoing mitral valve (MV) repair for degenerative disease were included. Early and late postoperative electrocardiograms were evaluated for the incidence and type of atrial arrhythmia (atrial fibrillation [AF] or atrial tachycardia [AT]). RESULTS: The 192 patients were included. Early atrial arrhythmias occurred in 100/192 (52.1%) patients; AF in 61 (31.8%) patients, early AT in 15 (7.8%) and both in 24 (12.5%). In total 89% of patients were discharged in sinus rhythm. During a follow-up time of 7.3 years, 14 patients (7.3%) died and 49 (25.5%) patients developed late atrial arrhythmias. At 10 years, the cumulative incidence of any late atrial arrhythmia, with death as competing risk, was 64% (95% confidence interval [CI] = 55%-72%). On Fine-Gray model analysis, only early postoperative AF lasting >24 h was related to the development of late AF (hazard ratio 5.99, 95% CI = 1.78%-20.10%, p = .004). Early postoperative ATs were related to the development of late tachycardias, independent of their duration (<24 h hazard ratio 4.25, 95% CI = 1.89-9.57, p = .001 and >24 h hazard ratio 3.51, 95% CI = 1.65-7.46, p = .001). CONCLUSIONS: Early and late atrial arrhythmias were common after MV repair surgery. Only early postoperative AF lasting >24 h was a risk factor for the occurrence of late AF. Conversely, any postoperative AT was correlated to the development of late ATs.

Association between COVID-19 vaccination and atrial arrhythmias in individuals with cardiac implantable electronic devices.

INTRODUCTION: The impact of mRNA-based coronavirus disease-2019 (COVID-19) vaccines on atrial arrhythmias (AA) and ventricular arrhythmias incidence is unknown. METHODS: BIOTRONIK Home Monitoring data and Medicare Claims data were utilized to identify individuals implanted with a cardiac implantable electronic device (CIED) between 2010 and 2020 who received one or more doses of COVID-19 vaccine in 2021. The burden of AA (%) in the 3 months postvaccination was compared to those noted in the preceding 3 months using the Wilcoxon signed rank test. Sub-analyses comparing the effects of the influenza vaccine against the COVID-19 vaccine were also evaluated for individuals who received the influenza vaccine in 2020. A 1:1 propensity score match comparison between COVID-19 vaccine and non-vaccinated patients was also performed. RESULTS: First and second doses of the COVID-19 vaccine were administered to 7757 and 6579 individuals with a CIED (age 76.2 ± 9.0 years, 49% males), respectively. While a small but statistically significant increase in the burden of AA was noted in the 3 months postvaccination compared to the preceding 3 months after the first dose of the COVID-19 vaccine (0.43 ± 9.04%, p = .028) a similar rise in AA was found following the influenza vaccine and for matched patients who did not receive the COVID-19 vaccine. No significant difference in device therapies was seen pre- and postvaccination. CONCLUSIONS: Though we report a small but significant increase in the number of CIED-detected AAs following vaccination for COVID-19 over a 3-month window, we believe these results correlate more with time and the progressive nature of AF rather than the vaccine itself. While these data should not dissuade from the use of these vaccines, increased vigilance and prompt treatment of AF is required for high-risk groups, specifically males over 70 years of age, following vaccination.

Atypical atrial flutter ablation: follow-up and predictors of arrhythmia recurrence.

BACKGROUND: Ablation techniques have evolved greatly with advances in high-density 3D mapping systems over the last few years. Some patients develop atypical atrial flutter (AAFL) after pulmonary vein isolation (PVI). The data regarding follow-up after AAFL ablation as well as predictors of arrhythmia recurrence are lacking. This analysis aims to report procedure success rates and establish predictors of long-term success. METHODS AND RESULTS: This retrospective cohort study included 45 patients (median age: 69 years; 40% female) who qualified for their first AAFL after PVI. The procedures were performed with the use of conventional ablation-index-guided ThermoCool Smarttouch SF and QDOT MICRO catheters. Freedom from arrhythmia recurrence was used as a primary end point. After 52 weeks of follow-up, 60% of patients suffered from arrhythmia recurrence, but over 70% of the studied cohort reported symptom improvement. In multivariate analysis, class I antiarrhythmics prescription (HR = 0.24 [95% CI 0.06-0.94], p = 0.04) was associated with the lack of arrhythmia recurrence during the follow-up, while cardioversion during procedure was associated with increased risk of arrhythmia recurrence (HR = 7.05 [95% CI 2.09-23.72], p = 0.002). CONCLUSIONS: Long-term success of AAFL ablation procedures is not satisfactory despite improvement in symptoms. Class I antiarrhythmics prescription at the discharge contributes to higher chances of sinus rhythm maintenance, whereas cardioversion during the procedure is related to increased risk of arrhythmia recurrence.

Atrial Arrhythmia and Bradycardia as a Presentation of Congenital Long QT Syndrome.

We present a term newborn with atrial arrhythmia on the first day of life (DOL). An echocardiogram showed normal structure and normal function; laboratory testing showed normal electrolytes and thyroid function. After initiation of flecainide, the EKG on DOL 2 showed significant and increasing bradycardia with atrial arrhythmia and extremely prolonged QTc interval. Flecainide was stopped and esmolol started. After 6 h of treatment, atrial tachycardia was suppressed, and the rhythm converted to sinus. Genetic testing found variants of unknown significance in the ALPK3 gene and KCNQ1 gene, which has been associated with long QT syndrome (LQTs). LQTs in infants can present as bradycardia, 2:1 AV block, or torsades de pointes. Our review of the literature found only one other case report of atrial arrhythmia in a newborn with congenital LQTs. Diagnosis of LQTs via EKG alone is difficult in neonates since the ST segment and T wave on the first DOL are usually flattened, making correct measurement of the QTc interval difficult. ß-blockers, the first line of treatment for LQTs, are known to shorten QTc intervals and prevent arrhythmia events. As in our patient, ß-blockers may be helpful for atrial arrhythmia prevention in patients with adrenergically mediated atrial tachycardia. In conclusion, atrial arrhythmia with bradycardia can be a presentation of congenital LQTs and be difficult to recognize. For neonates with this presentation with no evidence of myocarditis, congenital heart disease, or significant respiratory illness, genetic congenital LQTs should be highly suspected, especially when associated with low resting heart rates.

Predictors of Atrial Arrhythmia in Adults with Repaired Tetralogy of Fallot.

Tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease in adults, has excellent long-term survival. However, many patients (30-45%) develop late arrhythmias. Previous studies have identified predictors of arrhythmia (atrial or ventricular) using clinical markers that predate arrhythmia onset by many years. Our objective was to develop a predictive model for incident atrial arrhythmias within two years of clinical evaluation and diagnostic testing. A single-center nested unmatched case-control study of 174 adults with repaired TOF. We included only patients with results from ECG and echocardiogram data in the required time interval (3-24 months before first arrhythmia for cases; 24 months of follow-up for controls). A predictive multivariable model for risk of incident atrial arrhythmia was developed using logistic regression with a least absolute shrinkage and selection operator (LASSO). Of 41 demographic, surgical, and diagnostic variables, six were selected as having predictive value for atrial arrhythmia based on cross validation. The factors with the greatest predictive value in decreasing order were moderate / severe tricuspid regurgitation (adjusted odds ratio (OR) 149.42), QRS fragmentation (OR 28.08), severe pulmonary regurgitation (OR 8.22), RV systolic dysfunction (OR 2.95), 1st degree AV block (OR 2.59), and age at time of surgical repair (OR 1.02). Predictors for atrial arrhythmia in our study suggested abnormal right ventricle anatomical function and electrophysiologic properties (conduction and repolarization) as the primary underlying substrate.

An objective tool for quantifying atrial fibrillation substrate in rats.

The utility of rodents for research related to atrial fibrillation (AF) is growing exponentially. However, the obtained arrhythmic waveforms are often mixed with ventricular signals and the ability to analyze regularity and complexity of such events is limited. Recently, we introduced an implantable quadripolar electrode adapted for advanced atrial electrophysiology in ambulatory rats. Notably, we have found that the implantation itself leads to progressive atrial remodeling, presumably because of mechanical loading of the atria. In the present study, we developed an algorithm to clean the atrial signals from ventricular mixing and thereafter quantify the AF substrate in an objective manner based on waveform complexity. Rats were sequentially examined 1-, 4-, and 8-wk postelectrode implantation using a standard AF triggering protocol. Preburst ventricular mixing was sampled and automatically subtracted based on QRS detection in the ECG. Thereafter, the "pure" atrial signals were analyzed by Lempel-Ziv complexity algorithm and a complexity ratio (CR) was defined for each signal by normalizing the postburst to the preburst values. Receiver operating characteristic (ROC) curve analysis indicated an optimal CR cutoff of 1.236 that detected irregular arrhythmic events with high sensitivity (94.5%), specificity (93.1%), and area under the curve (AUC) (0.96, 95% confidence interval, 0.945-0.976). Automated and unbiased analysis indicated a gradual increase in signal complexity over time with augmentation of high frequencies in power spectrum analysis. Our findings indicate that CR algorithm detects irregularity in a highly efficient manner and can also detect the atrial remodeling induced by electrode implantation. Thus, CR analysis can strongly facilitate standardized AF research in rodents.NEW & NOTEWORTHY Rodents are increasingly used in AF research. However, because of technical difficulties including atrial waveform mixing by ventricular signals, most studies do not discriminate between irregular (i.e., AF) and regular atrial arrhythmias. Here, we develop an unbiased computerized tool to "pure" the atrial signals from ventricular mixing and thereafter analyze AF substrate based on the level of irregularity in an objective manner. This novel tool can facilitate standardized AF research in rodents.

Impact of unipolar voltage criteria for left atrial posterior wall on atrial fibrillation recurrence after pulmonary vein isolation.

INTRODUCTION: Beyond pulmonary vein isolation (PVI), additional therapeutic strategies for atrial fibrillation (AF) have not been established. Remodeling of the left atrium (LA) could impact AF recurrence post-PVI. We investigated the impact of unipolar voltage (UV) criteria for the LA posterior wall (LA-PW) on AF recurrence post-PVI. METHODS: We reviewed the cases of 106 AF patients (mean age 63.8 years, nonparoxysmal AF: 59%) who underwent extensive encircling PVI by radiofrequency ablation guided by a 3-dimension mapping system, investigating the impact on AF recurrence of the UV criteria of the LA. RESULTS: Out of all patients, 26 patients had AF recurrence during post-PVI follow-up [median 603 days]. They showed a higher percentage of nonparoxysmal AF (80.8 vs. 52.5%, p = .011), longer AF duration (2.9 ± 2.7 vs. 1.0 ± 1.7 years, p = .002), and larger area size of UV < 2.0 mV in LA-PW (2.8 ± 1.8 vs. 1.0 ± 1.5 cm2 , p < .001) than those without recurrence. Cox Hazard analysis for AF recurrence adjusted by age, gender, AF duration, body mass index and left atrial volume index revealed that an area size over 2.0 cm2 of UV < 2.0 mV in LA-PW (HR 6.9 [95% CI:1.3-35.5], p = .021) posed independent risks for AF recurrence post-PVI. The atrial arrhythmia-free survival rate was higher in those with no area of UV < 3.0 mV in LA-PW compared to those with a sizable area (>2.0 cm2 ) of UV < 3.0 mV and <2.0 mV (95.0% vs. 74.2% vs. 57.1%, Log-Rank: p < .001). In the AF etiology of patients with AF recurrence, 9 of 14 patients who underwent the 2nd procedure had no PV reconnection, and 8 patients required the LA-PW isolation for their non-PV AF. CONCLUSION: UV criteria of LA-PW is a useful parameter for AF-recurrence post-PVI. Lower UV in LA-PW as an indication of electrical remodeling could indicate a higher risk of AF recurrence and the need for further therapeutic strategies.

Differences in postablation cardiac MRI scar between radiofrequency and cryoballoon ablation: A DECAAF II subanalysis.

INTRODUCTION: Pulmonary vein isolation (PVI) using radiofrequency (RF) and cryoballoon (Cryo) ablation are standard approaches for rhythm control in patients with symptomatic atrial fibrillation. Both strategies create scars in the left atrium (LA). There have been few studies investigating the difference in scar formation between patients undergoing RF and Cryo using cardiac magnetic resonance (CMR) imaging. METHODS: The current study is a subanalysis of the control arm of the Delayed-Enhancement MRI Determinant of Successful Catheter Ablation of Atrial Fibrillation study (DECAAF II). The study was a multicenter, randomized, controlled, single-blinded trial that evaluated atrial arrhythmia recurrence (AAR) between PVI alone and PVI plus CMR atrial fibrosis-guided ablation. Preablation CMR and 3- to 6-month postablation CMR were obtained to assess baseline LA fibrosis and scar formation, respectively. RESULTS: Of the 843 patients randomized in the DECAAF II trial, we analyzed the 408 patients in the primary analysis control arm that received standard PVI. Five patients received combined RF and Cryo ablations, so they were excluded from this subanalysis. Of the 403 patients analyzed, 345 underwent RF and 58 Cryo. The average procedure duration was 146 min for RF and 103 min for Cryo (p = .001). The rate of AAR at ~15 months occurred in 151 (43.8%) patients in the RF group and 28 (48.3%) patients in the Cryo group (p = .62). On 3-month post-CMR, the RF arm had significantly more scar (8.8% vs. 6.4%, p = .001) compared to Cryo. Patients with ≥6.5% LA scar (p < .001) and ≥2.3% LA scar around the PV antra (p = .01) on 3-month post-CMR had less AAR independent of the ablation technique. Cryo caused a greater percentage of right and left pulmonary vein (PV) antral scar (p = .04, p = .02) and less non-PV antral scar (p = .009) compared to RF. On Cox regression, Cryo patients free of AAR had a greater percentage of left PV antral scar (p = .01) and less non-PV antral scar (p = .004) compared to RF free of AAR. CONCLUSION: In this subanalysis of the control arm of the DECAAF II trial, we observed that Cryo formed a more significant percentage of PV antral scar and less non-PV antral scar compared to RF. Post ablation LA scar ≥6.5% predicted freedom from AAR, independent of ablation technique. These findings may have prognostic implications in ablation technique selection and freedom from AAR.

Catheter ablation of atrial tachyarrhythmias in patients with atrioventricular septal defect.

AIMS: The incidence of atrial tachyarrhythmias is high in patients with atrioventricular septal defect (AVSD). No specific data on catheter ablation have been reported so far in this population. We aimed to describe the main mechanisms of atrial tachyarrhythmias in patients with AVSD and to analyse outcomes after catheter ablation. METHODS AND RESULTS: This observational multi-centric cohort study enrolled all patients with AVSD referred for catheter ablation of an atrial tachyarrhythmia at six tertiary centres from 2004 to 2022. The mechanisms of the different tachyarrhythmias targeted were described and outcomes were analysed. Overall, 56 patients (38.1 ± 17.4 years, 55.4% females) were included. A total of 87 atrial tachyarrhythmias were targeted (mean number of 1.6 per patient). Regarding main circuits involved, a cavo-annular isthmus-dependent intra-atrial re-entrant tachycardia (IART) was observed in 41 (73.2%) patients and an IART involving the right lateral atriotomy in 10 (17.9%) patients. Other tachyarrhythmias with heterogeneous circuits were observed in 13 (23.2%) patients including 11 left-sided and 4 right-sided tachyarrhythmias. Overall, an acute success was achieved in 54 (96.4%) patients, and no complication was reported. During a mean follow-up of 2.8 ± 3.8 years, 22 (39.3%) patients had at least one recurrence. Freedom from atrial tachyarrhythmia recurrences was 77.5% at 1 year. Among 15 (26.8%) patients who underwent repeated ablation procedures, heterogeneous circuits including bi-atrial and left-sided tachyarrhythmias were more frequent. CONCLUSION: In patients with AVSD, most circuits involve the cavo-annular isthmus, but complex mechanisms are frequently encountered in patients with repeated procedures. The acute success rate is excellent, although recurrences remain common during follow-up.

Up-regulated small-conductance calcium-activated potassium currents contribute to atrial arrhythmogenesis in high-fat feeding mice.

AIMS: Metabolic syndrome (MetS) is associated with arrhythmias and cardiovascular mortality. Arrhythmogenesis in MetS results from atrial structural and electrical remodelling. The small-conductance Ca2+-activated K+ (SK) currents modulate atrial repolarization and may influence atrial arrhythmogenicity. This study investigated the regulation of SK current perturbed by a high-fat diet (HFD) to mimic MetS. METHODS AND RESULTS: Thirty mice were divided into two groups that were fed with normal chow (CTL) and HFD for 4 months. Electrocardiography and echocardiography were used to detect cardiac electrical and structure remodelling. Atrial action potential duration (APD) and calcium transient duration (CaTD) were measured by optical mapping of Langendorff-perfused mice hearts. Atrial fibrillation (AF) inducibility and duration were assessed by burst pacing. Whole-cell patch clamp was performed in primarily isolated atrial myocytes for SK current density. The SK current density is higher in atrial myocytes from HFD than in CTL mice (P ≤ 0.037). The RNA and protein expression of SK channels are increased in HFD mice (P ≤ 0.041 and P ≤ 0.011, respectively). Action potential duration is shortened in HFD compared with CTL (P ≤ 0.015). The shortening of the atrial APD in HFD is reversed by the application of 100 nM apamin (P ≤ 0.043). Compared with CTL, CaTD is greater in HFD atria (P ≤ 0.029). Calcium transient decay (Tau) is significantly higher in HFD than in CTL (P = 0.001). Both APD and CaTD alternans thresholds were higher in HFD (P ≤ 0.043), along with higher inducibility and longer duration of AF in HFD (P ≤ 0.023). CONCLUSION: Up-regulation of apamin-sensitive SK currents plays a partial role in the atrial arrhythmogenicity of HFD mice.

Atrial tachyarrhythmias after lung transplantation in children: A common occurrence.

BACKGROUND: Atrial arrhythmia's (AA) following lung transplant in adults are a well-described clinical finding. In pediatrics, however, there are limited data with some reports suggesting that arrhythmias are rare. METHODS: We performed a single-center retrospective review of lung transplant recipients from January 2013 to June 2020. A detailed evaluation of clinical characteristics, presence of arrhythmias, and outcomes was completed. Arrhythmias were documented based on inpatient telemetry or remote Holter monitoring. Analyses assessing risk factors for arrhythmias and associations with clinical outcomes were performed. RESULTS: Ninety-one lung transplants were performed in 90 patients. Post-operative AA occurred following 19% transplants. Ectopic atrial tachycardia was seen in 14%, atrial flutter in 2%, and a combination in 2%. The majority of these arrhythmias occurred within the first 45 days post-operatively. Antiarrhythmic treatment was required in 59%, but none required ablation or electrical cardioversion. In patients followed for a year or more, 88% had resolution of their arrhythmia. Arrhythmias were not associated with mortality. In further analysis, however, the presence of arrhythmia was associated with an increased length of ICU stay (median of 12 days (IQR 6, 23) versus 5 days (IQR 4, 9); p = .019) and overall length of hospital stay (median of 26 days (IQR 19, 36) versus 17 days (IQR 19, 36); p = .043). CONCLUSIONS: Atrial tachyarrhythmias after lung transplantation are common in the pediatric population and usually occur early. Although they frequently require medical therapy and are associated with longer stays, there is no associated increased mortality. In addition, the arrhythmias typically self-resolve.

Improvements in Accuracy and Confidence in Rhythm Identification After Cardiac Surgery Using the AtriAmp Signals.

Objectives: Following cardiac surgery, 50% to 60% of patients with congenital heart disease will experience an arrhythmia. These arrhythmias are associated with increased morbidity and mortality. Therefore, rapid and accurate identification is paramount to the improvement of patient outcome. We hypothesize that the AtriAmp, a device which allows atrial electrogram (AEG) display on the bedside monitors, will increase provider accuracy and confidence in arrhythmia diagnosis. Design: A prospective observational study. Electrograms were collected from post-operative patients from the bedside monitors surface ECG and an AEG using the AtriAmp. A 12-question online survey was given to critical care and cardiology providers at 9 different programs across the country as well as being posted to the AAP SOCC fall newsletter. Six questions displayed signals from only the surface leads, while the other 6 showed the same arrhythmias with an AEG obtained from the AtriAmp. Answers were then evaluated for confidence and accuracy. A paired t-test along with mixed method modeling was used to assess the data. Setting: Cardiac pediatric ICU. Subjects: Providers in pediatric cardiology and pediatric critical care were evaluated on their ability to diagnose arrhythmias on surface ECG and AEG obtained from bedside monitor. Interventions: The accuracy and confidence of diagnosis of both surface and AEG signals were evaluated through an on-line survey. Results: Eighty-eight providers completed the survey. The study showed that interpreting with the AtriAmp signal, compared to the surface ECG only, significantly increased the accuracy (P = .002) and confidence in provider rhythm diagnosis (P < .001). Junctional ectopic tachycardia, sinus tachycardia, and complete heart block had the most significant increase in accuracy of diagnose when using the AtriAmp signal (P < .001, P = .002, P = .010, respectively). Conclusion: Use of the AtriAmp increased provider accuracy and confidence in post-operative rhythm diagnosis when compared to diagnosis using the surface electrograms only.

Combined Atrial Volume is Associated with Significant Atrial Arrhythmias in Total Cavopulmonary Connection Fontan Patients.

Atrial arrhythmias are a common late manifestation after Fontan palliation and are known to contribute to significant morbidity and mortality. Atrial volume by cardiac magnetic resonance imaging has been increasingly used in patients with congenital heart disease with no reports in those with Fontan palliation. In acquired heart disease, left atrial volume has been shown to be a strong predictor of outcomes of sustained atrial arrhythmias, including recurrence of atrial fibrillation. We hypothesized that combined atrial volume (CAV) in patients with total cavopulmonary connection (TCPC) Fontan palliation may be associated with increased risk of significant atrial arrhythmias (SAA). This is a single center retrospective case-control study. Cases were defined as patients with TCPC Fontan palliation ≥ 18 years of age, with SAA requiring intervention. Only those with advanced imaging for 3D rendering between 2013 and 2022 were included. CAV was analyzed from a 3-dimensional (3D) data set, including both the left and right atria, excluding the Fontan baffle. Seventeen TCPC Fontan case patients and 17 control patients were included. There was no difference in age between the two groups. There was no difference between gender, type of Fontan palliation, atrio-ventricular valve regurgitation, or combined ventricular function between the two groups. CAV was higher in SAA group compared to controls, and all control patients had indexed CAV ≤ 80 mL/kg. This is the first data suggesting CAV is associated with SAA in TCPC Fontan patients. Indexed CAV ≥ 80 mL/kg may be a valuable marker for SAA risk.

HotBalloon Pulmonary Vein Isolation Registry Study　- Real-World Efficacy and Safety of HotBalloon Ablation.

BACKGROUND: Radiofrequency hotballoon (RHB) is an ablation device used for atrial fibrillation (AF) treatment. The efficacy and safety of RHB-based pulmonary vein isolation (PVI) in real-world practice are unknown.Methods and Results: A multicenter, prospective registry study (UMIN000029567) enrolled AF patients who underwent RHB-PVI. The primary endpoint was the AF recurrence-free survival rate at 12 months after PVI. Of the 679 patients enrolled, 613 (90.3%; paroxysmal AF, n=370; persistent AF, n=136; long-standing AF, n=107) underwent initial RHB-PVI. Acute isolation using only the RHB was successful for 55.6% of patients and 83.5% of pulmonary veins (PVs). The acute isolation rate was higher for patients with paroxysmal AF and more experienced centers. Antiarrhythmic drugs were prescribed after 3 months for 47.5% of patients. The AF recurrence-free survival rate at 12 months was 83.7%. Procedure-related complications including atrio-esophageal fistula (n=1) and phrenic nerve injury (persistent; n=4, permanent; n=2) were observed in 19 (3.1%) patients. Five (1.7%) of the 302 patients who underwent pre-procedural and post-procedural multidetector computed tomography had severe PV stenosis. CONCLUSIONS: The size-adjustable RHB has been used for the treatment of various AF types. The arrhythmia recurrence-free rate at 12 months, with the use of antiarrhythmic drugs in approximately half of the patients, was acceptable, but the acute isolation rate using the RHB requires further improvement.

Short coupling interval with high burden of atrial ectopy predicts recurrence after atrial fibrillation ablation.

Atrial ectopy (AE) with a short coupling interval (S-AE) causes atrial fibrillation (AF). A higher burden of AE is associated with recurrence after AF ablation. However, a few reports have evaluated the prognostic impact of both AE burden and S-AE after the acute phase of ablation. This study aimed to assess the characteristics of AE beyond the blanking period in predicting the recurrence. We retrospectively analyzed 173 patients who underwent first catheter ablation for AF and 24-h Holter recording following a 3-month blanking period. AE was defined as a narrow QRS complex occurring < 75% earlier than the prior reference R-R interval. We investigated the relationship between the AE's characteristics in Holter recordings and atrial arrhythmia recurrence. Forty-two patients (24%) had a recurrence during a median 488-day follow-up. Patients with S-AE (minimum coupling interval ratio of AE ≤ 45%) had a higher recurrence rate than those without S-AE (44.9% vs. 16.1%, p < 0.001). Moreover, patients with AE ≥ 241/day exhibited a significantly higher recurrence rate than those with AE < 241/day (44.3% vs. 10.7%, p < 0.001). In multivariate analysis, S-AE with a higher AE burden was an independent predictor of recurrence (hazard ratio 5.82, 95% confidence interval: 2.64-12.82, p < 0.001). Kaplan-Meier analysis showed that patients with S-AE and a higher AE burden had the worst prognosis for recurrence (p < 0.001). The combination of a higher AE burden with S-AE could be an efficient predictor of recurrence. These results can help to develop follow-up strategies after AF ablation.

Effects of Chronic Remote Ischemic Conditioning on Atrial Fibrillation Burden in Patients with Permanent Pacemakers.

This study aimed to evaluate the effects of chronic remote ischemic conditioning (CRIC) on atrial fibrillation burden in patients with an implanted pacemaker. Sixty-six patients with permanent pacemakers were randomly divided into the CRIC group and control group after 4 weeks of screening. CRIC treatment was performed twice daily for 12 weeks. The remote ischemic conditioning protocol consisted of 4 × 5 minutes inflation/deflation of the blood pressure cuff applied in the upper arm to create intermittent arm ischemia. Sixty-one patients (31 patients in the CRIC group and 30 patients in the control group) completed the study. CRIC was well tolerated by patients after 12 weeks of treatment. The burden of atrial fibrillation (AF) in the CRIC group decreased significantly at 4 weeks compared with that at 0 weeks (14.7% ± 18.5% versus 17.0% ± 20.7%, P < 0.001), which further decreased at 12 weeks compared with that at 0 weeks (8.6% ± 10.2% versus 17.0% ± 20.7%, P < 0.001) and that at 4 weeks (8.6% ± 10.2% versus 14.7% ± 18.5%, P < 0.001), which was not observed in the control group. AF burden also reduced significantly after 12-week CRIC compared with that in the control group (8.6% ± 10.2% versus 17.6% ± 19.5%, P = 0.013). Repeated measurement ANOVA showed that the changes in AF burden were associated with CRIC instead of time (P < 0.01). In addition, there were trends that the longest duration of AF and cumulative numbers of atrial high-rate episodes (AHREs) reduced after 12-week CRIC. This study suggests that a 12-week course of CRIC treatment could reduce AF burden in patients with permanent pacemakers, supporting the widespread use of CRIC in the daily lives of these patients, which needs to be verified in the future.

Impaired Left Atrial Function in Patients with Atrial Septal Defect and History of Atrial Fibrillation.

In patients with atrial septal defect (ASD), atrial left-to-right shunting causes left atrial (LA) remodeling and dysfunction, leading to atrial fibrillation (AF). In adults with ASD and concomitant AF, LA function should be evaluated after ASD closure plus AF radiofrequency catheter ablation (RFCA).This multicenter retrospective cohort study included patients who underwent transcatheter ASD closure at one of the four leading hospitals. Patients with a history of AF also underwent preceding RFCA. The association between AF history and LA ejection fraction (EF) (indicating LA global function) at 6-12 months following ASD closure was evaluated. To account for differences in baseline characteristics between patients with and without a history of AF, we conducted the following statistical methods: (1) multivariate regression analysis in the prepropensity score (PS)-matched cohort and (2) univariate comparisons in the PS-matched cohort.Overall, this study included 231 patients (30 with AF history, 201 without). Multiple regression analysis showed that AF history was independently associated with impaired LAEF (ß = -10.425, P < 0.001, model created prior to propensity matching). A one-to-one PS matching (25 pairs) showed that the LAEF at 6-12 months following ASD closure was significantly impaired in patients with ASD and AF history compared to that in patients without history of AF (median LAEF, 37.5% (interquartile range [IQR] 29.4%-48.5%) versus 52.3 [IQR 50.0%-56.6%]; P < 0.001).LA function was impaired in patients with ASD and a history of AF at 6-12 months after successful transcatheter ASD closure and on maintenance of sinus rhythm by RFCA.

Practical Considerations for the Application of Nonlinear Indices Characterizing the Atrial Substrate in Atrial Fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and in response to increasing clinical demand, a variety of signals and indices have been utilized for its analysis, which include complex fractionated atrial electrograms (CFAEs). New methodologies have been developed to characterize the atrial substrate, along with straightforward classification models to discriminate between paroxysmal and persistent AF (ParAF vs. PerAF). Yet, most previous works have missed the mark for the assessment of CFAE signal quality, as well as for studying their stability over time and between different recording locations. As a consequence, an atrial substrate assessment may be unreliable or inaccurate. The objectives of this work are, on the one hand, to make use of a reduced set of nonlinear indices that have been applied to CFAEs recorded from ParAF and PerAF patients to assess intra-recording and intra-patient stability and, on the other hand, to generate a simple classification model to discriminate between them. The dominant frequency (DF), AF cycle length, sample entropy (SE), and determinism (DET) of the Recurrence Quantification Analysis are the analyzed indices, along with the coefficient of variation (CV) which is utilized to indicate the corresponding alterations. The analysis of the intra-recording stability revealed that discarding noisy or artifacted CFAE segments provoked a significant variation in the CV(%) in any segment length for the DET and SE, with deeper decreases for longer segments. The intra-patient stability provided large variations in the CV(%) for the DET and even larger for the SE at any segment length. To discern ParAF versus PerAF, correlation matrix filters and Random Forests were employed, respectively, to remove redundant information and to rank the variables by relevance, while coarse tree models were built, optimally combining high-ranked indices, and tested with leave-one-out cross-validation. The best classification performance combined the SE and DF, with an accuracy (Acc) of 88.3%, to discriminate ParAF versus PerAF, while the highest single Acc was provided by the DET, reaching 82.2%. This work has demonstrated that due to the high variability of CFAEs data averaging from one recording place or among different recording places, as is traditionally made, it may lead to an unfair oversimplification of the CFAE-based atrial substrate characterization. Furthermore, a careful selection of reduced sets of features input to simple classification models is helpful to accurately discern the CFAEs of ParAF versus PerAF.

A new implantable tool for repeated assessment of supraventricular electrophysiology and atrial fibrillation susceptibility in freely moving rats.

The complex pathophysiology of atrial fibrillation (AF) is governed by multiple risk factors in ways that are still elusive. Basic electrophysiological properties, including atrial effective refractory period (AERP) and conduction velocity, are major factors determining the susceptibility of the atrial myocardium to AF. Although there is a great need for affordable animal models in this field of research, in vivo rodent studies are limited by technical challenges. Recently, we introduced an implantable system for long-term assessment of AF susceptibility in ambulatory rats. However, technical considerations did not allow us to perform concomitant supraventricular electrophysiology measurements. Here, we designed a novel quadripolar electrode specifically adapted for comprehensive atrial studies in ambulatory rats. Electrodes were fabricated from medical-grade silicone, four platinum-iridium poles, and stainless-steel fixating pins. Initial quality validation was performed ex vivo, followed by implantation in adult rats and repeated electrophysiological studies 1, 4, and 8 wk postimplantation. Capture threshold was stable. Baseline AERP values (38.1 ± 2.3 and 39.5 ± 2.0 using 70-ms and 120-ms S1-S1 cycle lengths, respectively) confirmed the expected absence of rate adaptation in the unanesthetized state and validated our prediction that markedly higher values reported under anesthesia are nonphysiological. Evaluation of AF substrate in parallel with electrophysiological parameters validated our recent finding of a gradual increase in AF susceptibility over time and demonstrated that this phenomenon is associated with an electrical remodeling process characterized by AERP shortening. Our findings indicate that the miniature quadripolar electrode is a potent new tool, which opens a window of opportunities for better utilization of rats in AF research.NEW & NOTEWORTHY Rodents are increasingly used in AF research. However, technical challenges restrict long-term supraventricular electrophysiology studies in these species. Here, we developed an implantable electrode adapted for such studies in the rat. Our findings indicate that this new tool is effective for long-term follow-up of critical parameters such as atrial refractoriness. Obtained data shed light on the normal electrophysiology and on the increased AF susceptibility that develops in rats with implanted atrial electrodes over time.